Histoplasma Urinary Antigen for the Diagnosis Histoplasmosis in Non‐ HIV Individuals

BACKGROUND: Histoplasmosis is an endemic mycosis in the Americas. While urinary Histoplasma antigen enzyme immunoassay testing (HAET) has been validated mainly in HIV-infected patients with disseminated disease, its performance in HIV-negative populations with heterogeneous clinical presentations is unclear. OBJECTIVES: To describe the performance of urinary HAET for the diagnosis of histoplasmosis in a cohort of Brazilian HIV-negative patients. MATERIAL AND METHODS: We conducted a retrospective study at Einstein Hospital Israelita (Brazil) including HIV-negative patients whose urine samples were analysed by Histoplasma antigen enzyme immunoassay test (HAET) from January 2022 to October 2025. Factors associated with positive urinary HAET were analysed using univariable and multivariable models. Among 346 patients, histoplasmosis was diagnosed in 43 (12%); 16 (37%) were immunocompromised and 14 (33%) had disseminated disease. Urinary HAET was positive in eight patients (19%), with antigen levels from 0.3 to > 15 ng/mL. Sensitivity and specificity were 19% and 100%, respectively; positive and negative predictive values were 100% and 90%. Sensitivity increased to 45% in immunocompromised patients with multiorgan involvement, and immunocompromised status independently predicted HAET positivity (p = 0.008). In HIV-negative patients, HAET demonstrates excellent specificity but low sensitivity, performing best in immunocompromised individuals with disseminated histoplasmosis.