Transactions of the Royal Society of Tropical Medicine and Hygiene (2008) 102/S1, S66 S70 available at www.sciencedirect.com journal homepage: www.elsevierhealth.com/journals/trst Seropositivity to Burkholderia pseudomallei does not reflect the development of cell-mediated immunity Sharon M. Lazzaroni a , Jodie L. Barnes a , Natasha L. Williams a , Brenda L. Govan a , Robert E. Norton b,c , Justin T. LaBrooy b, 1 , Natkunam Ketheesan a,b, * a School of Veterinary and Biomedical Sciences, James Cook University, Queensland 4811, Australia b School of Medicine, James Cook University, Queensland 4811, Australia c Queensland Health Pathology Services, Townsville, Queensland 4811, Australia KEYWORDS Melioidosis Burkholderia pseudomallei Seroprevalence Indirect haemagglutination assay Cell-mediated immunity Antibodies Summary Cell-mediated immunity to Burkholderia pseudomallei, the causative agent of melioidosis, provides protection from disease progression. An indirect haemagglutination assay was used to detect antibodies to B. pseudomallei in 1500 healthy donors in an endemic region of Australia. Lymphocyte proliferation, activation and cytokine expression to B. pseudomallei antigen were determined in eight donors who were seropositive and in eight age- and sex-matched controls. In North Queensland, 2.5% of the population was seropositive for B. pseudomallei, which is less than half that which was previously described. Of clinical significance was the observation that while 75% of the seropositive individuals had increased lymphocyte proliferation to B. pseudomallei antigens, there were no significant differences observed in lymphocyte activation or production of cytokines. © 2008 Published by Elsevier Ltd on behalf of Royal Society of Tropical Medicine and Hygiene. 1. Introduction Burkholderia pseudomallei, the causative agent of melioi- dosis, is a Gram-negative facultative intracellular bacillus. Melioidosis is an important cause of morbidity and mortality in northern Australia and Southeast Asia. Clinical manifestations of this infection are broad ranging and are difficult to differentiate from other febrile tropical infections. 1,2 Melioidosis is becoming recognized as an entity in several other tropical regions where it was previously not recognized as a problem. There are clinical 3,4 and experimental data 5 7 to suggest that the development of adaptive cell-mediated immune responses (CMI) may be essential for survival following infection. Individuals exposed to B. pseudomallei who do not become ill, may seroconvert and develop a strong CMI that could protect them from disease progression. 3 It is possible that healthy individuals who become seropositive for B. pseudomallei *Corresponding author. Tel.: +61 7 4781 6876; fax: +61 7 4779 1526. E-mail address: n.ketheesan@jcu.edu.au (N. Ketheesan). following exposure to the organism may become symp- tomatic due to activation of latent infection if their immunity is suppressed. However, there is no information in the literature regarding the CMI status of healthy individuals who are seropositive for B. pseudomallei. Therefore, to address this issue, we firstly determined the extent of exposure to B. pseudomallei in the general population by screening healthy volunteers. We then selected individuals with evidence of antibodies to B. pseudomallei and looked for evidence of CMI, in vitro. 2. Materials and methods 2.1. Subjects Following informed consent, serum samples (n = 1500) were collected over a 3-year period from healthy blood donors attending the Red Cross Blood Bank in Townsville, Queensland, a region endemic for melioidosis. Once antibody status was established, for determining CMI in the second phase of the study, further consent was obtained from eight individuals who were seropositive 1 Present address: Royal Adelaide Hospital, North Terrace, Adelaide 5000, Australia. 0035-9203/ $ see front matter © 2008 Published by Elsevier Ltd on behalf of Royal Society of Tropical Medicine and Hygiene.