S2.2d Evaluation of new tools for the diagnosis of histoplasmosis
Authors: Leclere Aude Sturny , Garcia-Hermoso Dea , Alanio Alexandre , Donald Sigrid Mac , Vreden Stephen , van Eer Marja , Moussiegt Aurore , Nacher Mathieu , Lortholary Olivier , Adenis Antoine , Lanternier Fanny 
Published: September 2022

S2.2 Histoplasmosis and talaromycosis, September 21, 2022, 3:00 PM - 4:30 PM

In sub-Saharan Africa (SSA) and West African countries, histoplasmosis is rarely diagnosed probably due to lack of epidemiological information, insufficient training and awareness of frontline healthcare workers, and clinical features very similar to those of tuberculosis that can be misleading. This fungal infection mainly affects immunocompromised patients and particularly advanced HIV patients, with a high case-fatality rate in the absence of treatment (from &lt;10% to &gt;40%). The classical diagnostic methods are microscopic observation of yeasts with suggestive morphology and a positive culture from a biological sample. However, direct examination requires regular practice, and the yeasts can be confused with other pathogens and culture takes prolonged incubation (often 2-6 weeks) and involves, when positive, handling in a level 3 security laboratory.

Implementing non-invasive diagnostic tools will allow us to improve histoplasmosis diagnosis for the most exposed patients and also to evaluate the prevalence of this fungal infection in countries where data are still lacking. Rapid diagnostic tests (RDTs) such as the TB Lam for the diagnosis of tuberculosis or the Cryptococcal antigen (CrAg) lateral flow assay (LFA) for cryptococcosis have demonstrated their usefulness for the management of advanced HIV patients in similar contexts.

Recently, two RDTs have been made commercially available for the diagnosis of histoplasmosis, based on urinary monoclonal antigen detection: (1) Histoplasma Capsulatum Urinary Antigen Rapid Test from Optimium Imaging Diagnostics (OIDx) and (2) Histoplasma Urine Antigen Lateral Flow Assay from MiraVista Diagnostics (MV).

Objectives and Methods

Our objective was to evaluate these new tools, by experimenting with their feasibility in low-and middle-income countries (LMICs) and by studying their diagnostic performances using different sample collections recovered from patients with disseminated histoplasmosis (culture proven), other HIV-related infections, and proven negative urines (culture and other Histoplasma antigen detections).

Results

Preliminary results were obtained using the EDIRAPHIS study frozen samples from hospitalized patients diagnosed with proven positive and negative histoplasmosis from French Guiana and Suriname (n = 43) tested with OIDx and MV tests. We calculated a Se = 74.2% and a Sp = 83.3% for OIDx and a Se = 77.4% and a Sp = 91,7% for MV. A low number of false positives for both tests, &lt;17% for OIDx and &lt;9% for MV were observed. We have a perfect correlation between the observers with a Kappa coefficient of 100% for both tests. Overall, the probabilities that the patient had histoplasmosis with a positive test were 92% and 96% for OIDx and MV respectively.

Conclusion

These first results are very promising and will be completed with two other specimen collections to increase the total numbers of our sampling and get a whole picture of the performances of these two RDTs. The next step will be to implement these new tools at the bedside or in laboratories together with other tests in different settings across SSA.

Diffusion of RDTs together with appropriate training of clinical and laboratory teams and accessibility to treatment may help reduce the burden of histoplasmosis in endemic areas of SSA where the prevalence of the advanced-HIV disease is high.