A case-control study was conducted in four hospitals in northeastern Thailand to identify risk factors for melioidosis and bacteremic melioidosis. Cases were patients with culture-proven melioidosis, and there were two types of controls (those with infections, i.e., with community-acquired septicemia caused by other bacteria, and those without infection, i.e., randomly selected patients admitted with noninfectious diseases to the same hospitals). Demographic data, clinical presentations, and suspected risk factors were analyzed. Diabetes mellitus, preexisting renal diseases, thalassemia, and occupational exposure, classified by the soil and water risk assessment, were confirmed to be significant risk factors for melioidosis and bacteremic melioidosis. Only diabetes mellitus was a significant factor associated with bacteremic melioidosis, as compared with nonbacteremia. A significant interaction was found between diabetes mellitus and occupational exposure. Thus, diabetic rice farmers would be the most appropriate population group for targeted control measures such as vaccination in the future.

This was a study of IgG antibody responses to two S-type lipopolysaccharides (LPS I and LPS II) and flagellin of Burkholderia pseudomallei in patients with melioidosis. The specificity of these antibodies was 91.7%, 90.3%, and 93.8%, respectively, when compared to responses in a population where the organism is not endemic. Only the level of antibody to LPS II (anti-LPS II) was significantly higher in patients who survived than in those who died, as well as in patients with nonsepticemic vs. septicemic melioidosis. Results of logistic regression analysis, controlled for confounding factors such as duration of illness before treatment and bacteremic status, confirmed that a high level of anti-LPS II was a significant factor protective against fatal melioidosis. Thus, LPS II of B. pseudomallei would be a potentially useful component of a vaccine developed against fatal melioidosis. Further studies are in progress to determine the level of this antibody among those with asymptomatic infection in areas where melioidosis is endemic.

Platelet-activating factor (PAF) is a potent endogenous proinflammatory mediator implicated in the pathogenesis of septic shock. A double-blind randomized placebo-controlled trial of an intravenous PAF receptor antagonist (lexipafant) was conducted with 131 adult Thai patients with suspected severe sepsis (66 of whom had positive blood cultures). Detailed serial clinical, biochemical, and cytokine measurements were performed. Lexipafant treatment was well tolerated. The 28-day mortality in the lexipafant group (61.4%) was similar to that in the placebo group (62.6%). There was also no evidence that lexipafant affected clinical or biochemical measures of disease severity or the profile of sequentially measured plasma cytokine levels. PAF may not have an important role in the pathogenesis of severe sepsis.Despite significant advances in antimicrobial treatment and intensive care support, sepsis remains a difficult medical management problem with mortality rates between 30 and 50% (5, 11). Proinflammatory cytokines and platelet-activating factor (PAF) are generated in large amounts during the septic response (1). PAF, an ether-linked phospholipid, is one of the most hypotensive and inflammatory agents yet discovered (1, 2, 3, 7). The effects of PAF are mediated through specific PAF receptors. PAF is produced by a broad range of cell types, including monocytes, macrophages, eosinophils, and platelets as well as vascular, kidney glomerular, and gastrointestinal endothelial cells. A wide variety of mediators stimulate these cells to produce PAF; many of these mediators are secreted during the cytokine cascade associated with septic shock. These include tumor necrosis factor (TNF), thrombin, leukotrienes, and bradykinin. PAF has several biological actions characteristic of a proinflammatory agent. When administered systemically to animals, it produces many of the features of septic shock. In experimental septic shock, blocking either the proinflammatory cytokines TNF and interleukin 1 (IL-1) or lipid mediators such as PAF decreases the severity of the disease (12, 13). In one study, the PAF antagonist BN 52021 was shown to be a safe and promising treatment of patients with severe gram-negative sepsis (6).Lexipafant (BB-882; British Biotechnology Ltd., Watlington, Oxford, United Kingdom) is another newly developed PAF antagonist. Lexipafant was shown to be a potent antagonist of PAF in in vitro studies involving the inhibition of [ 3 H]PAF receptor binding and in a PAF receptor binding assay conducted on human platelet membranes. In the latter system, lexipafant bound to the receptor seven times more avidly than native PAF (unpublished data). We report here results of a randomized placebo-controlled study to evaluate the clinical safety and efficacy of lexipafant as an adjunct to the treatment of severe sepsis. Lexipafant has been shown to be well tolerated when given intravenously to volunteers, to patients with pancreatitis, and to patients with sepsis (unpublished data). MATERIALS AND METHODSStudy design and patient ...