T-Cell Responses Are Associated with Survival in Acute XXXX @entity1 .

@entity1 @entity8 @entity295 @entity404 @entity697 @entity6 @entity6943 @entity988 @entity6942 @entity204 @entity405
BACKGROUND: @entity6942 is an increasingly recognised cause of @entity295 and @entity204 across South East Asia and Northern Australia, caused by the bacterium @entity6943 . Risk factors include @entity6 , @entity988 and @entity8 , and a vaccine targeting at-risk populations is urgently required. A better understanding of the protective immune response in naturally infected @entity1 is essential for vaccine design. METHODS: We conducted a longitudinal clinical and immunological study of 200 @entity1 with @entity6942 on admission, 12 weeks (n = 113) and 52 weeks (n = 65) later. Responses to whole killed @entity6943 were measured in peripheral blood mononuclear cells (PBMC) by interferon-gamma (IFN-y) ELIspot assay and flow cytometry and compared to those of control subjects in the region with @entity6 (n = 45) and without @entity6 (n = 43). RESULTS: We demonstrated strong @entity404 + and @entity405 + responses to @entity6943 during @entity697 , 12 weeks and 52 weeks later. 28-day mortality was 26% for @entity6942 @entity1 , and @entity6943 -specific cellular responses in fatal cases (mean 98 IFN-y cells per million PBMC) were significantly lower than those in the survivors (mean 142 IFN-y cells per million PBMC) in a multivariable logistic regression model (P = 0.01). A J-shaped curve association between circulating neutrophil count and mortality was seen with an optimal count of 4000 to 8000 neutrophils/ l. @entity6942 @entity1 with known @entity6 had poor @entity6 control (median glycated haemoglobin HbA1c 10.2%, interquartile range 9.2-13.1) and showed a stunted @entity6943 -specific cellular response during acute illness compared to those without @entity6 . CONCLUSIONS: The results demonstrate the role of both @entity404 + and @entity405 + T-cells in protection against @entity6942 , and an interaction between @entity6 and cellular responses. This supports development of vaccine strategies that induce strong T-cell responses for the control of intracellular pathogens such as @entity6943 .
