Project Details

Volatile Organic Compounds as Diagnostic Biomarkers of Pediatric Visceral Leishmaniasis

Alex Green, MD

Summary

BACKGROUND: Visceral leishmaniasis (VL) remains one of the most lethal neglected tropical diseases, imparting 50,000-90,000 cases annually, a fatality rate >95% without treatment, and a disproportionate pediatric burden. Diagnosis of VL relies on hazardous, invasive procedures (e.g. splenic aspirates), or serologic assays with a propensity for early false-negative results and prolonged positivity post-infection. Novel diagnostic modalities for VL are urgently needed. GAP: No published studies have investigated volatile organic compounds as biomarkers of human VL. HYPOTHESIS: Hypothesis #1: Human VL will share a subset of VOC biomarkers reported in canine VL. Specific Aim #1: Identify conserved mammalian VOC biomarkers via targeted metabolomics. Hypothesis #2: Human VL will be characterized by a subset of unique VOC biomarkers. Specific Aim #2: Identify human-specific VOC biomarkers via untargeted metabolomics. Hypothesis #3: Candidate VOC biomarkers are influenced by host and parasite factors. Specific Aim #3: Analyze VOC performance in the context of parasite density and host serostatus. METHODS: We will enroll 30 VL cases and 30 age-matched controls ≤21 years at a high-volume clinic at IMT-RN in Natal, Brazil. VL diagnosis will be established by serology with confirmatory PCR. Controls will be recruited from household contacts negative by both modalities. Breath and skin VOC samples will be collected using field-adapted protocols validated in our prior pediatric studies. Samples will be analyzed via established two-dimensional workflows. Boruta feature selection and random forest modeling will be used to identify discriminatory VOCs and evaluate diagnostic performance. RESULTS: Discriminatory VOC biomarkers have been reported in canine leishmaniasis; other hosts have not been studied. IMPACT: We will establish the first VOC profile of human VL, enabling subsequent development of noninvasive, field-deployable diagnostics.