Sero-epidemiological studies of pathogen burden: A scoping review.

BACKGROUND: Methodological advances in serological testing have made it feasible to quantify antibodies to multiple pathogens simultaneously. This has been used to study the impact of pathogen burden, i.e., cumulative lifetime exposure to persistent pathogens, on health and mortality outcomes. However, definitions for pathogen burden using serological data vary considerably. It is unclear how to best combine serological data for multiple pathogens for exposure/outcome definitions in epidemiological studies. METHODS: Following PRISMA-ScR guidelines, we conducted a scoping review of all relevant publications from MEDLINE, Embase, and Scopus until May 1 st, 2025, with no language restrictions. We identified epidemiological studies defining pathogen burden, and which included at least three different pathogens. RESULTS: We included a total of 74 studies from 19 countries (published 2000-2025). Serology data from 50 different pathogens were analysed across all studies, with pathogen burden measured by combining a range of 3-17 pathogens across studies into a single metric. Approaches included counts of seropositive result, quantiles of antibody titres, and more complex statistical analyses to group pathogens. No study gave a clinical/scientific rationale for the approaches chosen. CONCLUSIONS: Various analytical approaches have been used to define pathogen burden but there was limited justification for the chosen methodological approaches. More integrated approaches are needed for combining scientific and clinical knowledge of the interaction across different pathogens and epidemiological evidence into a meaningful measure of pathogen burden.