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| ABSTRACT |
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| INTRODUCTION |
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| MATERIALS AND METHODS |
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1:40 and IgG titers
1:64 were considered positive. Fifteen months after exposure, electronic charts of the 38 Marines were examined for any interim health care visits that might suggest delayed onset melioidosis. Because of subsequent deployment of the members overseas, follow-up serologic testing was not performed. This study was not designed before deployment and thus pre-deployment serologies were not available. We compared military personnel with and without positive serologies by one-tailed Fisher exact and rank sum tests to identify potential risk factors for disease acquisition (STATA 10.0; STATA, College Station, TX).
A 20-year-old previously healthy Marine developed fatigue, fevers, and night sweats while in Thailand. These symptoms continued to worsen, and 4 weeks after leaving Thailand, he was admitted with a fever of 104.7°F, night sweats, and a 12-lb weight loss. Laboratory evaluation showed a white blood cell count of 15,900 cells/mm3, an erythrocyte sedimentation rate of 99 mm/h, and elevated transaminases (aspartate aminotransferase [AST], 302 IU/L; alanine aminotransferase [ALT], 221 IU/L). Further evaluation showed multiple bilateral pulmonary nodules and small abscesses in the liver, spleen, kidney, and skin. A bone scan showed osteomyelitis of several bones, including the skull, wrist, and femur. An MRI showed extensive medullary osteomyelitis of his left distal femur extending for 17 cm (Figure 1
). Cultures from both sputum and skin biopsies grew B. pseudomallei, and he was diagnosed with disseminated melioidosis. HIV serology was negative.
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| RESULTS |
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A total of 13 (38%) of the 34 Marines who had serologic testing were positive, including the case reported. Of the positives serologies, nine were IgM and four were IgG; none were positive for both IgG and IgM. In addition to the case above, four other members with positive serologies developed interval symptoms (Table 1
), including one who had ongoing cough, facial pain, night sweats, and an unintentional 15-lb weight loss. This possible second clinical case was further evaluated with computed tomography, which showed a 4-mm right upper lobe nodule and pansinusitis. A nasal culture grew Staphylococcus aureus, and treatment of sinusitis was initiated. His symptoms resolved, and he exited military service without further follow-up.
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| DISCUSSION |
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Most cases in western countries occur in persons returning from endemic regions, but the degree of risk is less well characterized. Risk estimates are complicated by the organisms ability to lay dormant for years before the disease becomes symptomatic; for instance, one case occurred 62 years after exposure.8 This led to concern about a "medical time bomb" in Vietnam veterans in which recrudescent disease would appear years later. 9,10 Serologic studies found positive titers in 8–21% of returning military personnel. 11,12 In the early 1970s, many patients were seen with delayed presentation, but few have been reported among Vietnam veterans since this time. 13 As the ease of global travel has increased, the concern today focuses on the risk faced by short-term travelers.
Our study is unique in that it evaluated the risk of a group who had been in an endemic area for only 2 weeks, an exposure duration similar to that of many travelers. One US Marine developed severe melioidosis. Of the 34 others for whom serology was obtained, 38% were seropositive. This is higher than previous reports, even for more extensive exposures during the war in Vietnam 11,12 and may be caused in part by the serologic test used. Most previous studies have used indirect hemagglutination (IHA), which has been shown to be less sensitive than the IFA used in this study. 14 Another important difference is the timing of the serologic study. In this study, all patients had serology performed 4 months after a known, short exposure period. This may explain the high number of positive IgM results. Although cross-reactivity to Legionella has been shown, false positives were infrequent in early studies, and the specificity of IgM IFA has been reported at 99%. 14 There are very little published data on the sensitivity and specificity of the IFA method since then. No pre-deployment serology was available, so it cannot be definitively determined whether the seropositive results were caused by true seroconversions or were false positives. It is possible that the seropositive Marines seen in this study showed true infection in young, healthy individuals who may remain asymptomatic or have a mild self-limited illness. Because of war-related deployments, most members of the group were not available for later evaluations but may be at risk for delayed presentation of disease.
Melioidosis is usually acquired by cutaneous inoculation or inhalation, and rice farmers are often thought to become infected while wading through fields through small cuts in their feet. In our study group, 70% recalled significant mud exposure and 40% recalled skin cuts or sores. A greater percentage of the seropositive group recalled mud exposure or wading through rice fields, but this was not statistically significant in this small cohort.
The activities of this group of US Marines differ from typical tourists but perhaps not from those of adventure or occupational travelers. Conventional tourists may more closely resemble American diplomats living in Bangkok, who were found to have a 2.7% seropositivity rate using IHA testing. 15 This study, however, was limited by an ill-defined exposure period and the decreased sensitivity of IHA. Our study is limited by the lack of pre-deployment serology and the relatively sparse data on the specificity of IFA serology. Nevertheless, it might be a better estimate for travelers with more extensive environmental exposures and those whose occupations require field work.
Our study suggests that healthy, young adults usually have a mild self-limited disease or remain completely asymptomatic. Severe, acute disease may reflect either a high inoculum or impaired immunity and seems to occur in a small percentage of infected, healthy adults. Our case patient had an open wound on his hand and waded in rice fields and therefore may have developed disease because of a high inoculum. The majority of those infected will not develop clinically apparent, acute disease but may develop late-onset disease, which can be precipitated by relatively minor disruptions to host defenses, such as surgery, trauma, or the development of diabetes. 13 In summary, our study suggests that up to 40% of high-risk short-term travelers may develop asymptomatic B. pseudomallei infections with travelers occasionally experiencing severe melioidosis.
Received July 28, 2008. Accepted for publication August 4, 2008.
Disclaimer: The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Government.
* Address correspondence to Nancy Crum-Cianflone, Division of Infectious Disease, Naval Medical Center San Diego, 34800 Bob Wilson Drive, Ste. 5, San Diego, CA 92134-1005. E-mail: nancy.crum{at}med.navy.mil ![]()
Authors addresses: Karl C. Kronmann, April A. Truett, Braden R. Hale, and Nancy F. Crum-Cianflone, Naval Medical Center San Diego, Infectious Disease Clinic, 34800 Bob Wilson Drive, San Diego, CA 92134.
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