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Outbreak of E. anophelis puzzles investigators
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Most infectious disease outbreaks are solved. In rare cases when the cause of an outbreak is not pinpointed, investigators usually are able to identify a general source.
They know, for example, that a common ingredient caused a recent outbreak of Escherichia coli at Chipotle Mexican Grill restaurants — the specific culprit, however, remains a mystery.
“It’s really rare that we don’t have any clue,” Christopher R. Braden, MD, director of the Division of Foodborne, Waterborne and Environmental Diseases in the National Center for Emerging and Zoonotic Infectious Diseases at the CDC, told Infectious Disease News.
Yet for the first time that he can remember in his 23 years with the agency, Braden said the CDC has been stumped by a significant outbreak.
Despite months of investigation, state and federal health officials remain puzzled by a spate of related infections caused by Elizabethkingia anophelis bacteria that began in Wisconsin last fall and spread to two neighboring states. Although dozens of patients — mostly older adults — were sickened by the same strain of the gram-negative bacteria, an exhaustive search has so far failed to determine a cause, and no new cases have been reported since May.
“We’re running out of ideas,” Braden said.
A rare unexplained outbreak
It is the largest documented outbreak of Elizabethkingia in history: 66 cases matching the same strain of E. anophelis have been reported in three Midwestern states since November, including 63 in Wisconsin.
Most of the cases involved bloodstream infections, but isolates also came from the respiratory systems and joints of some patients, the CDC said. Twenty-one patients died, although linking their deaths to the infections is difficult because all but one of them had a serious underlying condition, a significant risk factor for Elizabethkingia infections.
The median age of the patients in the outbreak was 72 years, and the most commonly reported symptoms were weakness and shortness of breath. They lived mostly in private residences at the time of their infection — unusual for Elizabethkingia, which primarily affects patients in health care settings.
Although 66 cases may not seem like a large outbreak, it is more than enough for an investigation, Braden said.
“This is the first time that we’ve had an outbreak of this size and have investigated to this extent, and we don’t even have a type of source that we can point to,” he said.
Cases in Michigan, Illinois linked to Wisconsin outbreak
Despite months without a new case, the Wisconsin Department of Health Services (DHS) said it continues to run a full-scale investigation into the source and will keep testing for infections.
“While the extent of our outbreak is unique,” Jennifer Miller, a DHS spokeswoman, told Infectious Disease News, “health care providers in Wisconsin are now aware of the possibility for infections of Elizabethkingia anophelis and how to test for it and treat it.”
Discovery of the cases in Wisconsin led to increased surveillance around the country as health departments looked for more infections. Cases related to the Wisconsin outbreak were found in Illinois and Michigan, but investigations there also have failed to turn up a source.
In Illinois, officials continue to request that E. anophelis clusters be reported to the state health department, which is how two cases genetically linked to the Wisconsin outbreak were found.
“If clusters are identified, an epidemiologic investigation would occur to attempt to identify contributing factors for the cluster,” Melaney Arnold, of the Illinois Department of Public Health, told Infectious Disease News.
In Michigan, one case was linked to Wisconsin after the CDC confirmed that an Elizabethkingia isolate in a blood sample taken from a patient who died in February matched the outbreak strain.
According to the CDC, Elizabethkingia was detected in 11 other states, with half of the isolates testing positive for E. anophelis, but none matched the Wisconsin strain. The enhanced surveillance and discovery of new cases should help the CDC learn more about Elizabethkingia, according to Braden.
“We hadn’t done very much in the way of research with it before,” he said.
Search comes up empty
Braden detailed how the CDC investigates outbreaks — and why it might not always get the answers it is seeking.
Most outbreaks are point-source outbreaks, in which patients are infected by a common source in a short period of time. The first thing the CDC does is rule out so-called pseudo outbreaks — clusters of cases that turn out not to be outbreaks at all. One way a pseudo outbreak happens is through contamination in the diagnostics laboratory, which can produce positive test results for uninfected patients. This was not the case in the E. anophelis outbreak, the CDC found.
The agency also ruled out the possibility that new diagnostics or enhanced surveillance, such as calls for more testing, were causing a pseudo outbreak.
Finally, whole-genome sequencing showed that the 66 isolates from Wisconsin, Michigan and Illinois were closely related — even more evidence that the outbreak was real.
“The more we learned about this particular outbreak of Elizabethkingia,” Braden said, “the more we were convinced that it was actually an outbreak.”
Elizabethkingia is named for Elizabeth O. King, the CDC bacteriologist who first documented it in the 1950s, mostly in infants. King’s 1959 article in the American Journal of Clinical Pathology described the previously unclassified organism as causing “both sporadic infections and well-defined hospital outbreaks.”
In fact, Elizabethkingia bacteria are common in the environment, but rarely cause human infections — although increased awareness after the Wisconsin outbreak led to the discovery that infections are more common than previously thought, affecting an average of five to 10 people per state annually.
Elizabethkingia is often found in soil, river water and reservoirs, and one of the things that makes looking for the source of an outbreak so difficult is that the bacteria can contaminate any number of things.
Early on, the CDC sent five disease detectives to Wisconsin to look for the origin of the outbreak, and they began by testing water, soil and various health care products, none of which turned up as the source. Since then, the CDC has ruled out hospitals and the patients’ homes as sources of contamination, and it has not found any evidence that patients are transmitting the infections to each other.
Investigators are still trying to devise hypotheses that could be tested in the event of more cases. One way they are doing this is through focus groups involving patients who have closely related isolates, or who live in the same town or work the same job — all in the service of discovering a source.
Basically, Braden said, much of what is left is waiting to see if there are additional cases that offer more evidence.
In other words, the investigation has slowed, but remains open.
“It’s not as if we have a file and we stamp ‘closed’ on it and it goes into a file cabinet,” he said. “Obviously this will remain on our radar for some period of time in the future.” – by Gerard Gallagher
- References:
- King EO. Am J Clin Pathol. 1959;doi:10.1093/ajcp/31.3.241.
- Walters MS, et al. Elizabethkingia outbreak. Presented at: ASM Microbe; June 16-20, 2016; Boston.
Disclosures: Arnold is a spokeswoman for the Illinois Department of Public Health. Braden reports no relevant financial disclosures. Miller is a spokeswoman for the Wisconsin Department of Health Services.