Understanding the Propensity of ETEC Diarrhea in Endemic Settings—A Review of Epidemiological and Immunological Factors and Vaccine-Related Preventive Measures Using a Multisectoral Approach

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of bacterial diarrheal illness in low- and middle-income countries and among travelers to endemic regions, impacting morbidity and mortality and impairing childhood development. Despite its significant importance in public health, the propensity of ETEC diarrhea in endemic settings is influenced by complex interactions among epidemiological, immunological, environmental, and pathogen-related factors. This review aims to provide a comprehensive understanding of ETEC diarrhea in endemic regions by examining epidemiological trends, host immune responses, environmental determinants, and progress in current ETEC vaccine development. We discuss disease burden, seasonality, age-specific susceptibility, toxin and colonization factor diversity, and their relation to diarrheal disease severity at the community level and in hospitalized patients. In addition, we summarize current knowledge on natural immunity, including mucosal and systemic immune responses induced in ETEC-infected diarrheal patients. The review further highlights advances in ETEC vaccine development, focusing on candidate vaccines, safety, immunogenicity, protective efficacy, and challenges associated with implementation in resource-limited settings. By integrating clinical, microbiological, immunological, environmental, and public health perspectives, this review provides a multisectoral framework to better understand ETEC pathogenesis and prevention. It also highlights future research priorities, vaccine strategies, and policy interventions to reduce the burden of ETEC-associated diarrhea in endemic settings.