During JEV infection, elevated levels of proinflammatory cytokines and chemokines are associated with a poor outcome, but whether they are simply a correlate of severe disease or contribute to pathogenesis remains to be determined.

The attenuation and immunogenicity of two novel Salmonella vaccine strains, Salmonella enterica serovar Typhi (Ty2 ⌬aroC ⌬ssaV, designated ZH9) and S. enterica serovar Typhimurium (TML ⌬aroC ⌬ssaV, designated WT05), were evaluated after their oral administration to volunteers as single escalating doses of 10 7 , 10 8 , or 10 9 CFU. ZH9 was well tolerated, not detected in blood, nor persistently excreted in stool. Six of nine volunteers elicited anti-serovar Typhi lipopolysaccharide (LPS) immunoglobulin A (IgA) antibody-secreting cell (ASC) responses, with three of three vaccinees receiving 10 8 and two of three receiving 10 9 CFU which elicited high-titer LPS-specific serum IgG. WT05 was also well tolerated with no diarrhea, although the administration of 10 8 and 10 9 CFU resulted in shedding in stools for up to 23 days. Only volunteers immunized with 10 9 CFU of WT05 mounted detectable serovar Typhimurium LPS-specific ASC responses and serum antibody responses were variable. These data indicate that mutations in type III secretion systems may provide a route to the development of live vaccines in humans and highlight significant differences in the potential use of serovars Typhimurium and Typhi.

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Typhoid fever is an infectious disease of global distribution. Although there is a wealth of data on Salmonella typhimurium infection in the mouse and the interaction of this serovar with human cell lines in vitro, there is a relatively small amount of data on S. typhi and the pathogenesis of typhoid fever. In this review we focus on three areas: adherence to and invasion of gut epithelial cells, dissemination to systemic sites, and survival and replication within host cells. In addition, we attempt to put current salmonella research into the context of typhoid fever.

Currently, the laboratory diagnosis of typhoid fever is dependent upon either the isolation of