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Am. J. Trop. Med. Hyg., 80(2), 2009, pp. 182-184
Copyright © 2009 by The American Society of Tropical Medicine and Hygiene

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Melioidosis after Brief Exposure: A Serologic Survey in US Marines

Karl C. Kronmann, April A. Truett, Braden R. Hale, AND Nancy F. Crum-Cianflone*
Division of Infectious Disease, Naval Medical Center, San Diego, California; Navy Medicine Manpower, Personnel, Training, and Education Command, Bethesda, Maryland; Infectious Diseases Clinical Research Program, USUHS, Bethesda, Maryland


ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Melioidosis is endemic to Southeast Asia. The incidence of infection in visitors is not well known, especially for short visits. Thirteen (38%) of 34 previously unexposed US Marines had positive serology after 2 weeks in Thailand, and one developed acute disseminated disease. Asymptomatic infection with Burkholderia pseudomallei may be common, even from brief exposures.


INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Melioidosis is a disease of protean manifestations caused by the saprophytic gram-negative bacteria, Burkholderia pseudomallei. Most disease occurs among residents of Southeast Asia and Australia, but cases have been reported in returning travelers. 1,2 The degree of risk to travelers for brief visits is unknown. We report a case of melioidosis and the results of an epidemiologic survey among US Marines returning from military exercises on the coast of Thailand.


MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
A joint multi-national military exercise was conducted on the coast of Thailand near Utapao in May 2006. One US Marine from a participating platoon was diagnosed with disseminated melioidosis and treated at our medical facility. The majority (N = 38) of the other members of his platoon (N = 47) were evaluated by a history and physical examination, written epidemiologic survey regarding exposures, and serologic testing. They were also asked about symptoms during or after the exercise. The assessment was completed 4 months after return; no member traveled to other melioidosis-endemic areas in this time period. Blood samples of 34 Marines were tested for antibody titers of IgG and IgM to B. pseudomallei by indirect fluorescence assay (IFA; Focus Diagnostics, Cypress, CA). IgM titers ≥ 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 1Go). Cultures from both sputum and skin biopsies grew B. pseudomallei, and he was diagnosed with disseminated melioidosis. HIV serology was negative.


Figure 1
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FIGURE 1. T1-weighted MRI image showing extensive osteomyelitis of the distal left femur.

 
The patient was treated with ceftazidime, trimethoprim-sulfamethaxazole (TMP-SMX), and doxycycline for 14 weeks. He responded well clinically, and repeat imaging showed resolution of the abscesses. Surgery was considered for the femur osteomyelitis, but because of the rapid clinical recovery and potential morbidity of the procedure, medical therapy alone was given. Because of the extensive bone involvement of the femur, a prolonged 12-month total course of therapy with doxycycline and TMP-SMX was prescribed, and he recovered without any physical limitations. He was cleared to return to full military duty and was subsequently deployed to Iraq.


RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Thirty-eight Marines completed the physician interview and survey, and serology was obtained among 34. All were men, and each reported that this was his first trip to Thailand or any other country with endemic melioidosis. The mean age was 23 years, with 71% Caucasian, 26% Hispanic/white, and 3% African Americans.

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 1Go), 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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TABLE 1
Descriptive characteristics, laboratory data, and clinical symptoms among seropositive melioidosis cases

 
Epidemiologic data were compared between the seropositive and seronegative groups. Characteristics of the seropositive patients are shown in Table 1Go. Fifty-six percent of Hispanics were seropositive compared with 32% of non-Hispanics, but this was not statistically significant (P = 0.25). There was no difference in age between the groups. Only four of the Marines recalled wading through rice fields; three of these four had positive serology (relative risk [RR] of 2.25; P = 0.15). Eighty-five percent of the seropositive Marines recalled being exposed to mud compared with 62% of seronegative Marines (RR of 2.39; P = 0.14). There were no differences in skin cuts or lesions, illnesses, swimming, or exposures to water or dust between the groups.


DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Melioidosis is a disease endemic to a small part of the world but can be seen worldwide in returning travelers. The majority of disease occurs in Southeast Asia and northern Australia, where it is the most common cause of severe community-acquired pneumonia.3 Mortality rates range from 20% to 50%.4 Exposure is ubiquitous in many areas; B. pseudomallei has been isolated from > 50% of rice field samples, and serostudies suggest that 80% children in northeast Thailand are exposed by 4 years of age.57

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 organism’s 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 Back

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.


REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Ezzedine K, Heenen M, Halvy D, 2007. Imported cutaneous melioidosis in traveler, Belgium. Emerg Infect Dis 13: 946–947.[Medline]
  2. Yazdanpanah Y, Lemaire X, Senneville E, Delcey V, Viget N, Mouton Y, Ajana F, Dubreuil L, 2002. Melioidotic osteomyelitis of the femur occurring in a traveler. J Travel Med 9: 53–54.[Medline]
  3. Currie BJ, Fisher DA, Howard DM, Burrow JN, Lo D, Selva-Nayagam S, Anstey NM, Huffam SE, Snelling PL, Marks PJ, Stephens DP, Lum GD, Jacups SP, Krause VL, 2000. Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature. Clin Infect Dis 31: 981–986.[Web of Science][Medline]
  4. Cheng AC, Currie BJ, 2005. Melioidosis: epidemiology, pathophysiology, and management. Clin Micro Rev 18: 383–416.[Abstract/Free Full Text]
  5. Smith MD,WuthiekanunV,WalshAL,White NJ, 1995. Quantitative recovery of Burkholderia pseudomallei from soil in Thailand. Trans R Soc Trop Med 89: 488–490.[Medline]
  6. Stone R, 2007. Racing to defuse a bacterial time bomb. Science 317: 1022–1024.[Abstract/Free Full Text]
  7. Kanaphun P, Thirawattanasuk N, Supputtamongkol Y, Naigowit P, Dance DA, Smith MD, White NJ, 1993. Serology and carriage of Pseudomonas pseudomallei : a prospective study in 1000 hospitalized children in northeast Thailand. J Infect Dis 167: 230–233.[Web of Science][Medline]
  8. Ngauy V, Lemeshev Y, Sadkowski L, Crawford G, 2005. Cutaneous melioidosis in a man who was taken as a prisoner of war by the Japanese during World War II. J Clin Micro 43: 970–972.[Abstract/Free Full Text]
  9. Greenberg JH, 1969. Public health problems relating to the Vietnam returnee. JAMA 207: 697–702.[Abstract/Free Full Text]
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  11. Kishimoto RA, Brown GL, Blair EB, Wenkheimer D, 1971. Melioidosis: serologic studies on US army personnel returning from Southeast Asia. Mil Med 136: 694–698.[Medline]
  12. Clayton AJ, Lisella RS, Martin DG, 1973. Melioidosis: a serological survey in military personnel. Mil Med 138: 24–26.[Web of Science][Medline]
  13. Jackson AE, Moore WL, Sanford JP, 1972. Recrudescent melioidosis associated with diabetic ketoacidosis. Arch Intern Med 130: 268–271.[Abstract/Free Full Text]
  14. Ashdown LR, Johnson RW, Koehler JM, Cooney CA, 1989. Enzyme-linked immunosorbant assay for the diagnosis of clinical and subclinical melioidosis. J Infect Dis 160: 253–260.[Web of Science][Medline]
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