Controlled Human Infection Models in Enteric Infectious Disease Research

Purposeful human infection challenge studies, or, controlled human infection models (CHIMs) have become recognized in infectious disease research for the study of pathogenesis, immune response and vaccine development or improved therapeutic intervention. In the absence of a suitable animal model, CHIMs can provide a rigorous scientific platform to evaluate the potential efficacy of vaccine candidates and to identify vaccine induced immune correlates of protection. Since the 1970s, CHIMs have undergone ethical, scientific, and legal scrutiny and oversight. However, several issues remain for universal acceptance of the model. These include issues of standardized informed consent of volunteers, capability of investigators and research sites, safety of individuals and community perception. Since many of these studies are primarily intended for populations of endemic regions, often in low- and middle-income countries, there are ongoing questions about the relevance of CHIMs outcomes generated in high-income, non-endemic settings. In this paper, the status of CHIMs applications in enteric infectious disease research will be reviewed highlighting areas of success, as well as limitations and future directions.