A deadly soil bacterium common in tropical and subtropical climates has mysteriously infected three people in three different US states, killing at least one, according to a health alert from the Centers for Disease Control and Prevention.

While US cases of the infection periodically pop up in travelers, none of the three infected people have recent travel history that could easily explain how they picked up the dangerous germ. The bacteria, Burkholderia pseudomallei, usually infects by direct contact with an environmental source, i.e. contaminated soil or water. It most often attacks through breaks in the skin and it very rarely jumps from human to human. Yet genetic analyses of the bacterial strains in the latest US cases indicate that the three, geographically-separated infections are related.

The curious cluster of cases suggests there was a common source of the bacteria. Investigators speculate that a yet-unidentified imported product or animal could be a common source. For instance, iguanas and monkeys imported with infections have been linked to cases in the past. But the cluster also resurfaces concern that B. pseudomallei is no longer a mere interloper in the US, rather it may have become a permanent, low-key resident.

The Great Mimicker

The distinction is not only critical for infection prevention efforts but also clinical care. Infections with B. pseudomallei cause melioidosis, which can be fatal in 10 percent to 50 percent of cases. People with diabetes, kidney disease, chronic lung disease, and alcoholism are most at risk. But the symptoms can be vague and widely variable. They include everything from localized pain, swelling, fever, ulceration, and abscesses, to coughing, chest pain, headaches, anorexia, respiratory distress, abdominal discomfort, joint pain, disorientation, weight loss, stomach or chest pain, muscle pain, joint pain, and seizures.

The symptoms are so nebulous, melioidosis is sometimes called the “Great Mimicker” because it’s often mistaken for other serious conditions, such as tuberculosis. Without a travel history that may hint at an exposure to B. pseudomallei, doctors may misdiagnose it—and that can quickly turn deadly. B. pseudomallei is resistant to many antibiotic treatments. Delayed diagnosis and improper treatment can allow the infection to go systemic, which can be fatal in 90 percent of cases.

In the three new cases occurring in two adults and one child, the symptoms ranged from cough and shortness of breath, to weakness, fatigue, nausea, vomiting, intermittent fever, and rash on the trunk, abdomen, and face, the CDC said.

The cases occurred in Texas, Kansas, and Minnesota. One identified in March was fatal. The person had several risk factors for melioidosis, including chronic obstructive pulmonary disease (COPD) and cirrhosis, and this person died ten days after being hospitalized. Of the remaining two cases, one is still hospitalized and one has been transferred to a transitional care unit.

None of the three patients or members of their families reported traveling outside the continental US. In the health alert, the CDC recommended that healthcare providers, “Consider melioidosis in patients with a compatible illness even if they do not have a travel history to a disease-endemic country.” It’s a recommendation that’s been made before.

Connections

This is not the first time that US residents with no recent travel have turned up with a mysterious B. pseudomallei infection. In 2018, a 63-year-old Texas resident, who had not left the state in 30 years, turned up with a near fatal case of melioidosis. To try to track down the infection source, state and federal health investigators thoroughly swabbed the man’s small rural ranch, which had no running water. They sampled soil, surfaces, plumbing, and his water tanks, including the 1,600-gallon water storage tank that the man climbed into on a monthly basis to clean. They found no trace of B. pseudomallei.

But similar to the three new linked cases, the strain of B. pseudomallei infecting the Texas resident in 2018 was genetically linked to other strains that had popped up in US residents. In fact, the closest genetic match to the 2018 Texas case was a strain collected from a 2004 Texas case in the very same county, Atascosa. In that case, too, the Texas resident didn’t seem to have any recent travel history that explained the infection. (It’s unclear how the strains from the three new cases relate to others found in North America and elsewhere.)

In a case report of the 2018 case published last year, health investigators with the CDC and the Texas Health Department highlighted the link to the 2004 cases. In particular, they noted that it was “originally hypothesized that the 2004 patient was infected 62 years before disease onset, while serving during World War II in Southeast Asia.” But the strain of B. pseudomallei  infecting the 2004 Texas case was not related to strains from Southeast Asia, the investigators wrote—the strain was related to other strains from the Americas.

Besides the 2004 Texas case, the next closest genetic match to the 2018 Texas strain was to a strain from a 1999 case in Arizona. Though it was isolated from a patient who had recently emigrated from El Salvador, the strain was more genetically similar to the North American isolates than anything seen in Central America.

To the CDC and Texas investigators looking into the 2018 case, the possibility was clear that B. pseudomallei may be endemic to the US. They wrote:

The source of this patient’s infection remains unknown. However, genomic analysis showed that the patient isolate groups with existing isolates collected from other patients in the southwestern United States. Isolates TX2004 and TX2018b were collected ≈15 years apart from patients living in the same Texas county at time of illness onset and group together, a finding that suggests B. pseudomallei might be present in the environment in this area.

The investigators were also skeptical of the suggestion that a B. pseudomallei infection might “reactivate,” as was the speculation in the 2004 Texas case. “Instead of a 62-year incubation period, the patient infected with TX2004 might have had an unknown local environmental exposure that preceded symptom onset,” they wrote. And the investigators suggested that this long incubation idea may have misled previous investigations away from the possibility that the dangerous bacteria may, in fact, be endemic to the US. They noted a melioidosis case reported in 1991 in a patient living in New Mexico, who hadn’t left the country in years. Doctors evaluating the patient attributed the infection to an exposure during the Vietnam War, 18 years earlier.

The bottom line

Most importantly, the CDC and Texas investigators concluded that “B. pseudomallei infection should be included in a differential diagnosis for a patient with compatible disease, even without reported travel history.”

“Only when B. pseudomallei is isolated from the environment can it be definitively stated that B. pseudomallei is endemic to the continental United States,” they note. But, “increased awareness among healthcare workers and diagnostic laboratory personnel for melioidosis as a disease potentially endemic to the southwestern United States is critical to improve case outcomes and prevent laboratory exposures.”

The message largely echoes that from a 2015 report, which noted an uptick in melioidosis cases in the US between 2008 and 2013. Though most of the 34 human cases identified in the report were linked to travel, two were not.

“Given the slight increase in the number of melioidosis cases reported since 2009, melioidosis might be considered an emerging disease in the United States,” the authors wrote. “Physicians and other health-care personnel should be aware of the increase of cases reported in the United States, especially given the identification of infected persons without travel histories to endemic areas or known risk factors.”

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