Experimental human typhoid fever challenge was first described in 1896 by Wright, who vaccinated two men against typhoid fever and challenged one with what was then known as Salmonella typhosa. While challenge models are sometimes controversial, they offer enormous potential to study the pathogenesis of disease and to accelerate vaccine development, particularly in human-restricted pathogens such as Salmonella enterica serovar Typhi. The Maryland typhoid human challenge model, which ran from 1952 to 1974, led to insights into typhoid fever and facilitated the development of live attenuated typhoid vaccine Ty21a.
