E.W. "Al" Thrasher
Status: Funded - Open
Summary
BACKGROUND: Typhoid fever, caused by Salmonella Typhi, leads to approximately 11 million cases and 117,000 deaths annually, mostly in children under 15. While antibiotics have reduced mortality, antimicrobial resistance is rising, particularly in Asia and Africa, creating an imminent risk of untreatable typhoid outbreaks. GAP: Current burden estimates, based on blood culture surveillance, are unreliable due to limited infrastructure, cost, and low sensitivity (~60%). Many mild or asymptomatic cases go undetected, contributing to disease transmission. Even though effective vaccines exist for S. Typhi, without valid data, governments and international agencies cannot effectively tackle this pediatric crisis. Our team developed a serologic assay that predicts up to 44 times higher incidence in high-burden settings like Dhaka, Bangladesh. This study aims to clarify the link between serologic evidence of infection and clinical disease in children. HYPOTHESIS: We hypothesize that the serologic assay will not only detect symptomatic cases but also uncover a significant number of asymptomatic or mild cases that evade clinical detection. We expect that symptomatic cases will represent approximately 5% of all infections, while 95% will be asymptomatic or mild. METHODS: We will follow a cohort of 600 children under 10 years, who will provide dried blood spots every three months for 18 months. Daily symptoms will be recorded, biweekly interviews conducted, and medical evaluations provided if participants meet study criteria. We will compare symptom/disease episodes to seroincidence. RESULTS: Pending. IMPACT: This study will improve understanding of typhoid burden and provide a low-cost surveillance tool for policymakers in low-resource settings, potentially informing vaccine deployment and water quality interventions. As the arrival of typhoidal Salmonella strains resistant to all antimicrobials materializes, a low-cost tool could rapidly provide evidence to support policy steps that would save children’s lives. Website: https://lubylab.stanford.edu/