Medical mystery: What caused a melioidosis outbreak in four states
Key Takeaways
A confluence of genetic sequencing, boots-on-the-ground investigation, and some luck identified the strange source of a melioidosis outbreak, a disease typical of Southeast Asia and Australia.
The case highlights how global supply chains and product distribution, as well as climate change, may make melioidosis more common in the US.
The case also presents an exception to the medical maxim, “When you hear hoofbeats, think horses, not zebras.”
It’s an NEJM Brief Report that reads like a clinical detective novel.[]
Between March 13 and July 12, 2021, four patients from four different states contracted melioidosis, a bacterial infection typically sometimes called “great imitator” for its mimicry of other diseases such as pneumonia and tuberculosis. Melioidosis is also typically linked to Southeast Asia and Australia. None of the patients had visited either region.
Tragically, two of the patients were children: a girl, 4, and a boy, 5. The girl recovered, but cannot speak and must use a wheelchair. The boy became neurologically unresponsive and died after 4 days in the hospital. One adult recovered; the other did not.
In an interview for this story, William Bower, MD, a primary investigator on the case, told MDLinx how CDC investigators found that the four cases came from the same source [See below for more from Dr. Bower].
How the CDC identified the source of this outbreak—and how this rare infection didn’t claim more lives—is a fascinating story of genetic sequencing, shoe-leather investigation, and plain luck.
The mysterious origin
Patient No. 1 was a 53-year-old Kansas woman with COPD, cirrhosis from hepatitis C, coronary artery disease, hypothyroidism, and a history of substance abuse. She was hospitalized on March 13, 2021, with shortness of breath, cough, malaise, and weakness.
Eventually, a blood culture identified the source of the problem: burkholderia pseudomallei, a bacteria typically found in tropical and sub-tropical soil and water that’s responsible for melioidosis.[]
Localized, it can cause ulceration or abscesses. Pulmonary cases often involve cough, chest pain, or high fever. Melioidosis can also present as a bloodstream or disseminated infection. Each year, the CDC typically receives reports of about a dozen cases, mostly acquired via travel.
Patient No. 1, and the rest of the patients in this case, hadn’t traveled. Unfortunately, despite her care team’s efforts, she died 9 days after admission.
Patient No. 2 was the Texas girl. She had no significant medical history, and saw her pediatrician on May 31 with fever, decreased activity, and decreased appetite. Prior to the fever, she’d been vomiting for a day.
Her condition deteriorated over 2 days before she was hospitalized. She had a persistent fever, and was tachycardic and tachypneic. She developed septic shock and a lower respiratory culture grew B. pseudomallei. Eventually, she stabilized, but 3 months after leaving the hospital, she couldn’t speak and needed a wheelchair.
Patient No. 3 was a 53-year-old Minnesota man with a history of alcohol dependence and tobacco use. His family discovered him in an altered mental state on May 29. He was admitted with acute metabolic encephalopathy and degenerative hip pain.
A culture of aspirate from the hip joint tested positive for B. pseudomallei. After nearly a month in the hospital, he was discharged to a transitional care facility, but when he left, he remained confused and his hip showed signs of osteonecrosis.
And finally, there was patient No. 4, the 5-year-old Georgia boy, who was hospitalized on July 12 with fever, tachycardia, an elevated white-cell count, and COVID-19. He was transferred to the ICU with declining oxygen saturation. A chest X-ray revealed bilateral opacities with effusions in the lower lobes of the lungs. He died under intensive care 4 days after hospitalization. A swab of lung tissues during autopsy grew B. pseudomallei.
The CDC faced a mystery: How did these patients, none of whom had been to Southeast Asia or Australia, contract melioidosis within 4 months of each other?
Assessing the sources
William Bower, MD, was the CDC’s epidemiological team leader for these investigations and one of the authors of the NEJM report. In an exclusive MDLinx interview, he said that genetic sequencing of the isolates from these four cases were clonal, indicating that they came from the same source.
“They were so closely related that we knew they had to be connected, even though they were distributed widely across the United States,” he said.
But what was the source? Bower said CDC field investigators began at the usual points of origin, visiting the patients’ homes, asking if any had used yard products from areas of the world where b. pseudomallei is found in the soil. They discovered nothing.
“You go back to what the organism likes. We know it likes water,” Bower said.
They repeated the process, this time focusing on liquid products to which the pediatric patients might have been exposed. Bower said that they focused on the children because it’s likely they were exposed to a smaller subset of the thousands of liquid products that could be in a home.
Eventually, they tested an aromatic room spray from the home of the 5-year-old boy. Whole-genome sequencing revealed the isolates from the spray bottle and the patients were a match. They’d found the common thread.
"You’ve heard the quote, ‘Sometimes it’s better to be lucky than good'? I think we were lucky that out of thousands of products that could have been in the home, we picked the right one.""
— William Bower, MD
Fortunately, the lucky breaks continued.
Containing the outbreak
According to Bower, this could have been a larger tragedy for two reasons. The first: how melioidosis spreads. In Australia, melioidosis outbreaks sometimes follow extreme weather events. Hard rains and driving winds aerosolize B. pseudomallei; then people aspirate it.
“If you were going to disseminate this bacteria, a spray bottle such as what was being used with these aromatic sprays would be a very good way to disseminate it,” Bower said.
The second stroke of luck was in how the spray was sold and distributed. According to the US Consumer Product Safety Commission, Walmart had about 3,900 units of this product, which it recalled in November 2021.[]
While that may seem like a lot, Bower said the spray was limited in quantity and distribution. Walmart was trying to weigh consumer demand for the product. Also, much of the stock never reached store shelves.
"I’ll tell you how we were lucky: that this was a pilot product. There could have been more, for sure."
— William Bower, MD
Lessons for physicians
Bower said that the number of melioidosis cases in the US is increasing, stemming from travel to and products sourced from endemic areas. He added that climate change could be making the US environment more hospitable to the disease. He expects to see more cases here going forward.
If you get a microlab identification of B. pseudomallei, don’t disregard it because you think it’s just a contaminant, Bower advised.
And sometimes, when you hear hoofbeats, it is a zebra.
"In medical school, you’re taught that melioidosis is something travel-associated. Don’t discount melioidosis as part of your differential just because a person doesn’t have a travel history."
— William Bower, MD
What this means for you
While melioidosis is typically acquired via travel, the global nature of supply chains and climate change may lead to more US cases. If physicians encounter cases that resemble melioidosis, you may want to inquire about potential exposure to products sourced in part or entirely from Southeast Asia and/or Australia, as well as note the presence of B. pseudomallei in lab work as potentially more than just contamination.