Authors
Matthew Laurens, Ezekiel Ackah, Francis Agyapong, Kristen Aiemjoy, Ghulam Rahim Awab, Isaac Bogoch, Robert Breiman, Rita Cardona, Richelle Charles, John Crump, Denise Garrett, Melita Gordon, Sonia Hegde, Kondwani Jambo, Sarah Kelly, Farhana Khanam, Xinxue Lin, Jonathan Mandolo, James Meiring, Emmanuel Mugisha, Kathleen Neuzil, Priyanka Patel, Virginia Pitzer, James Platts-Mills, Andrew Pollard, Firdausi Qadri, Jessica Seidman, Jo Walker. Tian Yun Wang, Kirsten Vannice
Background
Typhoid conjugate vaccine (TCV) is recommended for countries with high typhoid burden or antimicrobial-resistant Salmonella Typhi (S. Typhi). Blood culture, while specific and essential for antimicrobial resistance monitoring, is operationally demanding and variably sensitive; it is often limited to urban sentinel sites in endemic settings. Seroepidemiology offers a complementary, scalable approach to estimate recent infection incidence from cross-sectional antibody data.
Meeting
On 18 July 2025, an expert consultation reviewed typhoid seroepidemiology evidence and programmatic readiness: antigen and isotype choice (anti-HlyE IgG vs anti-HlyE IgA), assay platforms and analytics, cross-reactivity, external validity across geographies and ages, operational feasibility, and communication for vaccine policy.
Key findings
(1) Anti-HlyE IgA shows more consistent decay kinetics than anti-HlyE IgG and appears less sensitive to reinfection-driven boosting, supporting its use for typhoid seroincidence estimation. (2) Where paired data exist, anti-HlyE IgA-derived seroincidence aligns with blood culture-derived incidence, especially beyond age five years. (3) Sample sets with bloodstream infections other than S. Typhi show little problematic cross-reactivity; because HlyE is also expressed by S. Paratyphi A, HlyE-based measures reflect enteric fever. (4) Multiple surveys indicate substantial seropositivity in several African settings, sometimes comparable to highly endemic Asian locations. (5) Kinetic ELISA is the anti-HlyE IgA reference; multiplex bead assays await validation and standardization.
Conclusions
The group concluded that anti-HlyE IgA-based seroepidemiology represents a valuable and increasingly actionable source of evidence to support TCV decision-making. In settings where validation data are available, it can meaningfully inform programmatic decisions when interpreted alongside existing surveillance data. In settings where validation data remain limited, seroincidence estimates should be interpreted cautiously and used alongside complementary data sources. Across contexts, seroepidemiology can provide insights into transmission intensity and population risk. Key priorities include development of best-practice guidance for sampling, assays, analytics, and communication, and expanded paired clinical-serologic studies, especially in Africa.
Click here to read the full meeting report on VeriXiv.
