Role of Environmental Factors in Shaping Spatial Distribution of Salmonella enterica Serovar Typhi, Fiji.

Fiji recently experienced a sharp increase in reported typhoid fever cases. To investigate geographic distribution and environmental risk factors associated with Salmonella enterica serovar Typhi infection, we conducted a cross-sectional cluster survey with associated serologic testing for Vi capsular antigen-specific antibodies (a marker for exposure to Salmonella Typhi in Fiji in 2013. Hotspots with high seroprevalence of Vi-specific antibodies were identified in northeastern mainland Fiji. Risk for Vi seropositivity increased with increased annual rainfall (odds ratio [OR] 1.26/quintile increase, 95% CI 1.12-1.42), and decreased with increased distance from major rivers and creeks (OR 0.89/km increase, 95% CI 0.80-0.99) and distance to modeled flood-risk areas (OR 0.80/quintile increase, 95% CI 0.69-0.92) after being adjusted for age, typhoid fever vaccination, and home toilet type. Risk for exposure to Salmonella Typhi and its spatial distribution in Fiji are driven by environmental factors. Our findings can directly affect typhoid fever control efforts in Fiji.

Salmonella enterica serovar Typhi and gallbladder cancer: a case-control study and meta-analysis.

In Chile, where gallbladder cancer (GBC) rates are high and typhoid fever was endemic until the 1990s, we evaluated the association between Salmonella enterica serovar Typhi (S. Typhi) antibodies and GBC. We tested 39 GBC cases, 40 gallstone controls, and 39 population-based controls for S. Typhi Vi antibodies and performed culture and quantitative polymerase chain reaction for the subset with bile, gallstone, tissue, and stool samples available. We calculated gender and education-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association with GBC. We also conducted a meta-analysis of >1000 GBC cases by combining our results with previous studies. GBC cases were more likely to have high Vi antibody titer levels than combined controls (OR: 4.0, 95% CI: 0.9-18.3), although S. Typhi was not recovered from bile, gallstone, tissue, or stool samples. In our meta-analysis, the summary relative risk was 4.6 (95% CI: 3.1-6.8, Pheterogeneity =0.6) for anti-Vi and 5.0 (95% CI: 2.7-9.3, Pheterogeneity  = 0.2) for bile or stool culture. Our results are consistent with the meta-analysis. Despite differences in study methods (e.g., S. Typhi detection assay), most studies found a positive association between S. Typhi and GBC. However, the mechanism underlying this association requires further investigation.

MyD88-dependent pro-inflammatory activity in Vi polysaccharide vaccine against typhoid promotes Ab switching to IgG.

Vi capsular polysaccharide is currently in use as a vaccine against human typhoid caused by Salmonella Typhi. The vaccine efficacy correlates with IgG anti-Vi Abs. We have recently reported that Vi can generate inflammatory responses through activation of the TLR2/TLR1 complex. In the present study, we show that immunization with Vi produces IgM as well as IgG Abs in wild type mice. This ability is not compromised in mice deficient in T cells. However, immunization of mice lacking the TLR adaptor protein, MyD88, with Vi elicits only IgM Abs. These results suggest that MyD88-dependent pro-inflammatory ability of the Vi vaccine might be vital in generating IgG Abs with this T-independent Ag.