Burden and Challenges in the Diagnosis and Treatment of Histoplasmosis Among Persons With Advanced HIV Disease in Uganda, 2025

Abstract Background Data on the true burden of histoplasmosis in Uganda are limited, largely due to the scarcity of epidemiological studies. We aimed to describe the nationwide burden of histoplasmosis among persons with advanced HIV disease (AHD), highlighting the major challenges in diagnosis and treatment under routine HIV care. Methods This was a prospective longitudinal study conducted at nine health facilities in Uganda. Persons with AHD (CD4 < 200 cells/mm3) were included and followed up for 2 years. Urine samples were sent to the Central Public Health Laboratories and tested using the Histoplasma galactomannan enzyme immunoassay in batches. Histoplasmosis was defined using standard criteria. Results We enrolled 332 participants with AHD, and 66.6% were newly diagnosed with HIV. Over half were female (51.5%), with a median age of 35 years (interquartile range [IQR] = 29–42) for all participants. The median CD4 T-cell count was 73 cells/µL (IQR = 30.5–126.5). Eight (2.4%) participants were diagnosed with probable histoplasmosis. None of the cases received the recommended antifungals because they were not available in the country. After 2 years, 5 cases were still alive, 2 were lost to follow-up, and 1 died. Major challenges included missed diagnosis, low index of clinical suspicion, overlap of symptoms with those of pulmonary TB, high cost, limited access to antifungals such as voriconazole and itraconazole, radiology and laboratory investigations, and lack of knowledge about treatment guidelines. Conclusions Histoplasmosis occurs at a low frequency among persons with AHD in Uganda. Numerous challenges hinder a definite diagnosis and treatment. However, despite these challenges, survival among persons with AHD in Uganda who have untreated histoplasmosis is relatively good.