Estimating enteric fever seroincidence in rural western Cambodia: findings from a population-based cross-sectional serosurvey

IntroductionEnteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi, remains an important cause of febrile illness in low- and middle-income countries (LMIC). However, the exact burden is difficult to estimate due to limitations in diagnosis and surveillance. MethodsSamples from a representative cross-sectional household serosurvey in rural western Cambodia were used to estimate enteric fever seroincidence among children and young adults. Participants were enrolled between April 7 and December 10, 2023, and 529 samples from individuals aged 5-25 years were analysed. Using IgA and IgG responses to hemolysin E antigen and established models of antibody decay after infection, we estimated seroincidence, conveying the rate of new infection in the population. Participants were enrolled between April and December 2023, and 529 samples from individuals aged 5-25 years were analysed. ResultsThe overall enteric fever seroincidence rate was 161.8/1,000 person-years (95%CI: 144.6, 181.0). Among children 5-15 years, it ranged between 149.5 (95%CI: 128.7, 173.7) and 239.0 (95%CI:169.2, 337.6) across districts. Seroincidence was numerically higher among children 5-15 years from households with unimproved drinking water sources or sanitation facilities, and districts with a higher proportion of households with unimproved WASH. ConclusionThese findings potentially support the introduction of the typhoid conjugate vaccine in rural western Cambodia. However, additional data on the relative contribution of S. Typhi versus S. Paratyphi is needed. We also demonstrate seroincidence as an adjunctive valuable surveillance tool in LMICs where facility-based surveillance may be inadequate. Key questionsO_ST_ABSWhat is already known on this topicC_ST_ABSO_LICambodia is estimated to have a high burden of enteric fever with a modelled incidence of 1.1/1,000 person-years among those under 20 years in 2023, but lacks population-level data. C_LIO_LIExisting estimates likely underestimate the burden because facility-based surveillance is affected by limitations on diagnosis sensitivity and healthcare access, and the modelled approach lacks country-specific incidence data. C_LIO_LIValidated antibody kinetics models using Hemolysin E (HlyE) antigen of Salmonella serovars Typhi and Paratyphi enable estimation of enteric fever seroincidence from cross-sectional serosurveys. C_LI What this study addsO_LIThis study provides the first population-based estimates of enteric fever seroincidence in rural western Cambodia using HlyE antibody kinetics. C_LIO_LIChildren 5-15 years showed high enteric fever seroincidence that potentially meets the WHO definition for a high-typhoid-incidence setting. C_LIO_LISeroincidence varied geographically and by age, with higher seroincidence in districts with poor water, sanitation and hygiene (WASH) access, and the patterns suggest variations in S. Typhi and S. Paratyphi attribution. C_LI How this study might affect research, practice or policyO_LIOur findings indicate a substantially higher enteric fever burden in rural western Cambodia than previously reported. C_LIO_LIHigh seroincidence among children supports the consideration of the typhoid conjugate vaccine introduction, while highlighting the need for blood culture data to clarify S. Typhi and S. Paratyphi attribution to guide vaccination strategies better. C_LIO_LIImproving WASH access should also be prioritised to reduce transmission of both S. Typhi and S. Paratyphi. C_LIO_LISeroincidence estimation from cross-sectional serosurveys offers a scalable approach for settings where blood culture surveillance is limited. C_LI