Human Challenge Studies for Cholera.

The human challenge model permits an estimate of the vaccine protection against moderate and severe cholera. It eliminates the difficulty in setting up a vaccine study in endemic area including uncertainties about the incidence of cholera and the logistic arrangements for capturing those who do/do not become ill. Valuable information from small groups of subjects can be obtained in a short period. Under proper precautions and study design, the challenge model is safe and efficient. Although the model has evolved since it was introduced over 50 years ago, it has been used extensively to test vaccine efficacy. Vaccine licensure has resulted from data obtained using the human challenge model. In addition, the model has been used to: (1) Establish and validate a standardized inoculum, (2) Identify immune markers and immune responses, (3) Determine natural immunity (in re-challenge studies), (4) Identify the role of the gastric acid barrier in preventing cholera infection, (5) Show homologous and heterologous infection-derived immunity, and (6) Test the efficacy of anti-diarrheal/anti-secretory small molecules. The aim of this chapter is to present an overview on the state of the art for human challenge models used to study cholera and new medical interventions against it.