Disseminated histoplasmosis in HIV — DTM&H MCQ

Correct answer: A — Disseminated histoplasmosis

The correct answer is A, disseminated histoplasmosis. This man has severe immunosuppression (CD4 31 cells/microlitre), a compatible geographic exposure (Amazon basin, an endemic region for Histoplasma capsulatum), and a classic multisystem picture of fever, weight loss, oral ulcers and pancytopenia from bone marrow involvement. The urine Histoplasma antigen test is a rapid, sensitive point-of-care assay specifically recommended by WHO for diagnosing progressive disseminated histoplasmosis in advanced HIV disease, and a positive result in this clinical context is diagnostic. WHO guidance highlights that this disease is often confused with tuberculosis but is confirmed by antigen detection in urine, serum or bronchoalveolar lavage. Why the other options are wrong: E. Talaromycosis: caused by Talaromyces marneffei, this presents similarly with fever, weight loss, cytopenias and skin lesions in advanced HIV, but it is geographically restricted to South and Southeast Asia, not the Amazon basin, and would not give a positive Histoplasma antigen. D. Secondary syphilis: causes rash, lymphadenopathy and mucocutaneous lesions but does not cause pancytopenia or a positive fungal urine antigen, and CD4 count of 31 is not a typical association. C. Miliary tuberculosis: an important differential in advanced HIV with fever, weight loss and pancytopenia, but it does not produce a positive Histoplasma urine antigen; diagnosis relies on AFB smear, culture or GeneXpert. B. Visceral leishmaniasis: causes fever, weight loss, pancytopenia and hepatosplenomegaly in advanced HIV, but is diagnosed by bone marrow or splenic aspirate microscopy/PCR, not a Histoplasma antigen test, and oral ulcers are not a typical feature. Key point: a positive urine Histoplasma antigen in a patient with advanced HIV disease (CD4 under 200) and compatible systemic features is diagnostic of disseminated histoplasmosis and should prompt immediate antifungal treatment rather than empirical anti-tuberculous therapy.

Reference: WHO, Guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy, Histoplasmosis chapter (2021), NCBI Bookshelf NBK620075 (https://www.ncbi.nlm.nih.gov/books/NBK620075/)