Diagnostic accuracy cohort study and clinical value of the Histoplasma urine antigen (ALPHA Histoplasma EIA) for disseminated histoplasmosis among HIV infected patients: A multicenter study

by Pedro Torres-González, María Dolores Niembro-Ortega, Areli Martínez-Gamboa, Víctor Hugo Ahumada-Topete, Jaime Andrade-Villanueva, Javier Araujo-Meléndez, Alberto Chaparro-Sánchez, Brenda Crabtree-Ramírez, Sofia Cruz-Martínez, Armando Gamboa-Domínguez, Oscar I. Flores-Barrientos, Jesús Enrique Gaytán-Martínez, Luz Alicia González-Hernández, Christian Hernández-León, Víctor Hugo Lozano-Fernandez, Marisol Manríquez-Reyes, Martin Magaña-Aquino, Pedro Martínez-Ayala, Juan Pablo Ramírez-Hinojosa, Andrea Rangel-Cordero, Norma Erendira Rivera-Martínez, Edgardo Reyes-Gutiérrez, Gustavo Reyes-Terán, Patricia Rodríguez-Zulueta, Jesús Ruíz-Quiñones, Janeth Santiago-Cruz, Nancy Guadalupe Velázquez-Zavala, José Sifuentes-Osornio, Alfredo Ponce de León


The Histoplasma urine antigen (HUAg) is the preferred method to diagnose progressive disseminated histoplasmosis (PDH) in HIV patients. In 2007, IMMY ALPHA Histoplasma EIA was approved for clinical for on-site use, and therefore useful for regions outside the United States. However, ALPHA-HUAg is considered inferior to the MVista-HUAg which is only available on referral. We aim to evaluate the diagnostic accuracy of ALPHA-HUAg.

Methodology/Principal findings

We conducted a multicenter, prospective, diagnostic test study in two secondary and eight tertiary-care facilities in Mexico. We included HIV patient with PDH suspicion and evaluated ALPHA-HUAg diagnostic accuracy using as reference standard the Histoplasma capsulatum growth on blood, bone marrow, and tissue cultures or compatible histopathologic exam (PDH–proven). We evaluated the results of 288 patients, 29.5% (85/288; 95% confidence interval [CI], 24.3–35.1) had PDH. The sensitivity of ALPHA-HUAg was 67.1% (95% CI, 56–76.8%) and the specificity was 97.5% (95% CI, 94.3%-99.1%). The positive likelihood ratio was 27.2 (95% CI; 11.6–74.4). In 10.5% of the PDH–proven patients, a co-existing opportunistic infection was diagnosed, mostly disseminated Mycobacterium avium complex infection.


We observed a high specificity but low sensitivity of IMMY-HUAg. The test may be useful to start early antifungals, but a culture-based approach is necessary since co-infections are frequent and a negative IMMY-HUAg result does not rule out PDH.

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