Dear Sir:
We note with interest the recent paper by Kronmann and others in the American Journal of Tropical Medicine and Hygiene showing antibodies to Burkholderia pseudomallei in 13 of 38 US Marines, only one of whom had culture-confirmed melioidosis.1 We caution against the use of a poorly validated serologic test to provide evidence of melioidosis in asymptomatic persons.
The authors use the indirect fluorescent antibody (IFA) assay, which has not been used in disease-endemic countries for many years, and no validation of this assay is presented. Although we may assume that the test is broadly similar to the previous descriptions of the IFA assay,2 the bacterial strains used (or if purified antigen was used, the nature of the antigen) are not defined. The authors cite earlier work by Ashdown and others who described a high specificity of the IFA assay, but in this report, only 11 of 89 patients had culture-confirmed melioidosis, with the remaining 78 diagnosed with subclinical melioidosis on the basis of serologic test results.3 The clinical significance of asymptomatic persons with positive serologic results is unclear; whether such people have truly been infected and harbor latent infection is not known. Nevertheless, as the authors note, it is apparent that overt melioidosis does not develop in most of such patients.
Furthermore, there may have been confounding by exposure to the antigenically similar but less virulent B. thailandensis that is present in Thailand but not in Australia. The higher prevalence of positive indirect hemagglutination (IHA) test results using B. pseudomallei antigen in Thai patients compared with those from northern Australia, with a broadly similar incidence of disease, may suggest that exposure to B. thailandensis may result in detectable antibodies against B. pseudomallei.4,5 Studies of cross-reactivity between the IHA using B. thailandensis as the antigen in patients with culture-confirmed melioidosis have not been consistent. 6,7
We suggest that the quantification of risk in groups exposed to mud and pooled surface water should be based on surveillance of culture-confirmed melioidosis in the population at risk. The authors do not offer any data on the incidence of melioidosis in occupationally exposed groups in the same area, such as during previous military exercises or in rice farmers. Approximately 20 cases of melioidosis per year are reported at the Chonburi Hospital approximately 80 km from the study site (with an unknown denominator), and a low rate of melioidosis has been documented in a hospital survey in the central region of Thailand compared with the northeast Issan region. 8,9
In summary, the clinical significance of seropositive asymptomatic persons in this study is doubtful, given the use of a poorly characterized serologic test, possible confounding by exposure to B. thailandensis, the lack of a non-exposed control group, and the lack of a clinical picture characteristic of melioidosis in all but one of these patients.
REFERENCES
- 1↑
Kronmann KC, Truett AA, Hale BR, Crum-Cianflone NF, 2009. Melioidosis after brief exposure: a serologic survey in US Marines. Am J Trop Med Hyg 80 :182–184.
- 2↑
Ashdown LR, 1981. Demonstration of human antibodies to Pseudomonas pseudomallei by indirect fluorescent antibody staining. Pathology 13 :597–601.
- 3↑
Ashdown LR, Johnson RW, Koehler JM, Cooney CA, 1989. Enzyme-linked immunosorbent assay for the diagnosis of clinical and subclinical melioidosis. J Infect Dis 160 :253–260.
- 4↑
Cheng AC, O’Brien M, Freeman K, Lum G, Currie BJ, 2006. Indirect hemagglutination assay in patients with melioidosis in northern Australia. Am J Trop Med Hyg 74 :330–334.
- 5↑
Wuthiekanun V, Amornchai P, Chierakul W, Cheng AC, White NJ, Peacock SJ, Day NP, 2004. Evaluation of immunoglobulin M (IgM) and IgG rapid cassette test kits for diagnosis of melioidosis in an area of endemicity. J Clin Microbiol 42 :3435–3437.
- 6↑
Gilmore G, Barnes J, Ketheesan N, Norton R, 2007. Use of antigens derived from Burkholderia pseudomallei, B. thailandensis, and B. cepacia in the indirect hemagglutination assay for melioidosis. Clin Vaccine Immunol 14 :1529–1531.
- 7↑
Tiyawisutsri R, Peacock SJ, Langa S, Limmathurotsakul D, Cheng AC, Chierakul W, Chaowagul W, Day NP, Wuthiekanun V, 2005. Antibodies from patients with melioidosis recognize Burkholderia mallei but not Burkholderia thailandensis antigens in the indirect hemagglutination assay. J Clin Microbiol 43 :4872–4874.
- 8↑
Waiwarawooth J, Jutiworakul K, Joraka W, 2008. Epidemiology and clinical outcome of melioidosis at Chonburi Hospital, Thailand. J Infect Dis Antimicrob Agents 25 :1–11.
- 9↑
Vuddhakul V, Tharavichitkul P, Na-Ngam N, Jitsurong S, Kunthawa B, Noimay P, Binla A, Thamlikitkul V, 1999. Epidemiology of Burkholderia pseudomallei in Thailand. Am J Trop Med Hyg 60 :458–461.