T-Cell Responses Are Associated with Survival in Acute Melioidosis Patients

Background: melioidosis is an increasingly recognised cause of sepsis and death across south east asia and northern australia,caused by the bacterium burkholderia pseudomallei. risk factors include diabetes,alcoholism and renal disease,and a vaccine targeting at-risk populations is urgently required. a better understanding of the protective immune response in naturally infected patients is essential for vaccine design. methods: we conducted a longitudinal clinical and immunological study of 200 patients with melioidosis on admission,12 weeks (n = 113) and 52 weeks (n = 65) later. responses to whole killed b. pseudomallei were measured in peripheral blood mononuclear cells (pbmc) by interferon-gamma (ifn-γ) elispot assay and flow cytometry and compared to those of control subjects in the region with diabetes (n = 45) and without diabetes (n = 43). results: we demonstrated strong cd4+ and cd8+ responses to b. pseudomallei during acute disease,12 weeks and 52 weeks later. 28-day mortality was 26% for melioidosis patients,and b. pseudomallei-specific cellular responses in fatal cases (mean 98 ifn-γ cells per million pbmc) were significantly lower than those in the survivors (mean 142 ifn-γ 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/μl. melioidosis patients with known diabetes had poor diabetic control (median glycated haemoglobin hba1c 10.2%,interquartile range 9.2–13.1) and showed a stunted b. pseudomallei-specific cellular response during acute illness compared to those without diabetes. conclusions: the results demonstrate the role of both cd4+ and cd8+ t-cells in protection against melioidosis,and an interaction between diabetes and cellular responses. this supports development of vaccine strategies that induce strong t-cell responses for the control of intracellular pathogens such as b. pseudomallei. © 2015 jenjaroen et al.