Controlled Human Infection Models “A well characterised strain of an infectious agent is administered at a controlled dose and by a specific route to carefully selected adult volunteers” Ensures exposure to an infective dose of the pathogen Useful for: Investigating pathophysiology Defining immune response Testing drugs Testing vaccines CHIMs have been used to develop vaccines for typhoid, cholera and malaria

Reasons for conducting CHIMS in LMICs Ethical / social reasons for carrying out CHIMS in countries where the disease exists Volunteers are the ‘natural’ hosts of the disease, differing from HIC volunteers in factors affecting host-pathogen and host-vaccine interactions Genetics Previous exposure to the pathogen / other infections Immune status Microbiome Environmental factors

Possible issues with conducting CHIMs in LMICs Need good clinical and laboratory facilities, careful monitoring, and good governance Inadequate regulatory framework Factors hampering fully informed consent Unfamiliarity of RECs with CHIMs Natural exposure to related pathogens during study Natural exposure to vectors during study