Melioidosis: An Emerging Tropical Health Problem JULIAN JOSEPHSON
and is often fatal, melioidosis has murky origins.
© 2001 American Chemical Society
T
CORBIS
A disease that strikes
he thought of contracting a difficult-to-diagnose and potentially fatal disease by drinking slowly a glass of water is disturbing enough. Imagine how unsettling it must be, then, to contemplate the possibility of developing symptoms (see sidebar on page 457A) of such an illness six months or more after being occupationally or recreationally exposed to contaminated surface water or sediment, or possibly by drinking water from a contaminated source. Melioidosis (Whitmore’s disease) is such a soil- and waterborne illness. Isolated cases of the illness have occurred in the Western Hemisphere in Brazil, Ecuador, Guyana, Haiti, Mexico, Panama, and Peru. A clustered outbreak of the disease caused by the bacterium Burkholderia pseudomallei occurred in Western Australia in 1997. Up to five confirmed cases occur annually among travelers and immigrants in the United States. In April 1998, Susan Dorman at the National Institutes of Health, Rockville, MD, and now at the Johns Hopkins University Medical School, Baltimore, MD, described a confirmed case of melioidosis in a Puerto Rican patient (1). Dorman notes, however, that the pathogen is rare outside northern Australia and Southeast Asia, where melioidosis is endemic, the greatest concentration of cases occurring in Thailand. There, and in neighboring countries, B. pseudomallei is a common contaminant found in laboratory cultures and has been isolated from soldiers of all nationalities serving in these areas (www.cdc.gov/ncidod/dbmd/diseaseinfo/ melioidosis_g.htm#whatis). Scientists discussed what is known so far about the disease (www.e-tiology.com) at the World Melioidosis Congress, held in Perth, West Australia, in September. They also discussed concerns about possible use of the microbe as a biological weapon.
NOVEMBER 1, 2001 / ENVIRONMENTAL SCIENCE & TECHNOLOGY I 455 A
TIMOTHY INGLIS, PATHCENTRE, PERTH, AUSTRALIA
Although exposure can occur occupationally or recreationally, the extent to which it is a problem in drinking water supplies remains unclear. Progress has been made in understanding the illness and its spread, but evidence that the infection is acquired by water ingestion, even when the organism is isolated from drinking water, “is [presently] very slim,” says David Dance, director of the Plymouth Public Health Laboratory, United Kingdom, and former medical microbiologist at the Wellcome–Mahidol University Oxford Tropical Medicine Research Programme, Bangkok, Thailand. The melioidosis outbreak that occurred in tropical Australia during the near-record rainfall of the 1990–1991 rainy season followed the recognized December–February wet-season pattern (cases of melioidosis normally present during the rainy season) (2). Angela Merianos, then with the Australian National University, Canberra, now with the Canberra Department of Health and Family Services, reported 33 cases in Australia’s tropical Northern Territories from November 1990 to June 1991, of which 25 occurred in Darwin, the territorial capital. Twelve patients died. Subsequently, the causative organism, B. pseudomallei, was isolated from 4% of soil samples and from 9% of surface water samples. Merianos notes that it is widespread in the soil of urban Darwin (2).
Burkholderia pseudomallei, infective agent of melioidosis.
The cluster of cases that occurred during the dry season of 1997, in a remote Western Australia coastal village, where water from a groundwater source is supplied via a treatment plant (aeration and chlorination) at a rate of ~500 kiloliters per day, was much more unusual (3). During the outbreak, five cases of acute septicemic or pneumonic melioidosis were diagnosed during a six-week period. Three of the patients died. Another resident of the community developed septicemia (blood poisoning) six months later. This infection was preceded by an episode of fever during the presumed exposure period, followed one month later by a soft-tissue infection. During the investigation following the outbreak, environmental sampling identified the local drinking water supply (groundwater) as a possible source of B. pseudomallei. Epidemiological studies ascribed the outbreak to acidic bore water, chlorination failure, recent replacement of water pipes, and the tropical climate (www.medscape.com/govmt/CDC/EID/2000/ v06.n01/e0601.08.ingl/e0601.08.ingl-01.html). An in456 A I ENVIRONMENTAL SCIENCE & TECHNOLOGY / NOVEMBER 1, 2001
tensive investigation by medical microbiologist Timothy Inglis and colleagues from the Western Australia Centre for Pathology and Medical Research (PathCentre) Perth and other regional public health units determined that the aerator at the treatment plant was the main source of the bacteria. The highest levels of B. pseudomallei were found in the spray from the upper aerator tray, and a high bacterial count was also noted upstream of the treatment plant. B. pseudomallei was also found in a water storage tank near the water treatment plant. To perform the diagnosis, clinical and environmental isolates were typed by pulsed-field gel electrophoresis, and the presence of B. pseudomallei was established by standard laboratory methods. The microbe’s identity was confirmed using polymerase chain reaction amplification of the species’ DNA sequences (4). Inglis and colleagues believe that aeration to correct acidic, ferric, or unusually warm groundwater supplies of the type often found in tropical regions can amplify B. pseudomallei growth. Indeed, in northeastern Thailand, where groundwater is highly acidic and melioidosis is endemic, naturally occurring aeration may be exacerbating the B. pseudomallei drinking water contamination problem, Inglis says. Late last year, the Australian Medical Research Council funded a three-year study of the role of drinking water as a possible source of melioidosis across Australia’s Top End—the warm-climate portion of northern Australia extending from Western Australia on the Indian Ocean, to Queensland on the Pacific Coast. The Australian federal government now recognizes the potential problem of B. pseudomallei in its drinking water guidelines. However, Inglis says, “Statutory testing is not yet required.” Much of the research on melioidosis is being performed at the Wellcome–Mahidol Programme, which has extensively studied the disease since 1986. Melioidosis also comprises at least 22 study projects being conducted by the Bangkok-based Royal Thai government’s Thailand Research Fund. “The vast majority of cases [are among] rice farmers,” says Dance, who believes that melioidosis is not confined to Australia and Southeast Asia. “I am sure that melioidosis could be underdiagnosed in Central and South America and in other parts of the tropics. In addition to numerous published cases, I also am aware of a further recent case from El Salvador,” he says. Reputedly, one case occurred in the continental United States in Oklahoma during the mid-1970s. A farmer pinned under his overturned tractor for two hours sustained deep lacerations and contracted a pelvic wound infection from an organism whose culture and biochemical characteristics were identical to those of B. pseudomallei. Identical organisms were recovered from the soil at the site of the accident (5), but Dance cautions that “there are a number of ways in which [contracting the illness] was atypical.” Scientists in Taiwan are also concerned about the possibility of melioidosis emerging as an infection there. From January 1982 through May 2000, 15 patients were diagnosed with an infection caused by B. pseudomallei. One case occurred in 1982, two in
Often difficult to diagnose, melioidosis frequently Other forms of melioidosis include focal abscesses at shows up in the form of acute septicemic illness, but it almost any body site and subclinical seroconversion— also can appear as acute pneumonitis, encephalitis, or development of antibodies in blood serum as a result of even early-onset organ system failure. Other symptoms infection—with no clinically evident features. In some include soft-tissue abscesses that can metastasize. parts of the endemic zone, school children are found to Recent studies peg the total mortality rate as high as have seroconverted during early childhood. 60–70%, Inglis says, adding that the mortality rate for About 25% of those who survive the acute infection septicemic illness “is at least 34%.” may develop recurrent septicemia, which can present Humans and animals can contract anew up to 30 years later, with a long melioidosis mainly by direct contact disease-free interval in between. “This with contaminated soil and surface is one reason why melioidosis has waters, the main pathway of infection, been called the Vietnam time bomb,” primarily during rainy seasons. B. Inglis explains. He notes further that B. pseudomallei also can enter the body pseudomallei can survive inside freevia dust inhalation, contaminated living amoebae and remain hidden. Its water ingestion, and contact with ability to survive intracellularly may A melioidosis infection has contaminated soil through skin abraaccount for disease-free intervals and severely damaged this human sions. For military personnel, there is the appearance of symptoms months spleen. an additional risk of war wounds or even years after an initial infection. being contaminated by it. Melioidosis is apparently not communicable, Melioidosis can be categorized as an acute localalthough two cases of sexual transmission have been ized infection (localized as a nodule through a break in reported. In both cases, the source patient had a clinithe skin that can spread); a pulmonary infection (rangcal history of chronic prostatitis. ing from mild bronchitis to severe pneumonia); and an No effective vaccine has been approved for human acute bloodstream infection, which can lead to anyuse. Although several antibiotics have shown action thing from abscesses throughout the body to septic against the microbe, Ceftazidime is the principal antibiotic shock. Melioidosis also can occur as a chronic suppuused for treatment and has helped reduce overall mortalirative infection that involves the organs of the body, ty to 34% of illnesses. Regimens of oral antibiotic cocktypically the spleen, liver, lung, and brain, as well as tails are administered to try to prevent recurrence or bones, joints, viscera, lymph nodes, and skin. relapse, although this may still occur in 5–10% of patients.
1994, and the balance occurred from 1996 to 2000. Of the total observed cases, 13 were considered indigenous, according to Hsueh Po-Ren and colleagues at the National Taiwan University Hospital in Taipei. Four patients died of melioidosis, and the B. pseudomallei isolated from them was shown, in vitro, to be susceptible to four antibiotics (6). Elsewhere, in the province of Bologna, Italy, B. pseudomallei was found in ~7% of 85 drinking water samples collected from public and private buildings. Observed levels were as high as 578 colonyforming units/100 mL, according to Franca Zanetti and colleagues at the University of Bologna (7 ). This report, however, has not been corroborated by other researchers, and there have not been any reports of clinical cases of melioidosis in the region.
A bioterrorist weapon? “There is considerable interest in biosafety aspects of B. pseudomallei as a bioterrorist weapon,” says Inglis. Indeed, stringent precautions are being taken by registered culture collections and public health laboratories to prevent inadvertent infection in the workplace or exposure of the public to culture concentrates during transit. Concerns for B. pseudomallei biosafety also extend to the former Soviet Union’s biological weapons research program, which included B. pseudomallei
VISANU THAMLIKITKUL, MAHIDOL UNIVERSITY, BANGKOK, THAILAND
The “Vietnam Time Bomb”
and a related microbe, Burkholderia mallei, the cause of a disease called glanders, at several locations in Russia during the Cold War (8). Recently, a civilian researcher at Fort Detrick, MD, doing research on B. mallei contracted glanders (9), which, if left untreated, is invariably fatal. Whether or not bioweapons research leads to the deliberate release of B. pseudomallei, melioidosis is an emerging infectious disease with serious international environmental and public health problem implications.
References (1) Dorman, S. E.; Gill, V. J.; Gallin, J. I.; Holland, S. M. Clin. Infect. Dis. 1998, 26 (4), 889–894. (2) Merianos, A.; et al. Southeast Asian J. Trop. Med. Pub. Health 1993, 24 (3), 425–435. (3) Inglis, T. J. J.; et al. Epidemiol. Infect. 1999, 123, 437–444. (4) Kunakorn, M.; Markham, B. J. Clin. Microbiol. 1995, 33, 2131–2135. (5) McCormick, J. B.; et al. J. Infect. Dis. 1977, 135, 103–107. (6) Hsueh, P.-R.; et al. Emerg. Infect. Dis. 2000, 7 (3), 428–433. (7) Zanetti, F.; De Luca, G.; Stampi, S. Int. J. Food Microbiol. 2000, 59 (1–2), 62–72. (8) Hoffman, D. Deadly Germs from Cold War. The Washington Post, June 7, 2000, p. A24. (9) Associated Press. Scientist Catches Disease at Army Research Center. The Washington Times, May 14, 2000, p. C11.
Julian Josephson is a contributing editor of ES&T. NOVEMBER 1, 2001 / ENVIRONMENTAL SCIENCE & TECHNOLOGY I 457 A
