Measuring enteric pathogen force of infection through antibody responses in children

Enteric pathogens account for a substantial global disease burden, yet population-based surveillance remains limited by the transient nature of pathogen shedding, which constrains the sensitivity of stool-based molecular testing to a narrow detection window. Detection of IgG responses in serological surveys could enable new insights into enteric pathogen transmission, but benchmarking serological measures relative to stool-based measures of infection remains a critical evidence gap. We compared measures of disease transmission in longitudinal birth cohort samples using multiplex IgG (1,601 dried blood spots, 370 children) and PCR assays (2,231 stool samples, 370 children) that overlapped for nine pathogens (norovirus GI, GII, Shigella/enteroinvasive Escherichia coli (EIEC), Campylobacter spp., enterotoxigenic Escherichia coli (LT-ETEC), Salmonella enterica, Giardia spp., Cryptosporidium spp., Entamoeba histolytica). LT-ETEC and Campylobacter ranked highest while E. histolytica and S. enterica ranked lowest by both IgG and PCR measures of infection. Measures of infection were less aligned for norovirus GI, norovirus GII, Cryptosporidium, Shigella/EIEC, and Giardia. Despite this, for most pathogens, and across both measures, force of infection was lowest in the urban city of Esmeraldas and substantially higher in more rural populations, with relative risks in assay measures (seroconversion rate and PCR detected prevalence) over 2.0 for pathogens with the largest differences (Shigella/EIEC and norovirus GI). Together, our results suggest that although absolute levels of infection differed between assays, IgG and PCR captured consistent relative risk of infection across geographic strata, suggesting either method can identify high- versus low-transmission settings.