Burkholderia pseudomallei growing on blood agar.

Burkholderia pseudomallei growing on blood agar.

Larry Stauffer, Oregon State Public Health Laboratory, USCDCP

Wake-up call for obscure but deadly infection

It may kill almost as many people as measles—probably close to 90,000 in 2015—but few have heard of it, even among physicians in areas where the deaths occur. It can manifest decades after infection and in many different ways: as an abscess; as a fulminant blood infection with fever, headache, and pain; or as a pulmonary infection with cough and chest pain that’s easy to confuse with tuberculosis.

The obscure disease is melioidosis and a research team today sounds the alarm about it in a paper that provides the first global estimates of its prevalence and the number of deaths it causes. “I’m very happy to see this paper published,” says Alfredo Torres, a microbiologist at the University of Texas Medical Branch in Galveston who wasn’t involved in the work. “It makes very clear that this disease has been underreported and that we need to pay more attention to it.”

Melioidosis is caused by the bacterium Burkholderia pseudomallei, which typically lives in the soil. People and a range of animals can become infected through skin abrasions or when inhaling contaminated dust or drinking contaminated water. The microbe can lead to acute disease immediately or lie dormant before exploding into full-blown melioidosis decades later, a trait that once earned it the nickname “Vietnamese time bomb." Melioidosis is resistant to many antibiotics; even when treated, up to half of the patients may die.

Discovered more than a hundred years ago in the Burmese capital Yangon, then named Rangoon, the disease has traditionally been seen as endemic to Southeast Asia and the northernmost parts of Australia. It is on the U.S. list of potential bioterror agents; B. pseudomallei can be aerosolized and had been investigated as a bioweapon by the United States and other countries. There has been a growing recognition that melioidosis is more widespread than people had thought. Recently, there have been reports of cases from several states in Africa and Latin America, for instance. Wherever people looked for the disease, they found it, Torres says: "Brazil, India. It’s the same story again and again.“ In 2014, an investigation by the U.S. Centers for Disease Control and Prevention (CDC) showed the disease to be endemic in parts of Puerto Rico as well.

To estimate the true global burden of disease, researcher Direk Limmathurotsakul from the Mahidol Oxford Tropical Medicine Research Unit in Bangkok used a model that cuts the globe’s land mass into 8 million squares measuring 5 by 5 kilometers. From data on soil characteristics, temperature, and rainfall, and more than 22,000 records of human or animal infections recorded in the past 100 years, he calculated how suitable the soil in each square is for B. pseudomallei. Using data from known endemic areas like Thailand, he then estimated how likely the disease was to actually be present. The model suggests that the disease is common throughout the tropics, including 34 countries where it has never been reported, Limmathurotsakul and his colleagues write online today in Nature Microbiology. They estimate that there were 165,000 cases in 2015, including 89,000 deaths. As with any modeling effort, the prediction comes with uncertainties, the authors give 68,000 to 412,000 cases as a credible interval and 36,000 to 227,000 deaths.

“I have long suspected that B. pseudomallei is present in many countries where it had not been previously identified,“ says David Speert, an infectious disease specialist at the University of British Columbia in Vancouver, Canada. Not only is melioidosis often misdiagnosed as another disease, but the  bacterium is also difficult to culture in the laboratory and hard to identify. “Add to these problems the fact that B. pseudomallei is most susceptible to extremely expensive antimicrobials and it is possible that the proper therapy would not be available even if the diagnosis was made,” Speert says.

In many countries where melioidosis has never been reported, clinicians simply have not learned to look for it. Limmathurotsakul and his colleagues have prioritized 79 countries as needing their diagnostic capacities for the disease and the microbe strengthened. “If the technicians are not aware that they need to test for this, they will just throw the culture away because it looks like a soil contaminant,” Limmathurotsakul says.

Only a few cases of melioidodis occur in the United States every year, almost all of them in people who have traveled to regions where the bacterium is endemic. But in a report last year summarizing data from 2008 to 2013, CDC noted that "three cases of melioidosis occurred in U.S. residents with no travel history either outside of the United States or to regions where melioidosis is endemic, possibly indicating unrecognized sources of exposure in the United States." Limmathurotsakul’s T model suggests that the southernmost states have the right environmental characteristics for survival of the bacterium in soil. "This sets the stage for subsequent infections if the organism should be introduced,” Speert says. In fact, in November 2014 an outbreak occurred at the Tulane Primate Research Center in Louisiana when the pathogen was spread from mice that were being experimentally infected to primates. Although the suitability level of the soil around the center is very low, the bacterium might become established in otheher areas in Lousiana, like New Orleans, the authors write.

“This study is important,” says Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, Texas. “It confirms a high number of global deaths, such that melioidosis ranks with visceral leishmaniasis as one of the leading causes of death by a neglected tropical disease.“ Melioidosis is so neglected however, that it’s not even on the World Health Organization’s list of neglected tropical diseases, Torres says. That needs to change, he argues. “I really hope this paper will open the eyes of some people involved in health policy.”