Histoplasma capsulatum antigen detection tests as an essential diagnostic tool for patients with advanced HIV disease in low and middle income countries: A systematic review of diagnostic accuracy studies

Abstract

IntroductionDisseminated histoplasmosis, a disease that often resembles and is mistaken for tuberculosis, is a major cause of death in patients with advanced HIV disease. Histoplasma antigen detection tests are an important addition to the diagnostic arsenal for patients with advanced HIV disease and should be considered for inclusion on the World Health Organization Essential Diagnostics List.ObjectiveOur objective was to systematically review the literature to evaluate the diagnostic accuracy of Histoplasma antigen tests in the context of advanced HIV disease, with a focus on low- and middle-income countries.MethodsA systematic review of the published literature extracted data on comparator groups, type of histoplasmosis, HIV status, performance results, patient numbers, whether patients were consecutively enrolled or if the study used biobank samples. PubMed, Scopus, Lilacs and Scielo databases were searched for published articles between 1981 and 2018. There was no language restriction.ResultsOf 1327 screened abstracts we included a total of 16 studies in humans for further analysis. Most studies included used a heterogeneousgroup of patients, often without HIV or mixing HIV and non HIV patients, with disseminated or non-disseminated forms of histoplasmosis. Six studies did not systematically use mycologically confirmed cases as a gold standard but compared antigen detection tests against another antigen detection test. Patient numbers were generally small (19–65) in individual studies and, in most (7/10), no confidence intervals were given. The post test probability of a positive or negative test were good suggesting that this non invasive diagnostic tool would be very useful for HIV care givers at the level of reference hospitals or hospitals with the infrastructure to perform ELISA tests. The first results evaluating point of care antigen detection tests using a lateral flow assay were promising with high sensitivity and specificity.ConclusionsAntigen detection tests are promising tools to improve detection of and ultimately reduce the burden of histoplasmosis mortality in patients with advanced HIV disease.

The Broad Clinical Spectrum of Disseminated Histoplasmosis in HIV-Infected Patients: A 30 Years’ Experience in French Guiana

“…PCRs have been developed in French Guiana, but the lack of commercially available kits, the lack of standardized methods, and the limited number of validation studies are the current limitations in performing histoplasma PCR [52][53][54]. However, in the near future, a simple test allowing a rapid diagnosis on easily obtainable samples (urine, blood) should emerge with the expected availability of a high performance antigen test (Histoplasma galactomannan single-monoclonal-antibody sandwich ELISA) [55,56]. Until these become available, antigenic tests of Aspergillus based on the detection of galactomannan in serum as surrogate marker can be used [57][58][59].…”

Role of western blot assay for the diagnosis of histoplasmosis in AIDS patients from a National Institute of Infectious Diseases in Rio de Janeiro, Brazil

“…Histoplasma galactomannan detection by radio immune assay was the first antigen detection test developed by MiraVista Diagnostics, which was subsequently modified as an EIA. A polyclonal EIA developed by CDC and a IMMY monoclonal EIA also have demonstrated accuracies similar to the EIA MiraVista Diagnostics . A meta‐analysis performed in 2016 to evaluate the diagnostic performance of these tests, demonstrated that the overall sensitivity for antigen detection in serum and urine was 81%, while specificity was 99% .…”

What is AIDS in the Amazon and the Guianas in the 90-90-90 era?

“…With the arrival of new Histoplasma antigen detection methods, [9][10][11] the possibility of screening for histoplasma, analogous to screening for cryptococcus [3], raises a new and important research question: should we screen all patients with less than 200 CD4 for histoplasmosis? Primary prophylaxis is in practice rarely implemented perhaps because of the fear of drug-drug interactions, antifungal resistance selection, and because physicians often expect that antiretroviral therapy will quickly restore immunity.…”