Seroepidemiology for Enteric Fever: Emerging Approaches and Opportunities

Abstract

Safe and effective typhoid conjugate vaccines (TCVs) are available, but many countries lack the high-resolution data needed to prioritize TCV introduction to the highest-risk communities. Here we discuss seroepidemiology-an approach using antibody response data to characterize infection burden-as a potential tool to fill this data gap. Serologic tests for typhoid have existed for over a hundred years, but only recently were antigens identified that were sensitive and specific enough to use as epidemiologic markers. These antigens, coupled with new methodological developments, permit estimating seroincidence-the rate at which new infections occur in a population-from cross-sectional serosurveys. These new tools open up many possible applications for enteric fever seroepidemiology, including generating high-resolution surveillance data, monitoring vaccine impact, and integrating with other serosurveillance initiatives. Challenges remain, including distinguishing Salmonella Typhi from Salmonella Paratyphi infections and accounting for reinfections. Enteric fever seroepidemiology can be conducted at a fraction of the cost, time, and sample size of surveillance blood culture studies and may enable more efficient and scalable surveillance for this important infectious disease.

Keywords: disease burden; enteric fever; seroepidemiology; serosurveillance; typhoid.

Figure 1.

Conceptual diagram for cross-sectional seroincidence estimation. The left panel illustrates quantitative antibody responses from a cross-sectional serosurvey conducted in both high and low burden settings. Each point corresponds to an individual's antibody response, measured in kinetic ELISA units, with the y-axis presented on a log scale. The right panel demonstrates antibody dynamics following confirmed enteric fever infection. The solid line represents the median response, while the dashed lines correspond to the upper 97.5th percentile and lower 2.5th percentile. The antibody kinetics are used to infer the most likely exposure time for each individual point in the cross-sectional serosurvey (as shown in the left panel), while accommodating heterogeneity in antibody responses.

Figure 2.

Enteric fever surveillance capture pyramid, where the base represents all infections and the apex represents culture-positive cases detected at surveillance sites.