The most common cause of Tuberculosis (TB) infection in solid organ transplant (SOT) recipients is reactivation of latent TB infection (LTBI), while 4% are donor-derived. Active tuberculosis infection in a donor is incompatible with organ donation. Screening protocols for deceased donors may also fail to detect TB on occasion. This report details a case of disseminated tuberculosis in an organ donor that resulted in negative outcomes for the recipients.
The giverThe donor was a female of 23 years old. At 36 weeks pregnant, she was admitted due to complaints of an intense headache. She developed a mild fever, cervical stiffness, and seizures within 72 hours of admission. Increased proteins and cellularity, but no microorganisms, were found in the CSF. Meningoencephalitis was treated empirically with ceftriaxone, followed by anti-tuberculosis medication and acyclovir. AFB (acid-fast bacilli) staining of respiratory secretions was negative. On the sixth day of admission, the patient’s level of consciousness decreased, and she underwent an emergency C-section. Brain CT imaging subsequently revealed a diffuse subarachnoid haemorrhage. On the ninth day of admission, the patient was diagnosed with brain death and elected to be an organ donor based on the diagnosis of CNS haemorrhage. The tracheal aspirate culture was positive for M. tuberculosis 2 months after her demise. Her infant was diagnosed with disseminated tuberculosis and successfully treated after presenting at two months of age with a fever of indeterminate origin.
The index case – simultaneous recipient of a pancreas and kidney A 45-year-old man with end-stage kidney disease and diabetes received a pancreas and kidney transplant at the same time. His prior tuberculin skin test (TST) was negative, and he denied exposure to TB. His post-transplant immune suppression regimen included basiliximab, prednisone, tacrolimus, and mycofenolate mofetil. On the second month following his transplant, he complained of fever, chills, and night sweating. His chest X-ray was normal, but an ultrasound of his abdomen revealed perigraft deposits (renal and pancreatic abscesses). With the administration of broad-spectrum antibiotics and drainage of the abscesses, his fever temporarily subsided. Anti-TB treatment (rifampin, isoniazid, pyrazinamide, and ethambutol) was initiated upon the discovery of AFB on ZN stain. Notify the transplant harvesting centre.
The patient manifested with drug-induced side effects related to the anti-TB medications, including hemolytic anaemia and blurred vision. Therefore, his medications were altered. The patient had disseminated disease affecting the grafts, lungs, central nervous system, and thyroid. This resulted in the discontinuation of immunosuppressive medications, which led to graft loss. After 18 months of treatment, the patient was declared to have been successfully treated for tuberculosis. Unfortunately, the patient passed away two years after transplantation due to end-stage renal disease and dialysis-related complications.
The organ recipientA 55-year-old male with Caroli disease and recurrent bacterial cholangitis received a liver transplant. Prior to surgery, the patient’s TST was positive; consequently, the patient was treated for LTBI with isoniazid monotherapy for six months immediately following the transplant. As of the time of publication, the patient had not developed active TB.
The beneficiary of the recipient’s heart The recipient of the heart was a 40-year-old woman who was diagnosed with Chagas cardiomyopathy and class IV heart failure. She presented with fever and malaise three months after the transplant and died within three days of admittance due to severe septic shock unresponsive to broad-spectrum antibiotics. Blood, urine, and tracheal aspirate samples did not contain any bacteria or fungi upon culture. No culture of mycobacteria was requested. Her chest CT revealed diffuse involvement of the lungs.
The other recipient of a kidney A 45-year-old man with systemic hypertension and end-stage hypertensive nephropathy received a transplant of his other kidney. The patient had to revert to dialysis after developing mesangioproliferative glomerulonephritis and graft loss during the second month following transplantation. Three months after the transplant, the patient presented to the hospital with sepsis of indeterminate origin despite antimicrobial treatment. No specific mycobacterial test was requested.
Discussion
Mortality and morbidity can be caused by infections in SOT recipients. The purpose of this case report was to emphasise the significance of donor selection in reducing the risk of transmission of potentially fatal but treatable diseases. In this instance, the donor had unrecognised TB transmission. Except for pregnancy, she had no previous TB or TB exposure history. She resided in an area with a moderate risk for tuberculosis. Screening for active or latent tuberculosis is not performed in all centres because the developed guidelines are not mandatory in all situations. No molecular analyses were performed on the patient because she had no respiratory symptoms and imaging did not reveal any respiratory involvement. Since the TB culture is time-consuming, the results were obtained two months following the transplant. The CSF analysis, however, revealed an elevated protein level and pleocytosis. In hindsight, the intracerebral haemorrhage was likely caused by cerebral vasculitis resulting from the TB infection. Current recommendations advise against organ donation if meningoencephalitis was the undetermined cause of death.
In this instance, the beneficiary of a liver transplant was treated for latent tuberculosis and did not develop active infection. The other two recipients perished due to organ failure and sepsis of unknown origin. These results are consistent with TB donor transmission, but transmission was only confirmed in the recipient who underwent spontaneous pancreas and kidney transplants.
Despite the fact that TB cultures are known to be time-consuming, the results should be disseminated to all involved centres and recipients. In this instance, there was no protocol that defined who was responsible for reviewing the pending results. This would have prompted clinicians to initiate treatment sooner, which could have prevented graft loss and mortality.
The purpose of this case report was to draw attention to the significance of prompt notification of any suspicious cases of infection transmitted by the donor, including tuberculosis, so that the recipients can be traced and, if possible, treatment can be initiated promptly.
Level Of Evidence: level four
Take Home Message
TB is a difficult disease to diagnose, requiring a high index of suspicion. Before a potential donor donor can be utilised in a deceased donor organ programme, the cause of death must be determined with certainty.
Effective communication between the donor hospital and the receiving institution is essential for reducing morbidity and mortality.
Donor derived TB accounts for less 4% of cases of TB . In KT , the frequency of active TB is about 20 to 74 times higher than in the general population.
TB in KT associated with high morbidity and mortality.
Identification of high risk donors minimize the risk of DD transmission, failure to Identification of them lead to transmission of potentially fatal disease to the recipient.
Active TB in the donor is a contraindication for organ donation.
In case of deceased donor, the diagnosis of TB may be not feasible. As screening protocol for deceased donorbbased on x ray, epidemiological risk and previous TB history so extrapulmonary TB and disseminated TB may be not recognized.
Failure of recognition of high risk donor leads to poor outcomes
This case report describes a case of unrecognized disseminated TB in the donor with a devastating outcomes for organ recipients. The donor was a pregnant woman who died soon after delivery due to TB involvement of the CNS and lungs.
The diagnosis was retrospectively established by mycobacterial culture of the respiratory sample two months after death and the diagnosis of congenital TB in her baby.
Recipients
1. First recipient had simultaneous pancreas kidney transplantation….disseminated TB….died 2 years after transplantation from ESRD complications
2. Kidney recipient ….died 3 months after transplantation due to sepsis of unknown origin
3. Heart recipient….. died 2 months after transplantation due to sepsis of unknown origin
4. Liver recipient diagnosed to have latent TB and treated
This case report calls the attention to the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases.
Level 4
Take home messages
This report highlights that communication gaps may result in donor derived infection.
There is need for a data bank and donor sample analysis to trace infections
The importance of better communication between transplantation teams and organ harvesting centers .
Improvement of screening strategies for TB to identify high risk donor to prevent DDI
This is a report case of donor with Tb of the central nervous system and lungs. The diagnosis was retrospectively established by mycobacterial culture of the respiratory sample (positive result obtained two months after donor death) and the diagnosis of congenital TB in her baby.
A 45-year-old male received a simultaneous pancreas kidney (SPK) transplant. During the second month posttransplant, he returned to the hospital complaining of fever, night sweats, and chills and bdominal ultrasonography revealed perigraft collections. analysis revealed acid-fast bacilli on Ziehl-Neelsen stain.The patient subsequently presented with anti-TB drug toxicities. Then he presented disseminated disease involving grafts, lungs, CNS, and thyroid. He developed acute cellular rejection of the grafts, and dual graft loss with return to hemodialysis and insulin therapy. The patient underwent exploratory laparotomy with a surgical finding of caseating necrosis all over the mesenterium and around pancreatic graft, but affecting the renal graft. The removal of the renal graft was the only viable treatment encountered. After several ultrasound guided punctures to drain intra-abdominal TB abscesses and 18 months of antiTB therapy, the patient was considered cured. However, he died from complications related to ESRD and dialysis, two years after transplantation.
The liver recipient was a 55-year-old man who was treated for LTBI with isoniazid, soon after the transplant. The treatment was maintained for six months, and the patient has not developed any manifestations compatible with active TB to date.
The heart recipient was a 40-yearold woman who after 3 months from the procedure, she was admitted to the hospital with fever and malaise. Within three days after admission, she developed severe septic shock and died despite broad-spectrum antibiotic therapy. Her chest CT revealed diffuse pulmonary involvement.
The kidney recipient was a 45-year-old man who during the second month after transplantation, he developed mesangio-proliferative glomerulonephritis and graft loss and returned to dialysis. Three months after transplantation, he returned to the hospital with sepsis of unknown origin and died despite antimicrobial therapy, without isolation of any specific infectious agent.
Both the kidney and heart recipients did no specific test for mycobacteria. Unfortunately, no autopsy was performed on the deceased organ recipients, and therefore, for both the heart and kidney recipients, the TB diagnosis is only presumptive.
the level of evidence is 5
take home message:
close communication is important to prevent morbidity and mortality.
Introduction:
The majority of tuberculosis (TB) cases in solid organ transplant (SOT) recipients result from the reactivation of latent TB infection (LTBI), while only a small percentage (4%) are caused by donor-derived tuberculosis (DD-TB). Current screening protocols for deceased donors primarily rely on chest X-ray findings, previous TB history, and epidemiological risks, which may not accurately identify extrapulmonary and disseminated TB. As a result, TB in the donor may go unrecognized, leading to donor-derived infections (DDI) in organ recipients. This report presents a case of undetected disseminated TB in a donor, with severe consequences for the organ recipients. The donor, a pregnant woman, died shortly after delivery due to TB involvement in the central nervous system (CNS) and lungs.
The Index Case:
A 45-year-old male underwent a simultaneous pancreas kidney (SPK) transplant due to diabetes and end-stage renal disease (ESRD). His previous tuberculin skin test (TST) was negative, indicating no previous TB exposure. Two months post-transplant, he was readmitted to the hospital with symptoms of fever, night sweats, and chills. Abdominal ultrasound revealed collections near the grafts (renal and pancreatic abscesses), while the chest X-ray appeared normal. He received broad-spectrum antibiotics and underwent percutaneous drainage of the abscesses. Further analysis showed acid-fast bacilli (AFB) on Ziehl-Neelsen stain, confirming TB. Anti-tuberculous therapy was initiated but led to complications. The patient’s condition worsened, with disseminated disease affecting the grafts, lungs, CNS, and thyroid. Immunosuppressive treatment was stopped, resulting in dual graft loss and a return to hemodialysis and insulin therapy. Despite the cure of TB, the patient died two years later due to complications related to ESRD and dialysis.
The Donor:
The donor was a pregnant woman who died after delivery due to TB involvement in the CNS and lungs. Analysis of cerebrospinal fluid (CSF) revealed increased cellularity and protein, but no microorganisms were found in the CSF and blood. Empirical treatment for meningoencephalitis was initiated. Respiratory secretions initially tested negative for AFB, but two months after the donor’s death, a tracheal aspirate culture became positive for Mycobacterium tuberculosis.
The Liver Recipient:
The liver recipient had a positive TST result for LTBI and received isoniazid treatment for six months after the transplant. The recipient remained asymptomatic and did not develop any manifestations consistent with active TB.
The Heart Recipient:
The heart recipient died two months after transplantation due to sepsis of unknown origin, although a chest CT scan revealed extensive pulmonary involvement.
The Other Kidney Recipient:
The other kidney recipient died three months after transplantation due to sepsis of unknown origin.
Discussion:
Careful donor selection plays a critical role in reducing the transmission risk of potentially lethal but treatable diseases. Donor-derived tuberculosis (DD-TB) is often associated with the donor’s epidemiological background and clinical history. When assessing the risk factors for DD-TB, it is important to consider various factors. These include evaluating the donor’s history for symptoms consistent with active TB and any past diagnosis of TB infection, whether active or latent. Additionally, factors such as homelessness, alcohol abuse or injection drug use, incarceration, recent exposure to individuals with active TB, and travel to areas where TB is endemic should be taken into account.
While molecular tests offer greater sensitivity and specificity in diagnosing TB, they are primarily employed when pulmonary TB is suspected. In the discussed case, the occurrence of intracerebral bleeding was likely a consequence of cerebral vasculitis resulting from TB infection.
To effectively manage cases of infection transmitted by the donor, including TB, it is crucial to promptly report any suspicious cases. This allows for timely identification and tracing of all recipients at risk, facilitating appropriate monitoring and intervention to prevent further transmission and ensure the well-being of the affected individuals.
The level of evidence provided by this article is classified as Level IV, which corresponds to a case report.
The main takeaway from this study can be summarized as follows. The current screening protocols for tuberculosis (TB) in deceased donors, which rely on chest X-ray results, epidemiological risks, and previous TB history, may not be sufficient to detect cases of TB that have spread beyond the lungs or become disseminated. To minimize the risk of transmitting TB from donors to recipients, it is crucial to identify high-risk donors. The study also highlights the significance of addressing communication gaps between organ procurement organizations and transplant centers, as these gaps can contribute to donor-derived infections and lead to adverse outcomes and even death for organ recipients. Implementing more effective screening protocols and improving communication channels are essential to prevent such scenarios. Additionally, the article suggests that organ donation should be avoided in cases where the cause of donor death is meningoencephalitis without a confirmed cause. Conducting autopsies becomes crucial in situations where the cause of death is unclear or poorly defined. Overall, this study emphasizes the importance of implementing enhanced screening measures, improving communication, and conducting thorough investigations in potential cases of donor-derived infections to ensure the safety and well-being of organ recipients.
Active TB is a contraindication for kidney transplantation
Screening methods: Epidemiological risk, history and chest radiograph
This case highlighted a young pregnant donor with disseminated TB- TB meningitis who was diagnosed with brain death post-emergency delivery and repeated CT brain showed diffuse subarachnoid bleeding (results were confirmed after 2 months of deceased donation- smear negative and culture positive for MTB).
Recipient background
Simultaneous kidney-pancreas
45-year-old
Primary kidney disease is DM
TST negative prior to transplant
Second-month post-transplant: fever, night sweats and chills- peri-graft collection positive for AFB—> Disseminated TB(lung, graft kidney, CNS, thyroid)
Acute rejection and graft loss
Died 2 years later due to a dialysis complication
Another kidney
45-year-old
Primary ds HPT
Second-month post-transplant developed MPGN and graft loss
Died 3 months after transplant for sepsis
Liver
55-year-old
The primary cause of liver failure is recurrent bacteria cholangitis (Caroli ds)
TST positive pre-transplant
Treatment starts immediately after the transplant
Heart
40-year-old
The primary disease of heart failure is Chagas cardiomyopathy
3-month post-transplant admitted for fever and septic shock
Died secondary to sepsis
What is the level of evidence provided by this article?
Level 5 (case report)
What is the take-home message?
Important to recognise active TB
Avoid donors with meningoencephalitis unknown cause
Level 4 eveidence Introduction:
-This article focusses on the development of TB in the recipient from the donor organ. —Donor derived TB is rare, at a small level of 4%.
-Donor derived TB is of because infections of different kinds are a major cause of morbidity and mortality in transplant recipients. This article highlights the necessity for careful donor selection to reduce risk of transmission of infection from donor to recipient.
-With donor transmission of TB, graft loss can occur in 20% of recipients. Conclusion
-Improvement of screening protocols along with development of standardized tests in this regard is need to further protect recipients.
1- Summarise this article
Introduction:
TB commonly occurring in transplantation are due to reactivation of latent in active TD, rather than transmission from the donor which is a rare cases.
This article reports 45 y old male patient undergo simultaneous kidney pancreases transplantation from a female who died of disseminated TB After delivery.
The transplantation regimen are induction with Basiliximab and maintenance with prednisolone, MMF, and tacrolimus .
Eight weeks post transplantation patient present as fever, night sweats, and chills. Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses), which was positive to ziehil-neelsen stain . After anti TB drug starting patient develop drug toxicity in the form of , rifampicin toxicity hemolytic anemia, ethembutol blurring of vision. The management required to stop immunosuppressive medication which lead to graft rejection and start of dialysis. Patient died of dialysis complication.
There was heart, liver beside of kidney donation from the same donor. All three donors died because of TB.
Discussion:
Infectious cause is important cause of mortality in post transplantation. Active tuberculosis is contraindication for transplantation.
Meningoencephalitis without proven cause is contra indication to donation.
The diagnosis of TB meningitis is challenging with poor sensitivity and specificity of available diagnostic modality.
Reactivation of disease needs time to occur. Desired to do TB PCR for diagnosis. TB culture is time consuming needs about 6 weeks for results.
Donor infection screening program depend on patients history, physical examination and lab results.
High-risk complications of the recipient with eventual connection with the donor, such as death or sepsis within 3 months of the procedure, should be actively notified. In the reported case, if a flag for a possible DDI was detected after the first recipient’s death, the others could certainly have had a better chance.
Screening program for donor infection is important for safe transplantation.
A more efficient reporting system will not prevent the event from occurring but may of course impact the outcome.
Specific policies may be established to improve the recognition of the disease in donors.
This paper underscores the importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner.
2- What is the level of evidence provided by this article?
The level is 4
3- What is the take-home message?
To prevent donor derived infection a screening strategy is needed the scope of screening will depend on history, physical examination, and lab result.
Donor-derived tuberculosis (DD-TB) accounts for less than 5% of TB cases and is considered a rare event.But when it occurs,it can lead to devastating consequences.In the transplant setting, the frequency of active TB is estimated to be 20 to 74 times higher than that in the general population, and it is associated with high mortality.
This article describes a case of DD-TB and emphasizes communication gaps that may occur between organ procurement organizations and transplant centers.This report describes a case of unrecognized disseminated TB in the donor with a devastating outcome for organ recipients.
DD-TB is considered proven if donor and recipient isolates were reported to be identical or clonal through molecular analysis. In the absence of definitive confirmation of similar isolates, DD-TB is classified as probable if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if donor and recipient shared more than one epidemiologic or clinical feature (e.g., TB diagnosis in a donor plus TB in the recipient early posttransplantation) or possible, if there is a suspected transmission event but the only criterion met is a donor risk factor for TB (e.g., donor residence in TB endemic area and absence of recipient risk factors for TB.
DD-TB is difficult to recognize in both donor and recipient. it presents itself early after SOT, most commonly as fever, and carries a high mortality risk.
What is the level of evidence provided by this article?
Level of Evidence-5
What is the take-home message?
communication gaps may occur between organ procurement organizations and transplant centers. Failure in reporting results, lack of exchanging information regarding recipients from the same donor, and inefficient communication between organ procurement organizations and transplant centers are lacks that may be prevented by a more efficient approach towards screening protocols and communication.
Most tuberculosis (TB) cases in solid organ transplant (SOT) recipients are caused by the reactivation of latent tuberculosis infection (LTBI), and only 4% are considered donor derived. Active TB in the donor is recognized as an unacceptable risk and contraindicates organ donation.
considering that the recipient’s TB abscesses were located near the grafts, suggesting donor involvement, the transplant harvesting center was contacted for additional information regarding the donor and the other organ recipients. At that time, two recipients had already died, and a look-back investigation was carried out.
Transplantation is the treatment of choice for some types of end-stage organ failure. However, transplantation has risks related to the procedure itself and due to immunosuppres- sion. Still, there are several holdups associated with care, including the lack of important and complete information concerning donor screening, which can potentially lead to a notable reduced quality of life or may even cause death.
The major limitation to confirm DDI is to have a positive donor sample and genetic sequencing of the pathogen match- ing donor and recipient samples. Usually, there is often a time gap between the donation and the development of the disease. In this reported case, TB was confirmed in a donor sample two months after donation, and the result was still not properly informed because there was no tracking system to request the pending microbiological results. As such, donor transmis- sion is usually considered probable or possible, depending on the data available, but is much less often confirmed.
Of note, these types of information may not interfere with the real-time quality of life. Finally, it should be pointed out that adverse events such as those described here are very rare but may occur in any place or situation. A more efficient reporting system will not prevent the event from occurring but may of course impact the outcome. All in all, a fully developed network that integrates transplant centers, OPO’s, and laboratories is mandatory and could allow the recognition of potential hazards followed by a more rapid intervention.
Introduction
Reactivation of a latent mycobacterium infection is a typical cause of tuberculosis after an organ transplant. There is a link between donor-derived mycobacterium infection and a 4 percent chance of the infection being passed on to the recipient, which can have a negative impact on both the transplant and the patient’s health.
This case report describes a pregnant woman who died of diffuse CNS tuberculosis during delivery and her baby who developed congenital TB. After 2 months, this deceased donor’s culture shows positive mycobacterium tubercles, and the recipient develops a terrible graft result. This study screens deceased donors for trace infections and emphasizes the need for greater communication between the transplantation team and the organ harvesting center.
Screening donors for latent TB using nonspecific chest X-rays, epidemiological hazards, and TB history Pancreas transplant
The recipient is a 45-year-old male on immunosuppressive medication (basiximab, prednisone, tacrolimus, and mycofenolate mofetil) with a negative tuberculin test. His donor had tuberculosis.
Second month: fever, chills, nocturnal sweats, stomach ache Pus nears graft on abdominal ultrasonography. Cultures from percutaneous drainage showed acid-fast bacilli. Normal chest X-ray and routine antitubercular treatment with rifampin, isoniazid, pyrazinamide, and ethambutol.
Recipients develop drug toxicity from anti-tuberculous therapy due to drug interaction with immunosuppressive therapy and disseminated TB, leading to clinical deterioration. They stop all immunosuppressive therapy, leading to graft failure, and return patients to dialysis and lapratomy done with removal of the renal graft and intravenous anti-tuberculous for long duration. Patients were cured but died after 2 years due to ESRD and dialysis. Liver transplant
A transplant was performed on a 55-year-old man with Caroli illness due to recurrent bacterial cholangitis. TST was positive prior to surgery, and the transplant recipient was treated for six months with isoniazid for LTBI. The patient has not acquired any symptoms consistent with active tuberculosis. Heart transplant
A heart transplant was performed on a 40-year-old woman with Chagas cardiomyopathy who had class IV heart failure. She was taken to the hospital three months following the procedure with fever and malaise. Within three days, she passed away due to acute septic shock, without mycobacterial infection being considered. Her chest CT revealed diffuse involvement of the lungs. Kidney transplant
Due to hypertension-induced nephropathy, the patient got a kidney transplant. Two months later, the patient developed mesangioproliferative glomerulonephritis and graft loss and returned to dialysis. After three months, the patient comes down with sepsis and dies in spite of antimicrobial therapy and the absence of particular testing to rule out mycobacterium infection; TB is strongly suspected. Discussion
The best treatment option for patients with ESRD is a kidney transplant, but there is a substantial risk of infection from donor-derived infection due to the potency of immunosuppressive drugs, particularly during the first six months. A life-threatening infection, like tuberculosis, can cause graft loss and raise the incidence of mortality. In these reported cases, tuberculosis infection is not confirmed but strongly suspected due to clinical manifestations that strongly suggested TB and the onset of symptoms within two months of transplantation. Furthermore, only two samples confirm the presence of acid-fast bacillus in the donor of the first case, and the patient died despite receiving anti-tuberculosis treatment. In another example, anti-tuberculosis treatment was effective despite the absence of acid-fast bacilli in both the donor and recipient samples; the donor had a history of tuberculosis exposure.
Before proceeding with a transplant, this article emphasizes the significance of donor selection and infection screening in both the donor and recipient. In addition, this research illuminated the significance of the interaction between the transplant team and the donor bank for the proper selection of donors to reduce infection risks.
What is the level of evidence provided by this article?
Level V
What is the take-home message?
Prompt notification of any suspicious cases of infection trasmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner.
Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
Only 4% of TB in solid organ recipients are donor-derived.
TB recognition is not always easy.
In many cases, pre-transplantation screening fails to identify TB in the donor.
This report highlights the need for data bank & donor sample analysis to trace TB infections and emphasizes the importance of better communication between transplantation teams &organ-harvesting centers.
TB diagnosis contributed to fatal outcome in one patient and may causative of infectious disease complication following transplantation in the other two.
Discussion
Infections are considered major cause of morbidity &mortality for SOT recipients.
Active TB is an absolute contraindication for donation.
Although sputum culture has higher sensitivity than AFB ,it takes long time; weeks to months .So, molecular tests present better sensitivity and specificity and are done when pulmonary TB is suspected.
Based on current recommendations, in cases of donor death due to meningoencephalitis without clear cause, the donation should be avoided .
To improve screening strategies, certain potential findings should be thought of such as existence of any comorbidity that may support stroke, presence of fever at illness presentation/admission in the potential donor, CT/MRI scan of the head, or CSF findings indicating infectious process, and whether the donor was an immunosuppressed or had any potential environmental exposures related to organisms causing meningoencephalitis.
There is often a gap between donation and development of the disease.
Despite that it is desirable to have molecular typing and analysis of patterns of the isolates, this is not always feasible..
M. tuberculosis is identified in culture after 4 – 6 weeks.
Organ donor screening for infections is based on donor history, clinical assessment, and laboratory testing.
High-risk complications of the recipient with eventual attribution with the donor, such as death and/ or sepsis within 3 months following transplantation, should be notified. In the reported case, if a flag for a possible DDI was discovered after the first recipient’s death, the other cases could certainly have had a better chance.
The surveillance of DDI has a strong indicator of transplant safety.
A more efficient reporting system will not prevent the event but may improve the outcome.
-Level of evidence IV.
1. Summarize the article Introduction Tuberculosis (TB) in a solid organ transplant recipient is mostly due to reactivation of latent TB infection (LTBI), only 4% being donor derived. Pre-transplant screening protocols may fail to identify TB in donor (especially in decease donor) and communication gaps in such scenario may lead to poor outcomes. Donor derived TB infection (DDI) in multiple recipients from a deceased donor, which was not detected at the time of transplant, leading to catastrophic consequences – due to communication gap, is narrated. The donor: 23-years female was admitted to hospital with 36 weeks pregnancy, headache, neck stiffness, seizures and fever. CSF abnormality showed increased protein and cellularity. Emergency Caesarean section was done, child being normal. No improvement to antibiotics and antivirals; subarachnoid haemorrhage on CT brain detected on day-6, and subsequent brain death declared on day 9 of hospital admission. Respiratory secretions were negative for acid-fast bacilli (AFB). Organs shared to 4 different recipients – one simultaneous pancreas kidney (SPK), a liver, a heart, and another kidney recipient. The SPK recipient: (index case) 45 years male diabetic and ESRD; no history of tuberculosis – negative TST. Had uneventful post-operative recovery. 2-months post-transplant, he was admitted to hospital with fever, chill, night sweats. Ultrasound revealed multiple abscess around pancreas and renal allograft. Percutaneous drainage of pus was positive for AFB. Patient improved after responded multiple percutaneous drainage and ATT given for 18months. ATT related toxicities like Haemolytic anaemia (Rifampicin) and blurred vison (Ethambutol) mandated change in regimen, and later cessation of immunosuppression due to clinical worsening, leading to dual-graft-failure. Pyonephrotic graft kidney removal and drainage of abscess along with 18months ATT cured the TB, but the patient died 2 years post-transplant due to complications related to TB, ESRD and dialysis. The heart recipient: 40-years female with uneventful post-operative period, presented 3 months post-transplant with fever and malaise, developed septic shock and died. No organism could be identified, but tuberculosis work up was not done, because of lack of suspicion and patient was sick all of a sudden, although CT chest showed diffuse pulmonary lesions. The other kidney recipient: 45-years male without history of TB, developed mesangio-proliferative glomerulonephritis and graft loss in second month post-transplant, the next month (3 months post-transplant) he died of sepsis. The liver recipient: 55-years male with, positive tuberculin skin test (TST), was treated for LTBI soon after transplant for 6 months – no complications related to TB was seen. The donor: After the intractable TB infection in the SPK recipient, the team contacted the retrieval unit about TB in the donor and tried to trace back about all other recipients who got organs from the same donor. The tracheal secretion culture taken at the time of admission grown M. tuberculosis, which was reported about 2 months later. The child after 2months post-delivery had disseminated TB, was found to be infected with same strain of M-TB and responded well to ATT. Discussion: This index case points towards careful selection of donor, including detailed history and epidemiological evaluation. Active TB infection is a contraindication for organ donation. The index donor had an unrecognized disseminated TB with no history related to TB (active TB, exposure to persons with TB, travel to regions with endemic TB, past history of TB, alcohol abuse, injectable drug abuse, homelessness, incarceration etc). The donor’s sputum culture for TB became positive after 2 months, molecular testing with higher sensitivity and specificity and rapid results could have been helpful in such scenario. The donor had intracerebral bleeding, which could have been due to TB related cerebral vasculitis – thus according to guidelines, in case of death due to unproven cause of meningoencephalitis, organ donation should be avoided. A donor-derived TB could be defined as proven (when the isolates in donor and recipient are identical or clonal), probable (when TB identified in multiple recipients of same donor or if donor and recipient have >1 shared epidemiologic or clinical feature), or possible (suspected transmission in presence of donor risk factor of TB). In the index case, donor sample confirmed TB 2 months post-donation, but there was lack of a mechanismto convey this result to the teams managing the different transplant recipients. Presence of perigraft collections, and infection in early post-transplant period point towards a diagnosis of donor-derived TB in the SPK recipient. Liver recipient received LTBI treatment and did not develop any symptoms The other 2 recipients died with sepsis with undiagnosed aetiology. A review of donor-derived TB showed a median time of diagnosis is 2.7 months – fever is the most common symptom, high mortality is reported in SOT recipients. The gaps identified in this scenario include: Lack of mechanism to convey the result of pending investigation results, notification of high-risk complications in recipient leading to death or graft loss, lack of communication regarding vertical transmission of TB (to the child from the mother), and lack of biovigilance system (donor traceability). Conclusion: A stringent donor screening with a robust reporting system to deal with investigation results coming late. Promptly communication regarding donor-derived infection to the transplant teams managing all the recipients, could help in avoiding such catastrophes. 2. What is the level of evidence provided by this article? Level of evidence: Level 4 – Case report 3. What is the take-home message?
Stringent donor selection criteria (especially for cadaver program) with detailed history and epidemiological evaluation.
2. In case of death due to unproven cause of meningoencephalitis, organ donation should be avoided.
Protocols of communication should be in place, regarding conveying of results of tests in the deceased donor coming late – through the organ sharing network, to recipients’ units for further treatment of the recipients. This can be like the infectious disease notification system.
Protocols to trace recipients be defined and any suspected donor-derived infection should be notified to all the transplant units managing those recipients.
The article is about DDI of TB
Donor- preganant, brain dead due to meningoencephalitis , CSF- infective cause
AFB negative ,
NO epidemiological risk factor
Tracheal AFB culture was not available at the tiem of transplantation
child at 2 mo has disseminated TB
TB WAS NOT SUSPECTED IN DONOR BASED ON ABOVE FINDINGS
Recipients
SPK patient is index case who died of ESRD complication but had proven disseminated TB , caseating lesion seen during laparatomy
liver recipient – latent TB diagnosed , treated SO HE IS ALIVE
other kidney recipient – died os sepsis , TB investigations were NOT REQUESTED , AS IT WAS NOT SUSPECTED
heart recipient – died of sepsis , TB investigation not requested
WHAT WOULD HAVE BEEN THE BETTER APPROACH OR LEARNING
Donor AFB culture was not followed up
Someone from donor team must take a responsibility to do the same
child had disseminated TB at 2 month – this is a notifiable fact and could have avoided some risk if latent TB was treated in heart and both kidney transplant recipient
Genetic study on AFB samples is must to say that TB is donor derived
INFORMATION GAP OR FAILURE TO NOTIFY THE DIAGNOSIS OF TB in donor and/or child is the take home message
Summarize the article; Introduction; Most tuberculosis case in SOT recipient are caused by the reactivation of latent tuberculosis infection, and only 4% are considered from donor. This is a case of 45 male who received Pancrease and Kidney from a pregnant women who was a undiagnosed with disseminated TB died post-delivery. Post-transplant immunosuppression was induction with Basiliximab and maitianence is prednisolone, MMF, and tacrolimus. Two months post-transplant he presented with symptoms was infection, and was diagnosed with peri-renal collection, drained and culture shows Ziehl-Neelsen stain was positive, ATT with four drug started. Latter on developed dessiminated disease with drug toxicity, rifampicin toxicity hemolytic anemia, ethembutol blurring of vision Stop immunosuppression à acute cellular rejection, After 18 months of ATT and multiple procedures TB cured but patient died of ESRD complication after two years. The recipient for liver was 55 year-old male, before transplant he was positive for TST, and given treatment for LTBI, latter on INH was continued for six month, he did not developed disease. The Heart recipient three months post-transplant has died of sepsis and septic shock, on further investigation shows disseminated pulmonary TB. Discussion; Infection has been a major risk factor for morbidity and mortality post-transplantation. Donor tuberculosis is absolute contraindication for SOT. Prevention of DDI is to improve screening strategies, good history, comorbidities, screening, if any suspected infection thorough investigation up-to CSF, MRI etc. Level of evidence IV. What is take home massage? Need to confirm the diagnosis of patient deceased with unknown cause, give prolong prophylaxes. A good history and contact history mandatory, Confirmation of any occult infection post-transplantation.
Most cases of Tuberculosis (TB) in post-transplantation are due to activation of latent disease, but about 4% are represented by tuberculosis transmitted by the donor. Countries with a high endemic rate have a higher risk and the screening that is performed for cadaver transplants can be a trap for transmission because it only uses chest X-ray and epidemiological risk assessment, which is not enough to rule out extra-pulmonary TB .
This article summarizes the cases of patients who received organs from a donor with CNS and pulmonary tuberculosis (diagnoses performed with culture results 2 months later and diagnosis of congenital TB in the baby) and presented evolutions with death of undetermined etiology or presented ALSO:
– Index case: kidney-pancreas recipient who was known not to have been exposed and tuberculin test was negative. He returned 2 months after the transplant with peri-graft collections that were later diagnosed with the presence of acid-fast bacilli (AFB). Unfortunately, the disease spread to the CNS, lung and thyroid and, with the suspension of immunosuppressants, the patient presented rejection. She managed to reach the cure thanks to the removal of the graft, but later died of infectious complications from returning to hemodialysis.
– Liver recipient: had a positive pre-transplant tuberculin skin test and thus started treatment for latent tuberculosis shortly after the transplant and this patient did not suffer any strange intercurrences.
– Heart recipient: after 3 months of transplantation, she was admitted with fever and malaise, progressing to septic shock and death of unknown etiology (negative bacterial and fungal cultures and exams for mycobacteria were not collected)
– Other renal recipient: During the second month after transplantation, he developed mesangioproliferative glomerulonephritis and graft loss and returned to dialysis. Three months after transplantation, he returned to the hospital with sepsis of unknown origin and died despite antimicrobial therapy, without isolation of any specific infectious agent.
In the specific case of tuberculosis, donation centers should obtain a donor history of symptoms consistent with active TB, such as a previous diagnosis of TB infection (active or latent), homelessness, alcohol abuse or injecting drug use, incarceration, recent exposure to people with active TB, or traveling to areas where tuberculosis is endemic, being advised to screen with radiographic imaging.
Another difficulty is that, in order to confirm the transmission of tuberculosis, a positive sample from the donor and the genetic sequencing of the pathogen compatible with the samples from the donor and recipient are required. Or, if transmission is suspected and TB has been identified in multiple recipients from a donor, or if donor and recipient share more than one epidemiological or clinical characteristic (e.g. diagnosis of TB in one donor plus TB in recipient at baseline post-trans plantation) or possible, if there is a suspected transmission event, but the only criteria met is a donor risk factor for TB (e.g., donor resides in a TB-endemic area and lack of recipient risk factors for ALSO).
Thus, the need for a specific policy for more efficient recognition of the disease in countries where its prevalence is higher is clear. However, these created guidelines are only recommendations and are not mandatory.
What is the level of evidence provided by this article?
This is a level 4 article, because it is the report of a series of cases.
What is the take-home message?
Transplant centers need a fully developed network with OPO and laboratories for reporting events.
Tuberculosis (TB) in a renal transplant recipient is mostly due to reactivation of latent TB infection (LTBI) with a miniscule (4%) being donor derived. Pre-transplant screening protocols may fail to identify TB in donor and communication gaps in such scenario may lead to poor graft and patient outcomes. The articles presents a case of deceased donor transplant to multiple recipients with donor derived infection (DDI) having catastrophic consequences in absence of communication gaps.
The donor: A 23-year-old female who was 36 weeks pregnant was admitted to hospital with headache, neck stiffness, seizures and fever, with CSF showing increased cellularity and protein. Emergency Caesarean section was done. CT brain revealed subarachnoid hemorrhage and brain death declared on day 9 of hospital admission. Respiratory secretions were negative for acid-fast bacilli (AFB). She became organ donor for 4 different recipients: a simultaneous pancreas kidney (SPK), a liver, a heart, and a kidney recipient.
The index case: SPK recipient. 45-year-old male with no past history of tuberculosis, uneventful post-operative period, developed fever and night sweats in second month post-transplant. Ultrasound revealed perigraft collections, which on drainage were found to be AFB stain positive. Patient was started on antituberculous therapy (ATT). He developed ATT related toxicities prompting change in therapy, but clinically worsened leading to cessation of immunosuppression, further causing graft failure and removal of graft (due to intrabdominal TB abscesses). Patient died 2 years post-transplant with complications related to TB and CKD.
The liver recipient: 55-year-old male with past history of positive tuberculin skin test (TST), was treated for LTBI soon post-transplant for 6 months. No complications seen in him.
The heart recipient: 40-year-old female with uneventful post-operative period, presented 3 months post-transplant with fever and malaise, developed septic shock and died. No specific organism could be identified. CT chest showed diffuse pulmonary lesions.
The other kidney recipient: 45-year-old male with no past history of TB, developed mesangioproliferative glomerulonephritis and graft loss in second month post-transplant. 3 months post-transplant, he died due to sepsis.
The donor: 2 months after donation. Tracheal secretion culture at time of her admission became positive for M. tuberculosis. Developed fever and detected to have disseminated TB, responding to ATT.
Discussion: The index donor in the case points towards the role of careful donor selection including detailed history and epidemiological evaluation. Active tB is a contraindication for organ donation. The index donor had an unrecognized disseminated TB with no history related to TB (active TB, exposure to persons with TB, travel to regions with endemic TB, past history of TB, alcohol abuse, injectable drug abuse, homelessness, incarceration etc). The donor’s sputum culture for TB became positive after 2 months, molecular testing with higher sensitivity and specificity and rapid results are helpful in such scenario. The donor had intracerebral bleeding, which could have been due to T related cerebral vasculitis. According to guidelines, any donor with death due to unproven cause of meningoencephalitis should be avoided.
A donor-derived TB could be defined as proven (when the isolates in donor and recipient are identical or clonal), probable (when TB identified in multiple recipients of same donor or if donor and recipient have >1 shared epidemiologic or clinical feature), or possible (suspected transmission in presence of donor risk factor of TB).
In the index case, donor sample confirmed TB 2 months post-donation, but there was lack of a mechanismto convey this result to the teams managing the different transplant recipients. Presence of perigraft collections, and infection in early post-transplant period point towards a diagnosis of donor-derived TB in the SPK recipient. Liver recipient received LTBI treatment and did not develop any symptoms The other 2 recipients died with sepsis with undiagnosed etiology.
A review of donor-derived TB showed that median time of diagnosis is 2.7 months with fever being most common symptom and high mortality.
The gaps identified in this scenario include: Lack of mechanism to convey the result of pending investigation results, notification of high-risk complications in recipient leading to death or graft loss, lack of communication regarding vertical transmission of TB (to the child from the mother), and lack of biovigilance system (donor traceability).
To conclude, a stringent donor screening with a robust reporting system to deal with investigation results coming in late, and promptly conveying communication regarding any donor-derived infection to the transplant teams managing all the recipients could help in avoiding such scenarios.
2. What is the level of evidence provided by this article?
Level of evidence: Level 4 – Case report
3. What is the take-home message?
Stringent deceased donor selection criteria with detailed history and epidemiological evaluation.
Avoid any deceased donor with death due to meningoencephalitis of unknown etiology.
Defined protocols should be in place regarding conveying of results of tests which come late: who should be contacted, and by whom.
Define protocols for trace recipients and prompt notification of any suspected donor-derived infection to all the transplant teams managing such recipient.
Introduction :
Tuberculosis (TB) in solid organ transplant (SOT) recipients are caused by the reactivation of latent tuberculosis infection (LTBI) and only 4% are considered donor-derived .
45-year-old male received a simultaneous pancreas kidney (SPK) transplant due to diabetes and endstage renal disease (ESRD) . second month posttransplant, he returned to the hospital complaining of
fever, night sweats, and chills anf on USG found perigraft collections (renal and pancreatic abscesses),He received broad-spectrum antibacterial treatment and underwent percutaneous drainage of the abscesses, with transient resolution of fever. Laboratorial analysis revealed acid-fast bacilli (AFB) on Ziehl-Neelsen stain. Antituberculous therapy was started with standard drugs.But lateron patient develop disseminate TB as patient has to stop ATT due to toxicities.Patient completed ATT 18 month and cosidered cure ,but died after 2 year.
The donor was a 23-year-old, 36-week pregnant woman with h/o meningitis,underwent cessearian section at 6th day and brain death decleared 9th day of operation.after 2 moth ,Tracheal aspirate shows groth of M. tuberculosis.
Among othe receipent,liver recipient was asymptomatic and heart and other kidney receipient died due to sepsis.
Discussion:
Infections represent a major cause of morbidity and mortality for SOT recipients.This case report calls attention to the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases.In this reported case, the donor had no detectable abnormalities on the chest X-ray and AFB-negative smears, whereas the culture became positive two months after procurement. The donor had no respiratory symptoms or compatible image, and the AFB was negative, and therefore, TB was not suspected. However, the CSF analysis showed an elevated protein level with pleocytosis. Subsequently, the patient continued to decline neurologically, and brain death occurred nine days postadmission. The intracerebral bleeding was likely secondary to cerebral vasculitis due to TB infection.
According to current recommendations, in cases of donor death due to meningoencephalitis (ME) without a proven cause, the donation should be avoided .In this case, donor cause of death was considered CNS bleeding.
the liver transplant recipient was treated for latent TB and did not develop the disease. The two other organ recipients from the same donor presented fever of unknown origin, sepsis, and organ dysfunction a few months after transplantation.
Concerning the information gaps, we should reinforce that the donor had cultures pending at the time of procurement. It should be commented that culture results are routinely checked on day 7. However, mycobacterial culture is more time-consuming, and this result is not systematically evaluated.
● Most TB cases in SOT recipients are caused by the reactivation of latent (LTBI)
● Only 4% are considered donor-derived
● Active TB in donor is contraindication for organ donation
● Unusual symptoms of TB makes the diagnosis not always feasible
● Donor-derived infections (DDI) may be associated with death or poor outcomes
● A case of unrecognized disseminated TB in the donor with a devastating outcome for organ recipients.
♡ The Index Case – Simultaneous Pancreas Kidney
☆ A 45-year-old male Recipient
☆ Received a simultaneous pancreas kidney (SPK) transplant due to diabetes and end-stage renal disease (ESRD) .
☆ No major clinical complications and was discharged on post-operative day 30.
☆ TST (-) and no history of TB exposure.
☆ The immunosuppressive regimen included basiliximab, steroid, tac, and MMF
☆ He complains fever, night sweats, and chills during second month posttransplant
☆ Perigraft collections (renal and pancreatic abscesses) in abdominal US
☆ chest radiograph was normal.
☆ He received broad-spectrum antibacterial treatment and percutaneous drainage of the abscesses
☆ Laboratorial analysis revealed acid-fast
bacilli (AFB) on Ziehl-Neelsen stain.
☆ Antituberculous therapy was started with standard drugs: rifampin, isoniazid,
pyrazinamide, and ethambutol
☆ At that time, two recipients had already died
☆ The patient presented with anti-TB drug toxicities and deterioration of his clinical state imposed IS cessation, leading to AR of the grafts, and dual graft loss with return to hemodialysis and insulin therapy.
☆ The removal of the renal graft was the only viable treatment encountered
☆ After several ultrasound guided punctures to drain intra-abdominal TB abscesses and 18 months of anti-TB therapy, the patient was considered cured.
☆ He died from complications related to ESRD and dialysis, two years after RTx
♡ The donor
☆ A 23-year-old
☆ 36-week pregnant woman
☆ A history of intense headache
☆ She was dmitted to the hospital ER
☆ She developed mild fever, neck stiffness, and seizures within 72 hours
☆ CSF was abnormal with increased cellularity and protein.
☆ No microorganisms were identified in the CSF and blood
☆ Treatment was started 72 hours after hospital admission (ceftriaxone, anti-TB standard treatment and acyclovir)
☆ Respiratory secretions were negative for acid-fast bacilli (AFB) stain.
☆ Her consciousness decreased, and she underwent an emergency caesarean section on the 6th day of admission.
☆ Brain CT scans revealed diffuse SAB
☆ Brain death occured in day 9 and had elected to be an organ donor, with diagnosis “CNS bleeding”
☆ Two months after her death, tracheal aspirate culture became positive for MTB
☆ At that time her child presented with fever of unknown origin and was admitted to the same hospital, being diagnosed with disseminated TB.and he was discharged after seven days of standard TB treatment.
♡ The Liver Recipient
☆ A 55-year-old man
☆ Caroli disease who was transplanted because of recurrent bacterial cholangitis.
☆ He was treated for LTBI with isoniazid,
due to a positive TST before surgery soon after the transplant for six months
☆ Patient has not developed any manifestations compatible with active TB
♡ The Heart Recipient
☆ 40-year-old woman
☆ Chagas cardiomyopathy who underwent a heart transplant for class IV heart failure
☆ Three months after RTx , she admitted to the hospital with fever and malaise.
☆ She developed severe septic shock and died Within three days
☆ No bacteria or fungi were identified in cultures (blood, urine, and tracheal aspirate samples)
☆ No specific mycobacterial direct.exam or culture was requested.
☆ Chest CT revealed diffuse pulmonary involvement.
☆ TB diagnosis is only presumptive
♡ The Other Kidney Recipient
☆45-year-old man
☆ Terminal hypertensive nephropathy
☆ During the second month after renal transplantation, he developed mesangioproliferative glomerulonephritis and graft loss and returned to dialysis.
☆ Three months after transplantation, he returned with sepsis of unknown origin and died despite antimicrobial therapy
☆ No specific test for mycobacteria was requested.
☆ TB diagnosis is only presumptive
♡ Discussion
● Active TB is a contraindication for organ donation.
● Risk factors should be assessed :
☆ Symptoms consistent with active TB
☆ Past diagnosis of TBi (active or latent)
☆ Homelessness
☆ Alcohol abuse
☆ Injection drug use
☆ Incarceration
☆ Recent exposure to persons with active TB
☆ Travel to areas where TB is endemic.
● If risk factors are identified radiological
assessments are warranted.
● In this case donor had an unrecognized disseminated TB, with no history of previous TB or exposure except for pregnancy, no known immunosuppressive conditions
● The donor had no abnormalities on the chest X-ray and AFB-negative smears,
whereas the culture became positive two months after procurement.
● The intracerebral bleeding was likely secondary to cerebral vasculitis due to TB infection
● In cases of donor death due to meningo encephalitis (ME) without a proven cause, the donation should be avoided
● So donor cause of death was considered CNS bleeding
● TB is classified as probable :
☆ If TB was identified in multiple recipients of one donor
☆ If diagnosis in a donor plus TB in the recipient early posttransplantation
☆ TB possible, if donor residence in TB endemic area and absence of recipient risk factors for TB
● In TB donor transmission, the onset of TB is early in the posttransplant period
● In this case the liver transplant recipient was treated for latent TB and did not develop the disease.
● A recent review retrieved 36 cases
☆ The median time to clinical presentation or diagnosis was 2.7 months
☆ fever was the most frequent presenting
symptom.
☆ Allograft involvement was common.
☆ Graft loss occurred in ~20% of patients.
☆ All-cause mortality was 25%
● Mycobacterial culture is time consuming and this result is not systematically evaluated.
● Level : 4
● Take home massage :
☆ TB is a serious complication in renal transplant recipients
☆ Immunosuppressive transplant recipients are at a higher risk of re-activating LTBI from within themselves or from the transplanted donor kidney.
☆ All donors and recipients are routinely screened for LTBI and active TB disease prior to transplant whenever possible.
☆ A high degree of awareness of the possibility of TB is required in all donors so that it can be diagnosed and treated early,
reducing the risk of loss of allograft.
☆ Importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner.
This article on a case study is very impressive, with a lot of knowledge and messages for transplant nephrologists.
This article demonstrates that DDI of TB is very minimal at 4% only,while high morbidity and mortality if you are going to do a transplant with an infected organ. As we know, the morbidity and mortality of TB post-SOT is 20 to 74%, which is quite a high rate foreign for TB before SOR is mandatory, especially since there are many proper scr challenges.
TB is not always easy to diagnose and treat. The lesson from this case is we need prober communications between the organ procurement centre and the transplant centre to share the important result and feed beck to them with all new results; especially we know that this case result was issued 2 months after .
Discussion
The TB is not feasible to be diagnosed before SOT. Active TB is an absolute contraindication for SOT.
Sputum cultuer has the higher sensitivity but tooks very long time to release the result (2 months ) which is valuble time for the donor .so we need to have other solid base for diagnosisng TB like molecular testing which is more sensitive and specific with shorter time ,but still need to be held in suspected cases .
Organ donor screening for infections is currently based on donor history, physical assessment, and laboratory testing.
High-risk complications of the recipient with eventual connection with the donor, such as death or sepsis within 3 months of the procedure, should be actively notified. In the reported case, if a flag for a possible DDI was detected after the first recipient’s death, the others could certainly have had a better chance.
The surveillance of DDI is a strong indicator of transplant safety.
A more efficient reporting system will not prevent the event from occurring but may of course impact the outcome.
level of evidence 4
SUMMARY
The article is about DDI of TB
Donor- preganant, brain dead due to meningoencephalitis , CSF- infective cause
AFB negative ,
NO epidemiological risk factor
Tracheal AFB culture was not available at the tiem of transplantation
child at 2 mo has disseminated TB
TB WAS NOT SUSPECTED IN DONOR BASED ON ABOVE FINDINGS
Recipients
SPK patient is index case who died of ESRD complication but had proven disseminated TB , caseating lesion seen during laparatomy
liver recipient – latent TB diagnosed , treated SO HE IS ALIVE
other kidney recipient – died os sepsis , TB investigations were NOT REQUESTED , AS IT WAS NOT SUSPECTED
heart recipient – died of sepsis , TB investigation not requested
WHAT WOULD HAVE BEEN THE BETTER APPROACH OR LEARNING
Donor AFB culture was not followed up
Someone from donor team must take a responsibility to do the same
child had disseminated TB at 2 month – this is a notifiable fact and could have avoided some risk if latent TB was treated in heart and both kidney transplant recipient
Genetic study on AFB samples is must to say that TB is donor derived
INFORMATION GAP OR FAILURE TO NOTIFY THE DIAGNOSIS OF TB in donor and/or child is the take home message
Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
Most tuberculosis (TB) cases in solid organ transplant (SOT) recipients are caused by the reactivation of latent tuberculosis infection (LTBI), and only 4% are considered donor-derived.
TB recognition is not always feasible, particularly when unusual symptoms are under differential diagnostic consideration and the potential donor has low-epidemiological risk .
Thus, unfortunately, despite organ procurement protocols, pretransplantation screening fails to identify TB in the donor in many cases.
Additionally, this report also highlights the need for a data bank and donor sample analysis to trace infections and reinforces the importance of better communication between transplantation teams and organ-harvesting centers.
The TB diagnosis contributed to the fatal outcome in one patient and may be the cause of infectious disease complication after transplantation in the other two.
Discussion
Infections represent a major cause of morbidity and mortality for SOT recipients.
active TB is an absolute contraindication for organ donation.
Although sputum culture has higher sensitivity than AFB ,the time to positivity ranges from weeks to months .In this situation, molecular tests present greater sensitivity and specificity but are done when pulmonary TB is suspected.
According to current recommendations, in cases of donor death due to meningoencephalitis (ME) without a proven cause, the donation should be avoided .
Additionally, to improve screening strategies, certain potential findings should be scrutinised such as the existence of any comorbidity that may support stroke, the presence of fever at illness presentation/admission in the potential donor, CT/MRI scan of the head, or CSF findings consistent with an infectious process, and whether the donor was an immunosuppressed host or had any potential environmental exposures associated with organisms causing ME.
mentioning that the diagnosis of tuberculous meningitis is challenging, and the available microbiological tests fail to attain the accuracy standards required, with poor sensitivity and delayed results.
there is often a time gap between the donation and the development of the disease.
Despite the fact that it is desirable to have molecular typing and analysis of patterns of the isolates, this is not always possible.
M. tuberculosis is only identified in culture after 4 to 6 weeks.
Organ donor screening for infections is currently based on donor history, physical assessment, and laboratory testing.
High-risk complications of the recipient with eventual connection with the donor, such as death or sepsis within 3 months of the procedure, should be actively notified. In the reported case, if a flag for a possible DDI was detected after the first recipient’s death, the others could certainly have had a better chance.
The surveillance of DDI is a strong indicator of transplant safety.
A more efficient reporting system will not prevent the event from occurring but may of course impact the outcome.
DONOR DERIVED TB;A CASE REPORT AND ROLE OF COMMUNICATION GAPS IN TRANSPLANATION SAFETY.
INTRODUCTION.
Majority of TB post transplant is reactivated LTBI with only 4% being donor derived.
1.1 Index case; Simultaneous pancreas kidney recipient.
–45 yr old SPK from DM nephropathy whose previous TST was negative,2/12 post transplant had B symptoms with peri graft collection that stained AAFBS.DI and SE led to cessation of immunosuppression with graft dysfunction, graft nephrectomy was done,pt reverted to HD but later on succumbed to ESRD and HD.
1.2 Donor.
-23 yr old ,36/40 woman who died from TB complication that was missed initially but later 2/12 after death diagnosed via tracheal aspirate. Baby too had disseminated TB.
1.3.Liver recipient.
-55 yr old with caroli dx with recurrent cholangitis and tx for LTBI from a +ve TST and did well without developing active TB.
1.4 Heart Recipient.
-40 yr old woman with chagas cardiomyopathy who had a heart transplant who died 3/12 post transplant after presenting in sepsis, TB was not investigated but her chest CT had diffuse pulmonary involvement.
1.5 The other kidney recipient.
-45 yr old HTN with ESRD who 2/12 post transplant had mesangio-proliferative GN and graft loss with reversion to HD but died from sepsis with TB again not being investigated.
DISCUSSION.
-We should carefully select our donors to avoid spread of lethal but curable infections.
-Hx, risk factors and previous tx for TB should be sort from donor and active TB to be considered a contraindication to organ donation.
-Mortality from meningoencephalitis of unknown cause should prevent organ harvesting as TB is a potential risk.
-Poor communication is a risk factor for DDI and results to TB transmission, Registry to identify those with vertical transmission might decrease risk of TB and facilitate early intervention.
-An integrated system involving transplant center, OPO and labs could allow quick spotting of TB with early intervention.
-All suspected cases of infection from donor including TB should be notified to trace all those at risk.
LEVEL OF EVIDENCE – IV
TAKE HOME MESSAGE.
-All health care workers and centers need to be conversant with screening of potentially transmissible infections ,notify one another and prevent transplanting those with unsure diagnosis esp if cause of death was from an infection not clearly diagnosed. Appropriate communication strategies need to be put in place to ensure we dont have gaps that will end up in mortality post transplant.
–
· Donor-derived tuberculosis (DD-TB) accounts for less than 5% of TB cases. Though rare, careful screening is crucial to identify TB in the donor, specially deceased donor is necessary. · This case report is discussed disseminated TB in the donor with poor outcome in organ recipients. · Active TB is absolute contraindication to donation. This case report highlights the importance of careful donor selection to reduce the risk of transmission of a potential serious but treatable disease. · In this case, the donor had an unrecognized disseminated TB, with no history of previous TB or exposure. So, specific policies may be taken to improve the recognition of the disease in donors to save the recipients. · Here, donor investigated for CXR; showed no abnormalities, negative AFB, culture (positive after 2month). · Sputum culture is more sensitive than AFB, but culture take long time, weeks to months. · In case of pulmonaryTB suspected molecular tests is more sensitive and specific. CSF analysis showed an elevated protein level with pleocytosis, leading to brain death in this case. Level of evidence: IV. Take-home message: Tuberculosis from donor is rare but when occurs it is fatal; though it is a treatable condition. Early diagnosis is the key to treatment. In any infectious disease it is always better to prevent than treatment. So, further research is necessary to yield diagnostic tools to detect TB in donor.
Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
Introduction
Most tuberculosis cases in solid organ transplant recipients are caused by the reactivation of latent tuberculosis infection (LTBI) in the recipients, and only 4% are considered donor-derived. Active TB in the donor is contraindicates organ donation. However, current screening protocols for deceased donors are usually based on chest X-ray findings (which may be nonspecific), epidemiological risks, and previous TB history. These features may miss extrapulmonary and disseminated TB. Unfortunately, despite organ procurement protocols, pretransplantation screening fails to identify TB in the donor in many cases and even when diagnosed, communication gaps may result in donor-derived infections (DDI), which may be associated with death or poor outcomes.
The mentioned case report of unrecognized disseminated TB in the donor caused grave outcome for recipients. The donor was a pregnant woman who died soon after delivery due to TB involvement of the central nervous system (CNS) and lungs. The diagnosis was retrospectively established late by mycobacterial culture of the respiratory sample.
1-The Index Case of Simultaneous Pancreas Kidney Recipient:
A 45-year-old male received a simultaneous pancreas kidney (SPK) transplant due to diabetes and ESRD. His previous tuberculin skin test (TST) was negative, and no history of TB exposure. The immunosuppressive regimen included basiliximab, prednisone, tacrolimus, and mycophenolate mofetil. During the second month posttransplant, he admitted to the hospital complaining of fever, night sweats, and chills. Abdominal ultrasonography revealed peri graft collections (renal and pancreatic abscesses), and chest radiograph was normal. He received broad-spectrum antibacterial treatment and underwent percutaneous drainage of the abscesses. Laboratorial analysis revealed (AFB) on Ziehl-Neelsen stain. Antituberculous therapy was started with standard drugs: rifampin, isoniazid, pyrazinamide, and ethambutol. Due to anti TB drugs toxicity (Rifampicin) which led to change in therapy. At this time, the patient presented disseminated disease involving grafts, lungs, CNS, and thyroid. In view of the clinical deterioration of the patient immunosuppressive was stopped, leading to acute cellular rejection of the grafts, and dual graft loss with return to hemodialysis and insulin therapy. After several ultrasound guided punctures to drain intra-abdominal TB abscesses and 18 months of anti TB therapy, the patient was considered cured. However, he died from complications related to ESRD and dialysis, two years after transplantation.
2-The Donor: The donor was a 23-year-old, 36-week pregnant woman with a history of intense headache who was admitted to the hospital emergency room, and within 72 hours of admission, she developed mild fever, neck stiffness, and seizures. Empirical treatment for meningoencephalitis was started 72 hours after hospital admission (ceftriaxone followed by anti-TB standard treatment and acyclovir. Respiratory secretions were negative for acid-fast bacilli (AFB) stain. Her level of consciousness decreased, and she underwent an emergency caesarean section on the 6th day of admission. Brain computed tomography (CT) scans performed after the procedure revealed diffuse subarachnoid bleeding. The patient was diagnosed with brain death (day 9) and had elected to be an organ donor, considering the cause of death is CNS bleeding. After two months after her death, the tracheal aspirate culture became positive for M. tuberculosis also her child presented with fever of unknown origin and was admitted to the same hospital, being diagnosed with disseminated TB.
3-The Liver Recipient:
The liver recipient was a 55-year-old man diagnosed with Caroli disease who was transplanted because of recurrent bacterial cholangitis. Due to a positive TST before surgery, he was treated for LTBI with isoniazid, soon after the transplant. The treatment was maintained for six months, and the patient has not developed any manifestations.
4-The Heart Recipient:
The heart recipient was a 40-year-old woman diagnosed with Chagas cardiomyopathy who underwent a heart transplant for class IV heart failure. Three months after the procedure, she was admitted to the hospital with fever and malaise. Within three days after admission, she developed severe septic shock and died despite broad-spectrum antibiotic therapy. No bacteria or fungi were identified in cultures.However, no specific mycobacterial direct exam or culture was requested. Her chest CT revealed diffuse pulmonary involvement.
5-The Other Kidney Recipient:
The kidney recipient was a 45-year-old man with systemic hypertension and terminal hypertensive nephropathy. During the second month after transplantation, he developed mesangioproliferative glomerulonephritis and graft loss and returned to dialysis. Three months after transplantation, he returned to the hospital with sepsis of unknown origin and died despite antimicrobial therapy, without isolation of any specific infectious agent. Also, no specific test for mycobacteria was requested.
This case report calls attention to the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases. Typically, DD-TB is commonly related to the donor’s epidemiology and clinical history. DD-TB is considered proven if donor and recipient isolates were reported to be identical or clonal through molecular analysis.
In the absence of definitive confirmation of similar isolates, DD-TB is classified as probable if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if donor and recipient shared more than one epidemiologic or clinical feature. DD-TB is difficult to recognize in both donor and recipient.
In the index case, the microbiological results were detained in the laboratory hospital in which the donor was assisted. It must be stated that there was no specific protocol defining who was responsible for checking the pending test results.
Introduction
4% of solid organ transplant (SOT) patients develop donor-derived tuberculosis (TB) due to LTBI reactivation. Active TB in the donor is a contraindication for organ donation. Despite organ procurement protocols, pretransplantation screening fails to identify TB in the donor in many cases.
The Cases Index case
A 45-year-old male received a simultaneous pancreas kidney (SPK) transplant. After transplantation, he had no major clinical complications and was discharged on postoperative day 30. His previous tuberculin skin test (TST) was negative and there was no TB exposure. . During the second month posttransplant, he visited to the hospital with fever, night sweats and chills. Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses) and the chest radiograph was normal. The patient was cured after ultrasound-guided punctures to empty intra-abdominal TB abscesses and 18 months of anti-TB treatment.
Two years after transplantation, died due to ESRD-related dialysis problems.
The donor, a 23-year-old, 36-week pregnant lady with a history of severe headaches with fever, neck stiffness, and convulsions. Acid-fast bacilli smear was negative from respiratory secretions. Chest x ray was normal. CSF protein levels were raised with pleocytosis. After nine days, the patient died from brain damage. Cerebral vasculitis causes intracerebral hemorrhage was the cause of brain death which was later diagnosed to be TB related cerebral vasculitis.
Moreover, her child had a fever two months after birth and was diagnosed with disseminated TB at the same hospital.
Liver transplant recipient
Due to a positive TST before surgery, he was treated for LTBI with isoniazid, soon after the transplant. The treatment was maintained for six months, and the patient has not developed any manifestations compatible with active TB .
Heart transplant recipient
Within three days after admission, she developed severe septic shock and died despite broad-spectrum antibiotic therapy. No bacteria or fungi were identified in cultures (blood, urine, and tracheal aspirate samples); however, no specific mycobacterial direct exam or culture was requested
Other kidney recipient
During the second month after transplantation, he developed mesangioproliferative glomerulonephritis and graft loss and returned to dialysis. Three months after transplantation, he returned to the hospital with sepsis of unknown origin and died despite antimicrobial therapy, without isolation of any specific infectious agent
Discussion
In this regard, active TB is an absolute contraindication for organ donation. Unfortunately, even active TB can be overlooked and therefore mistaken for other diseases.
The donor had a normal chest X-ray and AFB-negative smears, but the culture went positive two months following procurement
This case report emphasizes donor selection to limit the danger of transmitting potentially deadly but curable illnesses.
Even when these cases are identified, communication gaps may result in donor-derived infections (DDI), which may be associated with death or poor outcomes
What is the level of evidence provided by this article?
Level 4(Case report)
What is the take-home message?
1) High index of suspicion is need for TB diagnosis.
2)Good communication from donor hospital/ organ allocation committees or bodies to and from recipient hospital should be done for each and every detail of organ before, during and after the organ donation.
3)Latent TB is equally important than active TB
4)Infection are major complication after transplant, not only TB but every infection from donor to recipient needs evaluation.
5)Careful donor selection is needed to reduce the risk of transmission of potentially lethal but treatable diseases.
6)Information to be shared to the registry of local bodies looking for transplant about the outcome of transplant every quarterly or yearly.
7)Negative chest XR does not exclude TB.
I. Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
Summarise this article
Introduction
– donor-derived TB (DD-TB) is rare, it accounts for less than 5% of the TB cases
– most TB cases in SOT recipients are caused by reactivation of LTBI
– active TB in the donor is an unacceptable risk hence a contraindication to organ donation
– active TB in the transplant setting is 20-74times higher than that in the general population and is associated with high mortality
– it is therefore important to identify high-risk donors so as to reduce the risk of DD-TB
– however, TB recognition in the DD is not always feasible
– the case report describes a deceased donor, a pregnant woman who died post-delivery due to a CNS bleed (diffuse subarachnoid bleed) and probable CNS and pulmonary TB
– TB diagnosis was made retrospectively through a positive tracheal aspirate mycobacterial culture (the results were obtained 2 months after the donor’s death) and at that time her baby was diagnosed with congenital disseminated TB after presenting with fever of unknown origin
– some of the patients who received organs from the donor with TB actually died: –
The simultaneous pancreas-kidney recipient developed disseminated TB but got cured. Unfortunately, he died 2years post-transplantation due to ESKD complications.
The kidney transplant recipient died 3months post-transplantation secondary to sepsis of unknown origin.
The heart transplant recipient died 2months post-transplantation secondary to sepsis of unknown origin.
The liver transplant had a positive TST prior to surgery hence was initiated on LTBI treatment (6months INH) soon after the transplant. Luckily, he did not develop any features of active TB.
– no postmortem was performed on the deceased kidney and heart recipients hence the TB diagnosis remains presumptive int these two cases
Discussion
– transplantation is the treatment of choice for most ESKD patients however it is associated with numerous risks related to the surgery and the immunosuppressive therapy
– infections are a major cause of morbidity and mortality in SOT recipients
– it is therefore important to carefully select and screen donors to reduce the risk of transmission of lethal but treatable DDI (donor-derived infections)
– when risk factors for TB have been identified in a DD, then further testing and radiological assessment is warranted
– active TB is an absolute contraindication to organ donation
– the donor in this case report did not have respiratory symptoms or any suggestive imaging, AFB was negative hence TB was not suspected
– however, the CNS findings were suggestive of TB – elevated CSF protein, a decline in the neurological status, intracerebral bleed
– it is usually difficult to diagnose DD-TB and molecular typing and analysis if specimen isolates ought to be done but this is not always feasible
– organ donation should be avoided in cases of donor death due to meningoencephalitis without a proven cause
– communication gaps e.g., failure to report results, inefficient communication between organ procurement agencies and transplant centers, failure to exchange information regarding recipients from the same donor can be prevented by using more efficient strategies towards screening protocols and communication
– these communication gaps can result in DD-TB resulting in poor outcomes including death
– the case report highlights the importance of a data bank and donor sample analysis to trace DD infections and the significance of better communication between organ-harvesting centers and transplantation teams
– biovigilance initiatives (donor traceability) should be implemented with an aim of developing national surveillance systems for cells, tissues and organs
Level of evidence provided by this article
– Level IV
Take-home message
– it is important to report any suspicious cases of infections transmitted by the donor since this allows tracing of all the recipients at risk in a timely manner so as to avoid poor outcomes
– to support this initiative, data banks and donor sample analysis systems should be set up/ put in place
– biovigilance systems should be implemented and the communication systems between transplantation centers and organ procurement/ harvesting centers improved
This article has shed light upon very important issue of proper cadaveric donor selection to avoid serious consequences for the recipients.
Unfortunately the donor mentioned in this article was a pregnant female who died after a brief illness with CT showing subarachnoid hemorrhage and CSF suggestive of meningitis. The diagnosis of TB was confirmed two months after death with positive respiratory culture for AFB.
The fact that the unfortunate simultaneous kidney pancreas recipient developed disseminated TB and survived initially and two other ( Heart and kidney)died due to sepsis with no subsequent autopsy again raises the question of disseminated TB. The fourth lucky liver transplant recipient survived as he received prophylactic treatment for Latent TB.
This article has shown the importance of proper donor evaluation and communication with harvesting team in order to ensure safety of recipients. The communication gaps in this case has raised serious questions, timely information of vertical transmission in this case would have ensured earlier detection of fatal TB in recipient of various organs.
LEVEL OF EVIDENCE
4
TAKE HOME MESSAGE
Meticulous cadaveric donor selection is of prime importance. All cadaveric donors of sepsis should be thoroughly screened for the causative organism. A definitive protocol should be developed where timely communication should be ensured between transplant team.
DDI is important source of infection in about 4percent of cases.
Communication between centers is important as pretransplant work up like CXR and history won’t detect this risk.
Knowledge gap or lack of communication. Put recipient at devastating outcome as happened in our index case who died of CNS T.B and diagnoses retrospectively after 2months of death .
One patient died of TB and one recipient developed disseminated T.B.heart and kidney recipient died ,presumptively related to TB ,not confirmed ,autopsy’s examination not done.
What is the take-home message?
attention to the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases.
Typically, DD-TB is commonly related to the donor’s epidemiology and clinical history, even if TB is not initially recognized .
obtain a donor history of symptoms consistent with active TB, as past diagnosis of TB infection (active or latent), homelessness, alcohol abuse or injection drug use, incarceration, recent exposure to persons with active TB, or travel to areas where TB is endemic.
When risk factors are identified, further testing and radiological assessments are warranted.
According to current recommendations, in cases of donor death due to meningoencephalitis (ME) without a proven cause, the donation should be avoided .
prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner.
What is the level of evidence provided by this article?
Introduction
· Tuberculosis (TB) in solid organ transplant (SOT) recipients is mostly due to reactivation of latent TB, and only 4% are donor-derived.
· Chest X-ray could be normal in extrapulmonary and disseminated TB in deceased donors, and pre-transplantation screening fails to identify TB in the donor in many cases.
· The donor of this report was a pregnant woman who died soon after delivery due to TB involvement of the central nervous system (CNS) and lungs.
The Index Case
· A 45-year-old male received a simultaneous pancreas-kidney (SPK) transplant due to DM and ESRD.
· By second-month posttransplant, he returned to the hospital with fever, night sweats, and chills
· U/S abdomen revealed peri-graft collections (renal and pancreatic abscesses) with normal CX-R
· percutaneous drainage of the abscesses was done and he had + acid-fast bacilli.
· Anti-TB therapy was given: rifampin, isoniazid, pyrazinamide, and ethambutol
· He developed complications of anti-TB drugs, and clinically deteriorated, so immunosuppressive drugs were all stopped with graft loss.
· exploratory laparotomy for debridement and renal graft was removed.
· The patient died from complications of ESRD and dialysis, two years after transplantation.
The Donor
· a 23-year-old, 36-week pregnant woman with a history of intense headache, fever, and seizures, was treated with empirical treatment for meningoencephalitis as CSF and blood cultures were negative.
· Respiratory secretions were negative for acid-fast bacilli (AFB) stain, and her brain CT revealed diffuse subarachnoid bleeding
· The patient was diagnosed with brain death (day 9) and had elected to be an organ donor, considering as the primary diagnosis, CNS bleeding.
· two months after her death, the tracheal aspirate culture became positive for M. tuberculosis
· 2 months after delivery, her child presented with fever of unknown origin and was admitted to the same hospital, being diagnosed with disseminated TB.
· The M. tuberculosis strain isolated from the child presented no resistance to first-line anti-TB drugs
The Liver Recipient
· Caroli disease who was transplanted because of recurrent bacterial cholangitis
· treated for LTBI with isoniazid, soon after the transplant and doing well till now
The Heart Recipient
· Chagas cardiomyopathy, heart transplant due to class IV heart failure
· Three months post-transplant died due to septic shock
· Negative cultures for bacteria or fungi, but CT chest revealed diffuse pulmonary involvement.
The Other Kidney Recipient
· 2 months post-transplant, he developed mesangial-proliferative GN and graft loss and returned to dialysis.
· 3 months after transplantation, he died from sepsis of unknown origin.
Discussion
· Transplantation has the best outcome for patients with ESKD if the donor is screened well.
· Active TB is an absolute contraindication for organ donation, but it can be misdiagnosed.
· potential organ donors and recipients should be screened well for risk factors for Latent or active TB
· In this case as AFB was negative, TB was not suspected. But the CSF analysis showed an elevated protein level with pleocytosis, and the SAH was mostly due to TB vasculitis.
· In case of donor death due to meningoencephalitis without a proven cause, the donation should be avoided.
· DD-TB is classified as probable if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if the donor and recipient shared more than one epidemiologic or clinical feature
· There was a lack of getting positive data about the donor results after 2 months
· As the liver transplant recipient was treated for latent TB and did not develop the disease
· As the donor has pending results, she should be removed from the list.
· As the newborn was diagnosed with TB in the first 2 months of life, other transplant recipients should be investigated for TB at that time.
This is a case report evidence 4
Take home message:
· Donors with unknown definite cause of death should be excluded from the list
· Deceased donor with pending investigations should be removed from the list
· Any serious infectious disease should be followed well to discover the primary source of transmission.
4 transplantation surgeries from one deceased donor
The donor was pregnant lady came to the hospital with meningeonecephalitis which was investigated well but results of cultures came late and patient died from intracerebral hemorrahge and unfortunately was assessed for deceased donation and accepted
and 4 cases has SOT from the same donor .
Donor cultures came positive for TB + vertical transmission of TB to her son and no body informed
The recepients were:
1st one had pancreatic and kidney transplant and developed disseminated TB and suffered from medication side effects ,they stopped immunosuppression then graft failure and died after 2 years from ESRD related causes
2nd one has liver transplant which was diagnosed as latent TB received medications and became well with no further events
3rd one has heart transplant whom also developed disseminated TB and died undiagnosed with fever of unknown origin and died
earth one has kidney transplant died also from fever of unknown origin
Level of evidence:5 case report
Take home message :
1- Proper assessments for the cause of death and is this patient is fit for transplantation or not. (Here Patient was admitted with suspicion of infection so it is not only intracerebral hemorrahge)
2- If there is pending results for the patient considered for donation ,should be endorsed to transplant team to follow.
3- Review of cases should be on more than one level ,at the start assisstant then consultant review then multidisciplinary meeting ( more consultants and surgeons ,pharmacists,radiologists )
4- Even if informed after transplantation was done ,at least they can commence anttuberculous medications with better outcome
5- Good communications between the cadaveric assessment teams and transplant team .
Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
1. Summarise this article
2. What is the level of evidence provided by this article?
3. What is the take-home message?
Summary of this article:
Kidney transplant remains the best option of renal replacement therapy for patients living
with end-stage kidney disease, however, it is also accompanied by unintended
cardiovascular or infectious disease complications. This article focused on the development of TB in the recipient from the donor organ. This
is of particular importance, since generally recipient TB occurs from reactivation of
latent TB. Donor derived TB is rare, at a small level of 4% of cases are contracted from
the donor during SOT.
The current screening method for tuberculosis during work in SOT may miss out the
diagnosis of TB, particularly if is extrapulmonary, while communication could also be the
bane of a successful surgery
The article is the summaries of four recipients (SPK, Kidney, Heart, and liver) who
received diseased organs from a pregnant woman.
Despite screening recommendations, failures may lead to a breakdown in safety that
results in the transmission of potentially fatal diseases.
Case 1 :
A 45-year-old man received SPK & was discharged on day 30,
Previous TBST negative and denied TB exposure
presented 2 months post-surgery with fever, night sweat, and chill
Had drainage of peri-grafts abscess, covered with antibiotics
Had anti-TB treatment because of positive AFB from abscess sample
She had toxicity to anti-TB drugs with disseminated TB and had exploratory laparotomy,
kidney graft removal, and abscess drainage
She was considered cured after 18 months of anti-TB but died of dialysis complication 2
years after the surgery
DONOR:
A 23-year-old lady presented with a severe headache at 36-week gestation, and later developed fever, neck pain with seizure
Tests were done initially on CSF, respiratory secretions and blood was negative for tuberculosis
She had emergency CS and was later diagnosed with brain death, and organs were harvested for donation
The trachea aspirates became positive for TB 2 months after and the child was treated for TB with a good clinical response
Other organ recipients:
The heart recipient presented to the hospital three months after with features of septic shock and died within three days despite antibiotics being given.
The liver transplant received treatment for LTBI till after the surgery and he is still doing fine without any features of DD -TB
The other recipient of the kidney also return to the hospital three- month after with sepsis of unknown origin and died despite antibiotic administration.
DISCUSSION:
DD-TB is considered proven if donor and recipient isolates were reported to be identical or clonal through molecular analysis. In the absence of definitive confirmation of similar isolates, DD-TB is classified as probable if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if the donor and recipient shared more than one epidemiologic or clinical feature
It is very obvious in retrospect to note that the donor must have had disseminated TB to most of the organs harvested as evidenced by various manifestations among the recipients
CONCLUSION:
The TB diagnosis contributed to one patient’s death and could be to blame in the other two patients following transplantation.
Unfortunately, No autopsy was done on the deceased recipients, therefore the TB diagnosis is just presumptive for both the heart & kidney recipients.
LEVEL OF EVIDENCE :
This article is a case report ===> level of evidence IV.
HOME MESSAGE:
DD-TB is possible in a small % of recipients. If developed in the recipient, it can lead to significant harm, even causing graft loss. In order to prevent this, careful screening procedures are essential, along with testing for extra pulmonary TB in the form of CT and MRI along with culture.
Communication gaps between procurement centres and transplant team can lead to increase in risk of infection incidence in the recipient, and thus better communication strategies is encouraged.
Detailed history of donor including unrelated disease such as stroke is essential to confirm that no infection will pass on from the donor to the recipient through the transplant graft.
Organ donation should be avoided in meningoencephalitis without a definitive confirmed cause
Establishment of an effective and rapid communication system or links between different centers where organ retrieval and surgery are done
Careful donor selection to avoid transmission of infectious disease
Establishment of a donor data bank for samples and channels to trace results
Summary
Most common cause of TB in post-transplant recipients is reactivation of latent TB, however in 4% of cases its donor derived.
Active TB is an absolute contraindication to donation.
Currently screening programs for deceased donor are inadequate for identifying extra-pulmonary and disseminated TB.
The Case report
Donor: 23 year old 36 week pregnant woman who presented with intense headache initially diagnosed with meningoencephalitis later with diffuse subarachnoid bleed. Two months after her death her tracheal aspirate culture was positive for MTB and her baby was diagnosed with disseminated TB.
Recipients:
Liver recipient; received INH for LTBI and has not had symptoms for active TB.
Heart recipient; died 3 months after being admitted with septic shock.
Kidney recipient; developed mesangioproliferative glomerulonephritis and returned on dialysis. 3 months after transplant admitted with sepsis of unknown origin and passed.
Index case; Simultaneous pancreas-kidney transplant developed disseminated TB 2 months after transplant that complicated with graft loss and later died.
Discussion
This case reports calls for the need of careful donor selection to avoid transmission.
There are current guidelines for screening donor and recipient however they are not mandatory thus not always incorporated.
Risk factors assessments should include a detailed history that should screen for any active TB symptoms, recent contact of persons with TB, history of travel to endemic area, past TB history and lack of a permanent abode or being incarcerated.
Further testing and radiological evaluation should be done in those with identified risks.
Donor derived TB is considered proven when both door and recipient isolates are identical through molecular analysis.
Thus the major limitation is positive match between donor and recipient genetic sequencing.
This report identified that communication gaps can occur at multiple levels leading to adverse outcomes.
Another gap identified is lack of communication of vertical transmission of TB.
Level of evidence
This is a case report hence level V.
Take home message
Diagnosis of extra-pulmonary and disseminated TB requires molecular sensitivity testing.
Deceased donors with meningoencephalitis with no proven cause should be avoided.
There is need for a data bank and donor sample analysis to trace infections.
Reinforcement of better communication of transplant centres and organ harvesting centres is required.
Summary of Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety introduction
Communication plus careful screening is crucial to identify TB in the deceased donor as many cases of donor-derived infection will result in death and poor outcome.
This reported case is discussed disseminated TB in the donor with poor outcomes for organ recipients.
The donor is the pregnant woman who died soon after delivery due to TB involving the lung and CNS. Discussion
Active TB is absolute C/I to donation
This care reports highlight the importance of careful donor selection to reduce the risk of transmission of a potential lethal but treatable disease.
In the cases of recipient CXR normal AFB negative smear which the C/S became positive 2 months after transplant (time of positivity range from weeks to months)
So in this situation, the molecular test has general sensitivity but is done where TB is suspected.
Current recommendation
In case of donor death due to meningoencephalitis with that approval cause, the donation should be avoided. To improve screening strategies:-
1- Exclude any mobility to support the stroke.
2- Presence of few at presentation/admission in the potential donor.
3- CT/MRI of the head.
4- CSF finding consistent with the infection process. The limitation of the case 1– recipient confirmation of DD infection is to have a positive donor sample and genetic sequencing.
df the pathogen-making donor and recipient samples.
2-Gap between donation and development of the disease.
Historically, many guidelines and protocols emphasize the importance of a registry and the use of procedures for the safety and prevention of infectious disease transmission.
A more effective reporting system will not prevent the event from occurring but may of course impact the outcome.
All fully net work that integrates transplant center OPO and laboratory is mandatory and could allow the receiving patients of potential hazard followed by a more rapid interpterion. evidence level 5 case report
What is the take-home message?
for the deceased donor presence of the normal CXR and negative AFB is not enough to role out active or disseminated T.B, first of all, good communication with the transplant center and more information about the DD such as fever upon admission, CSF findings suggested infectious process, stroke without comorbidities and diagnosis of meningoencephalitis without evidence of the cause that means any transplant center should have their on policy to make sure the DD is clear from T.B before transplantation
TB is associated with in significant morbidity and mortality in SOT recipients. It is mostly resulted from reactivation of LTBI, and only 4% are donor-derived infection DDI. Despite screening protocol in deceased donor, screening may fails to identify TB cases, that lead to DDI especially when there is communication gap. The reported case: Donor : pregnant lady with of unrecognized disseminated TB, diagnosed initially as meningoencephalitis and died after CNS bleeding. Initial TB screening was negative, the diagnoses was retrospectively after 2 months when the cultures tuned positive and her baby diagnosed with disseminated TB. Organs transplanted in 4 recipients with a devastating outcome:
Simultaneous pancreas-kidney recipient : 2 months post transplantation he developed perigraft collections found later to be TB abscess. He was treated with anti-TB, after 2 months of treatment, his course complicated with disseminated TB, treatment related drug toxicity, rejection episode and dual graft loss. He was cured from TB after 18- months therapy. However, he died from complications related to ESRD and dialysis, two years after transplantation. Liver recipient: diagnosed as LTBI for positive TST, and treated with INH for 6 months. He did not develop any manifestations compatible with active TB to date. Heart Recipientdied 2 months after transplantation from sepsis of unknown origin, no specific TB test was done and her chest CT revealed diffuse pulmonary involvement. Other Kidney Recipient. Lost the graft after 2 months from MPGN and returned to dialysis, 3 months after transplantation he returned died from sepsis of unknown origin. No TB tests were done. -Infections represent a major cause of morbidity and mortality for SOT recipients. Active TB is an absolute contraindication for organ donation. -Several policies and guidelines established to improve the recognition of the disease in potential organ donors and recipients, they are not always incorporated into OPO standard procedures. -DD-TB is challenging and difficult to recognize; generally, it presents itself early after SOT, most commonly as fever, and carries a high mortality risk. – Proven DD-TB; if donor and recipient isolates were identical or clonal through molecular analysis. – Probable DD-TB; in the absence of definitive confirmation of similar isolates, or suspected transmission and TB was identified in multiple recipients of one donor, or if donor and recipient shared more than one epidemiologic or clinical feature. Information gaps, that donor pending culture at the time of procurement should be followed, there is no specific protocol defining who was responsible for checking the pending test results. Communication gaps in reporting DDI are frequent and may occur at multiple levels, contributing to adverse outcomes among affected organ recipients. Level of evidence: level 4 case report Take home massage: – DDI should be suspected especially in early post-transplant period and should be reported. -The need for a data bank and donor sample analysis to trace infections – Protocols to define who is responsible of tracing these results – Development national registry and public health reporting to facilitate traceability and communications – Reinforces the importance of communication between transplantation teams and organ-harvesting centers. – Development national surveillance systems for cells, tissues, and organs.
Introduction The majority of tuberculosis (TB) cases in solid organ transplant (SOT) recipients are caused by the reactivation of latent tuberculosis infection (LTBI), and only very small percentage are considered donor-derived , despite organ procurement protocols, pretransplantation screening sometimes fails to identify TB in the donors , which should be avoided by good evaluation of donors and good communications with the transplant centers . On the other hand active TB in the donors is contraindication to organ transplantation . The reported case :
This is an interesting and catastrophic case report of a deceased donor who was a young pregnant lady who died soon after delivery due to TB involvement of the central nervous system (CNS) and lungs. The diagnosis was retrospectively established by mycobacterial culture of the respiratory sample (positive result obtained two months after donor death) and the diagnosis of congenital TB in her baby.
Her organs were delivered to 4 recipients as following :
Simultaneous Pancreas Kidney Recipient: Developed disseminated TB with side effects of anti TB end with dual loss of graft and returned back to dialysis and insulin therapy died later due to complications of dialysis .
– The Liver Recipient.: Is the only survivor to date because of TB prophylaxis given post transplantation due to his positive skin test . – The Heart Recipient : Died of septic shock 3 months after transplant, of unknown organism without specific test for TB
The Other Kidney Recipient: Developed mesangioproliferative glomerulonephritis and graft loss he returned to dialysis 3 months after transplantation he developed septic shock of unknown organism and unfortunately without specific test for TB .
What is the level of evidence provided by this article?
-This is level IV of evidence ( case report ).
What is the take-home message?
-There should be better communications between the harvesting hospitals, OPOs ,and transplant centers .
-Whenever TB is suspected and patients have negative tests as in this reported case molecular tests are sensitive and specific with the result obtained much more earlier than the cultures .
-TB is a killing disease especially in SOT patients however it is treatable and even preventable by TB prophylaxis after kidney transplant for those who are at risk which should be evaluated by OPOs ( organ procurement organizations ) . – There should be increased awareness about the risk of TB in transplant centers and in all hospitals which are supposed to be harvesting centers for organ donation .
– Early notification of any suspected death of a transplant recipient is mandatory .
Summary: this is a case report of donor derived TB. The donor: female aged 23 ys old, pregnant in late pregnancy, admitted with severe headache, meningitis, developed brain death 2ry to subarachnoid haemorrhage. initial TB screening was negative in CSF fluid & sputum.2 months after death, bronchial aspirate came out to be positive for acid fast bacilli. Cesarian section was done. the child came after 2 months of delivery with fever, diagnosed as TB, received medications, improved. Simultaneous kidney pancreas transplant recipient: Developed Disseminated TB, Died 2 years after Transplantation from ESRD complications Kidney recipient: died 3 months after transplantation, Sepsis of unknown origin heart recipient: died 2 months after transplantation, Sepsis of, unknown origin liver recipient: developed latent TB discussion: – Active tb is an absolute contraindication for organ donation, but unfortunately it can be missed & misdiagnosed with other diseases. – If Risk factors (epidemiology, homelessness, exposure to person with active TB, IV drug or alcohol abuse, travel history & symptoms suggesting latent or active TB) are identified, radiological & further testing are warranted. – Consider that culture result may take time up to 6 weeks. Home messages: – To improve screening, if certain potential findings like unexplained CNS death, fever at presentation, findings suggesting infection process in the donor, incomplete culture results) should be considered & investigated. – If any suspicion of TB, extend culture results to up to 6 weeks to consider it negative. – The information & culture results should be followed by the transplant organization. – The outcome of the other donors & the baby should be recorded & analysed, reflecting the early diagnosis & intervention to the others. Level of evidence: Case report, level 5
Introduction: Tuberculosis in solid organ transplantation most commonly results from reactivation of latent TB, and rarely in 4% of cases it is donor derived infection. Active TB is a contraindication to organ donation, until treated. The detailed history of previous TB infection or exposure to TB, and chest x ray may not identify disseminated infection. Failure of identification of TB infection, and communication gaps during organ procurement may result in donor derived infections, associated with poor outcomes and death.
Study design and purpose: A retrospective case control study, in brazil, with review of 36 case reports on DD-TB. The index case was simultaneous pancreas kidney transplant in a 45-year-old male, ESRD was due to type 1 diabetes, he has no exposure to TB , and had a negative tuberculin skin test, with no symptoms of disease, he had a basiliximab induction, and MMF, tacrolimus, and steroid as maintenance, in the second month post transplant presented with fever, weight loss, and night sweats, ultrasound abdomen revealed perigraft collections, underwent subcutaneous drainage analysis and culture, AFB on Zeihl nelson stain was positive, chest x ray was normal, and received standard treatment for TB, he developed side effects to treatment and disseminated lung thyroid and CNS infection mandates discontinuation of immnuno-suppressive medications leading to loss of the grafts and back to insulin therapy and dialysis, in spite of successful treatment he died in 2 years after, due to dialysis complications.
Donor characteristics: 23 year-old- female, 36 week pregnant women, with minigoencephelitis and subsequent intracranial heamorrhage and death, all cultures and respiratory secretions were negative with no evidence of AFB, but CSF showed pleocytosis and high protein level, for which received empirical antibiotics including anti TB therapy within 72 hours of hospital admission, she underwent urgent delivery by C/S in day 6 of admission, and died on the 9th day of admission.
Other recipients chrachteristics: Other kidney recipient died 3 months post transplantation due to sepsis of unknown origin, heart recipient died 2 months after transplantation due to sepsis of unknown origin, liver recipient who received treatment of latent TB because of a positive TST for 6 months post transplant continued to be asymptomatic and disease free.
Risk factors assessment by: Obtaining a donor history of symptoms of active TB. Past diagnosis of TB infection (active or latent). Homelessness. Alcohol abuse or injection drug use, incarceration. Exposure to persons with active TB, or travel to endemic area. Radiological (CXR).
Discussion:
TB is a contraindication to donation, however the donor in this study had no X-ray finding and a negative AFB stains form CSF and respiratory secretions, but the culture came back with TB 2 months after death, it is well known that TB culture takes 4-8 weeks.
DD-TB proven if donor and recipient isolates were reported to be identical through molecular analysis, and probable if recipients of same donor organs, if the donor and recipient shared more than one epidemiologic or clinical feature, and donor residence in TB endemic area and absence of recipient risk factors for TB.
DD-TB is difficult to recognize in both donor and recipient. A recent review retrieved 36 cases of proven The median time to clinical presentation or diagnosis was 2.7 months, Fever was the most presenting symptom, Allograft involvement was common, Graft loss occurred in ~20% of patients, and All-cause mortality was 25%.
Communication gaps in reporting DD-TB are frequent and may occur at multiple levels, contributing to delay treatment, and adverse outcomes among affected organ recipients.
Conclusion: Prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner, facilitate early treatment, reduce the adverse events and death.
What is the level of evidence provided by this article? Level of evidence is IV – case report/case series study.
What is the take-home message? – Any brain death donor with unknown CNS infectious etiologies should be denied. – Assessment of TB status in a donor and recipient should be under taken in moderate and high prevalence countries, and put by standard donor and recipient protocols. – Disseminated TB, could present with normal chest X-ray and a negative AFB stain. – Closing communications gaps in transplant centers would improve patients care and survival.
Introduction Tuberculosis (TB) infection in solid organ transplant (SOT) recipients is most commonly caused by re-activation of latent TB infection (LTBI), and 4% are considered donor-derived. Active TB infection in the donor is a contradiction to organ donation. Screening protocols for deceased donors may also sometimes fail to diagnose TB. This report describes a case of disseminated TB in an organ donor, that led to poor outcomes for the recipients.
The donorThe donor was a 23 year old female. She was admitted due to complaints of an intense headache, at 36 weeks of pregnancy. Within 72 hours of admission, she developed mild fever, neck stiffness and seizures. The CSF had increased proteins and cellularity, and no microorganisms. Empirical treatment for meningoencephalitis was started, ceftriaxone followed by anti-TB treatment and acyclovir. Respiratory secretions were negative for acid-fast bacilli (AFB) stain. On the 6th day of admission, the patient’s level of consciousness decreased and she underwent an emergency C-section, after which brain CT scans revealed a diffuse subarachnoid hemorrhage. The patient was diagnosed with brain death on the 9th day of admission, and was elected to be an organ donor based on the diagnosis of CNS bleeding. 2 months after her death, the tracheal aspirate culture was positive for M. tuberculosis. Her child presented at 2 months of age, with fever of unknown origin and was diagnosed with disseminated TB and was treated successfully.
The index case – simultaneous pancreas and kidney recipient A 45 year old male, with end stage kidney disease and diabetes, received a simultaneous pancreas and kidney transplant. His previous tuberculin skin test (TST) was negative and denied known TB exposure. His immune suppression regimen post transplantation included basiliximab, prednisone, tacrolimus and mycofenolate mofetil. On the 2nd month post transplantation, he presented with complaints of fever, chills and night sweats. His chest X-ray was normal, abdominal ultrasound revealed perigraft collections (renal and pancreatic abscesses). He was started on broad-spectrum antibiotics and drainage of the abscesses, with transient resolution of the fever. Lab analysis revealed AFB on ZN stain, and anti-TB treatment was started (rifampin, isoniazid, pyrazinamide and ethambutol). The transplant harvesting center was notified. The patient the presented with drug toxicities related to the anti-TB medications: hemolytic anemia and blurred vision. His medications were therefore changed. The patient had disseminated disease involving the grafts, lungs, CNS and thyroid. This led to stopping the immune suppressive medications, leading to loss of the grafts. The patient was deemed successfully treated for TB infection, 18 months after treatment was initiated. Unfortunately, the patient passed on 2 years after transplantation due to complications related to end-stage renal disease and dialysis.
The liver recipientA 55 year old male, with a diagnosis of Caroli disease received the liver, due to recurrent bacterial cholangitis. The patient had a positive TST prior to surgery, hence was treated for LTBI with isoniazid monotherapy for 6 months, soon after the transplant. The patient had not developed active TB as of the date of publication.
The heart recipient The heart recipient was a 40 year old woman, she had a diagnosis of Chagas cardiomyopathy, with class IV heart failure. Three months after the transplantation, she presented with fever and malaise, and within three days of admission she passed on due to severe septic shock, unresponsive to broad-spectrum antibiotics. No bacteria and fungi were detected on culture of blood, urine and tracheal aspirate samples. No mycobacterial culture was requested. Her chest CT revealed diffuse pulmonary involvement.
The other kidney recipient The other kidney was transplanted in a 45 year old male with systemic hypertension and terminal hypertensive nephropathy. On the 2nd month after transplantation, the patient developed mesangioproliferative glomerulonephritis and graft loss, and hence had to return to dialysis. The patient then presented to the hospital three months after transplantation, due to sepsis of unknown origin despite antimicrobial therapy. No specific test for mycobacteria was requested.
Discussion Infections can cause mortality and morbidity in SOT recipients. The aim of this case report was to highlight the importance of careful donor selection, to reduce the risk of transmission of potentially fatal diseases that are treatable. In this case, the donor had disseminated TB that was unrecognized. She had no history of previous TB or TB exposure, except for pregnancy. She lived in an area whose prevalence was an intermediate risk for TB. Screening for active or latent TB is not practiced in all centers, as the guidelines developed are not mandatory for all scenarios. For the discussed patient, she had no respiratory symptoms, and imaging did not reveal any respiratory involvement, hence no molecular tests were done. The TB culture is time consuming, hence the results were obtained two months after the transplant. However, the CSF analysis showed an elevated protein level with pleocytosis. In retrospect, the intracerebral bleed was likely secondary to cerebral vasculitis due to the TB infection. Current recommendations advise avoiding organ donation if the patient’s death was due to meningoencephalitis without a proven cause. In this case, the liver transplant recipient was treated for latent TB, and did not develop active infection. The other two recipients passed on due to sepsis of unknown origin and organ dysfunction. These finding are compatible with TB donor transmission, but the transmission was only confirmed for the recipient who underwent spontaneous pancreas and kidney transplantation. It is known that the TB cultures are time consuming, however, results should be communicated to all centers and recipients involved. In this case, there was no specific protocol defining who was responsible for checking the pending results. This would have prompted the treating clinicians to initiate treatment earlier, and may have prevented graft loss and death. The case report hoped to call attention to the importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace the recipients and initiate treatment where possible, in a timely manner.
Level Of Evidence: LOE is level IV
Take Home Message TB is a challenging diagnosis to make and one has to have a high index of suspicion. In a deceased donor organ program, a clear cause of death needs to be identified before the potential donor donor can become a utilized donor Good communication between donor hospital and recipient institutions is key to reduce morbidities and mortalities
Summary of the article Introduction
Reactivation of a latent mycobacterium infection is a typical cause of tuberculosis after an organ transplant. There is a link between donor-derived mycobacterium infection and a 4 percent chance of the infection being passed on to the recipient, which can have a negative impact on both the transplant and the patient’s health.
This case report describes a pregnant woman who died of diffuse CNS tuberculosis during delivery and her baby who developed congenital TB. After 2 months, this deceased donor’s culture shows positive mycobacterium tubercles, and the recipient develops a terrible graft result. This study screens deceased donors for trace infections and emphasizes the need for greater communication between the transplantation team and the organ harvesting center.
Screening donors for latent TB using nonspecific chest X-rays, epidemiological hazards, and TB history Pancreas transplant
The recipient is a 45-year-old male on immunosuppressive medication (basiximab, prednisone, tacrolimus, and mycofenolate mofetil) with a negative tuberculin test. His donor had tuberculosis.
Second month: fever, chills, nocturnal sweats, stomach ache Pus nears graft on abdominal ultrasonography. Cultures from percutaneous drainage showed acid-fast bacilli. Normal chest X-ray and routine antitubercular treatment with rifampin, isoniazid, pyrazinamide, and ethambutol.
Recipients develop drug toxicity from anti-tuberculous therapy due to drug interaction with immunosuppressive therapy and disseminated TB, leading to clinical deterioration. They stop all immunosuppressive therapy, leading to graft failure, and return patients to dialysis and lapratomy done with removal of the renal graft and intravenous anti-tuberculous for long duration. Patients were cured but died after 2 years due to ESRD and dialysis. Liver transplant
A transplant was performed on a 55-year-old man with Caroli illness due to recurrent bacterial cholangitis. TST was positive prior to surgery, and the transplant recipient was treated for six months with isoniazid for LTBI. The patient has not acquired any symptoms consistent with active tuberculosis. Heart transplant
A heart transplant was performed on a 40-year-old woman with Chagas cardiomyopathy who had class IV heart failure. She was taken to the hospital three months following the procedure with fever and malaise. Within three days, she passed away due to acute septic shock, without mycobacterial infection being considered. Her chest CT revealed diffuse involvement of the lungs. Kidney transplant
Due to hypertension-induced nephropathy, the patient got a kidney transplant. Two months later, the patient developed mesangioproliferative glomerulonephritis and graft loss and returned to dialysis. After three months, the patient comes down with sepsis and dies in spite of antimicrobial therapy and the absence of particular testing to rule out mycobacterium infection; TB is strongly suspected.
Discussion
The best treatment option for patients with ESRD is a kidney transplant, but there is a substantial risk of infection from donor-derived infection due to the potency of immunosuppressive drugs, particularly during the first six months. A life-threatening infection, like tuberculosis, can cause graft loss and raise the incidence of mortality. In these reported cases, tuberculosis infection is not confirmed but strongly suspected due to clinical manifestations that strongly suggested TB and the onset of symptoms within two months of transplantation. Furthermore, only two samples confirm the presence of acid-fast bacillus in the donor of the first case, and the patient died despite receiving anti-tuberculosis treatment. In another example, anti-tuberculosis treatment was effective despite the absence of acid-fast bacilli in both the donor and recipient samples; the donor had a history of tuberculosis exposure.
Before proceeding with a transplant, this article emphasizes the significance of donor selection and infection screening in both the donor and recipient. In addition, this research illuminated the significance of the interaction between the transplant team and the donor bank for the proper selection of donors to reduce infection risks.
What is the level of evidence provided by this article?
Level of evidence V
What is the take-home message?
The significance of meticulous donor selection in order to lower the danger of transmission of potentially fatal but curable diseases Even if TB is not initially diagnosed, DD-TB is frequently tied to the donor’s epidemiology and clinical history. To increase the detection of TB in donors, specific policies may be created. The identification of potential risks and a quicker response are made possible by a fully built network that unite all responsible divisions.
Thankyou for the conclusions this disastrous incident shows that screening of donors and recipient is somtimes taken lightly.
A
donor with undiagnosed cause of death as the index case(diagnosed 2 months later) should be declined.
Tuberculosis in organ transplant is common and it’s caused from reactivation of latent mycobacterium infection. Donor derived considered 4% in transfer mycobacterium infection to recipient and leasing to poor outcome for both graft and individual survival.
This article is case report study on pregnant women dying during delivery because of disseminated CNS tuberculosis and her baby developing congenital TB, This deceased donor where culture done after 2 months post death shows positive mycobacterium tubercles and whereas this donor transplant to recipient who develop devastating graft outcome. So this study aim for screening for trace infection in deceased donor and reinforces the importance of better communication between transplantation teams and organ harvesting centre’s.
Screening donor with latent TB based on chest X-ray findings (nonspecific), epidemiological risks, and previous TB history. First case ( Pancreas Transplant due to diabetes and ESRD).
The recipient 45 years male with negative tuberculin test on immunosuppressive therapy ( basiliximab, prednisone, tacrolimus, and mycofenolate mofetil), his donor derived has previous exposure to tuberculosis.
On second month recipient presents with fever and chills and night sweating and abdominal pain. abdominal ultrasound shows collection of pus near to graft. Per cutaneous drainage done and culture shows positive acid fast bacillus. Chest X ray normal and Antituberculous therapy was started with standard drugs: rifampin, isoniazid, pyrazinamide, and ethambutol.
Recipient develop drug toxicity from anti tuberculous due to drug interaction with immunosuppressive therapy and disseminated TB leading to deterioration of clinical conditions and stop all immunosuppressive therapy lead to graft failure and return patients to dialysis and lapratomy done with removal of renal graft and intravenous anti tuberculous for long duration and patients cured but dia after 2 years because of ESRD and dialysis. Second case: Liver recipient
He was transplanted because of recurrent cholangitis and patient has history of latent TB and receive isoniazid for 6 months post transplant and no manifestation of deterioration of liver transplant. Third Case is heart transplant:
Middle age women develop heart failure due to chagas’ disease and transplanted after 3 days patient develop septic shock and septic work up is non significant and negative culture of mycobacterium but her chest CT shows diffuse pulmonary involvement.
Unfortunately patient dying within 2 months. Forth case is renal recipient:
Patient underwent kidney transplant due to hypertensive nephropathy and after 2 months patient develop mesangioproliferative glomerulonephritis and graft loss and returned to dialysis. After 3 months patient presents with sepsis and dying despite anti microbial therapy and specific investigations to role out mycobacterium infection not done and highly suspicious of TB. Discussion:
Kidney transplant is the best option in patients with ESRD but risk of infection high possibility from donor derived infection due intensity of immunosuppressive drug especially in first 6 months. Life threatening infection like tuberculosis may lead to graft loss and increase incidence of mortality. In these reported cases, tuberculosis infection is not confirmed but it’s highly suspected because clinical manifestations strongly suggested TB and appearance of symptoms within 2 months from transplantation and only 2 samples confirm acid fast bacillus in donor of first case and patient dying despite using anti tuberculosis treatment. In another case of liver transplant was successful treated with anti tuberculosis treatment despite acid fast bacillus not confirmed in both samples of donor and recipient; while donor had history of exposure to tuberculosis.
This article focus on importance selection of donor and intense screening of infection in both donor and recipient before proceed transplant. Also this article shed light on importance link between transplant team and donor bank for good selection of donor to avoid opportunities infection.
What is the level of evidence provided by this article?
Level 5
What is the take-home message?
It’s important to select proper donor and intense screening for infection is mandatory to avoid graft loss and patients risk.
Culture for TB takes weeks so is not at all helpful in undiagnosed cases as this donor was diagnosed after 2 months!!!
Reject a donor with an unknown cause of death to avoid some fatal surprises.
Donor-derived tuberculosis is only 4% of cases in post-transplant TB.
Most TB cases in posy-transplantation is due to reactivation.
To reduce the Donar Derived-TB transmission, all high-risk cases must be identified before transplantation.
Failure in screening usually lead to unintentionally transmission of this fatal disease.
Current screening includes
Chest X-ray, and history of prior TB disease. Unfortunately, extra-pulmonary & disseminated TB may not be recognized by these simple screening.
communication gap may lead to dissemination of different infections including TB.
Case report
A case of disseminated TB in the donor was described which was missed before transplantation, leading to a mishap. The donor was a pregnant lady who passed away shortly after giving birth having febrile infection as a result of TB infection in lungs & CNS involvement. The diagnosis was made retrospectively when congenital TB in her child was identified. This case highlighted the necessity of a data bank, donor sample analysis, & greater coordination between TX teams & organ-harvesting teams in order to track infections and prevent these mishaps.
Outcomes of recipients of the organs: The Index Case – SPK recipient:
Pre-TX TST was negative, & he denied known TB exposure.
IS regimen: basiliximab, prednisone, tacrolimus, & MMF.
He developed fever, night sweats, & chills during the 2nd post-TX month. Peri graft collections (renal & pancreatic abscesses) was found on US with a normal CXR. Percutaneous drainage of the abscesses was carried out.
Lab: AFB on ZN stain was found positive and diagnosed as disseminated TB.
ATT was started: rifampin, isoniazid, pyrazinamide, & ethambutol.
Because the recipient’s TB had damaged the graft due to close proximity of abscess to the graft, indicating graft involvement leading to graft failure and further complications due to ESRD.
The Liver recipient:
A 55-year-old man was Transplanted due to Caroli disease with recurrent bacterial cholangitis. TST was positive pre-TX. therefore, got Treated for LTBI with INH for 6 months. The patient has not developed any manifestations of active TB to date.
The Heart recipient:
A 40-year-old woman having Chagas Cardiomyopathy underwent cardiac transplantation. Had fever & related symptoms 3 months following TX. then developed septic shock. she died because of infection. Although cultures of blood, urine, & tracheal aspirate samples failed to reveal any bacteria or fungi, no particular mycobacterial direct exam or culture was ordered. Despite not making a precise diagnosis, the patient’s chest CT showed diffuse pulmonary involvement which pointed towards miliary TB.
The kidney recipient:
A 45-year-old man with hypertensive nephropathy had TX but had to return to dialysis during the 2nd month post-TX because of mesangioproliferative GN with graft loss.
Again, came the hospital 3 months later with sepsis of unknown origin & died despite antibiotic treatment.
What is the level of evidence provided by this article?
Level IV
Take-home message
It is important to select proper and disease-free donors to prevent lethal complications post-Transplant. DD-TB is related to the donor’s epidemiological exposure and previous history. Molecular investigation can reveal that the isolates from the donor & the recipient are identical, which can confirm DD-TB in such cases.
Post transplant TB is devastating disease owing to immune compromised host status. In the majority of cases its resultant from reactivation of latent TB in the recipient, in the minority of cases around 4% its derived from donor DD. Post transplant TB is frequently reported to be disseminated or miliary type with multiple organs involvement. Its management is potentially involving reduction or even interruption of anti-rejection protocol with consequent high risk of rejection and loss of the allograft.
Therefore, screening of donor and scrutinizing his TB status is crucial to prevent drastic infection in kidney recipient. Screening of donors for TB:
Basically, it depends on chest Xray screening, history of TB and identification of epidemiological risk. Unfortunately, such a protocol would not obviate the transmission of TB because it’s not sensitive and readily missing the non-pulmonary TB cases. Communication between transplant team and primary medical team:
In potential donor who is suspected of having underlying TB illness, few hazardous practices were highlighted by this article.
1] transplanting a cadaveric allograft from a donor who was expired with febrile illness before securing the primary diagnosis.
2] AFB culture Lowenstein-Jensen LJ media culture which is taking 2 months to denote a result.
3] Failure to communicate positive culture results of a dead patients to transplant team might lead to missing significant information and default to manage transplanted kidney patient with overwhelming potential tuberculosis.
Its basically a case series article with level of evidence 4.
Take home message:
I would advise against transplanting a patient from a donor who potentially died with a febrile illness before scrutinizing and rolling out TB.
Furthermore, I would advocate the utilization of Bactic media for TB culture to get the result within one to two weeks in order to expedite the commencement of anti TB for kidney transplant recipient of potentially TB infected cadaveric allograft.
Moreover, it might be applicable to consider routine anti TB for any recipient of a cadaveric kidney with a suspicion of TB before have the culture results.
Thankyou for your take home messages they are all important but Ithink the most important one is not to accept an unknown cause of death, specially unsolved clinical issues as the fever in the index donor.
Despite the low incidence of TBC in transplanted patients still, an important issue to consider taking into account the immunosuppression effect and reactivation of latent infection. Latent infection reactivation is usually the major cause though donor-derived TBc is also a potential. Screening with a simple chest x-ray may miss the diagnosis. Rather it will not identify extrapulmonary TBC. Here is a case report of rarely seen donor-derived TBC infection proved retrospectively post-mortem.
The index case is 45 years old man with combined kidney & pancreas transplantation screened with a tuberculin test and found negative. Post transplantation he had constitutional symptoms, fever, night sweats etc. His fist evaluation did not suggest pulmonary infection, chest x-ray was normal. Perinephric collections found positive for acid-fast microorganisms, renal and pancreatic abscesses were found, and drainage was performed. Two Other recipients out of the 4 died within three months after transplantation (one kidney and the other heart). Near to graft, the abscesses were suspected to be of donor origin, which was approved later.
Not surprisingly, the heart and the other kidney recipient did not have a definitive diagnosis for the origin of sepsis because of the nature of the infection is challenging to diagnose by simple stain and culture unless suspected. Nonpulmonary involvement is the major problem.
The low sensitivity of acid facts staining, which usually needs 3 confirmations of negativity, was found negative (nonsprisingly). The liver recipient was lucky because he has TST positive and received uncosting izonizdide regimen.
Unfortunately, even active tbc can be missed at the beginning. The recipients were lost nearly one month apart. Early communication between centres to clarify unexpected scenarios may be life-saving and is always helpful. Reporting such problems to the coordinator and building communication needs to be considered.
Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
This is a case report of unrecognized disseminated TB in the donor with a devastating outcome for organ recipients.
A. The donor:
· The donor was a 23-year-old, 36-week pregnant woman with a history of intense headache, mild fever, neck stiffness, and seizures. · CSF was considered abnormal with increased cellularity and protein. · No microorganisms were identified in the CSF and blood. · Empirical treatment for meningoencephalitis was started 72 hours after hospital admission (ceftriaxone followed by anti-TB standard treatment and acyclovir)… · Respiratory secretions were negative for acid-fast bacilli (AFB) stain. · Underwent C/S after decrease at her level of consciousness. · CT revealed diffuse subarachnoid bleeding. · The patient was diagnosed with brain death (day 9) and had elected to be an organ donor, considering as primary diagnosis, CNS bleeding. · Two months after her death, the tracheal aspirate culture became positive for M. tuberculosis. · Her child was diagnosed as disseminated TB at the age of 2 months and showed response to anti-TB.
B. The recipients:
1. The first kidney recipient:
· A 45-year-old male received a simultaneous pancreas kidney (SPK).
· Previous tuberculin skin test (TST) was negative, and he denied known TB exposure.
· The immuno-suppressive regimen included basiliximab, prednisone, tacrolimus, and mycofenolate mofetil.
· During the second month posttransplant, he returned to the hospital complaining of fever, night sweats, and chills.
· Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses), whereas the CXR was normal.
· Rx: percutaneous drainage of the abscesses, broad-spectrum antibacterial treatment. There was transient resolution of fever.
· Laboratorial analysis revealed acid-fast bacilli (AFB) on Ziehl-Neelsen stain. Antituberculous therapy was started with standard drugs: rifampin, isoniazid, pyrazinamide, and ethambutol.
· Considering that the recipient’s TB abscesses were located near the grafts, suggesting donor involvement.
· The patient subsequently presented with anti-TB drug toxicities and disseminated disease involving grafts, lungs, CNS, and thyroid.
· The clinical deterioration of the patient imposed immunosuppressive cessation, leading to acute cellular rejection of the grafts, and dual graft loss.
· Exploratory laparotomy revealed caseating necrosis all over the mesenterium and around pancreatic graft, but affecting the renal graft. Renal graft was removed.
· After punctures to drain intra-abdominal TB abscesses and 18 months of anti- TB therapy, the patient was considered cured.
· However, he died from complications related to ESRD and dialysis, two years after transplantation.
· At time of contacting the transplant harvesting center for additional information regarding the donor and the other organ recipients, two recipients had already died, and a look-back investigation was carried out.
2. The Liver Recipient: · 55-year-old man with Caroli disease, was transplanted because of recurrent bacterial cholangitis. · TST was positive before surgery and soon after the transplant was treated for LTBI with isoniazid for six months. · The patient has not developed any manifestations compatible with active TB. 3. The Heart Recipient: · 40-year- old woman with Chagas cardiomyopathy who underwent a heart transplant for class IV heart failure. · Three months after the procedure, she was admitted to the hospital with fever and malaise. Within three days, she died after severe septic shock without any consideration for mycobacterial infection. · Her chest CT revealed diffuse pulmonary involvement. 4. The Other Kidney Recipient: · 45-year-old man with systemic hypertension/ESRD. · During the second month after transplantation, he developed MPGN and graft loss. · Three months after transplantation, he returned with sepsis of unknown origin and died despite antimicrobial therapy. · Similar to the heart recipient, no specific test for mycobacteria was requested.
Discussion:
· Active TB is a well-known contraindication to organ donation.
· sputum culture has higher sensitivity than AFB, the time to positivity ranges from weeks to months.
· Molecular tests present greater sensitivity and specificity but are done when pulmonary TB is suspected.
· Donation should be avoided after death due to meningoencephalitis (ME) without a proven cause.
The level of evidence provided by this article:
This is a case report with level of evidence grade 5.
Take-home message:
· Careful and detailed screening for transmissible infection is crucial.
· Prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner.
Thank you Dr Assafi Ibrahim Annour Mohammed.
Your case summary can be summarised further as your summary is a little prolonged. Probably the take home message would be denying any brain death from cases with meningeoencephalitis without having microbiological confirmation.
Tuberculosis (TB) cases in solid organ transplant (SOT) recipients are caused by reactivation of latent TB, and only 4% are considered donor-derived.
Current screening protocols for deceased donors are based on chest X-ray findings, epidemiological risks, and previous TB history, but may not identify extrapulmonary and disseminated TB.
Despite organ procurement protocols, pretransplanta-tion screening fails to identify TB in many cases, resulting in donor-derived infections (DDI).
This report highlights the need for a data bank and donor sample analysis to trace infections and better communication between transplantation teams and organ-harvesting centers.
1.1. The Index Case – Simultaneous Pancreas Kidney Recipient
A 45-year-old male received a simultaneous pancreas kidney (SPK) transplant due to diabetes and end-stage renal disease (ESRD).
After transplantation, he had no major clinical complications and was discharged on post-operative day 30.
During the second month posttransplant,he returned to the hospital complaining of fever, night sweats, and chills.
Abdominal ultrasonog-raphy revealed perigraft collections (renal and pancreatic abscesses).
He received broad-spectrum antibacterial treatment and under-went percutaneous drainage of the abscesses, with transient resolution of fever.
Antituberculous therapy was started with standard drugs: rifampin, isoniazid, pyrazinamide, and ethambutol.
In the 2nd month of treatment, the patient presented disseminated disease involving grafts, lungs, CNS, and thyroid.
Immunosuppressive cessation led to acute cellular rejection of the grafts, and dual graft loss with return to hemodialysis and insulin therapy.
1.2. The Donor
The donor was a 23-year-old, 36-week pregnant woman with a history of intense headache who was admitted to the hospital emergency room with mild fever, neck stiffness, and seizures.
Empirical treatment for meningoencephalitis was started 72 hours after hospital admission, and other culture samples were collected.
Two months after her death, the tracheal aspirate culture became positive for M. tuberculosis.
1.3. The Liver Recipient.
The liver recipient was treated for LTBI with isoniazid for six months and has not developed any manifesta-tions compatible with active TB.
1.4. The Heart Recipient.
The heart recipient underwent a heart transplant for class IV heart failure, but developed septic shock and died despite broad-spectrum antibiotic therapy.
.5. The Other Kidney Recipient.
The other kidney recipient developed mesangioproliferative glomerulonephritis and graft loss and died despite antimicrobial therapy.
TB diagnosis contributed to fatal outcome in one patient, may cause infection complication in others.
No autopsy was performed on deceased organ recipients, making TB diagnosis presumptive.
This case report highlights the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases.
The donor had an unrecognized disseminated tuberculosis (DD-TB) with no history of previous TB or exposure and, except for pregnancy, no known immunosuppressive conditions.
The local TB prevalence for the donor’s area of residence is approximately 30 cases/100,000 inhabitants, representing an inter-mediate risk.
Specific policies may be established to improve the recog-nition of the disease in donors.
The donor had no detectable abnor-malities on chest X-ray and AFB-negative smears, and the culture became positive two months after pro-curement. However, the CSF analysis showed an elevated protein level with pleocytosis, and brain death occurred nine days postadmission.
The intracerebral bleeding was likely secondary to cerebral vasculitis due to TB infection.
To improve screen-ing strategies, certain potential findings should be scrutinised such as the existence of any comorbidity that may support stroke, the presence of fever at illness presentation/admission, CT/MRI scan of the head, or CSF findings consistent with an infectious process.
The diagnosis of tuberculous meningitis is challenging, and the available microbiological tests fail to attain the accuracy standards required.
DD-TB is considered proven if donor and recipient iso-lates are identical or clonal, probable if there is suspected transmission, or possible if there is a donor risk factor for TB.
Donor transmision is usually considered probable or possible, but is less often confirmed due to lack of tracking system.
The epide-miological link between the donor and recipient was based on early TB onset in the posttransplant period, indicating donor transmission.
The liver transplant recipient was treated for latent TB and did not develop the disease, but two other organ recipients from the same donor presented fever of unknown origin, sepsis, and organ dysfunction a few months after transplantation.
DD-TB is difficult to recognize in both donor and recipient, and a recent review found 36 cases of proven (n = 17), probable (n = 8), and possible (n = 11) DD-TB among 16 lung, 13 kidney, 6 liver, and 1 heart recipients.
The median time to clinical presentation or diagnosis was 2.7 months, and fever was the most frequent presenting symptom.
Graft loss was common, and all-cause mortality was 25%.
Information gaps should be addressed.
The most important details are that communication gaps in reporting DDI are frequent and may occur at multiple levels, contributing to adverse outcomes among affected organ recipients.
Additionally, high-risk complications of the recipient with eventual connection with the donor, such as death or sepsis within 3 months of the procedure, should be actively notified.
Finally, many guidelines and protocols emphasize the importance of registry and the use of procedures for the safety and prevention of infectious disease transmission.
Biovigilance initiatives have been implemented to develop national surveillance systems for cells, tissues, and organs.
Brazil does not have a biovigilance system for donor traceability, but the current system works on demand and is triggered when the transplant program communicates an adverse event.
This paper emphasizes the importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner.
=================================================================== What is the level of evidence provided by this article? What is the take-home message?
The level evidence is 4
====================================================================
The main strategy to minimize the risk of DD transmission is to identify high risk donors, but communication gaps between organ procurement organizations and transplant centers can be prevented by more efficient screening protocols and communication.
Kidney transplant still remains the best form of renal replacement therapy for patients living with end-stage kidney disease, however, it is also accompanied by unintended cardiovascular or infectious disease complications.
Tuberculosis is one such infectious disease that is reactivated or transmitted from the donor to the recipient even despite some degree of donor screening and about 4% of cases are considered to be contracted from the donor during SOT.
Furthermore, the current screening method for tuberculosis during work in SOT may miss out the diagnosis of TB, particularly if is extrapulmonary, while communication could also be the bane of a successful surgery
The article is the summaries of four recipients (SPK, Kidney, Heart, and liver) who received diseased organs from a pregnant woman.
Case 1 (index case)
A 45-year-old man received SPK without sequelae and was discharged on day POD 30
Previous TST negative and denied TB exposure
presented 2 months post-surgery with fever, night sweat, and chill
Had drainage of peri-grafts abscess, covered with antibiotics
Had anti-TB treatment because of positive AFB from abscess sample
She had toxicity to anti-TB drugs with disseminated TB and had exploratory laparotomy, kidney graft removal, and abscess drainage
She was considered cured after 18 months of anti-TB but died of dialysis complication 2 years after the surgery
The Donor
A 23-year-old lady presented with a severe headache at 36-week gestation, and later developed fever, neck pain with seizure
Tests were done initially on CSF, respiratory secretions and blood was negative for tuberculosis
She had emergency CS and was later diagnosed with brain death, and organs were harvested for donation
The trachea aspirates became positive for TB 2 months after and the child was treated for TB with a good clinical response
Other organ recipients
The heart recipient presented to the hospital three months after with features of septic shock and died within three days despite antibiotics being given.
The liver transplant received treatment for LTBI till after the surgery and he is still doing fine without any features of DD -TB
The other recipient of the kidney also return to the hospital three- month after with sepsis of unknown origin and died despite antibiotic administration.
Discussion
DD-TB is considered proven if donor and recipient isolates were reported to be identical or clonal through molecular analysis. In the absence of definitive confirmation of similar isolates, DD-TB is classified as probable if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if the donor and recipient shared more than one epidemiologic or clinical feature
It is very obvious in retrospect to note that the donor must have had disseminated TB to most of the organs harvested as evidenced by various manifestations among the recipients
The level of evidence is 4 – case report
Take home message
Organ donation should be avoided in meningoencephalitis without a definitive confirmed cause
Establishment of an effective and rapid communication system or links between different centers where organ retrieval and surgery are done
Careful donor selection to avoid transmission of infectious disease
Establishment of a donor data bank for samples and channels to trace results
Summaries this article Introduction Source of TB infection in post transplant recipient includes
· Reactivation of LTBI (commonest source)
· donor-derived tuberculosis (DD-TB): Only 4%
· Current infection after exposure
There is no diagnostic reference standard for TB screening and usually based on radiological finding, epidemiological risks, previous TB history and clinical suspicious based on non-specific symptoms.
This is a case of unrecognized disseminated TB in the donor and TB identified 2months after organs retrieval but missed due to communication gaps.4 patient received organs 3 of them died post-transplant and only one acid fast bacilli and TB was diagnosed.only the patient who received the liver who survived as he was already on INH for LTBI. What is the level of evidence provided by this article?
Level IV (case report) What is the take-home message? · Some organism needs culture for extended duration for screening
· Current TB screening is not sufficient and more sensitive rapid tests are needed.
· Donors should be labelled regarding risk of DDI into 3 main categories and high-risk donors should be mentioned and documented in recipient counseling.
· Alarming laboratory endorsement protocol should be discussed to fulfills the gap between organ procurement organizations and transplant centers.
This article focusses on the development of TB in the recipient from the donor organ. This is of particular importance, since generally recipient TB occurs from reactivation of latent TB. Donor derived TB is rare, at a small level of 4%.
Screening protocols for donor TB are done rigorously because active TB is a contraindication to donation. However, extra pulmonary and disseminated TB are often missed or are harder to identify. This can lead to donor derived TB in the recipient.
This article is based on one such case, where disseminated TB in the donor is not identified prior to the transplant, leading to poor outcome for the recipient. Other cases have also been mentioned, to achieve a more wholesome look at the subject.
Discussion
Donor derived TB is of high importance because infections of different kinds are a major cause of morbidity and mortality in transplant recipients. This article highlights the necessity for careful donor selection to reduce risk of transmission of infection from donor to recipient, particularly infections that are treatable.
Molecular tests are more accurate in determining TB, with good sensitivity and specificity. However, this is done only when pulmonary TB is suspected, such as the donor presenting with respiratory symptoms, or compatible X ray images, positive AFB.
In order to improve screening methodology, it is recommended to look for findings consistent with infectious process especially in immunocompromised host donor such as fever or illness presentation at the time of admission, CSF findings of infection, stroke.
Donor derived TB is concluded if donor and recipient isolates were identical in molecular analysis. It is suspected if multiple recipients of the same donor are identified to have TB, or if the donor and recipient share more than one epidemiological or clinical feature. Obtaining good samples is difficult in these cases. In the absence of isolates, the link can only be made through onset of TB early in the post transplant period. The crucial aspect is to identify that TB in the recipient developed from the graft, so as to clearly indicate donor transmission.
With donor transmission of TB, graft loss can occur in 20% of recipients. Thus, surveillance of DDI is a strong indicator of transplant safety.
A network that integrates transplant centers and laboratories is highly crucial to recognize fatal hazards so that quick and effective intervention can be done to achieve the highest possible level of good outcome for the graft and the patient both in the short term and long term.
Conclusion
Prompt notification of suspicious cases of infection from donor, in particular TB, is essential to trace all the recipients at risk. TB is treatable and thus should be carefully assessed before approving donor for any recipient.
Continuous improvement of screening protocols and their accuracy in a widespread manner along with development of standardized tests in this regard is need to further protect recipients from unwanted donor related risks.
Level of evidence
This article is a case report and hence warrants level of evidence 4.
Take home message
DD-TB is possible in a small percentage of recipients. If developed in the recipient, it can lead to significant harm, even causing graft loss. In order to prevent this, careful screening procedures are essential, along with testing for extra pulmonary TB in the form of CT and MRI along with culture. Communication gaps between procurement centres and transplant team can lead to increase in risk of infection incidence in the recipient, and thus better communication strategies is encouraged.
Detailed history of donor including unrelated disease such as stroke is essential to confirm that no infection will pass on from the donor to the recipient through the transplant graft.
Donor-derived tuberculosis (DD-TB) is a rare occurrence (<5% of cases of TB). Most TB cases in SOT recipients are due to reactivation of LTBI.
Active TB is 20 to 74 times more frequent in TX settings than in the general population, & it is linked to high mortality.
To reduce the likelihood of DD-TB transmission, high-risk donors must be identified.
Despite screening recommendations, failures may lead to a breakdown in safety that results in the transmission of potentially fatal diseases
Current screening tools for deceased donors are based on nonspecific results from chest X-rays, epidemiological dangers, & prior TB history. Unfortunately, extra-pulmonary & disseminated TB may not be recognized by these characteristics. Thus, it is not always easy to identify TB, especially when uncommon symptoms are being considered for differential diagnosis & the potential donor has a low epidemiological risk.
Even when these cases are discovered, communication gaps may lead to DD infections, which may cause mortality or poor results.
Case report
In this article, a case of undiagnosed disseminated TB in the donor is described, with disastrous results for organ recipients.
The donor was a pregnant lady who passed away shortly after giving birth as a result of TB infection of the lungs & CNS.
The diagnosis was made later when congenital TB in her child was identified by the mycobacterial culture of the respiratory sample.
This case also emphasizes the necessity of a data bank, donor sample analysis, & greater coordination between TX teams & organ-harvesting teams in order to track infections.
Outcomes of recipients of the organs: The Index Case – SPK recipient:
Pre-TX TST was negative, & he denied known TB exposure. IS regimen: basiliximab, prednisone, tacrolimus, & MMF.
Developed fever, night sweats, & chills during the 2nd post-TX month. Abdominal U/S showed perigraft collections (renal & pancreatic abscesses), & CXR was normal. He underwent percutaneous drainage of the abscesses and broad-spectrum antimicrobial therapy, and his fever briefly subsided.
Lab: AFB on ZN stain. Anti-TB was started: rifampin, isoniazid, pyrazinamide, & ethambutol.
The TX harvesting center was called for more information regarding the donor & the other organ recipients because the recipient’s TB damaged the grafts, indicating donor involvement. Two recipients had already passed away at that point, & a look-back examination was done.
The Liver recipient:
A 55-year-old man. Transplanted due to Caroli disease with recurrent bacterial cholangitis.
TST was positive pre-TX. Treated for LTBI with INH for 6 months. The patient has not developed any manifestations of active TB to date.
The Heart recipient:
A 40-year-old woman. Transplanted due to heart failure caused by Chagas cardiomyopathy.
Had fever & other symptoms 3 months following TX.
Developed acute septic shock 3 days after admission, & she died despite receiving broad-spectrum antibiotics. Although cultures of blood, urine, & tracheal aspirate samples failed to reveal any bacteria or fungi, no particular mycobacterial direct exam or culture was ordered.
Despite not receiving a precise diagnosis, the patient’s chest CT showed diffuse pulmonary involvement.
The other kidney recipient:
A 45-year-old man with hypertensive nephropathy.
He returned to dialysis during the 2nd month post-TX due to mesangioproliferative GN & graft loss. He returned to the hospital 3 months after the TX with sepsis of unknown origin & passed away despite antibiotic treatment without isolating any particular infectious agent. Similar to the recipient of a heart, no particular mycobacterial test was required.
Conclusion:
The TB diagnosis contributed to one patient’s death and could be to blame in the other two patients following transplantation.
Sadly, no autopsy was done on the deceased recipients, therefore the TB diagnosis is just presumptive for both the heart & kidney recipients.
======================= 2. What is the level of evidence provided by this article?
Level IV
======================= 3. What is the take-home message?
The importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases.
DD-TB is commonly related to the donor’s epidemiology and clinical history, even if TB is not initially recognized.
The importance of registry and the use of procedures for the safety and prevention of infectious disease transmission.
If a molecular investigation revealed that the isolates from the donor & the recipient were identical, DD-TB is regarded as confirmed.
DD-TB is categorized as probable if there is a suspected transmission event & TB was found in multiple recipients of one donor, or if the donor and recipient shared more than one epidemiologic or clinical feature.
A 45-year-old male received a simultaneous pancreas kidney (SPK) transplant due to diabetes and end-stage renal disease (ESRD).
During the second month posttransplant, he returned to the hospital complaining of fever, night sweats, and chills.
Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses), whereas the chest radiograph was normal.
He received broad-spectrum antibacterial treatment and underwent percutaneous drainage of the abscesses, with transient resolution of fever.
Laboratorial analysis revealed acid-fast bacilli (AFB) on Ziehl-Neelsen stain. Antituberculous therapy was started with standard drugs: rifampin, isoniazid, pyrazinamide, and ethambutol.
The patient subsequently presented with anti-TB drug toxicities: haemolytic anaemia (related to rifampicin) and blurred vision (due to ethambutol), both in the 2nd month of treatment resulting in a change of therapy.
The clinical deterioration of the patient imposed immunosuppressive cessation, leading to acute cellular rejection of the grafts, and dual graft loss with return to hemodialysis and insulin therapy.
The patient underwent exploratory laparotomy with a surgical finding of caseating necrosis all over the mesenterium and around pancreatic graft, but affecting the renal graft.
The removal of the renal graft was the only viable treatment encountered
However, he died from complications related to ESRD and dialysis, two years after transplantation
Donor:
The donor was a 23-year-old, 36-week pregnant woman with a history of intense headache
Within 72 hours of admission, she developed mild fever, neck stiffness, and seizures.
The cerebrospinal fluid (CSF) was considered abnormal with increased cellularity and protein.
Her level of consciousness decreased, and she underwent an emergency caesarean section on the 6th day of admission.
Brain computed tomography (CT) scans performed after the procedure revealed diffuse subarachnoid bleeding.
The patient was diagnosed with brain death (day 9) and had elected to be an organ donor, considering as primary diagnosis, CNS bleeding.
Nearly two months after her death, the tracheal aspirate culture became positive for M. tuberculosis
The M. tuberculosis strain isolated from the child presented no resistance to first-line anti-TB drugs, and he was discharged home after seven days of standard TB treatment.
The organ recipeints had following outcomes :
1. Other kidney recipient: died within 3 months due to sepsis
2. Heart recipient : died within 2 months due to sepsis
3. Liver recipient : had latent TB, asymptomatic
Discussion:
For risk factor assessment, we should obtain a donor history of symptoms consistent with active TB, as past diagnosis of TB infection (active or latent), homelessness, alcohol abuse or injection drug use, incarceration, recent exposure to persons with active TB, or travel to areas where TB is endemic
DD-TB is considered proven if donor and recipient isolates were reported to be identical or clonal through molecular analysis.
In the absence of definitive confirmation of similar isolates, DD-TB is classified as probable if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if donor and recipient shared more than one epidemiologic or clinical feature
High-risk complications of the recipient with eventual connection with the donor, such as death or sepsis within 3 months of the procedure, should be actively notified.
In the reported case, if a flag for a possible DDI was detected after the first recipient’s death, the others could certainly have had a better chance.
Another gap might be related to the compulsory communication of vertical TB transmission.
The newborn was diagnosed with TB in the first 2 months of life. If this information had been shared earlier, screening the other transplant recipients for TB would have been possible.
Level of evidence: Level 4
Lesson learnt:
The importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner
Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety.
Introduction
Wanessa T.C and colleagues, described a case of unrecognized disseminated TB in the donor with a devastating outcome for organ recipients. The donor was a pregnant woman who died soon after delivery due to TB involvement of the central nervous system (CNS) and lungs. The diagnosis was retrospectively established by mycobacterial culture of the respiratory sample (positive result obtained two months after donor death) and the diagnosis of congenital TB in her baby.
The Index Case – Simultaneous Pancreas Kidney Recipient. A 45-year-old male received a simultaneous pancreas kidney (SPK) transplant due to diabetes and end-stage renal disease (ESRD). During the second month posttransplant, he returned to the hospital complaining of fever, night sweats, and chills. Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses), whereas the chest radiograph was normal. He received broad-spectrum antibacterial treatment and underwent percutaneous drainage of the abscesses, with transient resolution of fever. Laboratory analysis revealed acid-fast bacilli (AFB) on Ziehl-Neelsen stain. Antituberculous therapy was started with standard drugs: rifampin, isoniazid, pyrazinamide, and ethambutol.
The patient subsequently presented with anti-TB drug toxicities: haemolytic anaemia (related to rifampicin) and blurred vision (due to ethambutol), both in the 2nd month of treatment resulting in a change of therapy. At this time, the patient presented disseminated disease involving grafts, lungs, CNS, and thyroid.The clinical deterioration of the patient imposed immunosuppressive cessation, leading to acute cellular rejection of the grafts, and dual graft loss with return to hemodialysis and insulin therapy
The Donor. The donor was a 23-year-old, 36-week pregnant woman with a history of intense headache who was admitted to the hospital emergency room, and within 72 hours of admission, she developed mild fever, neck stiffness, and seizures. The cerebrospinal fluid (CSF) was considered abnormal with increased cellularity and protein. Although no microorganisms were identified in the CSF and blood, empirical treatment for meningoencephalitis was started 72 hours after hospital admission (ceftriaxone followed by anti-TB standard treatment and acyclovir), and other culture samples were collected. Respiratory secretions were negative for acid-fast bacilli (AFB) stain. Brain computed tomography (CT) scans performed after the procedure revealed diffuse subarachnoid bleeding. The patient was diagnosed with brain death (day 9) and had elected to be an organ donor, considering as primary diagnosis, CNS bleeding. Nearly two months after her death, the tracheal aspirate culture became positive for M. tuberculosis.
Discussion
This case report calls attention to the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases. Typically, DD-TB is commonly related to the donor’s epidemiology and clinical history, even if TB is not initially recognized. In this case, the donor had an unrecognized disseminated TB, with no history of previous TB or exposure and, except for pregnancy, no known immunosuppressive conditions.
Conclusion
This paper underscores the importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner. Additionally, this report also highlights the need for a data bank and donor sample analysis to trace infections and reinforces the importance of better communication between transplantation teams and organ-harvesting centers.
Case Report Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
1. Summary of the case
This report describes a case of DD-TB and emphasizes communication gaps that may occur between organ procurement organizations and transplant centers.
Case report
The Recipient
A 45-year-old male received a simultaneous pancreas kidney (SPK) transplant due to diabetes and end stage renal disease (ESRD).
During the second month post-transplant, he complained of fever, night sweats, and chills.
Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses).
Analysis revealed acid-fast bacilli (AFB) on Ziehl-Neelsen stain. Antituberculous therapy was started with standard drugs.
Recipient’s TB abscesses were located near the grafts, suggesting donor involvement.
Later on the patient presented with anti-TB drug toxicities and disseminated TB.
Immunosuppressive medications were stopped because of clinical deterioration, leading to ACR and dual graft loss.
After 18 months of medical treatment the patient was considered cured.
He died from complications related to ESRD and dialysis, two years after transplantation.
The Donor
23-year-old, 36-week pregnant woman, presented with features of meningoencephalitis.
CSF showed increased cellularity and protein and was sent for culture.
Empirical treatment for meningoencephalitis was started 72 hours after hospital admission including anti-TB.
The patient deteriorated and underwent an emergency caesarean section.
CT scans performed revealed diffuse subarachnoid bleeding.
The patient was diagnosed with brain death and had elected to be an organ donor, considering as primary diagnosis, CNS bleeding.
Nearly two months after her death, the tracheal aspirate culture became positive for M. tuberculosis.
Her child at 2 months of age was also diagnosed with disseminated TB.
The Liver Recipient
Due to a positive TST before surgery, he was treated for LTBI with isoniazid, soon after the transplant.
In this recipient, no diagnosis compatible with active TB was reported.
The heart and the other Kidney recipients
Presented in 3 months post transplantation, with sepsis of unknown origin and died despite antimicrobial therapy, without isolation of any specific infectious agent. No specific test for mycobacteria was requested in both conditions.
For both recipients, the TB diagnosis is only presumptive.
Discussion
Most TB cases in solid organ transplant recipients are caused by the reactivation of latent tuberculosis infection, and only 4% are considered donor-derived.
Active TB in the donor is recognized as an unacceptable risk and contraindicates organ donation.
TB recognition in deceased donors is not always feasible.
Even when these cases are identified, communication gaps may result in donor-derived infections (DDI).
In this index case, the CSF analysis was abnormal. The intracerebral bleeding was likely secondary to cerebral vasculitis due to TB infection.
According to current recommendations, in cases of donor death due to meningoencephalitis without a proven cause, the donation should be avoided.
The diagnosis of tuberculous meningitis is challenging, and the available microbiological tests has poor sensitivity and delayed results.
Communication gaps in reporting DDI are frequent and may occur at multiple levels, contributing to adverse outcomes among affected organ recipients.
In this index case there were multiple communication gaps, reporting and checking the pending TB culture result, the first recipient’s death within 3 months should have been reported and the reporting of vertical transmission.
Conclusions
Specific policies may be established to improve the recognition of the TB in donors.
A fully developed network that integrates transplant centers, OPO’s, and laboratories is mandatory and could allow the recognition of potential hazards followed by a more rapid intervention.
Introduction
o Most TB cases in SOT recipients are caused by the reactivation of LTBI
o Only 4% are donor-derived tuberculosis (DD-TB)
o Current TB screening protocols for deceased donors are usually based on chest X-ray findings (which may be nonspecific), epidemiological risks, and previous TB history (may not identify extrapulmonary and disseminated TB)
o Despite organ procurement protocols, pre-transplantation screening may miss TB in the donor (due to communication gaps leading to donor-derived infections (DDI))
o This report describes a case of unrecognized disseminated TB in the donor with a devastating outcome for organ recipients (The donor was a pregnant woman who died soon after delivery due to TB involvement of the CNSand lungs)
The Index Case (Simultaneous Pancreas Kidney Recipient)
A 45-year-old male received a SPK transplant due to diabetes and ESRD. His previous TST was negative, and no TB exposure. Two months posttransplant, he returned to the hospital complaining of fever, night sweat, and chills. Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses), and chest radiograph was normal. He received broad-spectrum antibacterial treatment and underwent percutaneous drainage of the abscessesw. Laboratorial analysis revealed AFBon Ziehl-Neelsen stain. Anti-tuberculous therapy was started which latter leading to toxicities. At this time patient presented disseminated disease (grafts, lungs, CNS, and thyroid). The patient deteriorates and immunosuppressive stopped, leading to dual graft loss with return to hemodialysis and insulin therapy. The patient was considered cured. The patient died 2 years latter from complications related to ESRD and dialysis
The Donor
o A pregnant woman who died after delivery due to TB involvement of the CNS and lungs
o The CSF was abnormal with increased cellularity and protein but no microorganisms in the CSF and blood. Empirical treatment for meningoencephalitis was started
o Respiratory secretions were negative for AFB stain
o Latter patient deteriorates and CT scans revealed diffuse subarachnoid bleeding (primary diagnosis)
o Two months after death, the tracheal aspirate culture became positive for M. tuberculosis
The Liver Recipient
o TST was positive for LTBI and treated with isoniazid after the transplant (six months)
o Asymptomatic and not developed any manifestations compatible with active TB
The Heart Recipient
Died 2 months after transplantation due to sepsis of unknown origin (although chest CT revealed diffuse pulmonary involvement)
The Other Kidney Recipient
Died 3 months after transplantation of sepsis of unknown origin
Discussion
o Careful donor selection is important to reduce the risk of transmission of potentially lethal but treatable diseases
o DD-TB is commonly related to the donor’s epidemiology and clinical history
Risk factor assessment:
1. Donor history of symptoms consistent with active TB
2. Past diagnosis of TB infection (active or latent)
3. Homelessness
4. Alcohol abuse or injection drug use
5. Incarceration
6. Recent exposure to persons with active TB
7. Travel to areas where TB is endemic
o Molecular tests have greater sensitivity and specificity but are done when pulmonary TB is suspected
o The intracerebral bleeding was likely secondary to cerebral vasculitis due to TB infection
o Notify any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manners
What is the level of evidence provided by this article?
Level IV (case report)
What is the take-home message?
o Current TB screening protocols for deceased donors based on chest X-ray findings, epidemiological risks, and previous TB history may not be enough as it may not identify extrapulmonary and disseminated TB
o Identification of high-risk donors will minimize the risk of DD transmission
o Communication gap between organ procurement organizations and transplant centers may result in DDI with associated death and poor outcomes (prevented by a more efficient screening protocols and communication)
o Donation should be avoided in donor death due to meningoencephalitis without aproven cause
o Autopsy is required in ill-defined cause of death
I like your summary, level of evidence, analysis and take home messages. Autopsy!
I think you mean to suggest that retrieval of organ in donor operation needs to be supported by pathologist so that we do not miss a donor just because of suspicion of an infection or cancer that has been suspected but not proved.
Donor-derived tuberculosis (DD-TB) accounts for less than 5% of TB cases
Case report of unfurtnate outcome for many people who got organs from TB donnor, SPK, Kidney, Heart and Liver. The Liver Tx survived because of LTIT. all complications happened early post transplant. Sadely the SPK developed rejections due to stop the immunosupression medications.
Level of evidence: Case report level 4
Take Home massages:
Communication is key early post transplant.
It is critical to report that serious complications as ealy as possible and track other recipent as that could have saved lives if reported early.
Meticulious donnor selection is crucial
TB should be considred in differntial diangoses in the first few months post transplant when recipient present with fever and unusual presentations.
Introduction
Donor source for mycobacterium tuberculosis (TB) is one of the sporadic events reported in less than 5% following kidney transplantation. The common source of MBT is the reactivation of latent TB, and it’s more frequent in immunocompromised patients like SOT recipients compared to general populations, active MBI is an absolute contraindication for kidney donation and the screening of DD is considered one of the challenges in kidney transplantation as the screening limited including CXR(nonspecific), the history of previous exposure or previously treated PTB or donor source from an endemic area and latent TB in donor can be the risk of extrapulmonary TB and disseminated TB which can be easily missed due to the limitations in the current protocols for screening the Donors in addition to the communications gaps and this report show us the best example of missing a case of unrecognized disseminated TB in the donor with a distressing outcome for organ recipients. Case based discussion
This is a case report of pulmonary TB with CNS involvement died immediately after delivery and her child was also treated on the line vertical transmission TB with first line Anti TB 2 months later in the same hospital; her initial presentation includes headache and fever and treated on the line of meningoencephalitis (bacterial viral and anti-TB) she was from an intermediate endemic area for TB, however
The donor had no respiratory symptoms or well-matched image, and the AFB was negative, molecular tests present greater sensitivity and specificity but are done when pulmonary TB is suspected [30, 31]. and therefore, TB has not been assumed in her. and her course was complicated by SAH and the death certificate with ICB?? and the TB culture was positive from the tracheal aspirate sample resulted in two months after donation (delay in diagnosis, in addition, there was no autopsy biopsy from DD The cerebral bleeding was likely secondary to cerebral vasculitis (young lady with no comorbid and history of fever at presentation and headache, in addition, her CSF analysis suggestive of the infectious process in a retrospective study. According to present recommendations, in cases of donor death due to meningoencephalitis (ME) without a recognized cause, the donation should be avoided. Many reports about donor-derived TB addressed the challenges in delayed diagnosis, communications gaps including no clear protocols or proper tracking system to follow up or comminate the late results as TB cultures might need weeks which will impact the delay in treatment initiation as the MTB screening and diagnosis still consider one of the limitations and challenges of SOT
Figure one summarizes the outcome of the 4 recipients with organ transplantation from the same donor, 3 (HEART and second kidney recipients with unknown sepsis ended with death, 3rd recipient died with disseminated TB infection and dual graft loss, and one liver transplant was treated online LTBI What is the level of evidence provided by this article?
Case report level 4 of evidence What is the take-home message?
Written protocols for OPT regarding handling the DD infection source and creating proper channels of commination and tracking the information between the OPT and the transplant team
Identification of the donor epidemiological risk of certain infectious diseases including family history and social background
including family and social history, previous exposure, and screening, effective communication, and documentation by creating a data bank and donor
sample analysis to drop infections
Encourage, and reinforce the importance of writing such cases with high-risk complicated courses and outcomes as it will give a clear home message to prevent such complications in the future.
The main cause of tuberculosis in solid organ transplant recipients are the reactivation of latent tuberculosis infection . and only 4% are considered donor-derived.
Active TB in the donor is contraindication in organ donation.
The weak screening for deceased donors is not specific which depend on CXR, epidemiological risks, and previous TB,which is not enough to identify TB in donor. 2. Discussion
This case report for the importance of careful donor selection to reduce the risk of transmission of tuberculosis.
In this case report ,the donor had an unrecognized disseminated TB, with no history of previous TB or exposure.
Specific policies may be established to improve the recognition of the disease in donors.
Inspite of that no definitive recommendations for centers to how investigate donor.
In this case report the donors investigated for CXR(no abnormalities ), AFB (negative),culture (positive after 2month).
Sputum culture is more sensitive than AFB,but culture take long time (weeks to months).
When pulmonaryTB suspected molecular tests is more sensitive and specific.
CSF analysis showed an elevated protein level with pleocytosis, leading to brain death in this case.
DD TB is difficult to recognize in both donor and recipient. 3.Level of evidence :IV. 4. What is the take-home message
Tuberculosis is fatal but can be treated.
Appropriate history and examinations .
Research for diagnostic tools to detect TB in donor .
TB from donor is rare but can occure.
1-Summarise this article;
-This report describes a case of unrecognized disseminated TB in the donor with a devastating outcome for organ recipients.
-The Donor. The donor was a 23-year-old, 36-week pregnant woman who died soon after delivery due to TB involvement of the central nervous system (CNS) and lungs.
-The patient was diagnosed with brain death (day 9) and had elected to be an organ donor, considering as primary diagnosis, CNS bleeding.
-The diagnosis was retrospectively established by mycobacterial culture of the respiratory sample (positive result obtained two months after donor death) and the diagnosis of congenital TB in her baby.
-This donner donate 4 recepients;
*The Index Case – Simultaneous Pancreas Kidney Recipient;
Outcome—Disseminated TB Died 2 years after transplantation from ESRD complications.
*2nd recipient; the other Kidney;
Outcome—Died 3 month after transplantation with Sepsis of unknown origin.
*3rd recipient; Heart;
Outcome—Died 2 month after transplantation with Sepsis of unknown origin.
*4th recipient;Liver with (positive TST);
Outcome—Asymptomatic on Latent TB treatment.
-Unfortunately, no autopsy was performed on the deceased organ recipients, and therefore, for both the heart and kidney recipients, the TB diagnosis is only presumptive. Discussion; –DD-TB is classified as probable; if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if donor and recipient shared more than one epidemiologic or clinical feature(e.g.,TB diagnosis in a donor plus TB in the recipient early post-transplantation)or
-Possible, if there is a suspected transmission event but the only criterion met is a donor risk factor for TB (e.g., donor residence in TB endemic area and absence of recipient risk factors for TB).
-The major limitation to confirm DDI is to have a positive donor sample and genetic sequencing of the pathogen matching donor and recipient samples.
-Usually, there is often a time gap between the donation and the development of the disease.
-In this reported case, TB was confirmed in a donor sample two months after donation, and the result was still not properly informed because there was no tracking system to request the pending microbiological results.
-As such, donor transmission is usually considered probable or possible, depending on the data available, but is much less often confirmed. Conclusion; –High-risk complications of the recipient with eventual connection with the donor, such as death or sepsis within 3 months of the procedure, should be actively notified.
-In the reported case, if a flag for a possible DDI was detected after the first recipient’s death, the others could certainly have had a better chance.
2-What is the level of evidence provided by this article? This case report with (LOE IV) 3-What is the take-home message? –Donor-derived TB is uncommon, but it may happen.
-The importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner. -Risk of communication gaps that may occur between organ procurement organizations and transplant centers.
-Inefficient communication between organ procurement organizations and transplant centers may be prevented by a more efficient approach towards screening protocols and communication.
-The need for a data bank and donor sample analysis to trace infections and reinforces the importance of better communication between transplantation teams and organ-harvesting centers.
· Incidence of TB in SOT is 20 to 74 times higher than that in the general population.
· Mostly it results from reactivation of latent TB infection (LTBI), and only 4% are considered donor-derived (DD).
· TB is a fatal disease with high risk of mortality in SOT.
· DD-TB mainly presents within 2-3 months post-transplant, fever is a common manifestation, allograft involvement is common and lost in 25 % of cases. All cause mortality accounts for 25 %.
· Mis-communication can result in misconduction and reporting of data and lab results between organ harvesting center and organ transplantation service that can have detrimental effect on the graft and patient outcome.
· Active donor TB is absolute contraindication to donation. However, in deceased donor the exclusion is based on prior history of TB, epidemiological data about high risk locality and CXR which are not 100 % confident to exclude TB especially in case of extrapulmonary and disseminated disease.
· Current case report of (deceased pregnant lady who died with disseminated TB and infected her baby), the diagnosis was done retrospective from tracheal aspirate culture analysis after death revealing acid fast bacilli (AFB).
· She died with picture similar to meningitis and was treated with triple therapy (antibiotic, antiviral and anti TB), as the CT brain revealed subarachnoid hemorrhage (this was declared as cause of brain death) as CSF revealed no organism and respiratory secretions were negative for AFB.
· So, per guidelines deceased donor due to picture suggestive of meningoencephalitis (without bacteriologically confirmed or proven infection), the donation should be avoided as the diagnostic modalities lack specificity and sensitivity regarding AFB in CSF.
v One recipient has pancreas-kidney transplantation: presented in 2nd month post transplant.
1. He had complaint of night fever and sweating, multiple renal and pancreatic abscesses that revealed acid fast bacilli on Ziehl-Neelsen stain on aspiration and analysis.
2. Anti TB therapy was initiated with 4 drugs for the recipient: rifampin, isoniazid, pyrazinamide, and ethambutol. After 2months, he developed hemolytic anemia (rifampin side effect) and blurred vision (ethambutol) and then disseminated TB in CNS, LUNG and graft.
3. Surgical drainage of abscesses, graft nephrectomy and prolonged anti TB therapy for 18 months were done to cure TB, but he died from dialysis complications.
v The liver recipient:
1. He had +ve TST prior to transplantation and was labeled as latent TB and was on standard INH therapy for 6 months and did not develop active TB disease.
v The heart recipient: presented in 3rd month post-transplant.
1. Died from severe pulmonary involvement (apparent in CT) plus night fever and picture of septic shock.
2. The specific investigations for AFB were not requested.
v The other kidney recipient:presented in 2nd month post transplant and died in 3rd month.
1. Died with septic shock after return to dialysis due to graft failure.
· Confirmed donor derived TB needs molecular analysis and presence of similar isolates in both the donor and recipient.
· Probable if TB was identified in multiple recipients of one donor, or if donor and recipient shared more than one epidemiologic or clinical feature (e.g., TB diagnosis in a donor plus TB in the recipient early posttransplantation).
· Possible, if there is a suspected transmission with only criterion met (donor has risk factor for TB as residence in endemic area and absence of recipient risk factors for TB).
Level of evidence: case report (level V) Take home messages:
· Through screening of TB in donor especially deceased is essential to save lives and prevent donor derived TB with its destructive consequences.
· Extra pulmonary and disseminated TB are serious and may be confusing or difficult in diagnosis.
· Epidemiological data and risk stratification may help in diagnosis together with bacteriological identification.
· History of contact or exposure to TB cases, history of alcohol and drug abuse, low socioeconomic state and overcrowding should raise suspicion of TB.
· Sputum culture is more sensitive than smear examination with zeil nelsen stain, but time consuming (takes weeks and this is not applicable in screening of deceased donors).
· So, molecular tests have greater sensitivity and specificity but are done when pulmonary TB is suspected.
· There must be a tracking system to request the pending microbiological results.
· Need to obtain complete medical records, adequate training for through examination of the donor, and sufficient tight network to document and follow these data are essential to avoid any mistake in donor screening.
· Early detection or diagnosis of TB from donor specimens may save lives is therapy was initiated early.
· Early notification of any recipient death and in addition the neonatal outcome in such pregnant deceased donor would save lives of recipient through early diagnosis and management.
Summarise this article Donor derived tuberculosis is high cause of mortality and accounts for < 5% cases. In transplant recipients , the incidence is 20-74 times higher than general population. The main strategy to prevent this transmission is to identify high risk individuals. Active tuberculosis is a contraindication to transplantation but some times cases can be missed due to multiple factors , especially in the setting of cadaveric donation.
In this case report a female donor who had meningoencephalitis was donor. Multiple organs were retrieved but later she was found to have disseminated Tuberculosis. Diagnosis was made with positive culture 2 months after death and congenital TB in newborn.
First Recipient Diabetic transplant recipient who had combined kidney and pancreatic transplant. Induction with Basiliximab with maintenance with TAC, MMF and steroids. at 2 months post transplant developed fever, night sweats, and chills. Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses), whereas the chest radiograph was normal . Collection around graft was drained and was positive for acid-fast bacilli (AFB) on Ziehl-Neelsen stain. Antituberculous therapy was started with standard drugs: rifampin, isoniazid, pyrazinamide, and ethambutol. Patient developed disseminated TB and required multiple aspiration of collections.
Second Recipient Liver transplant recipient . Treated with INH due to positive TST before transplant
Third Recipient 40 Year old heart recipient developed septic shock. Cultures were negative and CT chest showed diffuse changes.
Fourth Recipient Developed MPGN and Graft loss . Cause of death was septic shock
What is the take-home message? Active TB is contraindication for transplantation Excellent communication is needed between organ harvesting centre and transplant team. In donor evaluation detailed history and examination should be done. Investigations should be done to rule out latent TB. Treatment soon after transplantation may prevent progression of TB. Sole dependence on chest ray should not done as there can be extrapulmonary TB. TB PCR is faster and AFB cultures are more accurate but take long time. Tuberculosis should be excluded if there is history of meningo encephalitis. High-risk complications of the recipient with eventual connection with the donor, such as death or sepsis within 3 months of the procedure A more efficient reporting system will not prevent the event from occurring but may of course impact the outcome
What is the level of evidence provided by this article? Case report Level V
Introduction
Just 4% of solid organ transplant (SOT) patients develop donor-derived tuberculosis (TB) due to LTBI reactivation. Active TB in donors precludes organ donation. Nevertheless, dead donor screening techniques are based on chest X-ray results (which may be vague), epidemiological hazards, and past TB history. These characteristics may miss extrapulmonary and disseminated TB. Hence, TB detection is difficult, especially when atypical symptoms are differentially diagnosed and the prospective donor has low epidemiological risk.
The Cases:
A 45-year-old man with diabetes and end-stage renal failure underwent an SPK transplant (ESRD)
He was released on day 30 post-transplantation without severe issues.
Despite a normal chest radiograph, abdominal ultrasonography showed peri-graft collections.
The fever subsided after percutaneous abscess drainage and broad-spectrum antibiotic therapy.
The patient was cured after ultrasound-guided punctures to empty intra-abdominal TB abscesses and 18 months of anti-TB treatment.
Two years after transplantation, ESRD-related dialysis problems killed him.
The donor, a 23-year-old, 36-week pregnant lady with a history of severe headaches, was taken to the emergency department and suffered minor fever, neck stiffness, and convulsions within 72 hours.
The CSF and blood were microorganism-free, empirical meningoencephalitis therapy began 72 hours after hospital admission, and more culture samples were taken.
Acid-fast bacilli were absent from respiratory secretions.
On the sixth day of hospitalization, she had an emergency cesarean.
Brain death and CNS hemorrhage led the patient to donate organs.
Her child had a fever two months after birth and was diagnosed with disseminated TB at the same hospital.
After seven days of normal TB therapy, the boy returned home since his M. tuberculosis strain was not resistant to first-line anti-TB medications.
Discussion :
This case report emphasizes donor selection to limit the danger of transmitting potentially deadly but curable illnesses. Even if TB is not first diagnosed, donor epidemiology and clinical history are often linked to DD-TB
The donor had undiagnosed disseminated TB, no history of TB or exposure, and no immunosuppressive conditions saved during pregnancy.
Pregnancy hormones and lymphocyte dysfunction modulate immunity. The donor lives in an intermediate-risk region with 30 TB cases per 100,000 people.
The donor had a normal chest X-ray and AFB-negative smears, but the culture went positive two months following procurement. Sputum culture is more sensitive than AFB, although positive results take weeks to months. When pulmonary TB is suspected, molecular testing is more sensitive and specific. TB was not suspected since the donor had no respiratory symptoms, a suitable picture, or AFB. CSF protein levels were raised with pleocytosis. After nine days, the patient died from brain damage. TB-induced cerebral vasculitis causes intracerebral hemorrhage.
What is the level of evidence provided by this article?
Level IV, Case report
What is the take-home message?
-To prevent disease transmission in dead donor transplantation, transplant teams and organ-harvesting institutions must communicate well.
-Organ donor screening for infections is currently based on donor history, physical assessment, and laboratory testing, but circumstances like the donor’s and her child’s neglect, incomplete medical records, a lack of training, and an insufficiently tight network for monitoring these results may have contributed to this catastrophic outcome.
-Notify the donor of high-risk recipient issues, including death or infection, within three months. After the first recipient’s death, a flag for DDI may have helped the others.
Vertical TB transmission-mandatory communication may be another gap.
-Extrapulmonary TB may develop, therefore a negative chest XR does not rule out TB. TB culture might take months to be positive, thus if TB is suspected, PCR can provide a quicker and more reliable diagnosis.
The prevalence of active TB is significantly higher than general population, around 20-74 times higher than general population
The main mode of transmission is through activation of latent TB, or acquiring new infection through air born transmission
Acquiring the disease from the graft (donor derived) is rare and accounts for < 5% of cases
Active TB of the donor is considered a contraindication to donation, but sometimes diagnosis is missed especially in deceased donor transplantation due to defective communication between transplant team and organ-harvesting centers and due to nonspecific findings found in CXR
The current case report describe a pregnant deceased donor who died due to meningoencephalitis, that donate her organs to multiple recipients, which was discovered later to be missed disseminated TB involving the lung and brain, the condition diagnosed post mortem by positive culture of the respiratory sample 2 months after death and the detection of congenital TB in the newborn.
The first recipient
Diabetic transplant recipient that receive simultaneous pancreas kidney (SPK) transplant form this donor, transplant recipient has no history of TB exposure, TST was negative
Patient received basiliximab induction with triple maintanace immunosupression (prednisone, tacrolimus, and MMF), and discharged at day 30 uneventfully
At 2nd month after transplantation patient was admistted for assessment of fever, chills and night sweats, CXR was normal and US revealed peripancreatic and perirenal collections, drainage done, stain for AFP and cultures taken, broad spectrum antibiotics given waiting culture result
AFP was detected in the fluid drained confirming the presence of TB
Treatment started in the form of rifampin, INH, pyrazinamide, and ethambutol, after 2 months of treatment the patient reported side effects form the drugs including rifampicin related haemolytic anaemia and ethambutol related blurred vision, so treametn plan changed
The patient developed disseminated TB affecting the graft, lungs, CNS, and thyroid gland, so immunosuppressive medications stopped with subsequent ACR ended by dual graft loss, renal graft was removed and the patient return again to insulin therapy and dialysis
Multiple US guided aspiration of TB abscesses was done together with anti TB drugs that was continued for 18 months, patient cured and then died from complication related to dialysis
The second recipient
This is a recipient who received liver transplant form this donor but fortunately the patient received treatment for latent TB soon after transplantation with INH for 6 months, due to positive TST and nothing happen to the patient until now
Third recipient
Heart recipient, which develop septic shock and diet 3 months after transplantation despite the use of broad spectrum antibiotics.
Fourth recipient
Other Kidney Recipient developed MPGN, complicated by graft loss and shifted again to dialysis at the second month after transplantation, 1 month later the patient develop septic shock and diet despite the use of broad spectrum antibiotics.
Conclusion and take-home message
Active TB is a contraindication to transplantation as it carry unacceptable risk to the recipient
In deceased donor transplantation, good communication between transplant team and organ-harvesting centers is required to avoid transmission of diseases from the donor to the recipient
Through history taking and investigations to exclude latent or active TB is mandatory in the setting of donor evaluation
Treatment of recipient latent TB soon after transplantation may be protective against donor derived TB and may avoid progression to active disease
Extra pulmonary TB can occur, and it is not wise to depend on negative chest XR to exclude TB
TB culture although is accurate in the diagnosis of TB but can take time up to months to be positive, so if TB is suspected PCR can have accurate and faster result
Any deceased donor died from unexplained meningoencephalitis should be excluded
What is the level of evidence provided by this article?
Introduction
· Just 4% of occurrences of tuberculosis (TB) in solid organ transplant (SOT) recipients are thought to be donor-derived; instead, the disease is brought on by the reactivation of latent tuberculosis infection (LTBI).
· The criteria used in the current screening procedures for dead donors are based on the results of chest X-rays, epidemiological dangers, and prior TB history, however, they may not catch extrapulmonary and disseminated TB.
· Pretransplantation screening frequently fails to detect TB despite organ procurement guidelines, leading to donor-derived infections (DDI), which can result in mortality or poor results.
Cases:
· A 45-year-old male received a simultaneous pancreas-kidney transplant due to diabetes and end-stage renal disease (ESRD). During the second month posttransplant, he returned to the hospital with a fever, night sweats, and chills. Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses). Antituberculous therapy was started, but the patient developed hemolytic anemia and blurred vision. Surgery was the only viable treatment. However, he died from complications related to ESRD and dialysis, two years after transplantation.
· The donor was a 23-year-old pregnant woman with a history of intense headaches who was admitted to the hospital emergency room with mild fever, neck stiffness, and seizures. CT scans revealed diffuse subarachnoid bleeding, and her tracheal aspirate culture was positive for M. tuberculosis. She was diagnosed with brain death and elected to be an organ donor. Two months after her death, her child was diagnosed with disseminated TB and was discharged home after seven days of standard TB treatment.
· The liver recipient was treated for LTBI with isoniazid for six months and has not developed any manifestations compatible with active TB.
· The heart recipient had Chagas cardiomyopathy and underwent a heart transplant, but developed septic shock and died despite broad-spectrum antibiotic therapy. Her chest CT revealed diffuse pulmonary involvement.
· The kidney recipient was a 45-year-old man with systemic hypertension and terminal hypertensive nephropathy who developed mesangioproliferative glomerulonephritis and graft loss after transplantation and died despite antimicrobial therapy without isolation of any specific infectious agent. No autopsy was performed on deceased organ recipients, making TB diagnosis presumptive.
Discussion
· Transplantation is the treatment of choice for end-stage organ failure, but there are risks related to the procedure and immunosuppression. Infections are a major cause of morbidity and mortality, and active TB is an absolute contraindication for organ donation. Unfortunately, even active TB can be overlooked and therefore mistaken for other diseases.
· The case report highlights the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases.
· DD-TB is related to the donor’s epidemiology and clinical history, with a local TB prevalence of 30 cases/100,000 inhabitants.
· OPOs should obtain a donor history of symptoms consistent with active TB, and further testing and radiological assessments are warranted when risk factors are identified.
· Molecular tests are used when pulmonary TB is suspected, but CSF analysis can show elevated protein levels with pleocytosis, leading to brain death in the reported case.
· The intracerebral bleeding was likely secondary to cerebral vasculitis due to TB infection and should be avoided in cases of donor death due to ME.
· To improve screening strategies, potential findings should be scrutinized. Diagnosis of tuberculous meningitis is challenging, with poor sensitivity and delayed results.
· DD-TB is considered proven if donor and recipient isolates are reported to be identical or clonal, probable if there is suspected transmission, or possible if there is a donor risk factor for TB.
· Donor transmission is usually considered probable or possible but is less often confirmed due to a lack of a tracking system.
· It is important to emphasize that the graft was the first topography for TB diagnosis in the recipient, a clear indication of donor transmission.
· The liver transplant recipient was treated for latent TB and did not develop TB, but two other organ recipients from the same donor presented fever, sepsis, and organ dysfunction. TB donor transmission was confirmed in SPK transplant recipients.
· The most important details are that the donor had cultures pending at the time of procurement, that mycobacterial culture is more time-consuming, and that the donor tests and samples were processed and held at the hospital where the donor was treated and removed for donation.
· Communication gaps in reporting DDI can lead to adverse outcomes among organ recipients.
· High-risk complications of the recipient with eventual connection with the donor should be notified within 3 months of the procedure.
· Screening other transplant recipients for TB could have prevented TB transmission in newborns.
· Biovigilance initiatives aim to develop national surveillance systems for transplant safety.
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What is the level of evidence provided by this article?
Level 4 (case report).
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What is the take-home message?
· Any early posttransplant death related to infectious diseases has to be informed and registered, and graft and recipient survival are mandatory.
· Adverse events such as those described here are rare but may occur in any place or situation.
· A fully developed network that integrates transplant centers, OPOs.
· Laboratories are mandatory and could allow for more rapid intervention.
Introduction : Ø Transplantation is the treatment of choice for some types of end-stage organ failure., transplantation has risks related to the procedure itself and immunosuppression. Ø Infections represent a major cause of morbidity and mortality for SOT recipients Ø Active TB is an absolute contraindication for organ donation., can be overlooked Ø The importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases Ø DD-TB is commonly related to the donor’s epidemiology and clinical history Recommendation :
1-Established specific policy to improve the recognition of the disease in donors.
2-Developed guidelines to assist in the screening of potential organ donors and recipients
3-Should obtain a donor history of symptoms consistent with active TB, as past diagnosis of TB infection (active or latent), homelessness, alcohol abuse or injection drug use, incarceration, recent exposure to persons with active TB, or travel to areas where TB is endemic
4-Improve screening strategies
5-It should be considered that the donor tests and samples are processed and held at the hospital where the donor was treated, and the organs were removed for donation.
6- Importance of registry and the use of procedures for the safety and prevention of infectious disease transmission
This article level : 4 Take home massage :
1-TB is fatal disease but is a treatable .
2- care full evaluation of deceased donor and take detailed history and full investigations Concerning the information gaps:
Specific protocol defining who was responsible for checking the pending test results complete medical records, training, and a tight network for monitoring the donor and patient result results
High-risk complications of the recipient should be actively notified
The importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner
Fully developed network that integrates transplant centers, OPO’s, and laboratories is mandatory and could allow the recognition of potential hazards followed by a more rapid intervention.
Notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner
This is a case study work (Level IV of scientific evidence) commenting on tuberculosis transmitted from a donor to his recipient.
Introduction
Active tuberculosis is an unacceptable risk and contraindicates organ donation, but current protocols are insufficient to generate this safety (X-rays, epidemiological risk and previous tuberculosis) and are not capable of diagnosing extrapulmonary disease.
This study is about a donor with disseminated tuberculosis who did not meet the criteria of the Brazilian protocol and transmitted the disease to the recipient.
Index case
Simultaneous pancreas-kidney donation.
ESRD and DM. Previous negative TST and denied exposure to tuberculosis
Immunosuppression – Basiliximab, tacrolimus, MMF, and prednisone.
Second-month post-transplant with fever, night sweats, and chills.
The image shows perigraft abscess.
Culture and acid-resistant bacilli were found in the drainage and a classic scheme for tuberculosis with RHZE was started.
Of the other recipients had died. He had side effects of the medications and spread of the disease with graft loss. There was dissemination throughout the mesentery and treatment with the classic scheme for 18 months until cure.
He died two years after the transplant due to complications from chronic kidney disease.
Donor
Pregnant woman with meningeal disease and meningoencephalitis. Two months after the death, the culture was positive for tuberculosis. The son was born and developed disseminated tuberculosis two months after delivery.
Liver receptor
Caroli’s disease underwent chemoprophylaxis for LTBI and did not develop symptoms of the disease.
Heart receptor
Chagas cardiomyopathy with severe heart failure after three months of transplantation with diffuse lung disease and died.
Other renal receptor
Hypertensive nephropathy after two months lost the graft due to glomerulonephritis and evolved with sepsis and death without identification of the germ.
Discussion
The difficulty in making an adequate diagnosis of tuberculosis, especially in extrapulmonary disease, increases the risk of transmission by transplantation. Brazil is an endemic country for the disease and does not have molecular diagnostics such as IGRAs in the public system, but has recently used GeneXpert with its interpretation limitations.
The absence of molecular methods in this screening made the diagnosis difficult and favored the transmission of the disease to recipients.
The diagnosis not performed on the donor was expanded to several other recipients, only be achieved in one of them. Culture with late results is common in tuberculosis and the lack of communication between services due to the lack of adequate records in a manual system, without the availability of an electronic medical record with complete information.
Take home messages
There is a need for better diagnostic methods for diseases and local epidemiology must be considered. The integration of information is extremely necessary.
What is your suggestion in regards to integration of information regarding availability of newer diagnostic tests and promptness of action on these reports?
I believe we can use GeneXpert for preemptive diagnostic
IGRAs and TST in Brazil is very difficult to interpret for being endemic disease, and for extrapulmonary pathology
Molecular methods are the best in trying to reach a better diagnosis.
1-Summary:
A case report of misdiagnosed donor derived TB. A deceased- donor with disseminated TB was not properly evaluated and accepted despite of having suspected meningeo-encephalitis of unknown cause.
after SPK transplantation, the recipient developed disseminated TB which necessitates stoppage of IS and graft nephrectomy and the patient died from CKD within 2 years.
because of this, they recalled the donor data which confirmed that donor had TB.
by reviewing other recipients, one with heart and one with kidney transplantation died from severe sepsis. only liver transplant patient who was maintained on anti-TB therapy for latent TB who survived without disease dissemination.
II- Level of evidence: IV III-Take home message:
1- Follow the guideline for all steps of donor and recipient preparation regardless the situation
2- Any DD with meningeo-encephalitis of unknown origin should be excluded
3- Proper communication is a must in the transplantation activity
4- Donor-derived TB is not common, but it can happen.
Of course renal transplantation is the best solution for ESRD on regular hemodialysis, but also complications related to immunosuppression is common finding and may endanger the patient life, so the suspicion is a good key to detect early and start early treatment.
TB one of the infectious disease that can be happened as a result of defective immune system.
TB in SOT result from reactivation of latent TB , and in 4% of the cases are donor derived, as in some donors, TB could not be diagnosed and identified and also there was a communication gap between the transplant team and the harvesting center of donors which leads to bad outcome in the recipient and disseminated TB in the recipient with high mortality.
Development of better strategy or protocol for early detection of disease and hence early treatment;
1- Better selection of donor as active TB is absolute contraindication for donation.
2- Better communication with the harvesting center to know every details about the donor like history, physical examinations, lab and radiological investigations, the story of his/her disease and its progression until the death time.
3- Follow up of any delayed sample or investigations which was done before death and not appeared until the time of donation.
4- Follow up of any post-mortem sample or culture or biopsy.
5- Set a coordinator staff responsible for the process of follow up.
6- Any culture negative for usual organisms, should be taken as a suspicion for TB.
7- Full history taken and physical examination and investigations of the donor and recipient to diagnose or exclude TB should be done.
level of evidence 4
home message:
1- infectious disease including TB is fatal complications in immunosuppressed patients like in SOT
2-early diagnosis and treatment in donor and recipient will save the life of the recipient latter.
3-good communication between different department is very important for better management of the cases
What is your suggestion regarding communication gap?
I like your summary, level of evidence, analysis and take home messages. What kind of screening program would you suggest that all those clinicians (stakeholders) can be informed well in time?
Introduction Most tuberculosis (TB) cases in solid organ transplant (SOT) recipients are caused by the reactivatio of tuberculosis infection” Current screening protocols for deceased donors are usually based on chest X-ray findings, epidemiological risks, and previous TB history. These features may not identify extrapulmonary and disseminated TB. Despite organ procurement protocols, pretransplantation screening fails to identify TB in the donor in many cases. Even when these cases are identified, communication gaps may result in donor-derived infections (DDI), which may be associated with death or poor outcomes. This report describes a case of unrecognized disseminated TB in the donor with a devastating outcome for organ recipients. This report highlights the need for a data bank and donor sample analysis to trace infections and reinforces the importance of better communication between transplantation teams and organ-harvesting centers. Index case simultaneous pancreas
A 45-year-old male received a simultaneous pancreas kidney (SPK) transplant due to diabetes and endstage renal disease (ESRD) After transplantation, he had no major clinical complications and was discharged on postoperative day 30. Abdominal ultrasonography revealed perigraft collections, whereas the chest radiograph was normal He received broad-spectrum antibacterial treatment and underwent percutaneous drainage of the abscesses, with transient resolution of fever. After several ultrasound guided punctures to drain intra-abdominal TB abscesses and 18 months of anti- TB therapy, the patient was considered cured. He died from complications related to ESRD and dialysis, two years after transplantation The doner
The donor was a 23-year-old, 36-week pregnant woman with a history of intense headache who was admitted to the hospital emergency room, and within 72 hours of admission, she developed mild fever, neck stiffness, and seizures. No microorganisms were identified in the CSF and blood, empirical treatment for meningoencephalitis was started 72 hours after hospital admission, and other culture samples were collected. Respiratory secretions were negative for acid fast bacilli stain Her level of consciousness decreased, and she underwent an emergency caesarean section on the 6th day of admission. The patient was diagnosed with brain death and had elected to be an organ donor, considering as primary diagnosis, CNS bleeding. At that time (2 months after delivery), her child presented with fever of unknown origin and was admitted to the same hospital, being diagnosed with disseminated TB. The M, tuberculosis strain isolated from the child presented no resistance to first-line anti-TB drugs, and he was discharged home after seven days of standard TB treatment The liver recipient
The liver recipient was a 55-year-old man diagnosed with caroli disease who was transplanted because of recurrent bacterial cholangitis. The treatment was maintained for six months, and the patient has not developed any manifestations compatible with active TB to date The heart recipient The heart recipient was a 40-yearold woman diagnosed with Chagas cardiomyopathy who underwent a heart transplant for class IV heart failure. The patient did not receive a specific diagnosis, her chest CT revealed diffuse pulmonary involvement
The other kidney recipient The kidney recipient was a 45-year-old man with systemic hypertension and terminal hypertensive nephropathy. During the second month after transplantation, he developed mesangioproliferative glomerulonephritis and graft loss and returned to dialysis. He returned to the hospital with sepsis of unknown origin and died despite antimicrobial therapy, without isolation of any specific infectious agent. Similar to the heart recipient, no specific test for mycobacteria was requested. Thereby, the TB diagnosis contributed to the fatal outcome in one patient and may be the cause of infectious disease complication after transplantation in the other two. No autopsy was performed on the deceased organ recipients, and for both the heart and kidney recipients, the TB diagnosis is only presumptive
Discussion
Infections represent a major cause of morbidity and mortality for SOT recipients. Risk level (RL) classification regarding DDI transmission involves the use of a grading system to rank recommendations, resulting in classifications that vary from a standard risk to an unacceptable risk. There are several holdups associated with care, including the lack of important and complete information concerning donor screening, which can potentially lead to a notable reduced quality of life or may even cause death. This case report calls attention to the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases. Several transplant scientific societies developed guidelines to assist in the screening of potential organ donors and recipients. The donor had no detectable abnormalities on the chest X-ray and AFB- negative smears, whereas the culture became positive two months after procurement. In cases of donor death due to meningoencephalitis (ME) without a proven cause, the donation should be avoided. Case Reports in Transplantation (a) (b) potential environmental exposures associated with organisms causing ME. Donor cause of death was considered CNS bleeding, and the same occurred in many other reported cases, resulting in DD-TB. DD-TB is considered proven if donor and recipient isolates were reported to be identical or clonal through molecular analysis. In the absence of definitive confirmation of similar isolates, DD-TB is classified as probable if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if donor and recipient shared more than one epidemiologic or clinical feature (e.g., TB diagnosis in a donor plus TB in the recipient early posttransplantation) or possible, if there is a suspected transmission event but the only criterion met is a donor risk factor for TB.
TB was confirmed in a donor sample two months after donation, and the result was still not properly informed because there was no tracking system to request the pending microbiological results.
It is important to emphasize that the graft was the first topography for TB diagnosis in the recipient, a clear indication of donor transmission. The two other organ recipients from the same donor presented fever of unknown origin, sepsis, and organ dysfunction a few months after transplantation. A compelling article [6] showed that communication gaps in reporting DDI are frequent and may occur at multiple levels, contributing to adverse outcomes among affected organ recipients. High-risk complications of the recipient with eventual connection with the donor, such as death or sepsis within 3 months of the procedure, should be actively notified. Take home message. To close the gap, communication between centers needs to be enabled. Any possible deceased donors should have training and experience in the clinical signs and symptoms of the infectious disease. Specific TB screening should be taken into consideration for high-risk donors. It is important to get the donor’s immunological status history. Level of evidence is 4
I like your summary, level of evidence, analysis and take home messages. What kind of screening program would you suggest that all those clinicians (stakeholders) can be informed well in time? What is your suggestion regarding communication gap?
When a person’s immune system is compromised or they may have recently been exposed to someone with active TB, screening tests are more frequently performed to detect latent TB.
Two tests are used to screen for tuberculosis:
A tuberculin skin test
Blood tests (interferon gamma release assay, QuantiFERON-TB Gold, and T-Spot)
Post transplant TB result from reactivation of latent TB or transmitted as donor-derived infection) only in 4% of cases).
A active TB is an absolute contraindication for organ donation.
In many cases, pre-transplant donor TB infection diagnosis is failed.
Discussion:
SOT is a life saving procedure hat improve quality of life & survival of recipients, but it carry a high risk of complication due to use of immunosuppression or surgery itself complications.
Careful donor selection is important in reducing TB transmission risk.
TB transmission risk is related to donor epidemiology & clinical history.
Recommendation of different guidelines can assist in donor & recipient screening, but these recommendations are not mandatory & not all transplant centers depend on these recommendations.
TB transmission risk factors include:
Donor history of symptoms related to active TB.
Homelessness.
Alcohol abuse or drug injection.
Incarceration.
Recent contact to patient with active TB.
Travel to TB endemic area.
Deceased donor due to meningoencephalitis with undetermined cause should be avoided.
Diagnosis of TB meningitis is challenging & microbiological tests have poor sensitivity & delayed results.
Proved DD-TB if donor & recipient isolates reported to be similar or clonal through molecular analysis.
Probable DD-TB if there is suspected transmission & TB diagnosed in multiple recipient of one donor or presence of one or more of epidemiological or clinical features between donor & recipients.
Possible DD-TB if transmission suspected events but only criterion met is donor risk factors for TB.
TB transmission presented early after SOT commonly as fever with high risk of mortality.
Communication gap in reporting DDI are frequent & can occur at multiple levels leading to poor outcome in affected organ recipients.
High risk complication of recipient with eventual connection with donor(e.g. death or sepsis within 3 months of transplantation).
Supervision of DDI is a strong indicator of transplant safety.
Fully developed network that integrate transplant centers, OPO & laboratory is mandatory & may facilitate recognition of infection risk & to initiate rapid intervention.
Level of evidence is 4.
Take-home messages:
DDI is treatable but fatal condition in SOT recipients.
Careful chosen donor with careful TB screening is essential.
Active communication between transplant center, hospital & laboratories is very important in early detection & intervention for DDI to reduce mortality & morbidity.
High suspicion of DD-TB in any SOT recipient with fever is important.
To overcome communication gap, donor test & processed sample should be kept at hospital when the donor was treated & organ removed for transplantation.
Donor-derived Tuberculosis Introduction TB reactivation is the most common source of TB infection post solid transplantation, as the latent infection is reactivated. The most source of TB infection is the latent infection reactivation from the recipient, only 4% are from the donor source. Active donor TB infection is considered a contraindication to donation. Based on the routine screening of the deceased donation (chest-x-ray, epidemiological risk, and previous TB history) which are not sensitive some donor-derived TB is acquired by the recipient. Challenges regarding TB infection post-transplantation
TB recognition is not always feasible.
Insensitive screening modalities.
Communication gap.
Policies and protocol screening are not applied to all cases.
A case report, organ donations
Simultaneous pancreas and kidney transplantation.
Disseminated TB
Died after 2 years as ESKD complication.
2. Kidney
Died 3 months after Tx due to sepsis of unknown origin.
3. Heart
Died 2 months after Tx due to sepsis of unknown origin
4.Liver + TST
Latent TB treatment
Discussion
Based on the relative risk (RL) classification for DDI transmission; TB is considered as CI to donation.
Infection post-transplant is considered a major cause of morbidity and mortality.
Crae full donor selection and screening is mandatory to reduce the infection risk and to save graft and recipient life.
DD-TB is almost, related to epidemiology and latent infection not to active TB ( in this case the donor had disseminated TB, no clinical picture of TB, no epidemiological relevance, and no previous exposure to infection).
The local TB prevalence for the donor area of residence is approximately 30 cases/100,000 inhabitants, representing an intermediate risk.
Specific donor history should include;
Symptoms related to TB.
Homelessness.
Alcohol abuse, or injection drug use.
Incarceration.
Recent exposure.
travel to an endemic area.
Other specific workup screening strategies should include;
Any potential deceased donor, who develops intracerebral hemorrhage without an obvious cause shouldn’t donate.
Comorbidities; stroke.
Fever
CT/MRI, or CSF analysis suggestive of infectious suspicion.
Is the donor immunocompromised or not?
Environmental exposure.
As in this case the culture takes time (weeks to months) donation is already done, so molecular tests have more sensitivity and specificity, but it is done for suspected cases.
In a recent review of 36 cases of proven, probable and possible DD-TB;
16 lungs, 13 kidneys, 6 liver, and 1 heart recipient.
The median time of diagnosis was 2.7 months.
Fever was the first common presentation.
Allograft involvement was common.
Graft loss occurred in 20% of cases
All-cause mortality was 25%
Home messages;
Communication between centers should be facilitated to fill the gap.
Training and experience in the clinical signs and symptoms of the infectious disease should be focused on any potential deceased donors.
High-risk donors should be considered for specific screening for TB.
A history of the immune status of the donor should be elicited.
Any unexplained intracerebral hemorrhages should be taken into consideration when considering organ donation.
I like your summary, level of evidence, analysis and take home messages. What kind of network would you suggest? What is your suggestion regarding communication gap?
thank you Prpf. for your comment
So communication gap should be filled as centers should be in contact via a network to avoid comorbid infection can develop in a transplant case.
As a culture it will take time so vital data should be obtained just to make alarm for clinical suspicion and to prevent infection.
In case of urgent transplantation when the results is coming the grafted kidney already it will be transplanted, so history of contact or exposure, or untreated TB should be focused on to determine going on for Tx or discard the kidney
The incident of tuberculosis(TB) in transplantation is higher than the general by > 20 times and it is associated with significant mortality.
Donor-derived TB accounts for < 5% of transmission but it is usually fatal and associated with disseminated disease.
This case reports highlighted the problems with face despite the screening recommendations e.g. poor communication, between organ procurement team and transplant team. This can be avoided by better communication and evaluation process
Case report
A 23 yrs old pregnant lady who presented with meningioencephalitis features and died shortly due massive subarachnoid hemorrhage. After two months her tracheal aspirates came positive for M. tuberculosis and her baby was diagnosed with disseminated TB. Mistakenly her organs were donated to 4 recipients:
The first recipient was a 45 years old male ; simultaneous pancreas-kidney transplant due to DM. He presented with fevers and disseminated TB, side effects of TB medications,and deteriorated quickly. His immune suppression was stopped due to severe infection and unfortunately developed rejection,graft loss,and returned back to dialysis. This patient was treated successfully for TB and died 2 years later due hemodialysis-related complications.
The second recipient was a 55 years old male ; He received her liver due to his recurrent cholangitis. He was given treatment for LTBI shortly after transplantation due to +ve TST before surgery. He did well so far and no any evidence of TB.
The third recipient was a 40 years old woman who got the heart due Chagas cardiomyopathy. Three months later, she died after presenting with septic shock resistant to antimicrobial therapy. Her cultures were negative but the CT chest showed diffuse pulmonary infiltrates.
The fourth recipient was a 45 years old male who was given the other kidney due hypertensive nephropathy. After two months, he lost the graft due to MPGN and returned back to hemodialysis. Three months later he came with sepsis not responding to all antibiotics and passed on.
The conclusion is TB diagnosis in one patient resulted in death and we cannot ruled it out completely in the other two patients
Q2.The was case report, level 4
Q3. Key messages
Lack of important and complete information regarding the donor may lead to reduced quality of life or death
Attention to the details of donor selection process to minimize risk of transmission of deadly diseases
Avoid donors diagnosed with meningioencephalitis of unproven cause
It is essential to promptly notify any suspicious of of infection transmitted by the donor including TB, to trace all recipients ( e.g.,bio-vigilance system) at risk as early as possible
A fully developed network or system that coordinates transplant centers, OPO’s, & laboratories is of paramount importance and could permit early identification of dangerous conditions. This should be accompanied by quick intervention
I like your summary, level of evidence, analysis and key messages. What kind of network system and biovigilence would you suggest? Is it central registry that you are suggesting or public health department?
Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety. Introduction.
Most tuberculosis cases in solid organ transplant (SOT) recipients are caused by the reactivation of latent tuberculosis infection (LTBI), and only 4% are considered donor-derived, despite organ procurement protocols, screening fails to identify TB in the donor in many cases and lead to DDI or if there is communication gaps in identified patient.
A case report of miserable story of Donor derived T.B infection from a case diagnosed 2 months post-mortem which lead to fatal outcome in one patient and may be the cause of infectious disease complication after transplantation in the other two. Discussion:
Active TB is an absolute contraindication for organ donation and careful donor selection is crucial, to reduce the risk of transmission of potentially lethal but treatable diseases, and some times is so much difficult to recognized patient with TB specially with those without history of previous TB or exposure.
So, OPOs should looking for a donor risk factors of TB such as( history of symptoms consistent with active TB, as past diagnosis of TB infection (active or latent), homelessness, alcohol abuse or injection drug use, incarceration, recent exposure to persons with active TB, or travel to areas where TB is endemic)
When risk factors are identified, further testing and radiological assessments are required and molecular tests present greater sensitivity and specificity but are done when pulmonary TB is suspected.
In this reported case, TB was confirmed in a donor sample two months after donation, and the result was still not properly informed because there was no tracking system to request the pending microbiological results which is considered an obstacle and lead to more confusion about final diagnosis in our recipients and DDI TB transmission identification is challenging, one of the most important issue that no team assigned to follow pending investigations result, incomplete medical records, and an insufficiently tight network for monitoring these results remain challenging. Level of evidence: case series (level IV). Home message:
Donor-Derived Tuberculosis is an important issue as it may lead to fatal infection for recipients early post kidney transplant, so , strict screening for donor specially those with high risk factors and tracking system with tight network system to follow up pending donors investigation is so important and transplantation centers should be directly updated.
I like your summary, level of evidence, analysis and take home messages. What kind of network would you suggest?
What is your suggestion regarding communication gap?
1- Summary Introduction
TB infection in SOT are usually due to the reactivation of latent tuberculosis infection (LTBI), and only 4% are donor-driven. Active TB infection may not be recognised in the donor specially in deceased donors even if identified communication gap can lead to donor-derived infections (DDI) and poor prognosis. This is a case report describing the scenario of a Deceased donor whom she was a pregnant lady died out off disseminated TB involving the brain leading to diffuse subarachnoid haemorrhage and brain death , she underwent CS and her delivered child was treated later for disseminated TB the TB diagnosis was obtained from the culture of lung tissues 2 months after death .
Her organs were given to 4 recipients Kidney and pancreas simultaneous recipient,without any evidence of past TB involvement ,he received induction with basiliximab and conventional maintenance therapy, he presented 2 months post transplant with TB manifestations mainly involving both grafts with abcess that was drained and anti TB therapy was started but anti tuberculous drugs side effects occurred ,it progressed to disseminated TB.
Therefore Immunosuppression was stopped ,both graft loss occurred and he returned to dialysis and insulin therapy, caseating necrosis occurred in the graft that was removed .
Finally he was considered cured of TB after draining intra-abdominal TB abscesses and 18 months of anti TB therapy.
Meanwhile he died 2 years post transplant due to ESRD and dialysis complications Liver transplant recipient due to Caroli disease , this patient had TST positive ,he was considered LTBI case and INH was started for 6 months and he was asymptomatic till this article’s date. Heart transplant recipient due to Chagas disease with heart failure, within 3 months she developed fever progressed to septic shock ,antibiotic coverage was given but cultures were not conclusive and no specific mycobacterium cultures were done her pulmonary CT showed extensive affection but no final diagnosis was given till her death. The other renal transplant recipient 2 months after transplant , mesangioproliferative nephritis occurred followed by rejection and he returned to dialysis then died at 3 months post transplant after antibiotic therapy and cultures but mycobacterium cultures were not taken .
For the heart and kidney recipients, TB diagnosis is only probable but not confirmed. Discussion
Organ transplant is the best choice for most organ failures but on the other hand it has lots of risks as the surgery itself and the immunosuppressive therapy there after .
There is risk level for donor derived infection DDI ranging from standard to unacceptable as active TB .
The donor did not have any previous evidence of previous TB infection.
Certain startegies have to be applied to detect infections in donors .
Donor screening recommendations are available but in fact not all are essential in each case that is why it is not standardized .
TB risk factors have to be evaluated starting from asking in the history for active TB symptoms then if the risk is noticed further testing can be done.
The current donor did not have any history or symptoms suggestive of TB ,AFB smear was negative and positive culture result appeared after 2 months.
The cerebral haemorrhage could be most likely due to vasculitis secondary to TB infection.
Current recommendations are that donors must be excluded if their death was due to meningoencephalitis (ME) without a proven etiology.
In the current case the donor had CNS bleeding out off underlying TB.
In fact TB meningitis diagnosis is challenging.
Donor derived -TB (DDTB)is considered if both donor and recipient isolates were identical or clonal through molecular analysis.
DD TB is suspected if more than a recipient of the same donor had TB detected or if both donor and recipient had the same TB symptom.
The main restriction to confirm DDTB is to have a positive donor sample and genetic sequencing of the organism matching donor and recipient samples also there is usually a time gap.
Another aspect is that Mycobacterium TB can arise in culture after 4-6 weeks .
In a study concerning DD TB ,the median time till clinical presentation or diagnosis
was 2.7 months presenting mainly by fever , and allograft affection involvement was common ,graft loss occurred in 20% of cases and mortality occurred in 25%.
Information and data availability time gap have to be manged and following cultures need to be done at 7 day with recording that.
Donor samples must be processed and held at the treating hospital where the organs will be
removed for donation and tests followed .
In the current case if the TB results were discovered earlier ,therapy could have been introduced earlier with better outcomes.
Studies demonstrated that communication gaps in DDI reporting DDI occurs at multiple levels, causing hazardous outcomes among affected organ recipients as in the current case if a certain communication existed between teams of the recipients the death of the first donor and his TB infection could have assisted in diagnosing the other recipients DDI.
Also the delayed information about vertical TB transmission is a sign of communication error.
Early death posttransplant due to infectious diseases has to be informed and registered.
Proper reporting system can definitely improve the outcomes.
2-level of evidence is IV
3-Take home message
Data bank and donor sample analysis availability is mandatory to follow infections and shed light on the significance of better communication between organ-harvesting centers and transplantation teams .
I like your summary, level of evidence, analysis and take home messages. What kind of data bank would you suggest?
Is it central registry that you are suggesting or public health department?
The most common cause of Tuberculosis (TB) infection in solid organ transplant (SOT) recipients is reactivation of latent TB infection (LTBI), while 4% are donor-derived. Active tuberculosis infection in a donor is incompatible with organ donation. Screening protocols for deceased donors may also fail to detect TB on occasion. This report details a case of disseminated tuberculosis in an organ donor that resulted in negative outcomes for the recipients.
The giverThe donor was a female of 23 years old. At 36 weeks pregnant, she was admitted due to complaints of an intense headache. She developed a mild fever, cervical stiffness, and seizures within 72 hours of admission. Increased proteins and cellularity, but no microorganisms, were found in the CSF. Meningoencephalitis was treated empirically with ceftriaxone, followed by anti-tuberculosis medication and acyclovir. AFB (acid-fast bacilli) staining of respiratory secretions was negative. On the sixth day of admission, the patient’s level of consciousness decreased, and she underwent an emergency C-section. Brain CT imaging subsequently revealed a diffuse subarachnoid haemorrhage. On the ninth day of admission, the patient was diagnosed with brain death and elected to be an organ donor based on the diagnosis of CNS haemorrhage. The tracheal aspirate culture was positive for M. tuberculosis 2 months after her demise. Her infant was diagnosed with disseminated tuberculosis and successfully treated after presenting at two months of age with a fever of indeterminate origin.
The index case – simultaneous recipient of a pancreas and kidney A 45-year-old man with end-stage kidney disease and diabetes received a pancreas and kidney transplant at the same time. His prior tuberculin skin test (TST) was negative, and he denied exposure to TB. His post-transplant immune suppression regimen included basiliximab, prednisone, tacrolimus, and mycofenolate mofetil. On the second month following his transplant, he complained of fever, chills, and night sweating. His chest X-ray was normal, but an ultrasound of his abdomen revealed perigraft deposits (renal and pancreatic abscesses). With the administration of broad-spectrum antibiotics and drainage of the abscesses, his fever temporarily subsided. Anti-TB treatment (rifampin, isoniazid, pyrazinamide, and ethambutol) was initiated upon the discovery of AFB on ZN stain. Notify the transplant harvesting centre.
The patient manifested with drug-induced side effects related to the anti-TB medications, including hemolytic anaemia and blurred vision. Therefore, his medications were altered. The patient had disseminated disease affecting the grafts, lungs, central nervous system, and thyroid. This resulted in the discontinuation of immunosuppressive medications, which led to graft loss. After 18 months of treatment, the patient was declared to have been successfully treated for tuberculosis. Unfortunately, the patient passed away two years after transplantation due to end-stage renal disease and dialysis-related complications.
The organ recipientA 55-year-old male with Caroli disease and recurrent bacterial cholangitis received a liver transplant. Prior to surgery, the patient’s TST was positive; consequently, the patient was treated for LTBI with isoniazid monotherapy for six months immediately following the transplant. As of the time of publication, the patient had not developed active TB.
The beneficiary of the recipient’s heart The recipient of the heart was a 40-year-old woman who was diagnosed with Chagas cardiomyopathy and class IV heart failure. She presented with fever and malaise three months after the transplant and died within three days of admittance due to severe septic shock unresponsive to broad-spectrum antibiotics. Blood, urine, and tracheal aspirate samples did not contain any bacteria or fungi upon culture. No culture of mycobacteria was requested. Her chest CT revealed diffuse involvement of the lungs.
The other recipient of a kidney A 45-year-old man with systemic hypertension and end-stage hypertensive nephropathy received a transplant of his other kidney. The patient had to revert to dialysis after developing mesangioproliferative glomerulonephritis and graft loss during the second month following transplantation. Three months after the transplant, the patient presented to the hospital with sepsis of indeterminate origin despite antimicrobial treatment. No specific mycobacterial test was requested.
Discussion
Mortality and morbidity can be caused by infections in SOT recipients. The purpose of this case report was to emphasise the significance of donor selection in reducing the risk of transmission of potentially fatal but treatable diseases. In this instance, the donor had unrecognised TB transmission. Except for pregnancy, she had no previous TB or TB exposure history. She resided in an area with a moderate risk for tuberculosis. Screening for active or latent tuberculosis is not performed in all centres because the developed guidelines are not mandatory in all situations. No molecular analyses were performed on the patient because she had no respiratory symptoms and imaging did not reveal any respiratory involvement. Since the TB culture is time-consuming, the results were obtained two months following the transplant. The CSF analysis, however, revealed an elevated protein level and pleocytosis. In hindsight, the intracerebral haemorrhage was likely caused by cerebral vasculitis resulting from the TB infection. Current recommendations advise against organ donation if meningoencephalitis was the undetermined cause of death.
In this instance, the beneficiary of a liver transplant was treated for latent tuberculosis and did not develop active infection. The other two recipients perished due to organ failure and sepsis of unknown origin. These results are consistent with TB donor transmission, but transmission was only confirmed in the recipient who underwent spontaneous pancreas and kidney transplants.
Despite the fact that TB cultures are known to be time-consuming, the results should be disseminated to all involved centres and recipients. In this instance, there was no protocol that defined who was responsible for reviewing the pending results. This would have prompted clinicians to initiate treatment sooner, which could have prevented graft loss and mortality.
The purpose of this case report was to draw attention to the significance of prompt notification of any suspicious cases of infection transmitted by the donor, including tuberculosis, so that the recipients can be traced and, if possible, treatment can be initiated promptly.
Level Of Evidence: level four
Take Home Message
TB is a difficult disease to diagnose, requiring a high index of suspicion. Before a potential donor donor can be utilised in a deceased donor organ programme, the cause of death must be determined with certainty.
Effective communication between the donor hospital and the receiving institution is essential for reducing morbidity and mortality.
Donor derived TB accounts for less 4% of cases of TB . In KT , the frequency of active TB is about 20 to 74 times higher than in the general population.
TB in KT associated with high morbidity and mortality.
Identification of high risk donors minimize the risk of DD transmission, failure to Identification of them lead to transmission of potentially fatal disease to the recipient.
Active TB in the donor is a contraindication for organ donation.
In case of deceased donor, the diagnosis of TB may be not feasible. As screening protocol for deceased donorbbased on x ray, epidemiological risk and previous TB history so extrapulmonary TB and disseminated TB may be not recognized.
Failure of recognition of high risk donor leads to poor outcomes
This case report describes a case of unrecognized disseminated TB in the donor with a devastating outcomes for organ recipients. The donor was a pregnant woman who died soon after delivery due to TB involvement of the CNS and lungs.
The diagnosis was retrospectively established by mycobacterial culture of the respiratory sample two months after death and the diagnosis of congenital TB in her baby.
Recipients
1. First recipient had simultaneous pancreas kidney transplantation….disseminated TB….died 2 years after transplantation from ESRD complications
2. Kidney recipient ….died 3 months after transplantation due to sepsis of unknown origin
3. Heart recipient….. died 2 months after transplantation due to sepsis of unknown origin
4. Liver recipient diagnosed to have latent TB and treated
This case report calls the attention to the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases.
Level 4
Take home messages
This report highlights that communication gaps may result in donor derived infection.
There is need for a data bank and donor sample analysis to trace infections
The importance of better communication between transplantation teams and organ harvesting centers .
Improvement of screening strategies for TB to identify high risk donor to prevent DDI
This is a report case of donor with Tb of the central nervous system and lungs. The diagnosis was retrospectively established by mycobacterial culture of the respiratory sample (positive result obtained two months after donor death) and the diagnosis of congenital TB in her baby.
A 45-year-old male received a simultaneous pancreas kidney (SPK) transplant. During the second month posttransplant, he returned to the hospital complaining of fever, night sweats, and chills and bdominal ultrasonography revealed perigraft collections. analysis revealed acid-fast bacilli on Ziehl-Neelsen stain.The patient subsequently presented with anti-TB drug toxicities. Then he presented disseminated disease involving grafts, lungs, CNS, and thyroid. He developed acute cellular rejection of the grafts, and dual graft loss with return to hemodialysis and insulin therapy. The patient underwent exploratory laparotomy with a surgical finding of caseating necrosis all over the mesenterium and around pancreatic graft, but affecting the renal graft. The removal of the renal graft was the only viable treatment encountered. After several ultrasound guided punctures to drain intra-abdominal TB abscesses and 18 months of antiTB therapy, the patient was considered cured. However, he died from complications related to ESRD and dialysis, two years after transplantation.
The liver recipient was a 55-year-old man who was treated for LTBI with isoniazid, soon after the transplant. The treatment was maintained for six months, and the patient has not developed any manifestations compatible with active TB to date.
The heart recipient was a 40-yearold woman who after 3 months from the procedure, she was admitted to the hospital with fever and malaise. Within three days after admission, she developed severe septic shock and died despite broad-spectrum antibiotic therapy. Her chest CT revealed diffuse pulmonary involvement.
The kidney recipient was a 45-year-old man who during the second month after transplantation, he developed mesangio-proliferative glomerulonephritis and graft loss and returned to dialysis. Three months after transplantation, he returned to the hospital with sepsis of unknown origin and died despite antimicrobial therapy, without isolation of any specific infectious agent.
Both the kidney and heart recipients did no specific test for mycobacteria. Unfortunately, no autopsy was performed on the deceased organ recipients, and therefore, for both the heart and kidney recipients, the TB diagnosis is only presumptive.
the level of evidence is 5
take home message:
close communication is important to prevent morbidity and mortality.
Introduction:
The majority of tuberculosis (TB) cases in solid organ transplant (SOT) recipients result from the reactivation of latent TB infection (LTBI), while only a small percentage (4%) are caused by donor-derived tuberculosis (DD-TB). Current screening protocols for deceased donors primarily rely on chest X-ray findings, previous TB history, and epidemiological risks, which may not accurately identify extrapulmonary and disseminated TB. As a result, TB in the donor may go unrecognized, leading to donor-derived infections (DDI) in organ recipients. This report presents a case of undetected disseminated TB in a donor, with severe consequences for the organ recipients. The donor, a pregnant woman, died shortly after delivery due to TB involvement in the central nervous system (CNS) and lungs.
The Index Case:
A 45-year-old male underwent a simultaneous pancreas kidney (SPK) transplant due to diabetes and end-stage renal disease (ESRD). His previous tuberculin skin test (TST) was negative, indicating no previous TB exposure. Two months post-transplant, he was readmitted to the hospital with symptoms of fever, night sweats, and chills. Abdominal ultrasound revealed collections near the grafts (renal and pancreatic abscesses), while the chest X-ray appeared normal. He received broad-spectrum antibiotics and underwent percutaneous drainage of the abscesses. Further analysis showed acid-fast bacilli (AFB) on Ziehl-Neelsen stain, confirming TB. Anti-tuberculous therapy was initiated but led to complications. The patient’s condition worsened, with disseminated disease affecting the grafts, lungs, CNS, and thyroid. Immunosuppressive treatment was stopped, resulting in dual graft loss and a return to hemodialysis and insulin therapy. Despite the cure of TB, the patient died two years later due to complications related to ESRD and dialysis.
The Donor:
The donor was a pregnant woman who died after delivery due to TB involvement in the CNS and lungs. Analysis of cerebrospinal fluid (CSF) revealed increased cellularity and protein, but no microorganisms were found in the CSF and blood. Empirical treatment for meningoencephalitis was initiated. Respiratory secretions initially tested negative for AFB, but two months after the donor’s death, a tracheal aspirate culture became positive for Mycobacterium tuberculosis.
The Liver Recipient:
The liver recipient had a positive TST result for LTBI and received isoniazid treatment for six months after the transplant. The recipient remained asymptomatic and did not develop any manifestations consistent with active TB.
The Heart Recipient:
The heart recipient died two months after transplantation due to sepsis of unknown origin, although a chest CT scan revealed extensive pulmonary involvement.
The Other Kidney Recipient:
The other kidney recipient died three months after transplantation due to sepsis of unknown origin.
Discussion:
Careful donor selection plays a critical role in reducing the transmission risk of potentially lethal but treatable diseases. Donor-derived tuberculosis (DD-TB) is often associated with the donor’s epidemiological background and clinical history. When assessing the risk factors for DD-TB, it is important to consider various factors. These include evaluating the donor’s history for symptoms consistent with active TB and any past diagnosis of TB infection, whether active or latent. Additionally, factors such as homelessness, alcohol abuse or injection drug use, incarceration, recent exposure to individuals with active TB, and travel to areas where TB is endemic should be taken into account.
While molecular tests offer greater sensitivity and specificity in diagnosing TB, they are primarily employed when pulmonary TB is suspected. In the discussed case, the occurrence of intracerebral bleeding was likely a consequence of cerebral vasculitis resulting from TB infection.
To effectively manage cases of infection transmitted by the donor, including TB, it is crucial to promptly report any suspicious cases. This allows for timely identification and tracing of all recipients at risk, facilitating appropriate monitoring and intervention to prevent further transmission and ensure the well-being of the affected individuals.
The level of evidence provided by this article is classified as Level IV, which corresponds to a case report.
The main takeaway from this study can be summarized as follows. The current screening protocols for tuberculosis (TB) in deceased donors, which rely on chest X-ray results, epidemiological risks, and previous TB history, may not be sufficient to detect cases of TB that have spread beyond the lungs or become disseminated. To minimize the risk of transmitting TB from donors to recipients, it is crucial to identify high-risk donors. The study also highlights the significance of addressing communication gaps between organ procurement organizations and transplant centers, as these gaps can contribute to donor-derived infections and lead to adverse outcomes and even death for organ recipients. Implementing more effective screening protocols and improving communication channels are essential to prevent such scenarios. Additionally, the article suggests that organ donation should be avoided in cases where the cause of donor death is meningoencephalitis without a confirmed cause. Conducting autopsies becomes crucial in situations where the cause of death is unclear or poorly defined. Overall, this study emphasizes the importance of implementing enhanced screening measures, improving communication, and conducting thorough investigations in potential cases of donor-derived infections to ensure the safety and well-being of organ recipients.
Summarise this article
Introduction
Recipient background
What is the level of evidence provided by this article?
Level 5 (case report)
What is the take-home message?
Level 4 eveidence
Introduction:
-This article focusses on the development of TB in the recipient from the donor organ. —Donor derived TB is rare, at a small level of 4%.
-Donor derived TB is of because infections of different kinds are a major cause of morbidity and mortality in transplant recipients. This article highlights the necessity for careful donor selection to reduce risk of transmission of infection from donor to recipient.
-With donor transmission of TB, graft loss can occur in 20% of recipients.
Conclusion
-Improvement of screening protocols along with development of standardized tests in this regard is need to further protect recipients.
1- Summarise this article
Introduction:
TB commonly occurring in transplantation are due to reactivation of latent in active TD, rather than transmission from the donor which is a rare cases.
This article reports 45 y old male patient undergo simultaneous kidney pancreases transplantation from a female who died of disseminated TB After delivery.
The transplantation regimen are induction with Basiliximab and maintenance with prednisolone, MMF, and tacrolimus .
Eight weeks post transplantation patient present as fever, night sweats, and chills. Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses), which was positive to ziehil-neelsen stain . After anti TB drug starting patient develop drug toxicity in the form of , rifampicin toxicity hemolytic anemia, ethembutol blurring of vision. The management required to stop immunosuppressive medication which lead to graft rejection and start of dialysis. Patient died of dialysis complication.
There was heart, liver beside of kidney donation from the same donor. All three donors died because of TB.
Discussion:
Infectious cause is important cause of mortality in post transplantation. Active tuberculosis is contraindication for transplantation.
Meningoencephalitis without proven cause is contra indication to donation.
The diagnosis of TB meningitis is challenging with poor sensitivity and specificity of available diagnostic modality.
Reactivation of disease needs time to occur. Desired to do TB PCR for diagnosis. TB culture is time consuming needs about 6 weeks for results.
Donor infection screening program depend on patients history, physical examination and lab results.
High-risk complications of the recipient with eventual connection with the donor, such as death or sepsis within 3 months of the procedure, should be actively notified. In the reported case, if a flag for a possible DDI was detected after the first recipient’s death, the others could certainly have had a better chance.
Screening program for donor infection is important for safe transplantation.
A more efficient reporting system will not prevent the event from occurring but may of course impact the outcome.
Specific policies may be established to improve the recognition of the disease in donors.
This paper underscores the importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner.
2- What is the level of evidence provided by this article?
The level is 4
3- What is the take-home message?
To prevent donor derived infection a screening strategy is needed the scope of screening will depend on history, physical examination, and lab result.
Summarise this article
Donor-derived tuberculosis (DD-TB) accounts for less than 5% of TB cases and is considered a rare event.But when it occurs,it can lead to devastating consequences.In the transplant setting, the frequency of active TB is estimated to be 20 to 74 times higher than that in the general population, and it is associated with high mortality.
This article describes a case of DD-TB and emphasizes communication gaps that may occur between organ procurement organizations and transplant centers.This report describes a case of unrecognized disseminated TB in the donor with a devastating outcome for organ recipients.
DD-TB is considered proven if donor and recipient isolates were reported to be identical or clonal through molecular analysis. In the absence of definitive confirmation of similar isolates, DD-TB is classified as probable if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if donor and recipient shared more than one epidemiologic or clinical feature (e.g., TB diagnosis in a donor plus TB in the recipient early posttransplantation) or possible, if there is a suspected transmission event but the only criterion met is a donor risk factor for TB (e.g., donor residence in TB endemic area and absence of recipient risk factors for TB.
DD-TB is difficult to recognize in both donor and recipient. it presents itself early after SOT, most commonly as fever, and carries a high mortality risk.
What is the level of evidence provided by this article?
Level of Evidence-5
What is the take-home message?
communication gaps may occur between organ procurement organizations and transplant centers. Failure in reporting results, lack of exchanging information regarding recipients from the same donor, and inefficient communication between organ procurement organizations and transplant centers are lacks that may be prevented by a more efficient approach towards screening protocols and communication.
Most tuberculosis (TB) cases in solid organ transplant (SOT) recipients are caused by the reactivation of latent tuberculosis infection (LTBI), and only 4% are considered donor derived. Active TB in the donor is recognized as an unacceptable risk and contraindicates organ donation.
considering that the recipient’s TB abscesses were located near the grafts, suggesting donor involvement, the transplant harvesting center was contacted for additional information regarding the donor and the other organ recipients. At that time, two recipients had already died, and a look-back investigation was carried out.
Transplantation is the treatment of choice for some types of end-stage organ failure. However, transplantation has risks related to the procedure itself and due to immunosuppres- sion. Still, there are several holdups associated with care, including the lack of important and complete information concerning donor screening, which can potentially lead to a notable reduced quality of life or may even cause death.
The major limitation to confirm DDI is to have a positive donor sample and genetic sequencing of the pathogen match- ing donor and recipient samples. Usually, there is often a time gap between the donation and the development of the disease. In this reported case, TB was confirmed in a donor sample two months after donation, and the result was still not properly informed because there was no tracking system to request the pending microbiological results. As such, donor transmis- sion is usually considered probable or possible, depending on the data available, but is much less often confirmed.
Of note, these types of information may not interfere with the real-time quality of life. Finally, it should be pointed out that adverse events such as those described here are very rare but may occur in any place or situation. A more efficient reporting system will not prevent the event from occurring but may of course impact the outcome. All in all, a fully developed network that integrates transplant centers, OPO’s, and laboratories is mandatory and could allow the recognition of potential hazards followed by a more rapid intervention.
Introduction
Reactivation of a latent mycobacterium infection is a typical cause of tuberculosis after an organ transplant. There is a link between donor-derived mycobacterium infection and a 4 percent chance of the infection being passed on to the recipient, which can have a negative impact on both the transplant and the patient’s health.
This case report describes a pregnant woman who died of diffuse CNS tuberculosis during delivery and her baby who developed congenital TB. After 2 months, this deceased donor’s culture shows positive mycobacterium tubercles, and the recipient develops a terrible graft result. This study screens deceased donors for trace infections and emphasizes the need for greater communication between the transplantation team and the organ harvesting center.
Screening donors for latent TB using nonspecific chest X-rays, epidemiological hazards, and TB history
Pancreas transplant
The recipient is a 45-year-old male on immunosuppressive medication (basiximab, prednisone, tacrolimus, and mycofenolate mofetil) with a negative tuberculin test. His donor had tuberculosis.
Second month: fever, chills, nocturnal sweats, stomach ache Pus nears graft on abdominal ultrasonography. Cultures from percutaneous drainage showed acid-fast bacilli. Normal chest X-ray and routine antitubercular treatment with rifampin, isoniazid, pyrazinamide, and ethambutol.
Recipients develop drug toxicity from anti-tuberculous therapy due to drug interaction with immunosuppressive therapy and disseminated TB, leading to clinical deterioration. They stop all immunosuppressive therapy, leading to graft failure, and return patients to dialysis and lapratomy done with removal of the renal graft and intravenous anti-tuberculous for long duration. Patients were cured but died after 2 years due to ESRD and dialysis.
Liver transplant
A transplant was performed on a 55-year-old man with Caroli illness due to recurrent bacterial cholangitis. TST was positive prior to surgery, and the transplant recipient was treated for six months with isoniazid for LTBI. The patient has not acquired any symptoms consistent with active tuberculosis.
Heart transplant
A heart transplant was performed on a 40-year-old woman with Chagas cardiomyopathy who had class IV heart failure. She was taken to the hospital three months following the procedure with fever and malaise. Within three days, she passed away due to acute septic shock, without mycobacterial infection being considered. Her chest CT revealed diffuse involvement of the lungs.
Kidney transplant
Due to hypertension-induced nephropathy, the patient got a kidney transplant. Two months later, the patient developed mesangioproliferative glomerulonephritis and graft loss and returned to dialysis. After three months, the patient comes down with sepsis and dies in spite of antimicrobial therapy and the absence of particular testing to rule out mycobacterium infection; TB is strongly suspected.
Discussion
The best treatment option for patients with ESRD is a kidney transplant, but there is a substantial risk of infection from donor-derived infection due to the potency of immunosuppressive drugs, particularly during the first six months. A life-threatening infection, like tuberculosis, can cause graft loss and raise the incidence of mortality. In these reported cases, tuberculosis infection is not confirmed but strongly suspected due to clinical manifestations that strongly suggested TB and the onset of symptoms within two months of transplantation. Furthermore, only two samples confirm the presence of acid-fast bacillus in the donor of the first case, and the patient died despite receiving anti-tuberculosis treatment. In another example, anti-tuberculosis treatment was effective despite the absence of acid-fast bacilli in both the donor and recipient samples; the donor had a history of tuberculosis exposure.
Before proceeding with a transplant, this article emphasizes the significance of donor selection and infection screening in both the donor and recipient. In addition, this research illuminated the significance of the interaction between the transplant team and the donor bank for the proper selection of donors to reduce infection risks.
Level V
Prompt notification of any suspicious cases of infection trasmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner.
Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
Only 4% of TB in solid organ recipients are donor-derived.
TB recognition is not always easy.
In many cases, pre-transplantation screening fails to identify TB in the donor.
This report highlights the need for data bank & donor sample analysis to trace TB infections and emphasizes the importance of better communication between transplantation teams &organ-harvesting centers.
TB diagnosis contributed to fatal outcome in one patient and may causative of infectious disease complication following transplantation in the other two.
Discussion
Infections are considered major cause of morbidity &mortality for SOT recipients.
Active TB is an absolute contraindication for donation.
Although sputum culture has higher sensitivity than AFB ,it takes long time; weeks to months .So, molecular tests present better sensitivity and specificity and are done when pulmonary TB is suspected.
Based on current recommendations, in cases of donor death due to meningoencephalitis without clear cause, the donation should be avoided .
To improve screening strategies, certain potential findings should be thought of such as existence of any comorbidity that may support stroke, presence of fever at illness presentation/admission in the potential donor, CT/MRI scan of the head, or CSF findings indicating infectious process, and whether the donor was an immunosuppressed or had any potential environmental exposures related to organisms causing meningoencephalitis.
There is often a gap between donation and development of the disease.
Despite that it is desirable to have molecular typing and analysis of patterns of the isolates, this is not always feasible..
M. tuberculosis is identified in culture after 4 – 6 weeks.
Organ donor screening for infections is based on donor history, clinical assessment, and laboratory testing.
High-risk complications of the recipient with eventual attribution with the donor, such as death and/ or sepsis within 3 months following transplantation, should be notified. In the reported case, if a flag for a possible DDI was discovered after the first recipient’s death, the other cases could certainly have had a better chance.
The surveillance of DDI has a strong indicator of transplant safety.
A more efficient reporting system will not prevent the event but may improve the outcome.
-Level of evidence IV.
1. Summarize the article
Introduction
Tuberculosis (TB) in a solid organ transplant recipient is mostly due to reactivation of latent TB infection (LTBI), only 4% being donor derived. Pre-transplant screening protocols may fail to identify TB in donor (especially in decease donor) and communication gaps in such scenario may lead to poor outcomes. Donor derived TB infection (DDI) in multiple recipients from a deceased donor, which was not detected at the time of transplant, leading to catastrophic consequences – due to communication gap, is narrated.
The donor: 23-years female was admitted to hospital with 36 weeks pregnancy, headache, neck stiffness, seizures and fever. CSF abnormality showed increased protein and cellularity. Emergency Caesarean section was done, child being normal. No improvement to antibiotics and antivirals; subarachnoid haemorrhage on CT brain detected on day-6, and subsequent brain death declared on day 9 of hospital admission. Respiratory secretions were negative for acid-fast bacilli (AFB). Organs shared to 4 different recipients – one simultaneous pancreas kidney (SPK), a liver, a heart, and another kidney recipient.
The SPK recipient: (index case) 45 years male diabetic and ESRD; no history of tuberculosis – negative TST. Had uneventful post-operative recovery. 2-months post-transplant, he was admitted to hospital with fever, chill, night sweats. Ultrasound revealed multiple abscess around pancreas and renal allograft. Percutaneous drainage of pus was positive for AFB. Patient improved after responded multiple percutaneous drainage and ATT given for 18months.
ATT related toxicities like Haemolytic anaemia (Rifampicin) and blurred vison (Ethambutol) mandated change in regimen, and later cessation of immunosuppression due to clinical worsening, leading to dual-graft-failure. Pyonephrotic graft kidney removal and drainage of abscess along with 18months ATT cured the TB, but the patient died 2 years post-transplant due to complications related to TB, ESRD and dialysis.
The heart recipient: 40-years female with uneventful post-operative period, presented 3 months post-transplant with fever and malaise, developed septic shock and died. No organism could be identified, but tuberculosis work up was not done, because of lack of suspicion and patient was sick all of a sudden, although CT chest showed diffuse pulmonary lesions.
The other kidney recipient: 45-years male without history of TB, developed mesangio-proliferative glomerulonephritis and graft loss in second month post-transplant, the next month (3 months post-transplant) he died of sepsis.
The liver recipient: 55-years male with, positive tuberculin skin test (TST), was treated for LTBI soon after transplant for 6 months – no complications related to TB was seen.
The donor: After the intractable TB infection in the SPK recipient, the team contacted the retrieval unit about TB in the donor and tried to trace back about all other recipients who got organs from the same donor. The tracheal secretion culture taken at the time of admission grown M. tuberculosis, which was reported about 2 months later.
The child after 2months post-delivery had disseminated TB, was found to be infected with same strain of M-TB and responded well to ATT.
Discussion:
This index case points towards careful selection of donor, including detailed history and epidemiological evaluation.
Active TB infection is a contraindication for organ donation.
The index donor had an unrecognized disseminated TB with no history related to TB (active TB, exposure to persons with TB, travel to regions with endemic TB, past history of TB, alcohol abuse, injectable drug abuse, homelessness, incarceration etc).
The donor’s sputum culture for TB became positive after 2 months, molecular testing with higher sensitivity and specificity and rapid results could have been helpful in such scenario.
The donor had intracerebral bleeding, which could have been due to TB related cerebral vasculitis – thus according to guidelines, in case of death due to unproven cause of meningoencephalitis, organ donation should be avoided.
A donor-derived TB could be defined as proven (when the isolates in donor and recipient are identical or clonal), probable (when TB identified in multiple recipients of same donor or if donor and recipient have >1 shared epidemiologic or clinical feature), or possible (suspected transmission in presence of donor risk factor of TB).
In the index case, donor sample confirmed TB 2 months post-donation, but there was lack of a mechanism to convey this result to the teams managing the different transplant recipients. Presence of perigraft collections, and infection in early post-transplant period point towards a diagnosis of donor-derived TB in the SPK recipient. Liver recipient received LTBI treatment and did not develop any symptoms The other 2 recipients died with sepsis with undiagnosed aetiology.
A review of donor-derived TB showed a median time of diagnosis is 2.7 months – fever is the most common symptom, high mortality is reported in SOT recipients.
The gaps identified in this scenario include: Lack of mechanism to convey the result of pending investigation results, notification of high-risk complications in recipient leading to death or graft loss, lack of communication regarding vertical transmission of TB (to the child from the mother), and lack of biovigilance system (donor traceability).
Conclusion:
A stringent donor screening with a robust reporting system to deal with investigation results coming late.
Promptly communication regarding donor-derived infection to the transplant teams managing all the recipients, could help in avoiding such catastrophes.
2. What is the level of evidence provided by this article?
Level of evidence: Level 4 – Case report
3. What is the take-home message?
2. In case of death due to unproven cause of meningoencephalitis, organ donation should be avoided.
SUMMARY :
The article is about DDI of TB
Donor- preganant, brain dead due to meningoencephalitis , CSF- infective cause
AFB negative ,
NO epidemiological risk factor
Tracheal AFB culture was not available at the tiem of transplantation
child at 2 mo has disseminated TB
TB WAS NOT SUSPECTED IN DONOR BASED ON ABOVE FINDINGS
Recipients
SPK patient is index case who died of ESRD complication but had proven disseminated TB , caseating lesion seen during laparatomy
liver recipient – latent TB diagnosed , treated SO HE IS ALIVE
other kidney recipient – died os sepsis , TB investigations were NOT REQUESTED , AS IT WAS NOT SUSPECTED
heart recipient – died of sepsis , TB investigation not requested
WHAT WOULD HAVE BEEN THE BETTER APPROACH OR LEARNING
Donor AFB culture was not followed up
Someone from donor team must take a responsibility to do the same
child had disseminated TB at 2 month – this is a notifiable fact and could have avoided some risk if latent TB was treated in heart and both kidney transplant recipient
Genetic study on AFB samples is must to say that TB is donor derived
INFORMATION GAP OR FAILURE TO NOTIFY THE DIAGNOSIS OF TB in donor and/or child is the take home message
LEVEL OF EVIDENCE – 3
Summarize the article;
Introduction;
Most tuberculosis case in SOT recipient are caused by the reactivation of latent tuberculosis infection, and only 4% are considered from donor.
This is a case of 45 male who received Pancrease and Kidney from a pregnant women who was a undiagnosed with disseminated TB died post-delivery.
Post-transplant immunosuppression was induction with Basiliximab and maitianence is prednisolone, MMF, and tacrolimus.
Two months post-transplant he presented with symptoms was infection, and was diagnosed with peri-renal collection, drained and culture shows Ziehl-Neelsen stain was positive, ATT with four drug started. Latter on developed dessiminated disease with drug toxicity, rifampicin toxicity hemolytic anemia, ethembutol blurring of vision
Stop immunosuppression à acute cellular rejection,
After 18 months of ATT and multiple procedures TB cured but patient died of ESRD complication after two years.
The recipient for liver was 55 year-old male, before transplant he was positive for TST, and given treatment for LTBI, latter on INH was continued for six month, he did not developed disease.
The Heart recipient three months post-transplant has died of sepsis and septic shock, on further investigation shows disseminated pulmonary TB.
Discussion;
Infection has been a major risk factor for morbidity and mortality post-transplantation.
Donor tuberculosis is absolute contraindication for SOT.
Prevention of DDI is to improve screening strategies, good history, comorbidities, screening, if any suspected infection thorough investigation up-to CSF, MRI etc.
Level of evidence IV.
What is take home massage?
Need to confirm the diagnosis of patient deceased with unknown cause, give prolong prophylaxes.
A good history and contact history mandatory,
Confirmation of any occult infection post-transplantation.
Most cases of Tuberculosis (TB) in post-transplantation are due to activation of latent disease, but about 4% are represented by tuberculosis transmitted by the donor. Countries with a high endemic rate have a higher risk and the screening that is performed for cadaver transplants can be a trap for transmission because it only uses chest X-ray and epidemiological risk assessment, which is not enough to rule out extra-pulmonary TB .
This article summarizes the cases of patients who received organs from a donor with CNS and pulmonary tuberculosis (diagnoses performed with culture results 2 months later and diagnosis of congenital TB in the baby) and presented evolutions with death of undetermined etiology or presented ALSO:
– Index case: kidney-pancreas recipient who was known not to have been exposed and tuberculin test was negative. He returned 2 months after the transplant with peri-graft collections that were later diagnosed with the presence of acid-fast bacilli (AFB). Unfortunately, the disease spread to the CNS, lung and thyroid and, with the suspension of immunosuppressants, the patient presented rejection. She managed to reach the cure thanks to the removal of the graft, but later died of infectious complications from returning to hemodialysis.
– Liver recipient: had a positive pre-transplant tuberculin skin test and thus started treatment for latent tuberculosis shortly after the transplant and this patient did not suffer any strange intercurrences.
– Heart recipient: after 3 months of transplantation, she was admitted with fever and malaise, progressing to septic shock and death of unknown etiology (negative bacterial and fungal cultures and exams for mycobacteria were not collected)
– Other renal recipient: During the second month after transplantation, he developed mesangioproliferative glomerulonephritis and graft loss and returned to dialysis. Three months after transplantation, he returned to the hospital with sepsis of unknown origin and died despite antimicrobial therapy, without isolation of any specific infectious agent.
In the specific case of tuberculosis, donation centers should obtain a donor history of symptoms consistent with active TB, such as a previous diagnosis of TB infection (active or latent), homelessness, alcohol abuse or injecting drug use, incarceration, recent exposure to people with active TB, or traveling to areas where tuberculosis is endemic, being advised to screen with radiographic imaging.
Another difficulty is that, in order to confirm the transmission of tuberculosis, a positive sample from the donor and the genetic sequencing of the pathogen compatible with the samples from the donor and recipient are required. Or, if transmission is suspected and TB has been identified in multiple recipients from a donor, or if donor and recipient share more than one epidemiological or clinical characteristic (e.g. diagnosis of TB in one donor plus TB in recipient at baseline post-trans plantation) or possible, if there is a suspected transmission event, but the only criteria met is a donor risk factor for TB (e.g., donor resides in a TB-endemic area and lack of recipient risk factors for ALSO).
Thus, the need for a specific policy for more efficient recognition of the disease in countries where its prevalence is higher is clear. However, these created guidelines are only recommendations and are not mandatory.
This is a level 4 article, because it is the report of a series of cases.
Transplant centers need a fully developed network with OPO and laboratories for reporting events.
1. Summarise this article
Tuberculosis (TB) in a renal transplant recipient is mostly due to reactivation of latent TB infection (LTBI) with a miniscule (4%) being donor derived. Pre-transplant screening protocols may fail to identify TB in donor and communication gaps in such scenario may lead to poor graft and patient outcomes. The articles presents a case of deceased donor transplant to multiple recipients with donor derived infection (DDI) having catastrophic consequences in absence of communication gaps.
The donor: A 23-year-old female who was 36 weeks pregnant was admitted to hospital with headache, neck stiffness, seizures and fever, with CSF showing increased cellularity and protein. Emergency Caesarean section was done. CT brain revealed subarachnoid hemorrhage and brain death declared on day 9 of hospital admission. Respiratory secretions were negative for acid-fast bacilli (AFB). She became organ donor for 4 different recipients: a simultaneous pancreas kidney (SPK), a liver, a heart, and a kidney recipient.
The index case: SPK recipient. 45-year-old male with no past history of tuberculosis, uneventful post-operative period, developed fever and night sweats in second month post-transplant. Ultrasound revealed perigraft collections, which on drainage were found to be AFB stain positive. Patient was started on antituberculous therapy (ATT). He developed ATT related toxicities prompting change in therapy, but clinically worsened leading to cessation of immunosuppression, further causing graft failure and removal of graft (due to intrabdominal TB abscesses). Patient died 2 years post-transplant with complications related to TB and CKD.
The liver recipient: 55-year-old male with past history of positive tuberculin skin test (TST), was treated for LTBI soon post-transplant for 6 months. No complications seen in him.
The heart recipient: 40-year-old female with uneventful post-operative period, presented 3 months post-transplant with fever and malaise, developed septic shock and died. No specific organism could be identified. CT chest showed diffuse pulmonary lesions.
The other kidney recipient: 45-year-old male with no past history of TB, developed mesangioproliferative glomerulonephritis and graft loss in second month post-transplant. 3 months post-transplant, he died due to sepsis.
The donor: 2 months after donation. Tracheal secretion culture at time of her admission became positive for M. tuberculosis. Developed fever and detected to have disseminated TB, responding to ATT.
Discussion: The index donor in the case points towards the role of careful donor selection including detailed history and epidemiological evaluation. Active tB is a contraindication for organ donation. The index donor had an unrecognized disseminated TB with no history related to TB (active TB, exposure to persons with TB, travel to regions with endemic TB, past history of TB, alcohol abuse, injectable drug abuse, homelessness, incarceration etc). The donor’s sputum culture for TB became positive after 2 months, molecular testing with higher sensitivity and specificity and rapid results are helpful in such scenario. The donor had intracerebral bleeding, which could have been due to T related cerebral vasculitis. According to guidelines, any donor with death due to unproven cause of meningoencephalitis should be avoided.
A donor-derived TB could be defined as proven (when the isolates in donor and recipient are identical or clonal), probable (when TB identified in multiple recipients of same donor or if donor and recipient have >1 shared epidemiologic or clinical feature), or possible (suspected transmission in presence of donor risk factor of TB).
In the index case, donor sample confirmed TB 2 months post-donation, but there was lack of a mechanism to convey this result to the teams managing the different transplant recipients. Presence of perigraft collections, and infection in early post-transplant period point towards a diagnosis of donor-derived TB in the SPK recipient. Liver recipient received LTBI treatment and did not develop any symptoms The other 2 recipients died with sepsis with undiagnosed etiology.
A review of donor-derived TB showed that median time of diagnosis is 2.7 months with fever being most common symptom and high mortality.
The gaps identified in this scenario include: Lack of mechanism to convey the result of pending investigation results, notification of high-risk complications in recipient leading to death or graft loss, lack of communication regarding vertical transmission of TB (to the child from the mother), and lack of biovigilance system (donor traceability).
To conclude, a stringent donor screening with a robust reporting system to deal with investigation results coming in late, and promptly conveying communication regarding any donor-derived infection to the transplant teams managing all the recipients could help in avoiding such scenarios.
2. What is the level of evidence provided by this article?
Level of evidence: Level 4 – Case report
3. What is the take-home message?
Introduction :
Tuberculosis (TB) in solid organ transplant (SOT) recipients are caused by the reactivation of latent tuberculosis infection (LTBI) and only 4% are considered donor-derived .
45-year-old male received a simultaneous pancreas kidney (SPK) transplant due to diabetes and endstage renal disease (ESRD) . second month posttransplant, he returned to the hospital complaining of
fever, night sweats, and chills anf on USG found perigraft collections (renal and pancreatic abscesses),He received broad-spectrum antibacterial treatment and underwent percutaneous drainage of the abscesses, with transient resolution of fever. Laboratorial analysis revealed acid-fast bacilli (AFB) on Ziehl-Neelsen stain. Antituberculous therapy was started with standard drugs.But lateron patient develop disseminate TB as patient has to stop ATT due to toxicities.Patient completed ATT 18 month and cosidered cure ,but died after 2 year.
The donor was a 23-year-old, 36-week pregnant woman with h/o meningitis,underwent cessearian section at 6th day and brain death decleared 9th day of operation.after 2 moth ,Tracheal aspirate shows groth of M. tuberculosis.
Among othe receipent,liver recipient was asymptomatic and heart and other kidney receipient died due to sepsis.
Discussion:
Infections represent a major cause of morbidity and mortality for SOT recipients.This case report calls attention to the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases.In this reported case, the donor had no detectable abnormalities on the chest X-ray and AFB-negative smears, whereas the culture became positive two months after procurement. The donor had no respiratory symptoms or compatible image, and the AFB was negative, and therefore, TB was not suspected. However, the CSF analysis showed an elevated protein level with pleocytosis. Subsequently, the patient continued to decline neurologically, and brain death occurred nine days postadmission. The intracerebral bleeding was likely secondary to cerebral vasculitis due to TB infection.
According to current recommendations, in cases of donor death due to meningoencephalitis (ME) without a proven cause, the donation should be avoided .In this case, donor cause of death was considered CNS bleeding.
the liver transplant recipient was treated for latent TB and did not develop the disease. The two other organ recipients from the same donor presented fever of unknown origin, sepsis, and organ dysfunction a few months after transplantation.
Concerning the information gaps, we should reinforce that the donor had cultures pending at the time of procurement. It should be commented that culture results are routinely checked on day 7. However, mycobacterial culture is more time-consuming, and this result is not systematically evaluated.
Introduction
● Most TB cases in SOT recipients are caused by the reactivation of latent (LTBI)
● Only 4% are considered donor-derived
● Active TB in donor is contraindication for organ donation
● Unusual symptoms of TB makes the diagnosis not always feasible
● Donor-derived infections (DDI) may be associated with death or poor outcomes
● A case of unrecognized disseminated TB in the donor with a devastating outcome for organ recipients.
♡ The Index Case – Simultaneous Pancreas Kidney
☆ A 45-year-old male Recipient
☆ Received a simultaneous pancreas kidney (SPK) transplant due to diabetes and end-stage renal disease (ESRD) .
☆ No major clinical complications and was discharged on post-operative day 30.
☆ TST (-) and no history of TB exposure.
☆ The immunosuppressive regimen included basiliximab, steroid, tac, and MMF
☆ He complains fever, night sweats, and chills during second month posttransplant
☆ Perigraft collections (renal and pancreatic abscesses) in abdominal US
☆ chest radiograph was normal.
☆ He received broad-spectrum antibacterial treatment and percutaneous drainage of the abscesses
☆ Laboratorial analysis revealed acid-fast
bacilli (AFB) on Ziehl-Neelsen stain.
☆ Antituberculous therapy was started with standard drugs: rifampin, isoniazid,
pyrazinamide, and ethambutol
☆ At that time, two recipients had already died
☆ The patient presented with anti-TB drug toxicities and deterioration of his clinical state imposed IS cessation, leading to AR of the grafts, and dual graft loss with return to hemodialysis and insulin therapy.
☆ The removal of the renal graft was the only viable treatment encountered
☆ After several ultrasound guided punctures to drain intra-abdominal TB abscesses and 18 months of anti-TB therapy, the patient was considered cured.
☆ He died from complications related to ESRD and dialysis, two years after RTx
♡ The donor
☆ A 23-year-old
☆ 36-week pregnant woman
☆ A history of intense headache
☆ She was dmitted to the hospital ER
☆ She developed mild fever, neck stiffness, and seizures within 72 hours
☆ CSF was abnormal with increased cellularity and protein.
☆ No microorganisms were identified in the CSF and blood
☆ Treatment was started 72 hours after hospital admission (ceftriaxone, anti-TB standard treatment and acyclovir)
☆ Respiratory secretions were negative for acid-fast bacilli (AFB) stain.
☆ Her consciousness decreased, and she underwent an emergency caesarean section on the 6th day of admission.
☆ Brain CT scans revealed diffuse SAB
☆ Brain death occured in day 9 and had elected to be an organ donor, with diagnosis “CNS bleeding”
☆ Two months after her death, tracheal aspirate culture became positive for MTB
☆ At that time her child presented with fever of unknown origin and was admitted to the same hospital, being diagnosed with disseminated TB.and he was discharged after seven days of standard TB treatment.
♡ The Liver Recipient
☆ A 55-year-old man
☆ Caroli disease who was transplanted because of recurrent bacterial cholangitis.
☆ He was treated for LTBI with isoniazid,
due to a positive TST before surgery soon after the transplant for six months
☆ Patient has not developed any manifestations compatible with active TB
♡ The Heart Recipient
☆ 40-year-old woman
☆ Chagas cardiomyopathy who underwent a heart transplant for class IV heart failure
☆ Three months after RTx , she admitted to the hospital with fever and malaise.
☆ She developed severe septic shock and died Within three days
☆ No bacteria or fungi were identified in cultures (blood, urine, and tracheal aspirate samples)
☆ No specific mycobacterial direct.exam or culture was requested.
☆ Chest CT revealed diffuse pulmonary involvement.
☆ TB diagnosis is only presumptive
♡ The Other Kidney Recipient
☆45-year-old man
☆ Terminal hypertensive nephropathy
☆ During the second month after renal transplantation, he developed mesangioproliferative glomerulonephritis and graft loss and returned to dialysis.
☆ Three months after transplantation, he returned with sepsis of unknown origin and died despite antimicrobial therapy
☆ No specific test for mycobacteria was requested.
☆ TB diagnosis is only presumptive
♡ Discussion
● Active TB is a contraindication for organ donation.
● Risk factors should be assessed :
☆ Symptoms consistent with active TB
☆ Past diagnosis of TBi (active or latent)
☆ Homelessness
☆ Alcohol abuse
☆ Injection drug use
☆ Incarceration
☆ Recent exposure to persons with active TB
☆ Travel to areas where TB is endemic.
● If risk factors are identified radiological
assessments are warranted.
● In this case donor had an unrecognized disseminated TB, with no history of previous TB or exposure except for pregnancy, no known immunosuppressive conditions
● The donor had no abnormalities on the chest X-ray and AFB-negative smears,
whereas the culture became positive two months after procurement.
● The intracerebral bleeding was likely secondary to cerebral vasculitis due to TB infection
● In cases of donor death due to meningo encephalitis (ME) without a proven cause, the donation should be avoided
● So donor cause of death was considered CNS bleeding
● TB is classified as probable :
☆ If TB was identified in multiple recipients of one donor
☆ If diagnosis in a donor plus TB in the recipient early posttransplantation
☆ TB possible, if donor residence in TB endemic area and absence of recipient risk factors for TB
● In TB donor transmission, the onset of TB is early in the posttransplant period
● In this case the liver transplant recipient was treated for latent TB and did not develop the disease.
● A recent review retrieved 36 cases
☆ The median time to clinical presentation or diagnosis was 2.7 months
☆ fever was the most frequent presenting
symptom.
☆ Allograft involvement was common.
☆ Graft loss occurred in ~20% of patients.
☆ All-cause mortality was 25%
● Mycobacterial culture is time consuming and this result is not systematically evaluated.
● Level : 4
● Take home massage :
☆ TB is a serious complication in renal transplant recipients
☆ Immunosuppressive transplant recipients are at a higher risk of re-activating LTBI from within themselves or from the transplanted donor kidney.
☆ All donors and recipients are routinely screened for LTBI and active TB disease prior to transplant whenever possible.
☆ A high degree of awareness of the possibility of TB is required in all donors so that it can be diagnosed and treated early,
reducing the risk of loss of allograft.
☆ Importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner.
This article on a case study is very impressive, with a lot of knowledge and messages for transplant nephrologists.
This article demonstrates that DDI of TB is very minimal at 4% only,while high morbidity and mortality if you are going to do a transplant with an infected organ. As we know, the morbidity and mortality of TB post-SOT is 20 to 74%, which is quite a high rate foreign for TB before SOR is mandatory, especially since there are many proper scr challenges.
TB is not always easy to diagnose and treat. The lesson from this case is we need prober communications between the organ procurement centre and the transplant centre to share the important result and feed beck to them with all new results; especially we know that this case result was issued 2 months after .
Discussion
The TB is not feasible to be diagnosed before SOT. Active TB is an absolute contraindication for SOT.
Sputum cultuer has the higher sensitivity but tooks very long time to release the result (2 months ) which is valuble time for the donor .so we need to have other solid base for diagnosisng TB like molecular testing which is more sensitive and specific with shorter time ,but still need to be held in suspected cases .
Organ donor screening for infections is currently based on donor history, physical assessment, and laboratory testing.
High-risk complications of the recipient with eventual connection with the donor, such as death or sepsis within 3 months of the procedure, should be actively notified. In the reported case, if a flag for a possible DDI was detected after the first recipient’s death, the others could certainly have had a better chance.
The surveillance of DDI is a strong indicator of transplant safety.
A more efficient reporting system will not prevent the event from occurring but may of course impact the outcome.
level of evidence 4
SUMMARY
The article is about DDI of TB
Donor- preganant, brain dead due to meningoencephalitis , CSF- infective cause
AFB negative ,
NO epidemiological risk factor
Tracheal AFB culture was not available at the tiem of transplantation
child at 2 mo has disseminated TB
TB WAS NOT SUSPECTED IN DONOR BASED ON ABOVE FINDINGS
Recipients
SPK patient is index case who died of ESRD complication but had proven disseminated TB , caseating lesion seen during laparatomy
liver recipient – latent TB diagnosed , treated SO HE IS ALIVE
other kidney recipient – died os sepsis , TB investigations were NOT REQUESTED , AS IT WAS NOT SUSPECTED
heart recipient – died of sepsis , TB investigation not requested
WHAT WOULD HAVE BEEN THE BETTER APPROACH OR LEARNING
Donor AFB culture was not followed up
Someone from donor team must take a responsibility to do the same
child had disseminated TB at 2 month – this is a notifiable fact and could have avoided some risk if latent TB was treated in heart and both kidney transplant recipient
Genetic study on AFB samples is must to say that TB is donor derived
INFORMATION GAP OR FAILURE TO NOTIFY THE DIAGNOSIS OF TB in donor and/or child is the take home message
LEVEL OF EVIDENCE – 3
Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
Most tuberculosis (TB) cases in solid organ transplant (SOT) recipients are caused by the reactivation of latent tuberculosis infection (LTBI), and only 4% are considered donor-derived.
TB recognition is not always feasible, particularly when unusual symptoms are under differential diagnostic consideration and the potential donor has low-epidemiological risk .
Thus, unfortunately, despite organ procurement protocols, pretransplantation screening fails to identify TB in the donor in many cases.
Additionally, this report also highlights the need for a data bank and donor sample analysis to trace infections and reinforces the importance of better communication between transplantation teams and organ-harvesting centers.
The TB diagnosis contributed to the fatal outcome in one patient and may be the cause of infectious disease complication after transplantation in the other two.
Discussion
Infections represent a major cause of morbidity and mortality for SOT recipients.
active TB is an absolute contraindication for organ donation.
Although sputum culture has higher sensitivity than AFB ,the time to positivity ranges from weeks to months .In this situation, molecular tests present greater sensitivity and specificity but are done when pulmonary TB is suspected.
According to current recommendations, in cases of donor death due to meningoencephalitis (ME) without a proven cause, the donation should be avoided .
Additionally, to improve screening strategies, certain potential findings should be scrutinised such as the existence of any comorbidity that may support stroke, the presence of fever at illness presentation/admission in the potential donor, CT/MRI scan of the head, or CSF findings consistent with an infectious process, and whether the donor was an immunosuppressed host or had any potential environmental exposures associated with organisms causing ME.
mentioning that the diagnosis of tuberculous meningitis is challenging, and the available microbiological tests fail to attain the accuracy standards required, with poor sensitivity and delayed results.
there is often a time gap between the donation and the development of the disease.
Despite the fact that it is desirable to have molecular typing and analysis of patterns of the isolates, this is not always possible.
M. tuberculosis is only identified in culture after 4 to 6 weeks.
Organ donor screening for infections is currently based on donor history, physical assessment, and laboratory testing.
High-risk complications of the recipient with eventual connection with the donor, such as death or sepsis within 3 months of the procedure, should be actively notified. In the reported case, if a flag for a possible DDI was detected after the first recipient’s death, the others could certainly have had a better chance.
The surveillance of DDI is a strong indicator of transplant safety.
A more efficient reporting system will not prevent the event from occurring but may of course impact the outcome.
level of evidence 4
SUMMARY
DONOR DERIVED TB;A CASE REPORT AND ROLE OF COMMUNICATION GAPS IN TRANSPLANATION SAFETY.
INTRODUCTION.
Majority of TB post transplant is reactivated LTBI with only 4% being donor derived.
1.1 Index case; Simultaneous pancreas kidney recipient.
–45 yr old SPK from DM nephropathy whose previous TST was negative,2/12 post transplant had B symptoms with peri graft collection that stained AAFBS.DI and SE led to cessation of immunosuppression with graft dysfunction, graft nephrectomy was done,pt reverted to HD but later on succumbed to ESRD and HD.
1.2 Donor.
-23 yr old ,36/40 woman who died from TB complication that was missed initially but later 2/12 after death diagnosed via tracheal aspirate. Baby too had disseminated TB.
1.3.Liver recipient.
-55 yr old with caroli dx with recurrent cholangitis and tx for LTBI from a +ve TST and did well without developing active TB.
1.4 Heart Recipient.
-40 yr old woman with chagas cardiomyopathy who had a heart transplant who died 3/12 post transplant after presenting in sepsis, TB was not investigated but her chest CT had diffuse pulmonary involvement.
1.5 The other kidney recipient.
-45 yr old HTN with ESRD who 2/12 post transplant had mesangio-proliferative GN and graft loss with reversion to HD but died from sepsis with TB again not being investigated.
DISCUSSION.
-We should carefully select our donors to avoid spread of lethal but curable infections.
-Hx, risk factors and previous tx for TB should be sort from donor and active TB to be considered a contraindication to organ donation.
-Mortality from meningoencephalitis of unknown cause should prevent organ harvesting as TB is a potential risk.
-Poor communication is a risk factor for DDI and results to TB transmission, Registry to identify those with vertical transmission might decrease risk of TB and facilitate early intervention.
-An integrated system involving transplant center, OPO and labs could allow quick spotting of TB with early intervention.
-All suspected cases of infection from donor including TB should be notified to trace all those at risk.
LEVEL OF EVIDENCE – IV
TAKE HOME MESSAGE.
-All health care workers and centers need to be conversant with screening of potentially transmissible infections ,notify one another and prevent transplanting those with unsure diagnosis esp if cause of death was from an infection not clearly diagnosed. Appropriate communication strategies need to be put in place to ensure we dont have gaps that will end up in mortality post transplant.
–
Summary:
· Donor-derived tuberculosis (DD-TB) accounts for less than 5% of TB cases. Though rare, careful screening is crucial to identify TB in the donor, specially deceased donor is necessary.
· This case report is discussed disseminated TB in the donor with poor outcome in organ recipients.
· Active TB is absolute contraindication to donation. This case report highlights the importance of careful donor selection to reduce the risk of transmission of a potential serious but treatable disease.
· In this case, the donor had an unrecognized disseminated TB, with no history of previous TB or exposure. So, specific policies may be taken to improve the recognition of the disease in donors to save the recipients.
· Here, donor investigated for CXR; showed no abnormalities, negative AFB, culture (positive after 2month).
· Sputum culture is more sensitive than AFB, but culture take long time, weeks to months.
· In case of pulmonaryTB suspected molecular tests is more sensitive and specific. CSF analysis showed an elevated protein level with pleocytosis, leading to brain death in this case.
Level of evidence: IV.
Take-home message:
Tuberculosis from donor is rare but when occurs it is fatal; though it is a treatable condition. Early diagnosis is the key to treatment. In any infectious disease it is always better to prevent than treatment. So, further research is necessary to yield diagnostic tools to detect TB in donor.
Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
Introduction
Most tuberculosis cases in solid organ transplant recipients are caused by the reactivation of latent tuberculosis infection (LTBI) in the recipients, and only 4% are considered donor-derived. Active TB in the donor is contraindicates organ donation. However, current screening protocols for deceased donors are usually based on chest X-ray findings (which may be nonspecific), epidemiological risks, and previous TB history. These features may miss extrapulmonary and disseminated TB. Unfortunately, despite organ procurement protocols, pretransplantation screening fails to identify TB in the donor in many cases and even when diagnosed, communication gaps may result in donor-derived infections (DDI), which may be associated with death or poor outcomes.
The mentioned case report of unrecognized disseminated TB in the donor caused grave outcome for recipients. The donor was a pregnant woman who died soon after delivery due to TB involvement of the central nervous system (CNS) and lungs. The diagnosis was retrospectively established late by mycobacterial culture of the respiratory sample.
1-The Index Case of Simultaneous Pancreas Kidney Recipient:
A 45-year-old male received a simultaneous pancreas kidney (SPK) transplant due to diabetes and ESRD. His previous tuberculin skin test (TST) was negative, and no history of TB exposure. The immunosuppressive regimen included basiliximab, prednisone, tacrolimus, and mycophenolate mofetil. During the second month posttransplant, he admitted to the hospital complaining of fever, night sweats, and chills. Abdominal ultrasonography revealed peri graft collections (renal and pancreatic abscesses), and chest radiograph was normal. He received broad-spectrum antibacterial treatment and underwent percutaneous drainage of the abscesses. Laboratorial analysis revealed (AFB) on Ziehl-Neelsen stain. Antituberculous therapy was started with standard drugs: rifampin, isoniazid, pyrazinamide, and ethambutol. Due to anti TB drugs toxicity (Rifampicin) which led to change in therapy. At this time, the patient presented disseminated disease involving grafts, lungs, CNS, and thyroid. In view of the clinical deterioration of the patient immunosuppressive was stopped, leading to acute cellular rejection of the grafts, and dual graft loss with return to hemodialysis and insulin therapy. After several ultrasound guided punctures to drain intra-abdominal TB abscesses and 18 months of anti TB therapy, the patient was considered cured. However, he died from complications related to ESRD and dialysis, two years after transplantation.
2-The Donor: The donor was a 23-year-old, 36-week pregnant woman with a history of intense headache who was admitted to the hospital emergency room, and within 72 hours of admission, she developed mild fever, neck stiffness, and seizures. Empirical treatment for meningoencephalitis was started 72 hours after hospital admission (ceftriaxone followed by anti-TB standard treatment and acyclovir. Respiratory secretions were negative for acid-fast bacilli (AFB) stain. Her level of consciousness decreased, and she underwent an emergency caesarean section on the 6th day of admission. Brain computed tomography (CT) scans performed after the procedure revealed diffuse subarachnoid bleeding. The patient was diagnosed with brain death (day 9) and had elected to be an organ donor, considering the cause of death is CNS bleeding. After two months after her death, the tracheal aspirate culture became positive for M. tuberculosis also her child presented with fever of unknown origin and was admitted to the same hospital, being diagnosed with disseminated TB.
3-The Liver Recipient:
The liver recipient was a 55-year-old man diagnosed with Caroli disease who was transplanted because of recurrent bacterial cholangitis. Due to a positive TST before surgery, he was treated for LTBI with isoniazid, soon after the transplant. The treatment was maintained for six months, and the patient has not developed any manifestations.
4-The Heart Recipient:
The heart recipient was a 40-year-old woman diagnosed with Chagas cardiomyopathy who underwent a heart transplant for class IV heart failure. Three months after the procedure, she was admitted to the hospital with fever and malaise. Within three days after admission, she developed severe septic shock and died despite broad-spectrum antibiotic therapy. No bacteria or fungi were identified in cultures.However, no specific mycobacterial direct exam or culture was requested. Her chest CT revealed diffuse pulmonary involvement.
5-The Other Kidney Recipient:
The kidney recipient was a 45-year-old man with systemic hypertension and terminal hypertensive nephropathy. During the second month after transplantation, he developed mesangioproliferative glomerulonephritis and graft loss and returned to dialysis. Three months after transplantation, he returned to the hospital with sepsis of unknown origin and died despite antimicrobial therapy, without isolation of any specific infectious agent. Also, no specific test for mycobacteria was requested.
This case report calls attention to the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases. Typically, DD-TB is commonly related to the donor’s epidemiology and clinical history. DD-TB is considered proven if donor and recipient isolates were reported to be identical or clonal through molecular analysis.
In the absence of definitive confirmation of similar isolates, DD-TB is classified as probable if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if donor and recipient shared more than one epidemiologic or clinical feature. DD-TB is difficult to recognize in both donor and recipient.
In the index case, the microbiological results were detained in the laboratory hospital in which the donor was assisted. It must be stated that there was no specific protocol defining who was responsible for checking the pending test results.
Summary
Introduction
4% of solid organ transplant (SOT) patients develop donor-derived tuberculosis (TB) due to LTBI reactivation. Active TB in the donor is a contraindication for organ donation. Despite organ procurement protocols, pretransplantation screening fails to identify TB in the donor in many cases.
The Cases
Index case
A 45-year-old male received a simultaneous pancreas kidney (SPK) transplant. After transplantation, he had no major clinical complications and was discharged on postoperative day 30. His previous tuberculin skin test (TST) was negative and there was no TB exposure. . During the second month posttransplant, he visited to the hospital with fever, night sweats and chills. Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses) and the chest radiograph was normal. The patient was cured after ultrasound-guided punctures to empty intra-abdominal TB abscesses and 18 months of anti-TB treatment.
Two years after transplantation, died due to ESRD-related dialysis problems.
The donor, a 23-year-old, 36-week pregnant lady with a history of severe headaches with fever, neck stiffness, and convulsions. Acid-fast bacilli smear was negative from respiratory secretions. Chest x ray was normal. CSF protein levels were raised with pleocytosis. After nine days, the patient died from brain damage. Cerebral vasculitis causes intracerebral hemorrhage was the cause of brain death which was later diagnosed to be TB related cerebral vasculitis.
Moreover, her child had a fever two months after birth and was diagnosed with disseminated TB at the same hospital.
Liver transplant recipient
Due to a positive TST before surgery, he was treated for LTBI with isoniazid, soon after the transplant. The treatment was maintained for six months, and the patient has not developed any manifestations compatible with active TB .
Heart transplant recipient
Within three days after admission, she developed severe septic shock and died despite broad-spectrum antibiotic therapy. No bacteria or fungi were identified in cultures (blood, urine, and tracheal aspirate samples); however, no specific mycobacterial direct exam or culture was requested
Other kidney recipient
During the second month after transplantation, he developed mesangioproliferative glomerulonephritis and graft loss and returned to dialysis. Three months after transplantation, he returned to the hospital with sepsis of unknown origin and died despite antimicrobial therapy, without isolation of any specific infectious agent
Discussion
In this regard, active TB is an absolute contraindication for organ donation. Unfortunately, even active TB can be overlooked and therefore mistaken for other diseases.
The donor had a normal chest X-ray and AFB-negative smears, but the culture went positive two months following procurement
This case report emphasizes donor selection to limit the danger of transmitting potentially deadly but curable illnesses.
Even when these cases are identified, communication gaps may result in donor-derived infections (DDI), which may be associated with death or poor outcomes
What is the level of evidence provided by this article?
Level 4(Case report)
What is the take-home message?
1) High index of suspicion is need for TB diagnosis.
2)Good communication from donor hospital/ organ allocation committees or bodies to and from recipient hospital should be done for each and every detail of organ before, during and after the organ donation.
3)Latent TB is equally important than active TB
4)Infection are major complication after transplant, not only TB but every infection from donor to recipient needs evaluation.
5)Careful donor selection is needed to reduce the risk of transmission of potentially lethal but treatable diseases.
6)Information to be shared to the registry of local bodies looking for transplant about the outcome of transplant every quarterly or yearly.
7)Negative chest XR does not exclude TB.
I. Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
Summarise this article
Introduction
– donor-derived TB (DD-TB) is rare, it accounts for less than 5% of the TB cases
– most TB cases in SOT recipients are caused by reactivation of LTBI
– active TB in the donor is an unacceptable risk hence a contraindication to organ donation
– active TB in the transplant setting is 20-74times higher than that in the general population and is associated with high mortality
– it is therefore important to identify high-risk donors so as to reduce the risk of DD-TB
– however, TB recognition in the DD is not always feasible
– the case report describes a deceased donor, a pregnant woman who died post-delivery due to a CNS bleed (diffuse subarachnoid bleed) and probable CNS and pulmonary TB
– TB diagnosis was made retrospectively through a positive tracheal aspirate mycobacterial culture (the results were obtained 2 months after the donor’s death) and at that time her baby was diagnosed with congenital disseminated TB after presenting with fever of unknown origin
– some of the patients who received organs from the donor with TB actually died: –
– no postmortem was performed on the deceased kidney and heart recipients hence the TB diagnosis remains presumptive int these two cases
Discussion
– transplantation is the treatment of choice for most ESKD patients however it is associated with numerous risks related to the surgery and the immunosuppressive therapy
– infections are a major cause of morbidity and mortality in SOT recipients
– it is therefore important to carefully select and screen donors to reduce the risk of transmission of lethal but treatable DDI (donor-derived infections)
– when risk factors for TB have been identified in a DD, then further testing and radiological assessment is warranted
– active TB is an absolute contraindication to organ donation
– the donor in this case report did not have respiratory symptoms or any suggestive imaging, AFB was negative hence TB was not suspected
– however, the CNS findings were suggestive of TB – elevated CSF protein, a decline in the neurological status, intracerebral bleed
– it is usually difficult to diagnose DD-TB and molecular typing and analysis if specimen isolates ought to be done but this is not always feasible
– organ donation should be avoided in cases of donor death due to meningoencephalitis without a proven cause
– communication gaps e.g., failure to report results, inefficient communication between organ procurement agencies and transplant centers, failure to exchange information regarding recipients from the same donor can be prevented by using more efficient strategies towards screening protocols and communication
– these communication gaps can result in DD-TB resulting in poor outcomes including death
– the case report highlights the importance of a data bank and donor sample analysis to trace DD infections and the significance of better communication between organ-harvesting centers and transplantation teams
– biovigilance initiatives (donor traceability) should be implemented with an aim of developing national surveillance systems for cells, tissues and organs
Level of evidence provided by this article
– Level IV
Take-home message
– it is important to report any suspicious cases of infections transmitted by the donor since this allows tracing of all the recipients at risk in a timely manner so as to avoid poor outcomes
– to support this initiative, data banks and donor sample analysis systems should be set up/ put in place
– biovigilance systems should be implemented and the communication systems between transplantation centers and organ procurement/ harvesting centers improved
This article has shed light upon very important issue of proper cadaveric donor selection to avoid serious consequences for the recipients.
Unfortunately the donor mentioned in this article was a pregnant female who died after a brief illness with CT showing subarachnoid hemorrhage and CSF suggestive of meningitis. The diagnosis of TB was confirmed two months after death with positive respiratory culture for AFB.
The fact that the unfortunate simultaneous kidney pancreas recipient developed disseminated TB and survived initially and two other ( Heart and kidney)died due to sepsis with no subsequent autopsy again raises the question of disseminated TB. The fourth lucky liver transplant recipient survived as he received prophylactic treatment for Latent TB.
This article has shown the importance of proper donor evaluation and communication with harvesting team in order to ensure safety of recipients. The communication gaps in this case has raised serious questions, timely information of vertical transmission in this case would have ensured earlier detection of fatal TB in recipient of various organs.
LEVEL OF EVIDENCE
4
TAKE HOME MESSAGE
Meticulous cadaveric donor selection is of prime importance. All cadaveric donors of sepsis should be thoroughly screened for the causative organism. A definitive protocol should be developed where timely communication should be ensured between transplant team.
DDI is important source of infection in about 4percent of cases.
Communication between centers is important as pretransplant work up like CXR and history won’t detect this risk.
Knowledge gap or lack of communication. Put recipient at devastating outcome as happened in our index case who died of CNS T.B and diagnoses retrospectively after 2months of death .
One patient died of TB and one recipient developed disseminated T.B.heart and kidney recipient died ,presumptively related to TB ,not confirmed ,autopsy’s examination not done.
What is the take-home message?
attention to the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases.
Typically, DD-TB is commonly related to the donor’s epidemiology and clinical history, even if TB is not initially recognized .
obtain a donor history of symptoms consistent with active TB, as past diagnosis of TB infection (active or latent), homelessness, alcohol abuse or injection drug use, incarceration, recent exposure to persons with active TB, or travel to areas where TB is endemic.
When risk factors are identified, further testing and radiological assessments are warranted.
According to current recommendations, in cases of donor death due to meningoencephalitis (ME) without a proven cause, the donation should be avoided .
prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner.
What is the level of evidence provided by this article?
Level of evidence lV.
Introduction
· Tuberculosis (TB) in solid organ transplant (SOT) recipients is mostly due to reactivation of latent TB, and only 4% are donor-derived.
· Chest X-ray could be normal in extrapulmonary and disseminated TB in deceased donors, and pre-transplantation screening fails to identify TB in the donor in many cases.
· The donor of this report was a pregnant woman who died soon after delivery due to TB involvement of the central nervous system (CNS) and lungs.
The Index Case
· A 45-year-old male received a simultaneous pancreas-kidney (SPK) transplant due to DM and ESRD.
· By second-month posttransplant, he returned to the hospital with fever, night sweats, and chills
· U/S abdomen revealed peri-graft collections (renal and pancreatic abscesses) with normal CX-R
· percutaneous drainage of the abscesses was done and he had + acid-fast bacilli.
· Anti-TB therapy was given: rifampin, isoniazid, pyrazinamide, and ethambutol
· He developed complications of anti-TB drugs, and clinically deteriorated, so immunosuppressive drugs were all stopped with graft loss.
· exploratory laparotomy for debridement and renal graft was removed.
· The patient died from complications of ESRD and dialysis, two years after transplantation.
The Donor
· a 23-year-old, 36-week pregnant woman with a history of intense headache, fever, and seizures, was treated with empirical treatment for meningoencephalitis as CSF and blood cultures were negative.
· Respiratory secretions were negative for acid-fast bacilli (AFB) stain, and her brain CT revealed diffuse subarachnoid bleeding
· The patient was diagnosed with brain death (day 9) and had elected to be an organ donor, considering as the primary diagnosis, CNS bleeding.
· two months after her death, the tracheal aspirate culture became positive for M. tuberculosis
· 2 months after delivery, her child presented with fever of unknown origin and was admitted to the same hospital, being diagnosed with disseminated TB.
· The M. tuberculosis strain isolated from the child presented no resistance to first-line anti-TB drugs
The Liver Recipient
· Caroli disease who was transplanted because of recurrent bacterial cholangitis
· treated for LTBI with isoniazid, soon after the transplant and doing well till now
The Heart Recipient
· Chagas cardiomyopathy, heart transplant due to class IV heart failure
· Three months post-transplant died due to septic shock
· Negative cultures for bacteria or fungi, but CT chest revealed diffuse pulmonary involvement.
The Other Kidney Recipient
· 2 months post-transplant, he developed mesangial-proliferative GN and graft loss and returned to dialysis.
· 3 months after transplantation, he died from sepsis of unknown origin.
Discussion
· Transplantation has the best outcome for patients with ESKD if the donor is screened well.
· Active TB is an absolute contraindication for organ donation, but it can be misdiagnosed.
· potential organ donors and recipients should be screened well for risk factors for Latent or active TB
· In this case as AFB was negative, TB was not suspected. But the CSF analysis showed an elevated protein level with pleocytosis, and the SAH was mostly due to TB vasculitis.
· In case of donor death due to meningoencephalitis without a proven cause, the donation should be avoided.
· DD-TB is classified as probable if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if the donor and recipient shared more than one epidemiologic or clinical feature
· There was a lack of getting positive data about the donor results after 2 months
· As the liver transplant recipient was treated for latent TB and did not develop the disease
· As the donor has pending results, she should be removed from the list.
· As the newborn was diagnosed with TB in the first 2 months of life, other transplant recipients should be investigated for TB at that time.
This is a case report evidence 4
Take home message:
· Donors with unknown definite cause of death should be excluded from the list
· Deceased donor with pending investigations should be removed from the list
· Any serious infectious disease should be followed well to discover the primary source of transmission.
This is a case report from Brazil:
4 transplantation surgeries from one deceased donor
The donor was pregnant lady came to the hospital with meningeonecephalitis which was investigated well but results of cultures came late and patient died from intracerebral hemorrahge and unfortunately was assessed for deceased donation and accepted
and 4 cases has SOT from the same donor .
Donor cultures came positive for TB + vertical transmission of TB to her son and no body informed
The recepients were:
1st one had pancreatic and kidney transplant and developed disseminated TB and suffered from medication side effects ,they stopped immunosuppression then graft failure and died after 2 years from ESRD related causes
2nd one has liver transplant which was diagnosed as latent TB received medications and became well with no further events
3rd one has heart transplant whom also developed disseminated TB and died undiagnosed with fever of unknown origin and died
earth one has kidney transplant died also from fever of unknown origin
Level of evidence:5 case report
Take home message :
1- Proper assessments for the cause of death and is this patient is fit for transplantation or not. (Here Patient was admitted with suspicion of infection so it is not only intracerebral hemorrahge)
2- If there is pending results for the patient considered for donation ,should be endorsed to transplant team to follow.
3- Review of cases should be on more than one level ,at the start assisstant then consultant review then multidisciplinary meeting ( more consultants and surgeons ,pharmacists,radiologists )
4- Even if informed after transplantation was done ,at least they can commence anttuberculous medications with better outcome
5- Good communications between the cadaveric assessment teams and transplant team .
Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
1. Summarise this article
2. What is the level of evidence provided by this article?
3. What is the take-home message?
Summary of this article:
Kidney transplant remains the best option of renal replacement therapy for patients living
with end-stage kidney disease, however, it is also accompanied by unintended
cardiovascular or infectious disease complications.
This article focused on the development of TB in the recipient from the donor organ. This
is of particular importance, since generally recipient TB occurs from reactivation of
latent TB. Donor derived TB is rare, at a small level of 4% of cases are contracted from
the donor during SOT.
The current screening method for tuberculosis during work in SOT may miss out the
diagnosis of TB, particularly if is extrapulmonary, while communication could also be the
bane of a successful surgery
The article is the summaries of four recipients (SPK, Kidney, Heart, and liver) who
received diseased organs from a pregnant woman.
Despite screening recommendations, failures may lead to a breakdown in safety that
results in the transmission of potentially fatal diseases.
Case 1 :
A 45-year-old man received SPK & was discharged on day 30,
Previous TBST negative and denied TB exposure
presented 2 months post-surgery with fever, night sweat, and chill
Had drainage of peri-grafts abscess, covered with antibiotics
Had anti-TB treatment because of positive AFB from abscess sample
She had toxicity to anti-TB drugs with disseminated TB and had exploratory laparotomy,
kidney graft removal, and abscess drainage
She was considered cured after 18 months of anti-TB but died of dialysis complication 2
years after the surgery
DONOR:
A 23-year-old lady presented with a severe headache at 36-week gestation, and later developed fever, neck pain with seizure
Tests were done initially on CSF, respiratory secretions and blood was negative for tuberculosis
She had emergency CS and was later diagnosed with brain death, and organs were harvested for donation
The trachea aspirates became positive for TB 2 months after and the child was treated for TB with a good clinical response
Other organ recipients:
The heart recipient presented to the hospital three months after with features of septic shock and died within three days despite antibiotics being given.
The liver transplant received treatment for LTBI till after the surgery and he is still doing fine without any features of DD -TB
The other recipient of the kidney also return to the hospital three- month after with sepsis of unknown origin and died despite antibiotic administration.
DISCUSSION:
DD-TB is considered proven if donor and recipient isolates were reported to be identical or clonal through molecular analysis. In the absence of definitive confirmation of similar isolates, DD-TB is classified as probable if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if the donor and recipient shared more than one epidemiologic or clinical feature
It is very obvious in retrospect to note that the donor must have had disseminated TB to most of the organs harvested as evidenced by various manifestations among the recipients
CONCLUSION:
The TB diagnosis contributed to one patient’s death and could be to blame in the other two patients following transplantation.
Unfortunately, No autopsy was done on the deceased recipients, therefore the TB diagnosis is just presumptive for both the heart & kidney recipients.
LEVEL OF EVIDENCE :
This article is a case report ===> level of evidence IV.
HOME MESSAGE:
DD-TB is possible in a small % of recipients. If developed in the recipient, it can lead to significant harm, even causing graft loss. In order to prevent this, careful screening procedures are essential, along with testing for extra pulmonary TB in the form of CT and MRI along with culture.
Communication gaps between procurement centres and transplant team can lead to increase in risk of infection incidence in the recipient, and thus better communication strategies is encouraged.
Detailed history of donor including unrelated disease such as stroke is essential to confirm that no infection will pass on from the donor to the recipient through the transplant graft.
Organ donation should be avoided in meningoencephalitis without a definitive confirmed cause
Establishment of an effective and rapid communication system or links between different centers where organ retrieval and surgery are done
Careful donor selection to avoid transmission of infectious disease
Establishment of a donor data bank for samples and channels to trace results
Summary
Most common cause of TB in post-transplant recipients is reactivation of latent TB, however in 4% of cases its donor derived.
Active TB is an absolute contraindication to donation.
Currently screening programs for deceased donor are inadequate for identifying extra-pulmonary and disseminated TB.
The Case report
Donor: 23 year old 36 week pregnant woman who presented with intense headache initially diagnosed with meningoencephalitis later with diffuse subarachnoid bleed. Two months after her death her tracheal aspirate culture was positive for MTB and her baby was diagnosed with disseminated TB.
Recipients:
Discussion
This case reports calls for the need of careful donor selection to avoid transmission.
There are current guidelines for screening donor and recipient however they are not mandatory thus not always incorporated.
Risk factors assessments should include a detailed history that should screen for any active TB symptoms, recent contact of persons with TB, history of travel to endemic area, past TB history and lack of a permanent abode or being incarcerated.
Further testing and radiological evaluation should be done in those with identified risks.
Donor derived TB is considered proven when both door and recipient isolates are identical through molecular analysis.
Thus the major limitation is positive match between donor and recipient genetic sequencing.
This report identified that communication gaps can occur at multiple levels leading to adverse outcomes.
Another gap identified is lack of communication of vertical transmission of TB.
Level of evidence
This is a case report hence level V.
Take home message
Diagnosis of extra-pulmonary and disseminated TB requires molecular sensitivity testing.
Deceased donors with meningoencephalitis with no proven cause should be avoided.
There is need for a data bank and donor sample analysis to trace infections.
Reinforcement of better communication of transplant centres and organ harvesting centres is required.
Is it level 5 evidence?
Thank you prof.
This was a case report making it level 5 evidence.
Summary of Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety introduction
Communication plus careful screening is crucial to identify TB in the deceased donor as many cases of donor-derived infection will result in death and poor outcome.
This reported case is discussed disseminated TB in the donor with poor outcomes for organ recipients.
The donor is the pregnant woman who died soon after delivery due to TB involving the lung and CNS.
Discussion
Active TB is absolute C/I to donation
This care reports highlight the importance of careful donor selection to reduce the risk of transmission of a potential lethal but treatable disease.
In the cases of recipient CXR normal AFB negative smear which the C/S became positive 2 months after transplant (time of positivity range from weeks to months)
So in this situation, the molecular test has general sensitivity but is done where TB is suspected.
Current recommendation
In case of donor death due to meningoencephalitis with that approval cause, the donation should be avoided.
To improve screening strategies:-
1- Exclude any mobility to support the stroke.
2- Presence of few at presentation/admission in the potential donor.
3- CT/MRI of the head.
4- CSF finding consistent with the infection process.
The limitation of the case
1– recipient confirmation of DD infection is to have a positive donor sample and genetic sequencing.
df the pathogen-making donor and recipient samples.
2-Gap between donation and development of the disease.
Historically, many guidelines and protocols emphasize the importance of a registry and the use of procedures for the safety and prevention of infectious disease transmission.
A more effective reporting system will not prevent the event from occurring but may of course impact the outcome.
All fully net work that integrates transplant center OPO and laboratory is mandatory and could allow the receiving patients of potential hazard followed by a more rapid interpterion.
evidence level 5 case report
for the deceased donor presence of the normal CXR and negative AFB is not enough to role out active or disseminated T.B, first of all, good communication with the transplant center and more information about the DD such as fever upon admission, CSF findings suggested infectious process, stroke without comorbidities and diagnosis of meningoencephalitis without evidence of the cause that means any transplant center should have their on policy to make sure the DD is clear from T.B before transplantation
Thankyou
Introduction:
TB is associated with in significant morbidity and mortality in SOT recipients. It is mostly resulted from reactivation of LTBI, and only 4% are donor-derived infection DDI.
Despite screening protocol in deceased donor, screening may fails to identify TB cases, that lead to DDI especially when there is communication gap.
The reported case:
Donor : pregnant lady with of unrecognized disseminated TB, diagnosed initially as meningoencephalitis and died after CNS bleeding. Initial TB screening was negative, the diagnoses was retrospectively after 2 months when the cultures tuned positive and her baby diagnosed with disseminated TB.
Organs transplanted in 4 recipients with a devastating outcome:
Simultaneous pancreas-kidney recipient : 2 months post transplantation he developed perigraft collections found later to be TB abscess. He was treated with anti-TB, after 2 months of treatment, his course complicated with disseminated TB, treatment related drug toxicity, rejection episode and dual graft loss. He was cured from TB after 18- months therapy. However, he died from complications related to ESRD and dialysis, two years after transplantation.
Liver recipient: diagnosed as LTBI for positive TST, and treated with INH for 6 months. He did not develop any manifestations compatible with active TB to date.
Heart Recipient died 2 months after transplantation from sepsis of unknown origin, no specific TB test was done and her chest CT revealed diffuse pulmonary involvement.
Other Kidney Recipient. Lost the graft after 2 months from MPGN and returned to dialysis, 3 months after transplantation he returned died from sepsis of unknown origin. No TB tests were done.
-Infections represent a major cause of morbidity and mortality for SOT recipients. Active TB is an absolute contraindication for organ donation.
-Several policies and guidelines established to improve the recognition of the disease in potential organ donors and recipients, they are not always incorporated into OPO standard procedures.
-DD-TB is challenging and difficult to recognize; generally, it presents itself early after SOT, most commonly as fever, and carries a high mortality risk.
– Proven DD-TB; if donor and recipient isolates were identical or clonal through molecular analysis.
– Probable DD-TB; in the absence of definitive confirmation of similar isolates, or suspected transmission and TB was identified in multiple recipients of one donor, or if donor and recipient shared more than one epidemiologic or clinical feature.
Information gaps, that donor pending culture at the time of procurement should be followed, there is no specific protocol defining who was responsible for checking the pending test results.
Communication gaps in reporting DDI are frequent and may occur at multiple levels, contributing to adverse outcomes among affected organ recipients.
Level of evidence: level 4 case report
Take home massage:
– DDI should be suspected especially in early post-transplant period and should be reported.
-The need for a data bank and donor sample analysis to trace infections
– Protocols to define who is responsible of tracing these results
– Development national registry and public health reporting to facilitate traceability and communications
– Reinforces the importance of communication between transplantation teams and organ-harvesting centers.
– Development national surveillance systems for cells, tissues, and organs.
You can add to your messages:
decline a DD with unknown cause of death specially meningoencephalitis.
Thank you prof.
Absolutely this is an important point
Introduction
The majority of tuberculosis (TB) cases in solid organ transplant (SOT) recipients are caused by the reactivation of latent tuberculosis infection (LTBI), and only very small percentage are considered donor-derived , despite organ procurement protocols, pretransplantation screening sometimes fails to identify TB in the donors , which should be avoided by good evaluation of donors and good communications with the transplant centers . On the other hand active TB in the donors is contraindication to organ transplantation
.
The reported case :
This is an interesting and catastrophic case report of a deceased donor who was a young pregnant lady who died soon after delivery due to TB involvement of the central nervous system (CNS) and lungs. The diagnosis was retrospectively established by mycobacterial culture of the respiratory sample (positive result obtained two months after donor death) and the diagnosis of congenital TB in her baby.
Her organs were delivered to 4 recipients as following :
Simultaneous Pancreas Kidney Recipient: Developed disseminated TB with side effects of anti TB end with dual loss of graft and returned back to dialysis and insulin therapy died later due to complications of dialysis .
– The Liver Recipient.: Is the only survivor to date because of TB prophylaxis given post transplantation due to his positive skin test
.
– The Heart Recipient : Died of septic shock 3 months after transplant, of unknown organism without specific test for TB
The Other Kidney Recipient: Developed mesangioproliferative glomerulonephritis and graft loss he returned to dialysis 3 months after transplantation he developed septic shock of unknown organism and unfortunately without specific test for TB
.
-This is level IV of evidence ( case report ).
-There should be better communications between the harvesting hospitals, OPOs ,and transplant centers .
-Whenever TB is suspected and patients have negative tests as in this reported case molecular tests are sensitive and specific with the result obtained much more earlier than the cultures .
-TB is a killing disease especially in SOT patients however it is treatable and even preventable by TB prophylaxis after kidney transplant for those who are at risk which should be evaluated by OPOs ( organ procurement organizations )
.
– There should be increased awareness about the risk of TB in transplant centers and in all hospitals which are supposed to be harvesting centers for organ donation .
– Early notification of any suspected death of a transplant recipient is mandatory .
Well done.
Summary:
this is a case report of donor derived TB.
The donor: female aged 23 ys old, pregnant in late pregnancy, admitted with severe headache, meningitis, developed brain death 2ry to subarachnoid haemorrhage. initial TB screening was negative in CSF fluid & sputum.2 months after death, bronchial aspirate came out to be positive for acid fast bacilli.
Cesarian section was done. the child came after 2 months of delivery with fever, diagnosed as TB, received medications, improved.
Simultaneous kidney pancreas transplant recipient:
Developed Disseminated TB, Died 2 years after Transplantation from ESRD complications
Kidney recipient:
died 3 months after transplantation, Sepsis of unknown origin
heart recipient:
died 2 months after transplantation, Sepsis of, unknown origin
liver recipient:
developed latent TB
discussion:
– Active tb is an absolute contraindication for organ donation, but unfortunately it can be missed & misdiagnosed with other diseases.
– If Risk factors (epidemiology, homelessness, exposure to person with active TB, IV drug or alcohol abuse, travel history & symptoms suggesting latent or active TB) are identified, radiological & further testing are warranted.
– Consider that culture result may take time up to 6 weeks.
Home messages:
– To improve screening, if certain potential findings like unexplained CNS death, fever at presentation, findings suggesting infection process in the donor, incomplete culture results) should be considered & investigated.
– If any suspicion of TB, extend culture results to up to 6 weeks to consider it negative.
– The information & culture results should be followed by the transplant organization.
– The outcome of the other donors & the baby should be recorded & analysed, reflecting the early diagnosis & intervention to the others.
Level of evidence:
Case report, level 5
Remember this is a DD molecular testing is needed as cultures are useless.
Summarise this article
Introduction:
Tuberculosis in solid organ transplantation most commonly results from reactivation of latent TB, and rarely in 4% of cases it is donor derived infection.
Active TB is a contraindication to organ donation, until treated.
The detailed history of previous TB infection or exposure to TB, and chest x ray may not identify disseminated infection.
Failure of identification of TB infection, and communication gaps during organ procurement may result in donor derived infections, associated with poor outcomes and death.
Study design and purpose:
A retrospective case control study, in brazil, with review of 36 case reports on DD-TB.
The index case was simultaneous pancreas kidney transplant in a 45-year-old male, ESRD was due to type 1 diabetes, he has no exposure to TB , and had a negative tuberculin skin test, with no symptoms of disease, he had a basiliximab induction, and MMF, tacrolimus, and steroid as maintenance, in the second month post transplant presented with fever, weight loss, and night sweats, ultrasound abdomen revealed perigraft collections, underwent subcutaneous drainage analysis and culture, AFB on Zeihl nelson stain was positive, chest x ray was normal, and received standard treatment for TB, he developed side effects to treatment and disseminated lung thyroid and CNS infection mandates discontinuation of immnuno-suppressive medications leading to loss of the grafts and back to insulin therapy and dialysis, in spite of successful treatment he died in 2 years after, due to dialysis complications.
Donor characteristics:
23 year-old- female, 36 week pregnant women, with minigoencephelitis and subsequent intracranial heamorrhage and death, all cultures and respiratory secretions were negative with no evidence of AFB, but CSF showed pleocytosis and high protein level, for which received empirical antibiotics including anti TB therapy within 72 hours of hospital admission, she underwent urgent delivery by C/S in day 6 of admission, and died on the 9th day of admission.
Other recipients chrachteristics:
Other kidney recipient died 3 months post transplantation due to sepsis of unknown origin, heart recipient died 2 months after transplantation due to sepsis of unknown origin, liver recipient who received treatment of latent TB because of a positive TST for 6 months post transplant continued to be asymptomatic and disease free.
Risk factors assessment by:
Obtaining a donor history of symptoms of active TB.
Past diagnosis of TB infection (active or latent).
Homelessness.
Alcohol abuse or injection drug use, incarceration.
Exposure to persons with active TB, or travel to endemic area.
Radiological (CXR).
Discussion:
Conclusion:
Prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner, facilitate early treatment, reduce the adverse events and death.
What is the level of evidence provided by this article?
Level of evidence is IV – case report/case series study.
What is the take-home message?
– Any brain death donor with unknown CNS infectious etiologies should be denied.
– Assessment of TB status in a donor and recipient should be under taken in moderate and high prevalence countries, and put by standard donor and recipient protocols.
– Disseminated TB, could present with normal chest X-ray and a negative AFB stain.
– Closing communications gaps in transplant centers would improve patients care and survival.
Thankyou well done.
Introduction
Tuberculosis (TB) infection in solid organ transplant (SOT) recipients is most commonly caused by re-activation of latent TB infection (LTBI), and 4% are considered donor-derived. Active TB infection in the donor is a contradiction to organ donation. Screening protocols for deceased donors may also sometimes fail to diagnose TB. This report describes a case of disseminated TB in an organ donor, that led to poor outcomes for the recipients.
The donorThe donor was a 23 year old female. She was admitted due to complaints of an intense headache, at 36 weeks of pregnancy. Within 72 hours of admission, she developed mild fever, neck stiffness and seizures. The CSF had increased proteins and cellularity, and no microorganisms. Empirical treatment for meningoencephalitis was started, ceftriaxone followed by anti-TB treatment and acyclovir. Respiratory secretions were negative for acid-fast bacilli (AFB) stain. On the 6th day of admission, the patient’s level of consciousness decreased and she underwent an emergency C-section, after which brain CT scans revealed a diffuse subarachnoid hemorrhage. The patient was diagnosed with brain death on the 9th day of admission, and was elected to be an organ donor based on the diagnosis of CNS bleeding. 2 months after her death, the tracheal aspirate culture was positive for M. tuberculosis. Her child presented at 2 months of age, with fever of unknown origin and was diagnosed with disseminated TB and was treated successfully.
The index case – simultaneous pancreas and kidney recipient A 45 year old male, with end stage kidney disease and diabetes, received a simultaneous pancreas and kidney transplant. His previous tuberculin skin test (TST) was negative and denied known TB exposure. His immune suppression regimen post transplantation included basiliximab, prednisone, tacrolimus and mycofenolate mofetil. On the 2nd month post transplantation, he presented with complaints of fever, chills and night sweats. His chest X-ray was normal, abdominal ultrasound revealed perigraft collections (renal and pancreatic abscesses). He was started on broad-spectrum antibiotics and drainage of the abscesses, with transient resolution of the fever. Lab analysis revealed AFB on ZN stain, and anti-TB treatment was started (rifampin, isoniazid, pyrazinamide and ethambutol). The transplant harvesting center was notified.
The patient the presented with drug toxicities related to the anti-TB medications: hemolytic anemia and blurred vision. His medications were therefore changed. The patient had disseminated disease involving the grafts, lungs, CNS and thyroid. This led to stopping the immune suppressive medications, leading to loss of the grafts. The patient was deemed successfully treated for TB infection, 18 months after treatment was initiated. Unfortunately, the patient passed on 2 years after transplantation due to complications related to end-stage renal disease and dialysis.
The liver recipientA 55 year old male, with a diagnosis of Caroli disease received the liver, due to recurrent bacterial cholangitis. The patient had a positive TST prior to surgery, hence was treated for LTBI with isoniazid monotherapy for 6 months, soon after the transplant. The patient had not developed active TB as of the date of publication.
The heart recipient The heart recipient was a 40 year old woman, she had a diagnosis of Chagas cardiomyopathy, with class IV heart failure. Three months after the transplantation, she presented with fever and malaise, and within three days of admission she passed on due to severe septic shock, unresponsive to broad-spectrum antibiotics. No bacteria and fungi were detected on culture of blood, urine and tracheal aspirate samples. No mycobacterial culture was requested. Her chest CT revealed diffuse pulmonary involvement.
The other kidney recipient The other kidney was transplanted in a 45 year old male with systemic hypertension and terminal hypertensive nephropathy. On the 2nd month after transplantation, the patient developed mesangioproliferative glomerulonephritis and graft loss, and hence had to return to dialysis. The patient then presented to the hospital three months after transplantation, due to sepsis of unknown origin despite antimicrobial therapy. No specific test for mycobacteria was requested.
Discussion
Infections can cause mortality and morbidity in SOT recipients. The aim of this case report was to highlight the importance of careful donor selection, to reduce the risk of transmission of potentially fatal diseases that are treatable. In this case, the donor had disseminated TB that was unrecognized. She had no history of previous TB or TB exposure, except for pregnancy. She lived in an area whose prevalence was an intermediate risk for TB. Screening for active or latent TB is not practiced in all centers, as the guidelines developed are not mandatory for all scenarios. For the discussed patient, she had no respiratory symptoms, and imaging did not reveal any respiratory involvement, hence no molecular tests were done. The TB culture is time consuming, hence the results were obtained two months after the transplant. However, the CSF analysis showed an elevated protein level with pleocytosis. In retrospect, the intracerebral bleed was likely secondary to cerebral vasculitis due to the TB infection. Current recommendations advise avoiding organ donation if the patient’s death was due to meningoencephalitis without a proven cause.
In this case, the liver transplant recipient was treated for latent TB, and did not develop active infection. The other two recipients passed on due to sepsis of unknown origin and organ dysfunction. These finding are compatible with TB donor transmission, but the transmission was only confirmed for the recipient who underwent spontaneous pancreas and kidney transplantation.
It is known that the TB cultures are time consuming, however, results should be communicated to all centers and recipients involved. In this case, there was no specific protocol defining who was responsible for checking the pending results. This would have prompted the treating clinicians to initiate treatment earlier, and may have prevented graft loss and death.
The case report hoped to call attention to the importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace the recipients and initiate treatment where possible, in a timely manner.
Level Of Evidence:
LOE is level IV
Take Home Message
TB is a challenging diagnosis to make and one has to have a high index of suspicion. In a deceased donor organ program, a clear cause of death needs to be identified before the potential donor donor can become a utilized donor
Good communication between donor hospital and recipient institutions is key to reduce morbidities and mortalities
Thankyou you highlighted that a dd with undiagnosed cause of meningoencephalitis should be declined.
Summary of the article
Introduction
Reactivation of a latent mycobacterium infection is a typical cause of tuberculosis after an organ transplant. There is a link between donor-derived mycobacterium infection and a 4 percent chance of the infection being passed on to the recipient, which can have a negative impact on both the transplant and the patient’s health.
This case report describes a pregnant woman who died of diffuse CNS tuberculosis during delivery and her baby who developed congenital TB. After 2 months, this deceased donor’s culture shows positive mycobacterium tubercles, and the recipient develops a terrible graft result. This study screens deceased donors for trace infections and emphasizes the need for greater communication between the transplantation team and the organ harvesting center.
Screening donors for latent TB using nonspecific chest X-rays, epidemiological hazards, and TB history
Pancreas transplant
The recipient is a 45-year-old male on immunosuppressive medication (basiximab, prednisone, tacrolimus, and mycofenolate mofetil) with a negative tuberculin test. His donor had tuberculosis.
Second month: fever, chills, nocturnal sweats, stomach ache Pus nears graft on abdominal ultrasonography. Cultures from percutaneous drainage showed acid-fast bacilli. Normal chest X-ray and routine antitubercular treatment with rifampin, isoniazid, pyrazinamide, and ethambutol.
Recipients develop drug toxicity from anti-tuberculous therapy due to drug interaction with immunosuppressive therapy and disseminated TB, leading to clinical deterioration. They stop all immunosuppressive therapy, leading to graft failure, and return patients to dialysis and lapratomy done with removal of the renal graft and intravenous anti-tuberculous for long duration. Patients were cured but died after 2 years due to ESRD and dialysis.
Liver transplant
A transplant was performed on a 55-year-old man with Caroli illness due to recurrent bacterial cholangitis. TST was positive prior to surgery, and the transplant recipient was treated for six months with isoniazid for LTBI. The patient has not acquired any symptoms consistent with active tuberculosis.
Heart transplant
A heart transplant was performed on a 40-year-old woman with Chagas cardiomyopathy who had class IV heart failure. She was taken to the hospital three months following the procedure with fever and malaise. Within three days, she passed away due to acute septic shock, without mycobacterial infection being considered. Her chest CT revealed diffuse involvement of the lungs.
Kidney transplant
Due to hypertension-induced nephropathy, the patient got a kidney transplant. Two months later, the patient developed mesangioproliferative glomerulonephritis and graft loss and returned to dialysis. After three months, the patient comes down with sepsis and dies in spite of antimicrobial therapy and the absence of particular testing to rule out mycobacterium infection; TB is strongly suspected.
Discussion
The best treatment option for patients with ESRD is a kidney transplant, but there is a substantial risk of infection from donor-derived infection due to the potency of immunosuppressive drugs, particularly during the first six months. A life-threatening infection, like tuberculosis, can cause graft loss and raise the incidence of mortality. In these reported cases, tuberculosis infection is not confirmed but strongly suspected due to clinical manifestations that strongly suggested TB and the onset of symptoms within two months of transplantation. Furthermore, only two samples confirm the presence of acid-fast bacillus in the donor of the first case, and the patient died despite receiving anti-tuberculosis treatment. In another example, anti-tuberculosis treatment was effective despite the absence of acid-fast bacilli in both the donor and recipient samples; the donor had a history of tuberculosis exposure.
Before proceeding with a transplant, this article emphasizes the significance of donor selection and infection screening in both the donor and recipient. In addition, this research illuminated the significance of the interaction between the transplant team and the donor bank for the proper selection of donors to reduce infection risks.
What is the level of evidence provided by this article?
Level of evidence V
What is the take-home message?
The significance of meticulous donor selection in order to lower the danger of transmission of potentially fatal but curable diseases
Even if TB is not initially diagnosed, DD-TB is frequently tied to the donor’s epidemiology and clinical history.
To increase the detection of TB in donors, specific policies may be created.
The identification of potential risks and a quicker response are made possible by a fully built network that unite all responsible divisions.
Thankyou for the conclusions this disastrous incident shows that screening of donors and recipient is somtimes taken lightly.
A
donor with undiagnosed cause of death as the index case(diagnosed 2 months later) should be declined.
Tuberculosis in organ transplant is common and it’s caused from reactivation of latent mycobacterium infection. Donor derived considered 4% in transfer mycobacterium infection to recipient and leasing to poor outcome for both graft and individual survival.
This article is case report study on pregnant women dying during delivery because of disseminated CNS tuberculosis and her baby developing congenital TB, This deceased donor where culture done after 2 months post death shows positive mycobacterium tubercles and whereas this donor transplant to recipient who develop devastating graft outcome. So this study aim for screening for trace infection in deceased donor and reinforces the importance of better communication between transplantation teams and organ harvesting centre’s.
Screening donor with latent TB based on chest X-ray findings (nonspecific), epidemiological risks, and previous TB history.
First case ( Pancreas Transplant due to diabetes and ESRD).
The recipient 45 years male with negative tuberculin test on immunosuppressive therapy ( basiliximab, prednisone, tacrolimus, and mycofenolate mofetil), his donor derived has previous exposure to tuberculosis.
On second month recipient presents with fever and chills and night sweating and abdominal pain. abdominal ultrasound shows collection of pus near to graft. Per cutaneous drainage done and culture shows positive acid fast bacillus. Chest X ray normal and Antituberculous therapy was started with standard drugs: rifampin, isoniazid, pyrazinamide, and ethambutol.
Recipient develop drug toxicity from anti tuberculous due to drug interaction with immunosuppressive therapy and disseminated TB leading to deterioration of clinical conditions and stop all immunosuppressive therapy lead to graft failure and return patients to dialysis and lapratomy done with removal of renal graft and intravenous anti tuberculous for long duration and patients cured but dia after 2 years because of ESRD and dialysis.
Second case: Liver recipient
He was transplanted because of recurrent cholangitis and patient has history of latent TB and receive isoniazid for 6 months post transplant and no manifestation of deterioration of liver transplant.
Third Case is heart transplant:
Middle age women develop heart failure due to chagas’ disease and transplanted after 3 days patient develop septic shock and septic work up is non significant and negative culture of mycobacterium but her chest CT shows diffuse pulmonary involvement.
Unfortunately patient dying within 2 months.
Forth case is renal recipient:
Patient underwent kidney transplant due to hypertensive nephropathy and after 2 months patient develop mesangioproliferative glomerulonephritis and graft loss and returned to dialysis. After 3 months patient presents with sepsis and dying despite anti microbial therapy and specific investigations to role out mycobacterium infection not done and highly suspicious of TB.
Discussion:
Kidney transplant is the best option in patients with ESRD but risk of infection high possibility from donor derived infection due intensity of immunosuppressive drug especially in first 6 months. Life threatening infection like tuberculosis may lead to graft loss and increase incidence of mortality. In these reported cases, tuberculosis infection is not confirmed but it’s highly suspected because clinical manifestations strongly suggested TB and appearance of symptoms within 2 months from transplantation and only 2 samples confirm acid fast bacillus in donor of first case and patient dying despite using anti tuberculosis treatment. In another case of liver transplant was successful treated with anti tuberculosis treatment despite acid fast bacillus not confirmed in both samples of donor and recipient; while donor had history of exposure to tuberculosis.
This article focus on importance selection of donor and intense screening of infection in both donor and recipient before proceed transplant. Also this article shed light on importance link between transplant team and donor bank for good selection of donor to avoid opportunities infection.
Level 5
It’s important to select proper donor and intense screening for infection is mandatory to avoid graft loss and patients risk.
Culture for TB takes weeks so is not at all helpful in undiagnosed cases as this donor was diagnosed after 2 months!!!
Reject a donor with an unknown cause of death to avoid some fatal surprises.
Introduction
Case report
Outcomes of recipients of the organs:
The Index Case – SPK recipient:
The Liver recipient:
The Heart recipient:
The kidney recipient:
What is the level of evidence provided by this article?
Take-home message
It is important to select proper and disease-free donors to prevent lethal complications post-Transplant. DD-TB is related to the donor’s epidemiological exposure and previous history. Molecular investigation can reveal that the isolates from the donor & the recipient are identical, which can confirm DD-TB in such cases.
You are right donor selection is most important and this depends on a well trained coordinator and not allow lack of communication.
Post transplant TB is devastating disease owing to immune compromised host status. In the majority of cases its resultant from reactivation of latent TB in the recipient, in the minority of cases around 4% its derived from donor DD. Post transplant TB is frequently reported to be disseminated or miliary type with multiple organs involvement. Its management is potentially involving reduction or even interruption of anti-rejection protocol with consequent high risk of rejection and loss of the allograft.
Therefore, screening of donor and scrutinizing his TB status is crucial to prevent drastic infection in kidney recipient.
Screening of donors for TB:
Basically, it depends on chest Xray screening, history of TB and identification of epidemiological risk. Unfortunately, such a protocol would not obviate the transmission of TB because it’s not sensitive and readily missing the non-pulmonary TB cases.
Communication between transplant team and primary medical team:
In potential donor who is suspected of having underlying TB illness, few hazardous practices were highlighted by this article.
1] transplanting a cadaveric allograft from a donor who was expired with febrile illness before securing the primary diagnosis.
2] AFB culture Lowenstein-Jensen LJ media culture which is taking 2 months to denote a result.
3] Failure to communicate positive culture results of a dead patients to transplant team might lead to missing significant information and default to manage transplanted kidney patient with overwhelming potential tuberculosis.
Its basically a case series article with level of evidence 4.
Take home message:
I would advise against transplanting a patient from a donor who potentially died with a febrile illness before scrutinizing and rolling out TB.
Furthermore, I would advocate the utilization of Bactic media for TB culture to get the result within one to two weeks in order to expedite the commencement of anti TB for kidney transplant recipient of potentially TB infected cadaveric allograft.
Moreover, it might be applicable to consider routine anti TB for any recipient of a cadaveric kidney with a suspicion of TB before have the culture results.
Thankyou for your take home messages they are all important but Ithink the most important one is not to accept an unknown cause of death, specially unsolved clinical issues as the fever in the index donor.
This is a case report with evidence of 5.
Despite the low incidence of TBC in transplanted patients still, an important issue to consider taking into account the immunosuppression effect and reactivation of latent infection. Latent infection reactivation is usually the major cause though donor-derived TBc is also a potential. Screening with a simple chest x-ray may miss the diagnosis. Rather it will not identify extrapulmonary TBC. Here is a case report of rarely seen donor-derived TBC infection proved retrospectively post-mortem.
The index case is 45 years old man with combined kidney & pancreas transplantation screened with a tuberculin test and found negative. Post transplantation he had constitutional symptoms, fever, night sweats etc. His fist evaluation did not suggest pulmonary infection, chest x-ray was normal. Perinephric collections found positive for acid-fast microorganisms, renal and pancreatic abscesses were found, and drainage was performed. Two Other recipients out of the 4 died within three months after transplantation (one kidney and the other heart). Near to graft, the abscesses were suspected to be of donor origin, which was approved later.
Not surprisingly, the heart and the other kidney recipient did not have a definitive diagnosis for the origin of sepsis because of the nature of the infection is challenging to diagnose by simple stain and culture unless suspected. Nonpulmonary involvement is the major problem.
The low sensitivity of acid facts staining, which usually needs 3 confirmations of negativity, was found negative (nonsprisingly). The liver recipient was lucky because he has TST positive and received uncosting izonizdide regimen.
Unfortunately, even active tbc can be missed at the beginning. The recipients were lost nearly one month apart. Early communication between centres to clarify unexpected scenarios may be life-saving and is always helpful. Reporting such problems to the coordinator and building communication needs to be considered.
Thankyou a well informed coordinator is very helpful and may be life saving as in the index case.
Summary of the article
Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
This is a case report of unrecognized disseminated TB in the donor with a devastating outcome for organ recipients.
A. The donor:
· The donor was a 23-year-old, 36-week pregnant woman with a history of intense headache, mild fever, neck stiffness, and seizures.
· CSF was considered abnormal with increased cellularity and protein.
· No microorganisms were identified in the CSF and blood.
· Empirical treatment for meningoencephalitis was started 72 hours after hospital admission (ceftriaxone followed by anti-TB standard treatment and acyclovir)…
· Respiratory secretions were negative for acid-fast bacilli (AFB) stain.
· Underwent C/S after decrease at her level of consciousness.
· CT revealed diffuse subarachnoid bleeding.
· The patient was diagnosed with brain death (day 9) and had elected to be an organ donor, considering as primary diagnosis, CNS bleeding.
· Two months after her death, the tracheal aspirate culture became positive for M. tuberculosis.
· Her child was diagnosed as disseminated TB at the age of 2 months and showed response to anti-TB.
B. The recipients:
1. The first kidney recipient:
· A 45-year-old male received a simultaneous pancreas kidney (SPK).
· Previous tuberculin skin test (TST) was negative, and he denied known TB exposure.
· The immuno-suppressive regimen included basiliximab, prednisone, tacrolimus, and mycofenolate mofetil.
· During the second month posttransplant, he returned to the hospital complaining of fever, night sweats, and chills.
· Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses), whereas the CXR was normal.
· Rx: percutaneous drainage of the abscesses, broad-spectrum antibacterial treatment. There was transient resolution of fever.
· Laboratorial analysis revealed acid-fast bacilli (AFB) on Ziehl-Neelsen stain. Antituberculous therapy was started with standard drugs: rifampin, isoniazid, pyrazinamide, and ethambutol.
· Considering that the recipient’s TB abscesses were located near the grafts, suggesting donor involvement.
· The patient subsequently presented with anti-TB drug toxicities and disseminated disease involving grafts, lungs, CNS, and thyroid.
· The clinical deterioration of the patient imposed immunosuppressive cessation, leading to acute cellular rejection of the grafts, and dual graft loss.
· Exploratory laparotomy revealed caseating necrosis all over the mesenterium and around pancreatic graft, but affecting the renal graft. Renal graft was removed.
· After punctures to drain intra-abdominal TB abscesses and 18 months of anti- TB therapy, the patient was considered cured.
· However, he died from complications related to ESRD and dialysis, two years after transplantation.
· At time of contacting the transplant harvesting center for additional information regarding the donor and the other organ recipients, two recipients had already died, and a look-back investigation was carried out.
2. The Liver Recipient:
· 55-year-old man with Caroli disease, was transplanted because of recurrent bacterial cholangitis.
· TST was positive before surgery and soon after the transplant was treated for LTBI with isoniazid for six months.
· The patient has not developed any manifestations compatible with active TB.
3. The Heart Recipient:
· 40-year- old woman with Chagas cardiomyopathy who underwent a heart transplant for class IV heart failure.
· Three months after the procedure, she was admitted to the hospital with fever and malaise. Within three days, she died after severe septic shock without any consideration for mycobacterial infection.
· Her chest CT revealed diffuse pulmonary involvement.
4. The Other Kidney Recipient:
· 45-year-old man with systemic hypertension/ESRD.
· During the second month after transplantation, he developed MPGN and graft loss.
· Three months after transplantation, he returned with sepsis of unknown origin and died despite antimicrobial therapy.
· Similar to the heart recipient, no specific test for mycobacteria was requested.
Discussion:
· Active TB is a well-known contraindication to organ donation.
· sputum culture has higher sensitivity than AFB, the time to positivity ranges from weeks to months.
· Molecular tests present greater sensitivity and specificity but are done when pulmonary TB is suspected.
· Donation should be avoided after death due to meningoencephalitis (ME) without a proven cause.
The level of evidence provided by this article:
This is a case report with level of evidence grade 5.
Take-home message:
· Careful and detailed screening for transmissible infection is crucial.
· Prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner.
Thank you Dr Assafi Ibrahim Annour Mohammed.
Your case summary can be summarised further as your summary is a little prolonged. Probably the take home message would be denying any brain death from cases with meningeoencephalitis without having microbiological confirmation.
I. Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
====================================================================
Summarise this article
Introduction
====================================================================
1.1. The Index Case – Simultaneous Pancreas Kidney Recipient
1.2. The Donor
1.3. The Liver Recipient.
1.4. The Heart Recipient.
.5. The Other Kidney Recipient.
TB diagnosis contributed to fatal outcome in one patient, may cause infection complication in others.
====================================================================
Discussion
===================================================================
What is the level of evidence provided by this article?
What is the take-home message?
The level evidence is 4
====================================================================
What is the take-home message?
SUMMARY
Introduction
Kidney transplant still remains the best form of renal replacement therapy for patients living with end-stage kidney disease, however, it is also accompanied by unintended cardiovascular or infectious disease complications.
Tuberculosis is one such infectious disease that is reactivated or transmitted from the donor to the recipient even despite some degree of donor screening and about 4% of cases are considered to be contracted from the donor during SOT.
Furthermore, the current screening method for tuberculosis during work in SOT may miss out the diagnosis of TB, particularly if is extrapulmonary, while communication could also be the bane of a successful surgery
The article is the summaries of four recipients (SPK, Kidney, Heart, and liver) who received diseased organs from a pregnant woman.
Case 1 (index case)
The Donor
Other organ recipients
The heart recipient presented to the hospital three months after with features of septic shock and died within three days despite antibiotics being given.
The liver transplant received treatment for LTBI till after the surgery and he is still doing fine without any features of DD -TB
The other recipient of the kidney also return to the hospital three- month after with sepsis of unknown origin and died despite antibiotic administration.
Discussion
DD-TB is considered proven if donor and recipient isolates were reported to be identical or clonal through molecular analysis. In the absence of definitive confirmation of similar isolates, DD-TB is classified as probable if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if the donor and recipient shared more than one epidemiologic or clinical feature
It is very obvious in retrospect to note that the donor must have had disseminated TB to most of the organs harvested as evidenced by various manifestations among the recipients
The level of evidence is 4 – case report
Take home message
I like your summary, level of evidence, analysis and take home messages.
Summaries this article
Introduction
Source of TB infection in post transplant recipient includes
· Reactivation of LTBI (commonest source)
· donor-derived tuberculosis (DD-TB): Only 4%
· Current infection after exposure
There is no diagnostic reference standard for TB screening and usually based on radiological finding, epidemiological risks, previous TB history and clinical suspicious based on non-specific symptoms.
This is a case of unrecognized disseminated TB in the donor and TB identified 2months after organs retrieval but missed due to communication gaps.4 patient received organs 3 of them died post-transplant and only one acid fast bacilli and TB was diagnosed.only the patient who received the liver who survived as he was already on INH for LTBI.
What is the level of evidence provided by this article?
Level IV (case report)
What is the take-home message?
· Some organism needs culture for extended duration for screening
· Current TB screening is not sufficient and more sensitive rapid tests are needed.
· Donors should be labelled regarding risk of DDI into 3 main categories and high-risk donors should be mentioned and documented in recipient counseling.
· Alarming laboratory endorsement protocol should be discussed to fulfills the gap between organ procurement organizations and transplant centers.
Summary
Introduction
This article focusses on the development of TB in the recipient from the donor organ. This is of particular importance, since generally recipient TB occurs from reactivation of latent TB. Donor derived TB is rare, at a small level of 4%.
Screening protocols for donor TB are done rigorously because active TB is a contraindication to donation. However, extra pulmonary and disseminated TB are often missed or are harder to identify. This can lead to donor derived TB in the recipient.
This article is based on one such case, where disseminated TB in the donor is not identified prior to the transplant, leading to poor outcome for the recipient. Other cases have also been mentioned, to achieve a more wholesome look at the subject.
Discussion
Donor derived TB is of high importance because infections of different kinds are a major cause of morbidity and mortality in transplant recipients. This article highlights the necessity for careful donor selection to reduce risk of transmission of infection from donor to recipient, particularly infections that are treatable.
Molecular tests are more accurate in determining TB, with good sensitivity and specificity. However, this is done only when pulmonary TB is suspected, such as the donor presenting with respiratory symptoms, or compatible X ray images, positive AFB.
In order to improve screening methodology, it is recommended to look for findings consistent with infectious process especially in immunocompromised host donor such as fever or illness presentation at the time of admission, CSF findings of infection, stroke.
Donor derived TB is concluded if donor and recipient isolates were identical in molecular analysis. It is suspected if multiple recipients of the same donor are identified to have TB, or if the donor and recipient share more than one epidemiological or clinical feature. Obtaining good samples is difficult in these cases. In the absence of isolates, the link can only be made through onset of TB early in the post transplant period. The crucial aspect is to identify that TB in the recipient developed from the graft, so as to clearly indicate donor transmission.
With donor transmission of TB, graft loss can occur in 20% of recipients. Thus, surveillance of DDI is a strong indicator of transplant safety.
A network that integrates transplant centers and laboratories is highly crucial to recognize fatal hazards so that quick and effective intervention can be done to achieve the highest possible level of good outcome for the graft and the patient both in the short term and long term.
Conclusion
Prompt notification of suspicious cases of infection from donor, in particular TB, is essential to trace all the recipients at risk. TB is treatable and thus should be carefully assessed before approving donor for any recipient.
Continuous improvement of screening protocols and their accuracy in a widespread manner along with development of standardized tests in this regard is need to further protect recipients from unwanted donor related risks.
Level of evidence
This article is a case report and hence warrants level of evidence 4.
Take home message
DD-TB is possible in a small percentage of recipients. If developed in the recipient, it can lead to significant harm, even causing graft loss. In order to prevent this, careful screening procedures are essential, along with testing for extra pulmonary TB in the form of CT and MRI along with culture. Communication gaps between procurement centres and transplant team can lead to increase in risk of infection incidence in the recipient, and thus better communication strategies is encouraged.
Detailed history of donor including unrelated disease such as stroke is essential to confirm that no infection will pass on from the donor to the recipient through the transplant graft.
I like your summary, level of evidence, analysis and take home messages.
Thank you professor.
1. Summarise this article
Introduction
Case report
Outcomes of recipients of the organs:
The Index Case – SPK recipient:
The Liver recipient:
The Heart recipient:
The other kidney recipient:
Conclusion:
=======================
2. What is the level of evidence provided by this article?
=======================
3. What is the take-home message?
I like your summary, level of evidence, analysis and take home messages.
Introduction:
only 4% are considered donor-derived
Recipient:
The organ recipeints had following outcomes :
1. Other kidney recipient: died within 3 months due to sepsis
2. Heart recipient : died within 2 months due to sepsis
3. Liver recipient : had latent TB, asymptomatic
Discussion:
Level of evidence: Level 4
Lesson learnt:
The importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner
I like your summary, level of evidence, analysis and ‘lessons learnt’.
Typing whole sentence in bold amounts to shouting.
Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety.
Introduction
Wanessa T.C and colleagues, described a case of unrecognized disseminated TB in the donor with a devastating outcome for organ recipients. The donor was a pregnant woman who died soon after delivery due to TB involvement of the central nervous system (CNS) and lungs. The diagnosis was retrospectively established by mycobacterial culture of the respiratory sample (positive result obtained two months after donor death) and the diagnosis of congenital TB in her baby.
The Index Case – Simultaneous Pancreas Kidney Recipient. A 45-year-old male received a simultaneous pancreas kidney (SPK) transplant due to diabetes and end-stage renal disease (ESRD). During the second month posttransplant, he returned to the hospital complaining of fever, night sweats, and chills. Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses), whereas the chest radiograph was normal. He received broad-spectrum antibacterial treatment and underwent percutaneous drainage of the abscesses, with transient resolution of fever. Laboratory analysis revealed acid-fast bacilli (AFB) on Ziehl-Neelsen stain. Antituberculous therapy was started with standard drugs: rifampin, isoniazid, pyrazinamide, and ethambutol.
The patient subsequently presented with anti-TB drug toxicities: haemolytic anaemia (related to rifampicin) and blurred vision (due to ethambutol), both in the 2nd month of treatment resulting in a change of therapy. At this time, the patient presented disseminated disease involving grafts, lungs, CNS, and thyroid.The clinical deterioration of the patient imposed immunosuppressive cessation, leading to acute cellular rejection of the grafts, and dual graft loss with return to hemodialysis and insulin therapy
The Donor. The donor was a 23-year-old, 36-week pregnant woman with a history of intense headache who was admitted to the hospital emergency room, and within 72 hours of admission, she developed mild fever, neck stiffness, and seizures. The cerebrospinal fluid (CSF) was considered abnormal with increased cellularity and protein. Although no microorganisms were identified in the CSF and blood, empirical treatment for meningoencephalitis was started 72 hours after hospital admission (ceftriaxone followed by anti-TB standard treatment and acyclovir), and other culture samples were collected. Respiratory secretions were negative for acid-fast bacilli (AFB) stain. Brain computed tomography (CT) scans performed after the procedure revealed diffuse subarachnoid bleeding. The patient was diagnosed with brain death (day 9) and had elected to be an organ donor, considering as primary diagnosis, CNS bleeding. Nearly two months after her death, the tracheal aspirate culture became positive for M. tuberculosis.
Discussion
This case report calls attention to the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases. Typically, DD-TB is commonly related to the donor’s epidemiology and clinical history, even if TB is not initially recognized. In this case, the donor had an unrecognized disseminated TB, with no history of previous TB or exposure and, except for pregnancy, no known immunosuppressive conditions.
Conclusion
This paper underscores the importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner. Additionally, this report also highlights the need for a data bank and donor sample analysis to trace infections and reinforces the importance of better communication between transplantation teams and organ-harvesting centers.
Level of evidence is level 4
Please use bold or underline to highlight headings and sub-headings. That will make it easier to read.
ok sir
Case Report Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety
1. Summary of the case
This report describes a case of DD-TB and emphasizes communication gaps that may occur between organ procurement organizations and transplant centers.
Case report
The Recipient
The Donor
The Liver Recipient
The heart and the other Kidney recipients
Discussion
Conclusions
I like your summary, level of evidence, analysis and key messages. What kind of network system would you suggest?
Is it central registry that you are suggesting or public health department?
Thank you professor, I would rather suggest a central registery.
Summarise this article
Introduction
o Most TB cases in SOT recipients are caused by the reactivation of LTBI
o Only 4% are donor-derived tuberculosis (DD-TB)
o Current TB screening protocols for deceased donors are usually based on chest X-ray findings (which may be nonspecific), epidemiological risks, and previous TB history (may not identify extrapulmonary and disseminated TB)
o Despite organ procurement protocols, pre-transplantation screening may miss TB in the donor (due to communication gaps leading to donor-derived infections (DDI))
o This report describes a case of unrecognized disseminated TB in the donor with a devastating outcome for organ recipients (The donor was a pregnant woman who died soon after delivery due to TB involvement of the CNSand lungs)
The Index Case (Simultaneous Pancreas Kidney Recipient)
A 45-year-old male received a SPK transplant due to diabetes and ESRD. His previous TST was negative, and no TB exposure. Two months posttransplant, he returned to the hospital complaining of fever, night sweat, and chills. Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses), and chest radiograph was normal. He received broad-spectrum antibacterial treatment and underwent percutaneous drainage of the abscessesw. Laboratorial analysis revealed AFBon Ziehl-Neelsen stain. Anti-tuberculous therapy was started which latter leading to toxicities. At this time patient presented disseminated disease (grafts, lungs, CNS, and thyroid). The patient deteriorates and immunosuppressive stopped, leading to dual graft loss with return to hemodialysis and insulin therapy. The patient was considered cured. The patient died 2 years latter from complications related to ESRD and dialysis
The Donor
o A pregnant woman who died after delivery due to TB involvement of the CNS and lungs
o The CSF was abnormal with increased cellularity and protein but no microorganisms in the CSF and blood. Empirical treatment for meningoencephalitis was started
o Respiratory secretions were negative for AFB stain
o Latter patient deteriorates and CT scans revealed diffuse subarachnoid bleeding (primary diagnosis)
o Two months after death, the tracheal aspirate culture became positive for M. tuberculosis
The Liver Recipient
o TST was positive for LTBI and treated with isoniazid after the transplant (six months)
o Asymptomatic and not developed any manifestations compatible with active TB
The Heart Recipient
Died 2 months after transplantation due to sepsis of unknown origin (although chest CT revealed diffuse pulmonary involvement)
The Other Kidney Recipient
Died 3 months after transplantation of sepsis of unknown origin
Discussion
o Careful donor selection is important to reduce the risk of transmission of potentially lethal but treatable diseases
o DD-TB is commonly related to the donor’s epidemiology and clinical history
Risk factor assessment:
1. Donor history of symptoms consistent with active TB
2. Past diagnosis of TB infection (active or latent)
3. Homelessness
4. Alcohol abuse or injection drug use
5. Incarceration
6. Recent exposure to persons with active TB
7. Travel to areas where TB is endemic
o Molecular tests have greater sensitivity and specificity but are done when pulmonary TB is suspected
o The intracerebral bleeding was likely secondary to cerebral vasculitis due to TB infection
o Notify any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manners
What is the level of evidence provided by this article?
Level IV (case report)
What is the take-home message?
o Current TB screening protocols for deceased donors based on chest X-ray findings, epidemiological risks, and previous TB history may not be enough as it may not identify extrapulmonary and disseminated TB
o Identification of high-risk donors will minimize the risk of DD transmission
o Communication gap between organ procurement organizations and transplant centers may result in DDI with associated death and poor outcomes (prevented by a more efficient screening protocols and communication)
o Donation should be avoided in donor death due to meningoencephalitis without aproven cause
o Autopsy is required in ill-defined cause of death
I like your summary, level of evidence, analysis and take home messages.
Autopsy!
I think you mean to suggest that retrieval of organ in donor operation needs to be supported by pathologist so that we do not miss a donor just because of suspicion of an infection or cancer that has been suspected but not proved.
Donor-derived tuberculosis (DD-TB) accounts for less than 5% of TB cases
Case report of unfurtnate outcome for many people who got organs from TB donnor, SPK, Kidney, Heart and Liver. The Liver Tx survived because of LTIT. all complications happened early post transplant. Sadely the SPK developed rejections due to stop the immunosupression medications.
Level of evidence: Case report level 4
Take Home massages:
Communication is key early post transplant.
It is critical to report that serious complications as ealy as possible and track other recipent as that could have saved lives if reported early.
Meticulious donnor selection is crucial
TB should be considred in differntial diangoses in the first few months post transplant when recipient present with fever and unusual presentations.
There are many spelling errors.
The following words need to be typed properly: ‘sadely’, ‘donnor’, ‘considred’.
Introduction
Donor source for mycobacterium tuberculosis (TB) is one of the sporadic events reported in less than 5% following kidney transplantation. The common source of MBT is the reactivation of latent TB, and it’s more frequent in immunocompromised patients like SOT recipients compared to general populations, active MBI is an absolute contraindication for kidney donation and the screening of DD is considered one of the challenges in kidney transplantation as the screening limited including CXR(nonspecific), the history of previous exposure or previously treated PTB or donor source from an endemic area and latent TB in donor can be the risk of extrapulmonary TB and disseminated TB which can be easily missed due to the limitations in the current protocols for screening the Donors in addition to the communications gaps and this report show us the best example of missing a case of unrecognized disseminated TB in the donor with a distressing outcome for organ recipients.
Case based discussion
This is a case report of pulmonary TB with CNS involvement died immediately after delivery and her child was also treated on the line vertical transmission TB with first line Anti TB 2 months later in the same hospital; her initial presentation includes headache and fever and treated on the line of meningoencephalitis (bacterial viral and anti-TB) she was from an intermediate endemic area for TB, however
The donor had no respiratory symptoms or well-matched image, and the AFB was negative, molecular tests present greater sensitivity and specificity but are done when pulmonary TB is suspected [30, 31]. and therefore, TB has not been assumed in her. and her course was complicated by SAH and the death certificate with ICB?? and the TB culture was positive from the tracheal aspirate sample resulted in two months after donation (delay in diagnosis, in addition, there was no autopsy biopsy from DD The cerebral bleeding was likely secondary to cerebral vasculitis (young lady with no comorbid and history of fever at presentation and headache, in addition, her CSF analysis suggestive of the infectious process in a retrospective study. According to present recommendations, in cases of donor death due to meningoencephalitis (ME) without a recognized cause, the donation should be avoided. Many reports about donor-derived TB addressed the challenges in delayed diagnosis, communications gaps including no clear protocols or proper tracking system to follow up or comminate the late results as TB cultures might need weeks which will impact the delay in treatment initiation as the MTB screening and diagnosis still consider one of the limitations and challenges of SOT
Figure one summarizes the outcome of the 4 recipients with organ transplantation from the same donor, 3 (HEART and second kidney recipients with unknown sepsis ended with death, 3rd recipient died with disseminated TB infection and dual graft loss, and one liver transplant was treated online LTBI
What is the level of evidence provided by this article?
Case report level 4 of evidence
What is the take-home message?
Written protocols for OPT regarding handling the DD infection source and creating proper channels of commination and tracking the information between the OPT and the transplant team
Identification of the donor epidemiological risk of certain infectious diseases including family history and social background
including family and social history, previous exposure, and screening, effective communication, and documentation by creating a data bank and donor
sample analysis to drop infections
Encourage, and reinforce the importance of writing such cases with high-risk complicated courses and outcomes as it will give a clear home message to prevent such complications in the future.
I like your summary, level of evidence, analysis and take home messages.
1.Introduction
The main cause of tuberculosis in solid organ transplant recipients are the reactivation of latent tuberculosis infection . and only 4% are considered donor-derived.
Active TB in the donor is contraindication in organ donation.
The weak screening for deceased donors is not specific which depend on CXR, epidemiological risks, and previous TB,which is not enough to identify TB in donor.
2. Discussion
This case report for the importance of careful donor selection to reduce the risk of transmission of tuberculosis.
In this case report ,the donor had an unrecognized disseminated TB, with no history of previous TB or exposure.
Specific policies may be established to improve the recognition of the disease in donors.
Inspite of that no definitive recommendations for centers to how investigate donor.
In this case report the donors investigated for CXR(no abnormalities ), AFB (negative),culture (positive after 2month).
Sputum culture is more sensitive than AFB,but culture take long time (weeks to months).
When pulmonaryTB suspected molecular tests is more sensitive and specific.
CSF analysis showed an elevated protein level with pleocytosis, leading to brain death in this case.
DD TB is difficult to recognize in both donor and recipient.
3.Level of evidence :IV.
4. What is the take-home message
Tuberculosis is fatal but can be treated.
Appropriate history and examinations .
Research for diagnostic tools to detect TB in donor .
TB from donor is rare but can occure.
I like your summary, level of evidence, analysis and take home messages.
1-Summarise this article;
-This report describes a case of unrecognized disseminated TB in the donor with a devastating outcome for organ recipients.
-The Donor. The donor was a 23-year-old, 36-week pregnant woman who died soon after delivery due to TB involvement of the central nervous system (CNS) and lungs.
-The patient was diagnosed with brain death (day 9) and had elected to be an organ donor, considering as primary diagnosis, CNS bleeding.
-The diagnosis was retrospectively established by mycobacterial culture of the respiratory sample (positive result obtained two months after donor death) and the diagnosis of congenital TB in her baby.
-This donner donate 4 recepients;
*The Index Case – Simultaneous Pancreas Kidney Recipient;
Outcome—Disseminated TB Died 2 years after transplantation from ESRD complications.
*2nd recipient; the other Kidney;
Outcome—Died 3 month after transplantation with Sepsis of unknown origin.
*3rd recipient; Heart;
Outcome—Died 2 month after transplantation with Sepsis of unknown origin.
*4th recipient;Liver with (positive TST);
Outcome—Asymptomatic on Latent TB treatment.
-Unfortunately, no autopsy was performed on the deceased organ recipients, and therefore, for both the heart and kidney recipients, the TB diagnosis is only presumptive.
Discussion;
–DD-TB is classified as probable; if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if donor and recipient shared more than one epidemiologic or clinical feature(e.g.,TB diagnosis in a donor plus TB in the recipient early post-transplantation)or
-Possible, if there is a suspected transmission event but the only criterion met is a donor risk factor for TB (e.g., donor residence in TB endemic area and absence of recipient risk factors for TB).
-The major limitation to confirm DDI is to have a positive donor sample and genetic sequencing of the pathogen matching donor and recipient samples.
-Usually, there is often a time gap between the donation and the development of the disease.
-In this reported case, TB was confirmed in a donor sample two months after donation, and the result was still not properly informed because there was no tracking system to request the pending microbiological results.
-As such, donor transmission is usually considered probable or possible, depending on the data available, but is much less often confirmed.
Conclusion;
–High-risk complications of the recipient with eventual connection with the donor, such as death or sepsis within 3 months of the procedure, should be actively notified.
-In the reported case, if a flag for a possible DDI was detected after the first recipient’s death, the others could certainly have had a better chance.
2-What is the level of evidence provided by this article?
This case report with (LOE IV)
3-What is the take-home message?
–Donor-derived TB is uncommon, but it may happen.
-The importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner.
-Risk of communication gaps that may occur between organ procurement organizations and transplant centers.
-Inefficient communication between organ procurement organizations and transplant centers may be prevented by a more efficient approach towards screening protocols and communication.
-The need for a data bank and donor sample analysis to trace infections and reinforces the importance of better communication between transplantation teams and organ-harvesting centers.
I like your summary, level of evidence, analysis and take home messages.
Donor-Derived Tuberculosis
Summary
· Incidence of TB in SOT is 20 to 74 times higher than that in the general population.
· Mostly it results from reactivation of latent TB infection (LTBI), and only 4% are considered donor-derived (DD).
· TB is a fatal disease with high risk of mortality in SOT.
· DD-TB mainly presents within 2-3 months post-transplant, fever is a common manifestation, allograft involvement is common and lost in 25 % of cases. All cause mortality accounts for 25 %.
· Mis-communication can result in misconduction and reporting of data and lab results between organ harvesting center and organ transplantation service that can have detrimental effect on the graft and patient outcome.
· Active donor TB is absolute contraindication to donation. However, in deceased donor the exclusion is based on prior history of TB, epidemiological data about high risk locality and CXR which are not 100 % confident to exclude TB especially in case of extrapulmonary and disseminated disease.
· Current case report of (deceased pregnant lady who died with disseminated TB and infected her baby), the diagnosis was done retrospective from tracheal aspirate culture analysis after death revealing acid fast bacilli (AFB).
· She died with picture similar to meningitis and was treated with triple therapy (antibiotic, antiviral and anti TB), as the CT brain revealed subarachnoid hemorrhage (this was declared as cause of brain death) as CSF revealed no organism and respiratory secretions were negative for AFB.
· So, per guidelines deceased donor due to picture suggestive of meningoencephalitis (without bacteriologically confirmed or proven infection), the donation should be avoided as the diagnostic modalities lack specificity and sensitivity regarding AFB in CSF.
v One recipient has pancreas-kidney transplantation: presented in 2nd month post transplant.
1. He had complaint of night fever and sweating, multiple renal and pancreatic abscesses that revealed acid fast bacilli on Ziehl-Neelsen stain on aspiration and analysis.
2. Anti TB therapy was initiated with 4 drugs for the recipient: rifampin, isoniazid, pyrazinamide, and ethambutol. After 2months, he developed hemolytic anemia (rifampin side effect) and blurred vision (ethambutol) and then disseminated TB in CNS, LUNG and graft.
3. Surgical drainage of abscesses, graft nephrectomy and prolonged anti TB therapy for 18 months were done to cure TB, but he died from dialysis complications.
v The liver recipient:
1. He had +ve TST prior to transplantation and was labeled as latent TB and was on standard INH therapy for 6 months and did not develop active TB disease.
v The heart recipient: presented in 3rd month post-transplant.
1. Died from severe pulmonary involvement (apparent in CT) plus night fever and picture of septic shock.
2. The specific investigations for AFB were not requested.
v The other kidney recipient: presented in 2nd month post transplant and died in 3rd month.
1. Died with septic shock after return to dialysis due to graft failure.
· Confirmed donor derived TB needs molecular analysis and presence of similar isolates in both the donor and recipient.
· Probable if TB was identified in multiple recipients of one donor, or if donor and recipient shared more than one epidemiologic or clinical feature (e.g., TB diagnosis in a donor plus TB in the recipient early posttransplantation).
· Possible, if there is a suspected transmission with only criterion met (donor has risk factor for TB as residence in endemic area and absence of recipient risk factors for TB).
Level of evidence: case report (level V)
Take home messages:
· Through screening of TB in donor especially deceased is essential to save lives and prevent donor derived TB with its destructive consequences.
· Extra pulmonary and disseminated TB are serious and may be confusing or difficult in diagnosis.
· Epidemiological data and risk stratification may help in diagnosis together with bacteriological identification.
· History of contact or exposure to TB cases, history of alcohol and drug abuse, low socioeconomic state and overcrowding should raise suspicion of TB.
· Sputum culture is more sensitive than smear examination with zeil nelsen stain, but time consuming (takes weeks and this is not applicable in screening of deceased donors).
· So, molecular tests have greater sensitivity and specificity but are done when pulmonary TB is suspected.
· There must be a tracking system to request the pending microbiological results.
· Need to obtain complete medical records, adequate training for through examination of the donor, and sufficient tight network to document and follow these data are essential to avoid any mistake in donor screening.
· Early detection or diagnosis of TB from donor specimens may save lives is therapy was initiated early.
· Early notification of any recipient death and in addition the neonatal outcome in such pregnant deceased donor would save lives of recipient through early diagnosis and management.
Why level V for a case report?
Sorry dear professor, it is level IV
Summarise this article
Donor derived tuberculosis is high cause of mortality and accounts for < 5% cases. In transplant recipients , the incidence is 20-74 times higher than general population. The main strategy to prevent this transmission is to identify high risk individuals.
Active tuberculosis is a contraindication to transplantation but some times cases can be missed due to multiple factors , especially in the setting of cadaveric donation.
In this case report a female donor who had meningoencephalitis was donor. Multiple organs were retrieved but later she was found to have disseminated Tuberculosis. Diagnosis was made with positive culture 2 months after death and congenital TB in newborn.
First Recipient
Diabetic transplant recipient who had combined kidney and pancreatic transplant. Induction with Basiliximab with maintenance with TAC, MMF and steroids. at 2 months post transplant developed fever, night sweats, and chills. Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses), whereas the chest radiograph was normal . Collection around graft was drained and was positive for acid-fast bacilli (AFB) on Ziehl-Neelsen stain. Antituberculous therapy was started with standard drugs: rifampin, isoniazid, pyrazinamide, and ethambutol.
Patient developed disseminated TB and required multiple aspiration of collections.
Second Recipient
Liver transplant recipient . Treated with INH due to positive TST before transplant
Third Recipient
40 Year old heart recipient developed septic shock. Cultures were negative and CT chest showed diffuse changes.
Fourth Recipient
Developed MPGN and Graft loss . Cause of death was septic shock
What is the take-home message?
Active TB is contraindication for transplantation
Excellent communication is needed between organ harvesting centre and transplant team.
In donor evaluation detailed history and examination should be done. Investigations should be done to rule out latent TB. Treatment soon after transplantation may prevent progression of TB. Sole dependence on chest ray should not done as there can be extrapulmonary TB.
TB PCR is faster and AFB cultures are more accurate but take long time.
Tuberculosis should be excluded if there is history of meningo encephalitis.
High-risk complications of the recipient with eventual connection with the donor, such as death or sepsis within 3 months of the procedure
A more efficient reporting system will not prevent the event from occurring but may of course impact the outcome
What is the level of evidence provided by this article?
Case report Level V
Why level V for a case report?
Sorry cae report iis level 4
Summary:
Introduction
Just 4% of solid organ transplant (SOT) patients develop donor-derived tuberculosis (TB) due to LTBI reactivation. Active TB in donors precludes organ donation. Nevertheless, dead donor screening techniques are based on chest X-ray results (which may be vague), epidemiological hazards, and past TB history. These characteristics may miss extrapulmonary and disseminated TB. Hence, TB detection is difficult, especially when atypical symptoms are differentially diagnosed and the prospective donor has low epidemiological risk.
The Cases:
A 45-year-old man with diabetes and end-stage renal failure underwent an SPK transplant (ESRD)
He was released on day 30 post-transplantation without severe issues.
Despite a normal chest radiograph, abdominal ultrasonography showed peri-graft collections.
The fever subsided after percutaneous abscess drainage and broad-spectrum antibiotic therapy.
The patient was cured after ultrasound-guided punctures to empty intra-abdominal TB abscesses and 18 months of anti-TB treatment.
Two years after transplantation, ESRD-related dialysis problems killed him.
The donor, a 23-year-old, 36-week pregnant lady with a history of severe headaches, was taken to the emergency department and suffered minor fever, neck stiffness, and convulsions within 72 hours.
The CSF and blood were microorganism-free, empirical meningoencephalitis therapy began 72 hours after hospital admission, and more culture samples were taken.
Acid-fast bacilli were absent from respiratory secretions.
On the sixth day of hospitalization, she had an emergency cesarean.
Brain death and CNS hemorrhage led the patient to donate organs.
Her child had a fever two months after birth and was diagnosed with disseminated TB at the same hospital.
After seven days of normal TB therapy, the boy returned home since his M. tuberculosis strain was not resistant to first-line anti-TB medications.
Discussion :
This case report emphasizes donor selection to limit the danger of transmitting potentially deadly but curable illnesses. Even if TB is not first diagnosed, donor epidemiology and clinical history are often linked to DD-TB
The donor had undiagnosed disseminated TB, no history of TB or exposure, and no immunosuppressive conditions saved during pregnancy.
Pregnancy hormones and lymphocyte dysfunction modulate immunity. The donor lives in an intermediate-risk region with 30 TB cases per 100,000 people.
The donor had a normal chest X-ray and AFB-negative smears, but the culture went positive two months following procurement. Sputum culture is more sensitive than AFB, although positive results take weeks to months. When pulmonary TB is suspected, molecular testing is more sensitive and specific. TB was not suspected since the donor had no respiratory symptoms, a suitable picture, or AFB. CSF protein levels were raised with pleocytosis. After nine days, the patient died from brain damage. TB-induced cerebral vasculitis causes intracerebral hemorrhage.
Level IV, Case report
-To prevent disease transmission in dead donor transplantation, transplant teams and organ-harvesting institutions must communicate well.
-Organ donor screening for infections is currently based on donor history, physical assessment, and laboratory testing, but circumstances like the donor’s and her child’s neglect, incomplete medical records, a lack of training, and an insufficiently tight network for monitoring these results may have contributed to this catastrophic outcome.
-Notify the donor of high-risk recipient issues, including death or infection, within three months. After the first recipient’s death, a flag for DDI may have helped the others.
Vertical TB transmission-mandatory communication may be another gap.
-Extrapulmonary TB may develop, therefore a negative chest XR does not rule out TB. TB culture might take months to be positive, thus if TB is suspected, PCR can provide a quicker and more reliable diagnosis.
I like your summary, level of evidence, analysis and take home messages.
Summarise this article
The prevalence of active TB is significantly higher than general population, around 20-74 times higher than general population
The main mode of transmission is through activation of latent TB, or acquiring new infection through air born transmission
Acquiring the disease from the graft (donor derived) is rare and accounts for < 5% of cases
Active TB of the donor is considered a contraindication to donation, but sometimes diagnosis is missed especially in deceased donor transplantation due to defective communication between transplant team and organ-harvesting centers and due to nonspecific findings found in CXR
The current case report describe a pregnant deceased donor who died due to meningoencephalitis, that donate her organs to multiple recipients, which was discovered later to be missed disseminated TB involving the lung and brain, the condition diagnosed post mortem by positive culture of the respiratory sample 2 months after death and the detection of congenital TB in the newborn.
The first recipient
The second recipient
Third recipient
Fourth recipient
Conclusion and take-home message
What is the level of evidence provided by this article?
Why level V for a case report?
Summarise this article
Introduction
· Just 4% of occurrences of tuberculosis (TB) in solid organ transplant (SOT) recipients are thought to be donor-derived; instead, the disease is brought on by the reactivation of latent tuberculosis infection (LTBI).
· The criteria used in the current screening procedures for dead donors are based on the results of chest X-rays, epidemiological dangers, and prior TB history, however, they may not catch extrapulmonary and disseminated TB.
· Pretransplantation screening frequently fails to detect TB despite organ procurement guidelines, leading to donor-derived infections (DDI), which can result in mortality or poor results.
Cases:
· A 45-year-old male received a simultaneous pancreas-kidney transplant due to diabetes and end-stage renal disease (ESRD). During the second month posttransplant, he returned to the hospital with a fever, night sweats, and chills. Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses). Antituberculous therapy was started, but the patient developed hemolytic anemia and blurred vision. Surgery was the only viable treatment. However, he died from complications related to ESRD and dialysis, two years after transplantation.
· The donor was a 23-year-old pregnant woman with a history of intense headaches who was admitted to the hospital emergency room with mild fever, neck stiffness, and seizures. CT scans revealed diffuse subarachnoid bleeding, and her tracheal aspirate culture was positive for M. tuberculosis. She was diagnosed with brain death and elected to be an organ donor. Two months after her death, her child was diagnosed with disseminated TB and was discharged home after seven days of standard TB treatment.
· The liver recipient was treated for LTBI with isoniazid for six months and has not developed any manifestations compatible with active TB.
· The heart recipient had Chagas cardiomyopathy and underwent a heart transplant, but developed septic shock and died despite broad-spectrum antibiotic therapy. Her chest CT revealed diffuse pulmonary involvement.
· The kidney recipient was a 45-year-old man with systemic hypertension and terminal hypertensive nephropathy who developed mesangioproliferative glomerulonephritis and graft loss after transplantation and died despite antimicrobial therapy without isolation of any specific infectious agent. No autopsy was performed on deceased organ recipients, making TB diagnosis presumptive.
Discussion
· Transplantation is the treatment of choice for end-stage organ failure, but there are risks related to the procedure and immunosuppression. Infections are a major cause of morbidity and mortality, and active TB is an absolute contraindication for organ donation. Unfortunately, even active TB can be overlooked and therefore mistaken for other diseases.
· The case report highlights the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases.
· DD-TB is related to the donor’s epidemiology and clinical history, with a local TB prevalence of 30 cases/100,000 inhabitants.
· OPOs should obtain a donor history of symptoms consistent with active TB, and further testing and radiological assessments are warranted when risk factors are identified.
· Molecular tests are used when pulmonary TB is suspected, but CSF analysis can show elevated protein levels with pleocytosis, leading to brain death in the reported case.
· The intracerebral bleeding was likely secondary to cerebral vasculitis due to TB infection and should be avoided in cases of donor death due to ME.
· To improve screening strategies, potential findings should be scrutinized. Diagnosis of tuberculous meningitis is challenging, with poor sensitivity and delayed results.
· DD-TB is considered proven if donor and recipient isolates are reported to be identical or clonal, probable if there is suspected transmission, or possible if there is a donor risk factor for TB.
· Donor transmission is usually considered probable or possible but is less often confirmed due to a lack of a tracking system.
· It is important to emphasize that the graft was the first topography for TB diagnosis in the recipient, a clear indication of donor transmission.
· The liver transplant recipient was treated for latent TB and did not develop TB, but two other organ recipients from the same donor presented fever, sepsis, and organ dysfunction. TB donor transmission was confirmed in SPK transplant recipients.
· The most important details are that the donor had cultures pending at the time of procurement, that mycobacterial culture is more time-consuming, and that the donor tests and samples were processed and held at the hospital where the donor was treated and removed for donation.
· Communication gaps in reporting DDI can lead to adverse outcomes among organ recipients.
· High-risk complications of the recipient with eventual connection with the donor should be notified within 3 months of the procedure.
· Screening other transplant recipients for TB could have prevented TB transmission in newborns.
· Biovigilance initiatives aim to develop national surveillance systems for transplant safety.
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What is the level of evidence provided by this article?
Level 4 (case report).
===========================================
What is the take-home message?
· Any early posttransplant death related to infectious diseases has to be informed and registered, and graft and recipient survival are mandatory.
· Adverse events such as those described here are rare but may occur in any place or situation.
· A fully developed network that integrates transplant centers, OPOs.
· Laboratories are mandatory and could allow for more rapid intervention.
I like your summary, level of evidence, analysis and take home messages.
Introduction :
Ø Transplantation is the treatment of choice for some types of end-stage organ failure., transplantation has risks related to the procedure itself and immunosuppression.
Ø Infections represent a major cause of morbidity and mortality for SOT recipients
Ø Active TB is an absolute contraindication for organ donation., can be overlooked
Ø The importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases
Ø DD-TB is commonly related to the donor’s epidemiology and clinical history
Recommendation :
1-Established specific policy to improve the recognition of the disease in donors.
2-Developed guidelines to assist in the screening of potential organ donors and recipients
3-Should obtain a donor history of symptoms consistent with active TB, as past diagnosis of TB infection (active or latent), homelessness, alcohol abuse or injection drug use, incarceration, recent exposure to persons with active TB, or travel to areas where TB is endemic
4-Improve screening strategies
5-It should be considered that the donor tests and samples are processed and held at the hospital where the donor was treated, and the organs were removed for donation.
6- Importance of registry and the use of procedures for the safety and prevention of infectious disease transmission
This article level : 4
Take home massage :
1-TB is fatal disease but is a treatable .
2- care full evaluation of deceased donor and take detailed history and full investigations
Concerning the information gaps:
Specific protocol defining who was responsible for checking the pending test results complete medical records, training, and a tight network for monitoring the donor and patient result results
High-risk complications of the recipient should be actively notified
The importance of prompt notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner
Fully developed network that integrates transplant centers, OPO’s, and laboratories is mandatory and could allow the recognition of potential hazards followed by a more rapid intervention.
Notification of any suspicious cases of infection transmitted by the donor, including TB, allowing to trace all recipients at risk in a timely manner
I like your summary, level of evidence, analysis and key messages. What kind of notification do you suggest?
Is it central registry that you are suggesting or public health department?
This is a case study work (Level IV of scientific evidence) commenting on tuberculosis transmitted from a donor to his recipient.
Introduction
Active tuberculosis is an unacceptable risk and contraindicates organ donation, but current protocols are insufficient to generate this safety (X-rays, epidemiological risk and previous tuberculosis) and are not capable of diagnosing extrapulmonary disease.
This study is about a donor with disseminated tuberculosis who did not meet the criteria of the Brazilian protocol and transmitted the disease to the recipient.
Index case
Simultaneous pancreas-kidney donation.
ESRD and DM. Previous negative TST and denied exposure to tuberculosis
Immunosuppression – Basiliximab, tacrolimus, MMF, and prednisone.
Second-month post-transplant with fever, night sweats, and chills.
The image shows perigraft abscess.
Culture and acid-resistant bacilli were found in the drainage and a classic scheme for tuberculosis with RHZE was started.
Of the other recipients had died. He had side effects of the medications and spread of the disease with graft loss. There was dissemination throughout the mesentery and treatment with the classic scheme for 18 months until cure.
He died two years after the transplant due to complications from chronic kidney disease.
Donor
Pregnant woman with meningeal disease and meningoencephalitis. Two months after the death, the culture was positive for tuberculosis. The son was born and developed disseminated tuberculosis two months after delivery.
Liver receptor
Caroli’s disease underwent chemoprophylaxis for LTBI and did not develop symptoms of the disease.
Heart receptor
Chagas cardiomyopathy with severe heart failure after three months of transplantation with diffuse lung disease and died.
Other renal receptor
Hypertensive nephropathy after two months lost the graft due to glomerulonephritis and evolved with sepsis and death without identification of the germ.
Discussion
The difficulty in making an adequate diagnosis of tuberculosis, especially in extrapulmonary disease, increases the risk of transmission by transplantation. Brazil is an endemic country for the disease and does not have molecular diagnostics such as IGRAs in the public system, but has recently used GeneXpert with its interpretation limitations.
The absence of molecular methods in this screening made the diagnosis difficult and favored the transmission of the disease to recipients.
The diagnosis not performed on the donor was expanded to several other recipients, only be achieved in one of them. Culture with late results is common in tuberculosis and the lack of communication between services due to the lack of adequate records in a manual system, without the availability of an electronic medical record with complete information.
Take home messages
There is a need for better diagnostic methods for diseases and local epidemiology must be considered. The integration of information is extremely necessary.
What is your suggestion in regards to integration of information regarding availability of newer diagnostic tests and promptness of action on these reports?
I believe we can use GeneXpert for preemptive diagnostic
IGRAs and TST in Brazil is very difficult to interpret for being endemic disease, and for extrapulmonary pathology
Molecular methods are the best in trying to reach a better diagnosis.
1-Summary:
A case report of misdiagnosed donor derived TB. A deceased- donor with disseminated TB was not properly evaluated and accepted despite of having suspected meningeo-encephalitis of unknown cause.
after SPK transplantation, the recipient developed disseminated TB which necessitates stoppage of IS and graft nephrectomy and the patient died from CKD within 2 years.
because of this, they recalled the donor data which confirmed that donor had TB.
by reviewing other recipients, one with heart and one with kidney transplantation died from severe sepsis. only liver transplant patient who was maintained on anti-TB therapy for latent TB who survived without disease dissemination.
II- Level of evidence: IV
III-Take home message:
1- Follow the guideline for all steps of donor and recipient preparation regardless the situation
2- Any DD with meningeo-encephalitis of unknown origin should be excluded
3- Proper communication is a must in the transplantation activity
4- Donor-derived TB is not common, but it can happen.
I like your summary, level of evidence, analysis and take home messages.
What is your suggestion regarding communication gap?
Of course renal transplantation is the best solution for ESRD on regular hemodialysis, but also complications related to immunosuppression is common finding and may endanger the patient life, so the suspicion is a good key to detect early and start early treatment.
TB one of the infectious disease that can be happened as a result of defective immune system.
TB in SOT result from reactivation of latent TB , and in 4% of the cases are donor derived, as in some donors, TB could not be diagnosed and identified and also there was a communication gap between the transplant team and the harvesting center of donors which leads to bad outcome in the recipient and disseminated TB in the recipient with high mortality.
Development of better strategy or protocol for early detection of disease and hence early treatment;
1- Better selection of donor as active TB is absolute contraindication for donation.
2- Better communication with the harvesting center to know every details about the donor like history, physical examinations, lab and radiological investigations, the story of his/her disease and its progression until the death time.
3- Follow up of any delayed sample or investigations which was done before death and not appeared until the time of donation.
4- Follow up of any post-mortem sample or culture or biopsy.
5- Set a coordinator staff responsible for the process of follow up.
6- Any culture negative for usual organisms, should be taken as a suspicion for TB.
7- Full history taken and physical examination and investigations of the donor and recipient to diagnose or exclude TB should be done.
level of evidence 4
home message:
1- infectious disease including TB is fatal complications in immunosuppressed patients like in SOT
2-early diagnosis and treatment in donor and recipient will save the life of the recipient latter.
3-good communication between different department is very important for better management of the cases
What is your suggestion regarding communication gap?
I like your summary, level of evidence, analysis and take home messages. What kind of screening program would you suggest that all those clinicians (stakeholders) can be informed well in time?
Introduction
Most tuberculosis (TB) cases in solid organ transplant (SOT) recipients are caused by the reactivatio of tuberculosis infection”
Current screening protocols for deceased donors are usually based on chest X-ray findings, epidemiological risks, and previous TB history.
These features may not identify extrapulmonary and disseminated TB.
Despite organ procurement protocols, pretransplantation screening fails to identify TB in the donor in many cases.
Even when these cases are identified, communication gaps may result in donor-derived infections (DDI), which may be associated with death or poor outcomes.
This report describes a case of unrecognized disseminated TB in the donor with a devastating outcome for organ recipients.
This report highlights the need for a data bank and donor sample analysis to trace infections and reinforces the importance of better communication between transplantation teams and organ-harvesting centers.
Index case simultaneous pancreas
A 45-year-old male received a simultaneous pancreas kidney (SPK) transplant due to diabetes and endstage renal disease (ESRD)
After transplantation, he had no major clinical complications and was discharged on postoperative day 30.
Abdominal ultrasonography revealed perigraft collections, whereas the chest radiograph was normal
He received broad-spectrum antibacterial treatment and underwent percutaneous drainage of the abscesses, with transient resolution of fever.
After several ultrasound guided punctures to drain intra-abdominal TB abscesses and 18 months of anti- TB therapy, the patient was considered cured.
He died from complications related to ESRD and dialysis, two years after transplantation
The doner
The donor was a 23-year-old, 36-week pregnant woman with a history of intense headache who was admitted to the hospital emergency room, and within 72 hours of admission, she developed mild fever, neck stiffness, and seizures.
No microorganisms were identified in the CSF and blood, empirical treatment for meningoencephalitis was started 72 hours after hospital admission, and other culture samples were collected.
Respiratory secretions were negative for acid fast bacilli stain
Her level of consciousness decreased, and she underwent an emergency caesarean section on the 6th day of admission.
The patient was diagnosed with brain death and had elected to be an organ donor, considering as primary diagnosis, CNS bleeding.
At that time (2 months after delivery), her child presented with fever of unknown origin and was admitted to the same hospital, being diagnosed with disseminated TB.
The M, tuberculosis strain isolated from the child presented no resistance to first-line anti-TB drugs, and he was discharged home after seven days of standard TB treatment
The liver recipient
The liver recipient was a 55-year-old man diagnosed with caroli disease who was transplanted because of recurrent bacterial cholangitis.
The treatment was maintained for six months, and the patient has not developed any manifestations compatible with active TB to date
The heart recipient
The heart recipient was a 40-yearold woman diagnosed with Chagas cardiomyopathy who underwent a heart transplant for class IV heart failure.
The patient did not receive a specific diagnosis, her chest CT revealed diffuse pulmonary involvement
The other kidney recipient
The kidney recipient was a 45-year-old man with systemic hypertension and terminal hypertensive nephropathy.
During the second month after transplantation, he developed mesangioproliferative glomerulonephritis and graft loss and returned to dialysis.
He returned to the hospital with sepsis of unknown origin and died despite antimicrobial therapy, without isolation of any specific infectious agent.
Similar to the heart recipient, no specific test for mycobacteria was requested.
Thereby, the TB diagnosis contributed to the fatal outcome in one patient and may be the cause of infectious disease complication after transplantation in the other two.
No autopsy was performed on the deceased organ recipients, and for both the heart and kidney recipients, the TB diagnosis is only presumptive
Discussion
Infections represent a major cause of morbidity and mortality for SOT recipients. Risk level (RL) classification regarding DDI transmission involves the use of a grading system to rank recommendations, resulting in classifications that vary from a standard risk to an unacceptable risk.
There are several holdups associated with care, including the lack of important and complete information concerning donor screening, which can potentially lead to a notable reduced quality of life or may even cause death.
This case report calls attention to the importance of careful donor selection to reduce the risk of transmission of potentially lethal but treatable diseases.
Several transplant scientific societies developed guidelines to assist in the screening of potential organ donors and recipients.
The donor had no detectable abnormalities on the chest X-ray and AFB- negative smears, whereas the culture became positive two months after procurement.
In cases of donor death due to meningoencephalitis (ME) without a proven cause, the donation should be avoided.
Case Reports in Transplantation (a) (b) potential environmental exposures associated with organisms causing ME.
Donor cause of death was considered CNS bleeding, and the same occurred in many other reported cases, resulting in DD-TB.
DD-TB is considered proven if donor and recipient isolates were reported to be identical or clonal through molecular analysis.
In the absence of definitive confirmation of similar isolates, DD-TB is classified as probable if there is a suspected transmission and TB was identified in multiple recipients of one donor, or if donor and recipient shared more than one epidemiologic or clinical feature (e.g., TB diagnosis in a donor plus TB in the recipient early posttransplantation) or possible, if there is a suspected transmission event but the only criterion met is a donor risk factor for TB.
It is important to emphasize that the graft was the first topography for TB diagnosis in the recipient, a clear indication of donor transmission.
The two other organ recipients from the same donor presented fever of unknown origin, sepsis, and organ dysfunction a few months after transplantation.
A compelling article [6] showed that communication gaps in reporting DDI are frequent and may occur at multiple levels, contributing to adverse outcomes among affected organ recipients.
High-risk complications of the recipient with eventual connection with the donor, such as death or sepsis within 3 months of the procedure, should be actively notified.
Take home message.
To close the gap, communication between centers needs to be enabled.
Any possible deceased donors should have training and experience in the clinical signs and symptoms of the infectious disease.
Specific TB screening should be taken into consideration for high-risk donors.
It is important to get the donor’s immunological status history.
Level of evidence is 4
I like your summary, level of evidence, analysis and take home messages. What kind of screening program would you suggest that all those clinicians (stakeholders) can be informed well in time?
What is your suggestion regarding communication gap?
When a person’s immune system is compromised or they may have recently been exposed to someone with active TB, screening tests are more frequently performed to detect latent TB.
Two tests are used to screen for tuberculosis:
Introduction:
Discussion:
Level of evidence is 4.
Take-home messages:
I like your summary, level of evidence, analysis and take-home messages. What is your suggestion regarding communication gap?
To overcome communication gap, donor test & processed sample should be kept at hospital when the donor was treated & organ removed for transplantation.
Donor-derived Tuberculosis
Introduction
TB reactivation is the most common source of TB infection post solid transplantation, as the latent infection is reactivated.
The most source of TB infection is the latent infection reactivation from the recipient, only 4% are from the donor source.
Active donor TB infection is considered a contraindication to donation.
Based on the routine screening of the deceased donation (chest-x-ray, epidemiological risk, and previous TB history) which are not sensitive some donor-derived TB is acquired by the recipient.
Challenges regarding TB infection post-transplantation
A case report, organ donations
2. Kidney
3. Heart
4.Liver + TST
Discussion
Home messages;
Level of evidence
level ((IV))
case report
I like your summary, level of evidence, analysis and take home messages. What kind of network would you suggest?
What is your suggestion regarding communication gap?
thank you Prpf. for your comment
So communication gap should be filled as centers should be in contact via a network to avoid comorbid infection can develop in a transplant case.
As a culture it will take time so vital data should be obtained just to make alarm for clinical suspicion and to prevent infection.
In case of urgent transplantation when the results is coming the grafted kidney already it will be transplanted, so history of contact or exposure, or untreated TB should be focused on to determine going on for Tx or discard the kidney
QI.
Introduction
Case report
A 23 yrs old pregnant lady who presented with meningioencephalitis features and died shortly due massive subarachnoid hemorrhage. After two months her tracheal aspirates came positive for M. tuberculosis and her baby was diagnosed with disseminated TB. Mistakenly her organs were donated to 4 recipients:
The conclusion is TB diagnosis in one patient resulted in death and we cannot ruled it out completely in the other two patients
Q2.The was case report, level 4
Q3. Key messages
I like your summary, level of evidence, analysis and key messages. What kind of network system and biovigilence would you suggest?
Is it central registry that you are suggesting or public health department?
Thanks prof,
Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety.
Introduction.
Most tuberculosis cases in solid organ transplant (SOT) recipients are caused by the reactivation of latent tuberculosis infection (LTBI), and only 4% are considered donor-derived, despite organ procurement protocols, screening fails to identify TB in the donor in many cases and lead to DDI or if there is communication gaps in identified patient.
A case report of miserable story of Donor derived T.B infection from a case diagnosed 2 months post-mortem which lead to fatal outcome in one patient and may be the cause of infectious disease complication after transplantation in the other two.
Discussion:
Active TB is an absolute contraindication for organ donation and careful donor selection is crucial, to reduce the risk of transmission of potentially lethal but treatable diseases, and some times is so much difficult to recognized patient with TB specially with those without history of previous TB or exposure.
So, OPOs should looking for a donor risk factors of TB such as( history of symptoms consistent with active TB, as past diagnosis of TB infection (active or latent), homelessness, alcohol abuse or injection drug use, incarceration, recent exposure to persons with active TB, or travel to areas where TB is endemic)
When risk factors are identified, further testing and radiological assessments are required and molecular tests present greater sensitivity and specificity but are done when pulmonary TB is suspected.
In this reported case, TB was confirmed in a donor sample two months after donation, and the result was still not properly informed because there was no tracking system to request the pending microbiological results which is considered an obstacle and lead to more confusion about final diagnosis in our recipients and DDI TB transmission identification is challenging, one of the most important issue that no team assigned to follow pending investigations result, incomplete medical records, and an insufficiently tight network for monitoring these results remain challenging.
Level of evidence: case series (level IV).
Home message:
Donor-Derived Tuberculosis is an important issue as it may lead to fatal infection for recipients early post kidney transplant, so , strict screening for donor specially those with high risk factors and tracking system with tight network system to follow up pending donors investigation is so important and transplantation centers should be directly updated.
I like your summary, level of evidence, analysis and take home messages. What kind of network would you suggest?
What is your suggestion regarding communication gap?
Thanks prof.
I think central registry
1- Summary
Introduction
TB infection in SOT are usually due to the reactivation of latent tuberculosis infection (LTBI), and only 4% are donor-driven. Active TB infection may not be recognised in the donor specially in deceased donors even if identified communication gap can lead to donor-derived infections (DDI) and poor prognosis.
This is a case report describing the scenario of a
Deceased donor whom she was a pregnant lady died out off disseminated TB involving the brain leading to diffuse subarachnoid haemorrhage and brain death , she underwent CS and her delivered child was treated later for disseminated TB the TB diagnosis was obtained from the culture of lung tissues 2 months after death .
Her organs were given to 4 recipients
Kidney and pancreas simultaneous recipient,without any evidence of past TB involvement ,he received induction with basiliximab and conventional maintenance therapy, he presented 2 months post transplant with TB manifestations mainly involving both grafts with abcess that was drained and anti TB therapy was started but anti tuberculous drugs side effects occurred ,it progressed to disseminated TB.
Therefore Immunosuppression was stopped ,both graft loss occurred and he returned to dialysis and insulin therapy, caseating necrosis occurred in the graft that was removed .
Finally he was considered cured of TB after draining intra-abdominal TB abscesses and 18 months of anti TB therapy.
Meanwhile he died 2 years post transplant due to ESRD and dialysis complications
Liver transplant recipient due to Caroli disease , this patient had TST positive ,he was considered LTBI case and INH was started for 6 months and he was asymptomatic till this article’s date.
Heart transplant recipient due to Chagas disease with heart failure, within 3 months she developed fever progressed to septic shock ,antibiotic coverage was given but cultures were not conclusive and no specific mycobacterium cultures were done her pulmonary CT showed extensive affection but no final diagnosis was given till her death.
The other renal transplant recipient 2 months after transplant , mesangioproliferative nephritis occurred followed by rejection and he returned to dialysis then died at 3 months post transplant after antibiotic therapy and cultures but mycobacterium cultures were not taken .
For the heart and kidney recipients, TB diagnosis is only probable but not confirmed.
Discussion
Organ transplant is the best choice for most organ failures but on the other hand it has lots of risks as the surgery itself and the immunosuppressive therapy there after .
There is risk level for donor derived infection DDI ranging from standard to unacceptable as active TB .
The donor did not have any previous evidence of previous TB infection.
Certain startegies have to be applied to detect infections in donors .
Donor screening recommendations are available but in fact not all are essential in each case that is why it is not standardized .
TB risk factors have to be evaluated starting from asking in the history for active TB symptoms then if the risk is noticed further testing can be done.
The current donor did not have any history or symptoms suggestive of TB ,AFB smear was negative and positive culture result appeared after 2 months.
The cerebral haemorrhage could be most likely due to vasculitis secondary to TB infection.
Current recommendations are that donors must be excluded if their death was due to meningoencephalitis (ME) without a proven etiology.
In the current case the donor had CNS bleeding out off underlying TB.
In fact TB meningitis diagnosis is challenging.
Donor derived -TB (DDTB)is considered if both donor and recipient isolates were identical or clonal through molecular analysis.
DD TB is suspected if more than a recipient of the same donor had TB detected or if both donor and recipient had the same TB symptom.
The main restriction to confirm DDTB is to have a positive donor sample and genetic sequencing of the organism matching donor and recipient samples also there is usually a time gap.
Another aspect is that Mycobacterium TB can arise in culture after 4-6 weeks .
In a study concerning DD TB ,the median time till clinical presentation or diagnosis
was 2.7 months presenting mainly by fever , and allograft affection involvement was common ,graft loss occurred in 20% of cases and mortality occurred in 25%.
Information and data availability time gap have to be manged and following cultures need to be done at 7 day with recording that.
Donor samples must be processed and held at the treating hospital where the organs will be
removed for donation and tests followed .
In the current case if the TB results were discovered earlier ,therapy could have been introduced earlier with better outcomes.
Studies demonstrated that communication gaps in DDI reporting DDI occurs at multiple levels, causing hazardous outcomes among affected organ recipients as in the current case if a certain communication existed between teams of the recipients the death of the first donor and his TB infection could have assisted in diagnosing the other recipients DDI.
Also the delayed information about vertical TB transmission is a sign of communication error.
Early death posttransplant due to infectious diseases has to be informed and registered.
Proper reporting system can definitely improve the outcomes.
2-level of evidence is IV
3-Take home message
Data bank and donor sample analysis availability is mandatory to follow infections and shed light on the significance of better communication between organ-harvesting centers and transplantation teams .
I like your summary, level of evidence, analysis and take home messages. What kind of data bank would you suggest?
Is it central registry that you are suggesting or public health department?
Central registry Prof. Ajay