Donor-Derived Fungal Infections in Organ Transplant
Donor-Derived Fungal Infections in Organ Transplant
Since histoplasmosis occurs in only 0.5% of transplant recipients from endemic areas and 1–5% of healthy subjects have positive tests for Histoplasma antigen or antibodies, respectively routine testing of all donors from an endemic area is not warranted. If screening were performed, positive results are expected in 10:1000 by antigen detection and in 50:1000 by antibody testing.
The evaluation of a potential living donor should begin with prior history of histoplasmosis at any time or undiagnosed pneumonia in the last 2 years (Supporting Figure S2). If documented, further investigation should include pulmonary imaging studies and diagnostic tests. The presence of an H precipitin band by agar gel immunodiffusion (AGID), complement fixation (CF) titers of ≥1:32, antigenuria or antigenemia suggest active infection, while M precipitin bands and CF titers of 1:8–1:16 may represent active or inactive histoplasmosis in which the yeasts are not viable. Symptoms of pneumonia, fever, sweats, weight loss and/or findings of undiagnosed pneumonia, noncalcified nodules or lymphadenopathy may represent active disease and warrant additional studies, including bronchoscopic specimens which should be tested for Histoplasma antigen or a diagnostic biopsy and cultures of lesions. An individual with active disease would be an unsuitable donor and should be treated with itraconazole for 3–6 months prior to organ donation. In the absence of a prior history or clinical or radiographic findings suggestive of histoplasmosis in the donor, routine antigen or antibody testing is not recommended.
The explanted organ should be inspected for granulomas which should be examined microscopically by fungal stain and by fungal culture. If donor granulomas are noted, antigen and antibody testing should be performed. The live donor should also be evaluated for antifungal therapy if not previously treated. The recipient should be tested for antigenemia and antigenuria at 3-month intervals during the first year after transplantation. Positive tests for antigen would be an indication for treatment for histoplasmosis.
Deceased donors from endemic areas hospitalized for nonhemorrhagic neurological disease, fever of unknown origin, or pneumonia of unknown etiology may have undiagnosed histoplasmosis. These findings would support further testing for histoplasmosis. Procurement of organs should not be delayed while awaiting test results which will facilitate the decision to use antifungal prophylaxis or therapy in the recipient. The liver and spleen should be inspected at the time of organ procurement from deceased donors. Findings suspicious for histoplasmosis include organomegaly or presence of focal lesions consistent with granulomas on the organ surfaces or cross sections. Some transplant programs do not use organs with unexplained organomegaly or lesions consistent with granulomas. However, if they are to be used, specimens should be obtained for fungal histopathology and culture. If lesions suspicious for H. capsulatum are noted, serum antigen and antibody testing and cultures of appropriate tissues should be performed (Supporting Figure S3).
The approach to the evaluation of the recipient should include antigen testing or histopathology that are sensitive and rapid and provide the basis for initial diagnosis in most cases. Testing urine, serum and bronchoalveolar lavage fluid in patients undergoing bronchoscopy offers the highest sensitivity for diagnosis by antigen detection. Serology in transplant recipients may not be reliably positive as antibodies have been positive in only 20% of the cases. Calcified and noncalcified lung nodules or mediastinal lymph nodes are common 'incidental' findings in individuals from endemic areas for histoplasmosis and usually do not indicate active infection or require further testing to exclude active histoplasmosis.
Donor and Recipient Evaluation
Since histoplasmosis occurs in only 0.5% of transplant recipients from endemic areas and 1–5% of healthy subjects have positive tests for Histoplasma antigen or antibodies, respectively routine testing of all donors from an endemic area is not warranted. If screening were performed, positive results are expected in 10:1000 by antigen detection and in 50:1000 by antibody testing.
The evaluation of a potential living donor should begin with prior history of histoplasmosis at any time or undiagnosed pneumonia in the last 2 years (Supporting Figure S2). If documented, further investigation should include pulmonary imaging studies and diagnostic tests. The presence of an H precipitin band by agar gel immunodiffusion (AGID), complement fixation (CF) titers of ≥1:32, antigenuria or antigenemia suggest active infection, while M precipitin bands and CF titers of 1:8–1:16 may represent active or inactive histoplasmosis in which the yeasts are not viable. Symptoms of pneumonia, fever, sweats, weight loss and/or findings of undiagnosed pneumonia, noncalcified nodules or lymphadenopathy may represent active disease and warrant additional studies, including bronchoscopic specimens which should be tested for Histoplasma antigen or a diagnostic biopsy and cultures of lesions. An individual with active disease would be an unsuitable donor and should be treated with itraconazole for 3–6 months prior to organ donation. In the absence of a prior history or clinical or radiographic findings suggestive of histoplasmosis in the donor, routine antigen or antibody testing is not recommended.
The explanted organ should be inspected for granulomas which should be examined microscopically by fungal stain and by fungal culture. If donor granulomas are noted, antigen and antibody testing should be performed. The live donor should also be evaluated for antifungal therapy if not previously treated. The recipient should be tested for antigenemia and antigenuria at 3-month intervals during the first year after transplantation. Positive tests for antigen would be an indication for treatment for histoplasmosis.
Deceased donors from endemic areas hospitalized for nonhemorrhagic neurological disease, fever of unknown origin, or pneumonia of unknown etiology may have undiagnosed histoplasmosis. These findings would support further testing for histoplasmosis. Procurement of organs should not be delayed while awaiting test results which will facilitate the decision to use antifungal prophylaxis or therapy in the recipient. The liver and spleen should be inspected at the time of organ procurement from deceased donors. Findings suspicious for histoplasmosis include organomegaly or presence of focal lesions consistent with granulomas on the organ surfaces or cross sections. Some transplant programs do not use organs with unexplained organomegaly or lesions consistent with granulomas. However, if they are to be used, specimens should be obtained for fungal histopathology and culture. If lesions suspicious for H. capsulatum are noted, serum antigen and antibody testing and cultures of appropriate tissues should be performed (Supporting Figure S3).
The approach to the evaluation of the recipient should include antigen testing or histopathology that are sensitive and rapid and provide the basis for initial diagnosis in most cases. Testing urine, serum and bronchoalveolar lavage fluid in patients undergoing bronchoscopy offers the highest sensitivity for diagnosis by antigen detection. Serology in transplant recipients may not be reliably positive as antibodies have been positive in only 20% of the cases. Calcified and noncalcified lung nodules or mediastinal lymph nodes are common 'incidental' findings in individuals from endemic areas for histoplasmosis and usually do not indicate active infection or require further testing to exclude active histoplasmosis.
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