Mycobacterium tuberculosis

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Adverse Occurrence type: 
Estimated frequency: 
The frequency given here relates to cases of Mycobacterium tuberculosum in solid organ transplant recipients (SOT) as a whole and is not specific to donor-derived transmissions. The most common cause of post-SOT Mycobacterium tuberculosis infection is reactivation. Of the 2,082 cases reported between 1998-2016, 82.56% were kidney recipients, 12.15% were liver recipients and only 77 heart, 25 lung and 8 kidney-pancreas recipients. The overall incidence of TB among SOT recipients was 2.37% which is several fold higher than the general population. Of interest, extrapulmonary TB occurred in 29.84% of cases while disseminated MTB was seen in 15.96%, while multidrug resistant MTB was rare. In terms of individual organ transplants, the incidence of MTB in kidney transplant recipients was 1.69%, liver transplant recipients 1.33%, heart recipients 1.46%, kidney-pancreas recipients 1.25% and lung recipients 0.96%. The highest TB incidences were reported from Asia and Europe, followed by the United States.
Time to detection: 
The time to detection of MTb depended on the type of infection, with reactivation representing the most common form followed by donor-derived transmission. With reactivation, the median time to clinical presentation for pulmonary MTB was 22.5 months based on cohort data. However, when case reports were compiled, the median time to presentation was 17.5 months. The onset of MTB occurred beyond the first year post-transplant overall (41%), but 40% occurred within 12 months post-transplant. Organ breakdown: 1. In kidney recipients, the time to clinical presentation for pulmonary TB was 33 months, 28.5 months with extrapulmonary TB and 18 months with disseminated MTB. 2. In liver recipients - presentation of pulmonary MTB at 4 months, extrapulmonary TB at 9 months (most commonly central nervous system) and disseminated MTB at 48 months. The median time to pulmonary MTB was 8 months, extrapulmonary TB was 18 months and disseminated MTB was 23 months. 3. In heart recipients - presentation of pulmonary MTB was 54.44% followed by disseminated disease (27.7%) and extrapulmonary disease (18.18%). 4. In lung recipients - disseminated MTB presented at 53 months while pulmonary MTB presented at 3 months, no data available for extrapulmonary MTB. The median time for identification of donor-derived transmission was 3 months post-transplant (range 0.2 - 29 months).
Alerting signals, symptoms, evidence of occurrence: 
In terms of the type of MTB manifestation, pulmonary MTB was the most common presentation (54.2%) followed by extrapulmonary MTB (29.84%) and dissemimnated MTB (15.96%) The most common presenting symptom was fever (86%). In terms of organ specific data: 1. Kidney recipients - pulmonary MTB most common (53.94%) compared to 32.06% with extrapulmonary MTB (the urinary tract was most common - 23.45%) and 14% with disseminated TB. 1/3 of patients with disseminated MTB had lung involvement. 2. Liver recipients - pulmonary MTB and extrapulmonary MTB were equivalent (36.51%, central nervous system involvement was most common at 29.17% followed by liver allograft) and disseminated MTB at 26.91%, pulmonary involvement most common at 82.35% followed by liver allograft 47%, other sites included CNS, lymph node, pleura, genitourinary, peritoneum, skin, bone marrow, spine and axilla). 3. Heart transplant recipients - limited data available (only 22 of 77 heart recipients), Fever was reported in 60% of cases with lung involvement in all but one case of disseminated MTB. Abnormal chest x-rays were found in 9 patients with pulmonary and disseminated MTB. Of note, one patient with pulmonary TB had a negative chest-ray. 4. Lung transplant recipients - pulmonary MTB was the most common presentation (78.95%), two cases with disseminated MTB presented with lung involvement, then two cases of extrapulmonary, one with a cardiac abscess and one with a lymph node. Fever present in 50% of cases, and most patients had abnormal chest-rays.
Demonstration of imputability or root cause: 
All cases were based on positive cultures or PCR of body fluid or tissue specimens, or if acid-fast bacilli or caseating granulomas were seen in the presence of compatible clinical presentation. In the cases of donor-derived MTB, cases were based on identical isolates of the donor and recipient (proven), probable if they shared the same clinical and epidemiological features or possible if only epidemiological criteria were met.
Imputability grade: 
Not Assessable
Suggest new keywords: 
Tuberculosis, Solid Organ Transplantation
Suggest references: 
Cybele Lara R. Abad, Raymund R. Razonable. Mycobacterium tuberculosis after solid organ transplantation: A review of more than 2000 cases. Clinical Transplantation. 2018;e13259.
The description given here is usually reserved for a reference that needs to be appended to a record, for information. I added a few sentences to make that clear and will keep the record but I think we need to be cautious about how to use papers of this nature. Agree it is important and relevant but there will be similar reviews on other pathogens too which we have not utilised.
Expert comments for publication: 
This document represents a significant volume of work in review of case reports and limited studies, and indicates an increase in the number of cases of donor derived MTB infections in a non-endemic country (USA) that may be related to immigration and transplant tourism, which is an important point to highlight and aid the clinician in including MTB in the differential diagnosis of transplant recipients with fevers, particularly with significant incidences of extrapulmonary manifestations and disseminated disease. This document represented a large volume of work in the English literature which may have resulted in limitations however, given the most updated number of cases reviewed (2082) between 1998 - 2016, this reports warrants inclusion in the database despite not necessarily addressing specifically the issue of donor-derived infection and invetigation of imputability.