Background:
Talaromycosis – caused by the dimorphic fungus Talaromyces marneffei (Tm) endemic in Southeast Asia – is a leading cause of death in patients with advanced HIV disease (AHD). Blood culture is the mainstay of diagnosis but is only positive during late-staged infection and can take up to 28 days, leading to delayed treatment and high mortality. We report interim results of an ongoing multi-center diagnostic validation study of a novel Tm-specific Mp1p antigen enzyme immunoassay (EIA) for diagnosis of talaromycosis.
Methods:
We prospective recruited hospitalized adult patients with AHD (CD4 < 100 cells/µL or WHO stage III/IV disease) who were ART-naïve or on ART for ≤3 months or >12 months at the National Hospital for Tropical Diseases in Hanoi and the Hospital for Tropical Diseases in Ho Chi Minh City. Mp1p EIA was performed on serum and urine samples at enrollment for all patients. Talaromycosis is diagnosed by conventional blood culture for all patients, alongside microscopic examination and cultures of skin lesions, lymph node, bone marrow or other body fluids as clinically indicated. We followed patients monthly over 6 months for development of culture-confirmed talaromycosis.
Results:
426 patients were recruited between Feb 2021 and July 2022 (follow up ongoing). Talaromycosis was diagnosed in 16.7% (71/426). Compared to the reference standard of culture-confirmed talaromycosis from any specimen over the 6-month follow-up period, the Mp1p EIA has a preliminary sensitivity of 84.5% (60/71, 95% CI: 73.5-91.4), specificity of 94.9% (337/355, 95% CI: 92.0-96.9), positive predictive value of 76.9% (95% CI: 65.7-85.4), and negative predictive value of 96.8% (95% CI: 94.2-98.3). The Mp1p EIA was significantly more sensitive than conventional blood culture: 84.5% (60/71) vs. 66.2% (47/71) patients (P=0.021, McNemar’s Chi-Square). Sensitivities were similar when tested in serum vs. urine samples (81.7%), but urine had a higher specificity (97.5% vs. 95.8%).
Conclusions:
We report a high prevalence of talaromycosis (16.7%) in hospitalized patients with AHD. The Mp1p EIA is superior to blood culture in sensitivity and his highly specific, making it an excellent rapid rule-in test for talaromycosis, allowing early antifungal treatment to reduce mortality. The assay performs very well in urine sample, potentially unlocking the ability to diagnose and screen for disease using a non-invasive sample.
