Antibodies in Melioidosis: The Role of the Indirect Hemagglutination Assay in Evaluating Patients and Exposed Populations

Melioidosis, a major cause of fatal community-acquired sepsis, is an increasing global public health concern, with an estimated 89,000 deaths per annum across tropical regions throughout the world.1,2 This disease is caused by Burkholderia pseudomallei (Bp), a Gram-negative soil-dwelling bacillus naturally found in the soil of rice paddies and stagnant water. People acquire infection through direct skin contact, inhalation, or ingestion of contaminated water, and most of the clinical cases have at least one risk factor for melioidosis, such as diabetes, preexisting renal disease, alcohol excess, or old age.3,4 Repeated natural exposure to Bp gives rise to detectable levels of specific antibodies in blood, although these antibodies may not be protective.5–8 The indirect hemagglutination assay (IHA) remains a widely used serological test for clinical epidemiology and case detection as it is cheap and relatively easy to perform. However, a high seropositive rate in healthy individuals living in highly endemic areas has been reported,7–9 and it has been hypothesized that such seropositivity may be due to cross-reactivity of IHA responses to avirulent soil Burkholderia species such as Burkholderia thailandensis (Bt). Studies have demonstrated that the IHA alone is insufficient for diagnosis and defining exposure to Bp because of its low specificity and sensitivity.10,11 Nevertheless, IHA is still used as a marker of exposure to Bp, so here we provide new data for the interpretation of IHA. It has been assumed that individuals who are regularly exposed to contaminated soil are more likely to have increased anti-Bp antibody levels, but few formal reports have been published so far. This study therefore aimed to evaluate the relationship of IHA seropositivity and the demographic profiles of healthy blood donors living in Ubon Ratchathani, an endemic province in northeast Thailand. The demographic profiles included occupation as rice farmer and residence in nonurban areas. There is a lack of data on the relationship between seropositivity and diabetes status, a major preexisting condition, in adult Asian patients with melioidosis. In this study, we then examined the association between IHA seropositivity and survival, diabetes status, and age in a unique longitudinal cohort of adult patients with culture-confirmed melioidosis. We also explored the 52-week dynamic of serological profiles in patients who survived the disease.