**5.3 Prophylaxis**

Prophylactic use of antifungal drugs has been studied only in persons with HIV infection [48]. A placebo-controlled trial showed that primary prophylaxis with itraconazole capsules prevents histoplasmosis in patients living with HIV infection, and even a survival benefit was not demonstrated [144].

Prophylaxis of histoplasmosis with 200 mg daily of itraconazole should be considered only in patients with HIV infection with CD4 cell counts <150 cells/ mm3 , in highly endemic areas in which the incidence of the disease is higher than 10 cases per 100 patient-years (A-I evidence-based recommendation).

In other immunosuppressed patients, daily prophylaxis with itraconazole may be appropriate, in specific circumstances (C-III). There are no data on the role and appropriate duration for prophylaxis in a patient who is receiving immunosuppressive therapy for organ transplantation, malignancy, or chronic inflammatory disease and who, concomitantly, exhibits radiographic or serologic evidence of past histoplasmosis [19]. On the other hand, the risk for histoplasmosis appears to be low in patients receiving immunosuppressive therapy for solid organ or bone marrow transplantation, with an estimated incidence less than 1%, even in endemic areas [145]. For patients receiving therapy with TNF antagonists, there is a risk for developing the disseminated form of the disease, histoplasmosis being considered the most common fungal infection associated with this treatment [146]. History of active histoplasmosis in the last 2 years could be considered a benchmark for initiating prophylaxis with itraconazole during immunosuppression. Also, patients who have finished treatment for histoplasmosis and who are about to receive a transplant or to start new immunosuppressive therapies should be tested for the levels of urinary histoplasma antigen before the intervention and then every 2 or 3 months after. An increase in urinary antigen levels indicates the need for further investigation for active histoplasmosis, but a consistent elevation of the urinary histoplasma antigen level should prompt empirically initiation of antifungal therapy, in the context of ongoing immunosuppression [19].

Transplacental transmission of *H. capsulatum* to the fetus [146] could be prevented by administering antifungal therapy before delivery, but there are no evidence-based guidelines for the management of the vertical mode of transmission. Histopathological examination of the placenta for granuloma and for other organisms resembling *H. capsulatum* should be performed [19].
