The molecular mechanisms of severe typhoid fever.

Salmonella typhi continues to cause severe disease in many parts of the world, its most feared complication being perforation of ulcerated Peyer's patches within the small intestine, leading to peritonitis with associated mortality. The pathogenesis of this process is not well understood. In this article, we present a theoretical mechanism as to how bacterial factors and host immunological mediators within infected tissue might contribute to the observed intestinal pathology, and propose that necrosis of the Peyer's patches observed in typhoid is caused by a mechanism similar to the Shwartzman and Koch reactions.     

Genomics of immune response to typhoid and cholera vaccines

Considerable variation in antibody response (AR) was observed among recipients of an injectable typhoid vaccine and an oral cholera vaccine. We sought to find whether polymorphisms in genes of the immune system, both innate and adaptive, were associated with the observed variation in response. For both vaccines, we were able to discover and validate several polymorphisms that were significantly associated with immune response. For the typhoid vaccines, these polymorphisms were on genes that belonged to pathways of polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signalling and eventual production of antimicrobial peptides. For the cholera vaccine, the pathways included epithelial barrier integrity, intestinal homeostasis and leucocyte recruitment. Even though traditional wisdom indicates that both vaccines should act as T-cell-independent antigens, our findings reveal that the vaccines induce AR using different pathways.