Open AccessDiagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico
Author(s) -
Areli Martínez-Gamboa,
María Dolores Niembro-Ortega,
Pedro Torres-González,
Janeth Santiago-Cruz,
Nancy Guadalupe Velázquez-Zavala,
Andrea Rangel-Cordero,
Brenda Crabtree-Ramírez,
Armando Gamboa-Domı́nguez,
Edgardo Reyes-Gutiérrez,
Gustavo ReyesTerán,
Víctor Hugo Lozano-Fernandez,
Víctor Hugo Ahumada-Topete,
Pedro Martínez-Ayala,
Marisol Manríquez-Reyes,
Juan Pablo Ramírez-Hinojosa,
Patricia RodríguezZulueta,
Christian Hernández-León,
Jesús Arturo Ruiz-Quiñones,
Norma E. Rivera-Martínez,
Alberto Chaparro-Sánchez,
Jaime Andrade-Villanueva,
Luz Alicia González-Hernández,
Sofia Cruz-Martínez,
Oscar Israel Flores-Barrientos,
Jesús Gaytán-Martı́nez,
Martín Magaña-Aquino,
Axel Cervantes-Sánchez,
Antonio Olivas-Martínez,
Javier Araujo-Meléndez,
María del Roció Reyes-Montes,
Esperanza Duarte-Escalante,
María Guadalupe Frías-De León,
José Antonio Ramírez,
Mária Lucía Taylor,
Alfredo Ponce de León-Garduño,
José Sifuentes–Osornio
Publication year - 2021
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0009215
Subject(s) - histoplasmosis , histoplasma , medicine , urine , prospective cohort study , gastroenterology , bone marrow , pathology , immunology , histoplasma capsulatum
Background The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283 220 SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine. Methodology/Principal findings We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H . capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78–30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4–76.2) / 96.2% (95% CI, 93.2–98.0) for IAHE, 91.3% (95% CI, 84.2–96.0) / 90.9% (95% CI, 87.0–94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0–95.3) / 92.3% (95% CI, 88.6–95.1) for MVHUALFA. The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3–72.5)/ 89.5% (95%CI, 86.0–93.0), 65.9% (95%CI, 56.0–75.8)/ 89.0% (95%CI, 85.2–92.9), 62.1% (95%CI, 44.4–79.7)/ 82.6% (95%CI, 71.7–93.6) and 34.9% (95%CI, 24.8–46.2)/ 67.3% (95%CI, 60.6–73.5) respectively; and 1281-1283 220 SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9–74.7)/ 58.8% (95%CI, 53.2–64.5), 70.8% (95%CI, 61.3–80.2)/ 52.9% (95%CI, 46.8–59.1), 71.4% (95%CI, 54.7–88.2)/ 40.4% (95%CI, 26.4–54.5) and 18.1% (95%CI, 10.5–28.1)/ 90.4% (95%CI, 85.5–94.0), respectively. Conclusions/Significance The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.