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.