Making an Early Diagnosis of Talaromycosis Using a Novel Antigen Test
Making an Early Diagnosis of Talaromycosis Using a Novel Antigen Test
This is a research study to determine whether a new antigen detection test called Mp1p EIA
 can make an early diagnosis of talaromycosis from the blood and urine of patients.
 Talaromycosis is a life-threatening infection caused by a fungus endemic in Southeast Asia
 commonly found in patients with advanced HIV disease called Talaromyces marneffei.
This study aims to determine the diagnostic and prognostic values and the clinical impact of
 Talaromyces marneffei antigenemia (TmAg) in patients with advanced HIV disease using a novel
 enzyme immunoassay (EIA) detecting Tm-specific cell wall mannoprotein Mp1p. The data
 generated will be used to inform the design of future diagnostic clinical trials to test the
 utility of screening and providing pre-emptive antifungal therapy to prevent disease and
 reduce HIV mortality in Southeast Asia.

 The primary objective is to screen for TmAg and determine its diagnostic and prognostic
 performance in symptomatic and asymptomatic HIV-infected patients with a CD4 count ≤100
 cells/mm3.

 We will test the following hypotheses:

 1. In symptomatic hospitalized patient Cohort 1, the sensitivity of the Mp1p EIA will be
 higher than conventional culture method while simultaneously specificity is higher than
 95% for diagnosing culture-confirmed talaromycosis over a six-month follow up period

 2. In asymptomatic outpatient Cohort 2, there will be at least 30% difference in risk of
 talaromycosis development in TmAg-positive patients compared to TmAg-negative patients
 over a twelve-month follow up period

 3. TmAg concentration predicts development of talaromycosis

 Secondary Objectives include:

 1. To assess the impact of presence of TmAg on clinical outcomes, including development of
 culture-confirmed talaromycosis, incidence of state III and IV AIDS events, subsequent
 hospitalizations, and death over six- to twelve-month follow up periods

 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

 We will test the following hypotheses:

 3. To model the health economic benefits of screening and pre-emptive treatment for
 pre-clinical infection

 4. To assess impact on clinic outcomes of screening all patients for cryptococcosis and
 histoplasmosis

 5. To collect additional blood samples and store left-over samples for future research to
 validate infectious disease diagnostics and research to understand genetic
 susceptibility to infectious diseases relevant to HIV population

 Participants in the study, will be asked questions about their medical and travel history.
 Participants will have blood and urine collected for the Mp1p EIA test to look for early
 talaromycosis infection and for other tests to look for common HIV-associated infections
 including tuberculosis, cryptococcosis, and histoplasmosis. They will be examined by a study
 doctor at least once weekly if they are in the hospital and will be followed in clinic
 monthly for between 6 and 12 months.
Inclusion Criteria:

 1. HIV-1 infection (at least 2 of 3 HIV antibody tests are positive), AND

 2. HIV-infected age ≥18 years, AND

 3. CD4 count ≤100 cells/mm3 within the past 3 months, AND

 4. Antiretroviral therapy (ART) naïve OR recent ART ≤3 months OR suspected or confirmed
 treatment failure on ART ≥12 months (defined as poor treatment adherence, treatment
 interruption, or having a confirmed HIV RNA ≥1,000 copies)

 5. Cohort 1: suspected to have an active infection

 6. Cohort 2: not suspected to have or being evaluated for an active infection

 Exclusion Criteria:

 1. Unlikely to attend regular clinic visits

 2. History of recent talaromycosis or histoplasmosis infection currently on antifungal
 therapy