Clinical Performance of the Mp1p Immunoassay for Rapid Diagnosis of Talaromyces marneffei Infection

Abstract

The gold standard to confirm Talaromyces marneffei infection (previously penicilliosis) is culture which can take up to 2 weeks. Diagnostic delay is associated with high mortality. Antigen detecting immunoassays offer rapid, specific and sensitive results, and have transformed management of other mycoses such as cryptococcosis. We describe the performance of the Mp1p immunoassay in a cohort of HIV-infected patients with talaromycosis and matched controls. We evaluated the performance of a novel monoclonal antibody-based immunoassay against Mp1p – an abundant mannoprotein in T. marneffei's cell wall. We used plasma samples from a case-control study: HIV-infected patients with culture-confirmed talaromycosis (N = 284 cases) and HIV-infected patients with other opportunistic infections (N = 332 controls) in Ho Chi Minh City between 2010 and 2015. Controls were matched to cases by age, sex, and CD4 count or WHO disease staging. We describe quantitative antigen dynamics over 90 days for 60 patients on treatment. The median CD4 count was 18 cells/mm3 (IQR: 4-22) in cases and 52 cells/mm3 (IQR: 11-56) in control patients. Amongst cases, blood culture (automated Bactec system) was positive in 200 (70%) patients. The other 84 patients had positive culture from skin lesions or lymph nodes. Common opportunistic infections in control patients included cryptococcal meningitis (N=83), oral or esophageal candidiasis (N=47), tuberculosis (N=46), bacterial pneumonia (N=33), PCP (N=22) toxoplasmosis (N=22), and bacterial sepsis (N=21). Based on an optical density cut-off value generated by a receiver operating characteristic curve (ROC) of 0.208, the sensitivity, specificity, positive predicted value, and negative predicted value of the assay were 89.8%, 92.6%, 91.1%, and 91.5%, respectively. Quantitative antigen testing for 60 patients showed that 90% of patients had cleared antigenemia by 3 months. The rates of antigenemia clearance were similar for patients treated with amphotericin B or itraconazole as induction therapy (P=0.079, Student t-test). The Mp1p immunoassay provides an accurate test for differentiating talaromycosis from other HIV-associated opportunistic infections with sensitivity higher than blood culture, thus allows antifungal therapy to begin sooner, and has the potential to reduce talaromycosis mortality.