Management
Prophylaxis
The approach to the prevention of infection in the recipient is based upon the likelihood that the allograft contained viable organisms. If histoplasmosis was the cause of death in the deceased donor or if cultures or antigen tests were positive, the transplant recipient should be treated for 1 year for possible disseminated histoplasmosis. If fungal stains were positive but cultures of the allograft and antigen tests of the donor blood and urine were negative or if the donor CF titers were ≥1:32 or if H and/or M precipitins were present; a 3- to 6-month course of itraconazole is recommended (Supporting Figure S3). Observation with monitoring for antigenemia and antigenuria at 3-month intervals is reasonable if CF titers were 1:8 or 1:16 since transplant recipients with pretransplant CF titers in this range did not develop histoplasmosis.
Treatment
Treatment of histoplasmosis is summarized in Table 3 and is based on the published guidelines. Liposomal amphotericin B for 1–2 weeks is recommended in patients with more severe illness, followed by itraconazole. Treatment should be continued for at least 1 year, and until Histoplasma antigen levels have become negative in the serum and have declined to <2 ng/mL in urine. Longer courses may be necessary depending upon the response. Antigen levels should be monitored at about 3-month intervals during therapy and for 1 year after discontinuation of therapy. Itraconazole is appropriate in patients with milder illness not requiring hospitalization. Consideration should be given to avoiding immunosuppression with T cell depleting antibodies.
Prolonged therapy with itraconazole may be required in some patients such as individuals in whom antigenemia and antigenuria fail to meet the criteria for discontinuation of therapy or who relapse upon discontinuation of therapy. Some physicians continue itraconazole indefinitely in patients who require augmented immunosuppression for rejection. Antigen levels should continue to be monitored at 3-month intervals during suppressive therapy. Voriconazole, posaconazole and fluconazole may be considered as alternatives to itraconazole (Table 4). Fluconazole is the least active of the azoles for histoplasmosis but has been used successfully for the treatment and may be the best alternative in patients with itraconazole intolerance.
Key Recommendations
Living donors with active histoplasmosis should be treated for 3–6 months prior to organ donation.
The liver and spleen from deceased donors should be inspected at the time of organ procurement. Visualization of granuloma in explanted organs does not absolutely contraindicate their use but serum should be tested for antigen and antibodies to Histoplasma if suspicious lesions are noted and cultures sent.
Antigenemia, antigenuria, H and/or M precipitin bands and CF titers of ≥1:32 provide strong evidence for active histoplasmosis.
Liposomal amphotericin followed by itraconazole is recommended as therapy for moderately severe and severe histoplasmosis. Milder cases may be treated with itraconazole. Voriconazole, posaconazole and fluconazole are alternatives to itraconazole.