Histoplasmosis in India: a systematic review of reported cases

Abstract

BACKGROUND: Histoplasmosis is a systemic fungal infection caused by Histoplasma capsulatum and is increasingly recognised in India, but its epidemiology, clinical spectrum, diagnosis, treatment, and outcomes remain poorly characterised. We conducted a systematic review of reported cases from India. METHODS: A PROSPERO-registered review (CRD42024556630) was conducted using PubMed, Embase, and Web of Science for studies published up to February 2025, without language restrictions. Two reviewers independently screened records and extracted individual patient-level data. Organ involvement was defined a priori using site-specific histopathological, cytological, microbiological, or molecular confirmation, with compatible clinico-radiological involvement accepted in confirmed cases. Descriptive and exploratory individual-level comparative analyses were performed. RESULTS: We included 320 studies contributing 508 unique cases. Reporting increased markedly after 2015. Cases were geographically widespread, with the highest numbers from Delhi (16.9%), West Bengal (13.8%), Punjab (12.0%), Haryana (9.4%), Maharashtra (8.3%), Uttar Pradesh (7.7%), and Rajasthan (7.1%). The mean age was 47.6 years (SD 16.5), and 403/493 (81.7%) were male. Immunosuppression was documented in 188/508 (37.0%), most commonly HIV infection and diabetes mellitus. Disease was frequently extrapulmonary and multisystemic, with cutaneous (31.5%), adrenal (29.9%), lymph node (29.8%), hepatic (26.0%), and splenic (25.6%) involvement most common. Pulmonary disease occurred in 15.2% and central nervous system disease in 1.6%. Diagnosis relied predominantly on microscopy, histopathology, or cytology (98.6%); culture (28.0%), antigen detection (4.3%), and PCR (3.0%) were infrequently used. Amphotericin B was used in 262/388 (67.5%) cases with available data, and itraconazole in 306/390 (78.5%). Outcome data were available for 425 patients, of whom 62/425 (14.6%) died. CONCLUSIONS: Reported histoplasmosis in India is geographically widespread and clinically heterogeneous, with prominent extrapulmonary and disseminated disease. These findings reflect published case patterns rather than true epidemiology, given selective reporting of severe, unusual, or biopsy-confirmed disease. Limited use of culture, antigen detection, and molecular diagnostics highlights important diagnostic gaps. Improved awareness, access to non-culture-based diagnostics, and prospective multicentre studies are needed to define the full clinical spectrum and burden of histoplasmosis in India.