Multicenter Validation of Commercial Antigenuria Reagents To Diagnose Progressive Disseminated Histoplasmosis in People Living with HIV/AIDS in Two Latin American Countries

Abstract

Histoplasmosis is an important cause of mortality in patients with AIDS, especially in countries with limited access to antiretroviral therapies and diagnostic tests. However, many disseminated infections in Latin America go undiagnosed. A simple, rapid method to detect infection in regions where histoplasmosis is endemic would dramatically decrease the time to diagnosis and treatment, reducing morbidity and mortality. The aim of this study was to validate a commercial monoclonal galactomannan (HGM) enzyme-linked immunosorbent assay (Immuno-Mycologics [IMMY], Norman, OK, USA) in two cohorts of people living with HIV/AIDS (PLHIV). We analyzed urine samples from 589 people (466 from Guatemala and 123 from Colombia), including 546 from PLHIV and 43 from non-PLHIV controls. Sixty-three of these people (35 from Guatemala and 28 from Colombia) had confirmed histoplasmosis by isolation of Using the standard curve provided by the quantitative commercial test, the sensitivity was 98% (95% confidence interval [CI], 95 to 100%) and the specificity was 97% (95% CI, 96 to 99%) (cutoff = 0.5 ng/ml). Semiquantitative results, using a calibrator of 12.5 ng/ml of galactomannan to calculate an enzyme immunoassay index value (EIV) for the samples, showed a sensitivity of 95% (95% CI, 89 to 100%) and a specificity of 98% (95% CI, 96 to 99%) (cutoff ≥ 2.6 EIV). This relatively simple-to-perform commercial antigenuria test showed a high performance with reproducible results in both countries, suggesting that it can be used to detect progressive disseminated histoplasmosis in PLHIV in a wide range of clinical laboratories in countries where histoplasmosis is endemic.

Evaluation of a Histoplasma antigen lateral flow assay for the rapid diagnosis of progressive disseminated histoplasmosis in Colombian patients with AIDS

“…Two other discrepant results were observed in two patients with salmonellosis who lacked positive culture for H capsulatum . However, these patients had clinical and epidemiological evidence of PDH, as well as positive urinary antigen measured by two different ELISAs and positive serology (one patient with complement fixation titres of 1:8, and both patients with immunodiffusion M band) for histoplasmosis . It is possible that these two patients truly had PDH despite lack of culture confirmation.…”

“…If these patients were also considered to be histoplasmosis cases, the specificity of the LFA would increase to 98% and the sensitivity increased to 92% by as read by the automated reader. 9,10 This study presents several limitations. Finally, as this assay obtains FDA and/or CE approval for in vitro diagnostic use, these labels will facilitate assay accessibility in many laboratories worldwide.…”

“…tients with immunodiffusion M band) for histoplasmosis. 9,10 It is possible that these two patients truly had PDH despite lack of culture confirmation. If these patients were also considered to be histoplasmosis cases, the specificity of the LFA would increase to 94% and the sensitivity to 96%.…”

“…All specimens used in the current study were obtained from an earlier prospective study conducted from May 2008 to August 2011 at the Hospital La María in Medellín, Colombia. 9,10 Briefly, patients presenting with at least three of the following symptoms were enrolled: fever, pancytopenia, weight loss, the presence of skin or mucosal lesions, and pulmonary involvement by radiography. Any patient who had previously received amphotericin B or itraconazole or who had a diagnosis of histoplasmosis prior to the enrolment period were excluded from the study.…”

“…8 Detection of Histoplasma antigen in patient specimens improves sensitivity and timeliness of diagnosis, but the current method by enzyme immunoassay must be performed by highly trained personnel in specialty laboratories. 9 Recently, the development of the lateral flow technology has provided a method that is simple to use and can be performed in a setting closer to the patient. In this study, a lateral flow assay (LFA) developed by MiraVista ® Diagnostics was evaluated for the detection of Histoplasma antigen in serum.…”