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

Abstract

BackgroundThe 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 findingsWe 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.Conclusions/SignificanceWe 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.

Diagnosis of Progressive Disseminated Histoplasmosis in Advanced HIV: A Meta-Analysis of Assay Analytical Performance

“…Of the 72 publications, 29 were selected; seven related to the validation of culture methodologies, five were related to assays for detection of antibodies, twelve were related to detection of circulating antigen, and five were related to molecular testing. By expert opinion, one study related to antigen testing validation that was not identified in the systematic review was included, increasing the number of studies related to antigen assay validation to thirteen and the total number of publications selected to 30, Figure 1 [16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43]. There were no identified studies related to histopathology validation.…”

Atypical Obstructive Pseudotumors in AIDS as the Initial Manifestation of Gastrointestinal Histoplasmosis

“…The detection of urine H. capsulatum antigens is used in the diagnosis of the pulmonary infection and the disseminated presentation [1,8,10].…”

Timely Diagnosis of Histoplasmosis in Non-endemic Countries: A Laboratory Challenge

“…It is particularly useful in progressive disseminated forms, and it has proven its applicability to infected animals that may act as potential reservoirs for humans (Cunningham et al, 2015;Rothenburg et al, 2019). Combined detection in serum and urine seem to provide the best diagnostic performance, with some differences in the diagnostic yield between FDA cleared tests (Theel et al, 2013;Fandiño-Devia et al, 2016;Azar and Hage, 2017;Torres-González et al, 2018). Antigen detection provides a clear improvement for the management of histoplasmosis, especially in highly endemic areas where this infection frequently coexists with tuberculosis (Bansal et al, 2019), and recently it has been included in the WHO list of essential diagnostic test 1 .…”