AI Summary
The text discusses the prevalence of typhoid and paratyphoid fever, the lack of a vaccine for paratyphoid fever, and the unclear mechanisms of protection against bacterial invasion. It mentions the enteric fever human challenge model as a way to study host-pathogen interactions. Previous studies using this model have shown that typhoidal Salmonella can be detected in the stool and blood in the early stages of infection.
INTRODUCTIONAn estimated 14.3 million cases of typhoid and paratyphoid fever, collectively referred to as enteric fever, occur each year (1). Systemic infection is caused by bacterial pathogens Salmonella enterica serovars Typhi and Paratyphi A-C, acquired from contaminated food and water. While a protein-polysaccharide conjugate vaccine has been recently demonstrated to be highly effective against typhoid fever in children, no vaccine against paratyphoid fever has yet been licensed (2, 3). S. Typhi is thought to invade the intestinal epithelium and disseminate systemically within the first 24 hours after infection (4). Infection is asymptomatic for up to 2 weeks (5), after which a secondary bacteremia occurs, often accompanied by fever and fatigue (6).It is unclear whether vaccination and natural immunity exert their protective effect on bacterial invasion of the intestinal epithelium at a later stage in infection or at multiple points during infection. Furthermore, mechanisms of protection, which may differ between natural immunity and vaccines, are unclear. The enteric fever human challenge model, where volunteers are orally exposed to typhoidal Salmonella, offers a unique opportunity to investigate host-pathogen interactions during the incubation period. Previous studies using the human challenge model have shown that live S. Typhi can be detected in stool in the first days after oral challenge, both for participants who go on to develop disease and those who stay healthy (7), suggesting that S. Typhi reaches the lower gastrointestinal tract in both groups. Likewise, S. Typhi DNA has been detected in the blood in the first few days after