Background

Talaromyces marneffei (Tm) is one of seven dimorphic human fungal pathogens that cause substantial global morbidity and mortality. Tm is endemic throughout Southeast Asia in a geographic region that encompasses more than half of the world’s population, and is a leading cause of death with a mortality of 30% in people with advanced HIV disease. Late diagnosis increases the mortality to 50%, up to 100% when misdiagnosed.

The most critical barrier to progress is our inability to make an early diagnosis. The current diagnosis is based on culture, which is only 70% sensitive and takes up to 14 days to grow.

We focused first on assessing optimal treatment in a multisite randomised controlled trial and now on developing novel molecular and immunoassays for rapid diagnosis to improve patient outcomes.

Preliminary data suggest that an antigen detection assay based on a novel Tm-specific mannoprotein Mp1p, which is abundantly secreted in the blood of patients, is superior in sensitivity to conventional culture diagnosis and will substantially shorten the time to diagnosis. In the current study, we aim to document the diagnostic predictive utility of this assay in a real-life clinical setting, and we aim to develop a strategy toward a screen-and-treat approach (as was previously developed in cryptococcosis) to prevent disease and mortality in high-risk patients with advanced HIV disease.

Primary objective

To determine the diagnostic and prognostic values and the clinical impact of testing for Talaromyces marneffei antigen (TmAg) in plasma, sera, and urine of patients with advanced HIV disease using a novel enzyme immunoassay (EIA) detecting Tm-specific cell wall mannoprotein Mp1p.

Secondary objectives

1. To assess the impact of TmAg on clinical outcomes;
2. To compare the diagnostic values of the Mp1p EIA when performed in plasma, sera, and urine samples and when performed in these matrices in combination;
3. To model the health-economic benefits of screening and pre-emptive treatment for pre-clinical infection;
4. To assess the impact on clinical outcomes of screening for other major HIV-associated opportunistic infections, including screening for tuberculosis, cryptococcosis and histoplasmosis.