John Gever, February 25, 2011
An undiagnosed genetic disease appears to have been the critical factor in the 2009 death of a University of Chicago researcher from plague, investigators have concluded.
The 60-year-old man, Malcolm Casadaban, PhD, had been working with an attenuated strain of Yersinia pestis, the plague bacterium, as part of his research. The strain was subsequently cultured from his blood after death.
Although a forensic team from state and local health departments and the CDC were unable to determine how exactly Casadaban came into contact with the organism, autopsy results also indicated he had hereditary hemochromatosis, according to a report in the Feb. 25 issue of the CDC's Morbidity and Mortality Weekly Report.Action Points
Note that this case report describes the first reported fatality from a laboratory-acquired infection with an attenuated strain of Y. pestis.
A possible explanation for the outcome in this patient is that hemochromatosis-induced iron overload might have allowed the infecting strain to overcome its iron-acquisition defects and become virulent.
The incident should heighten researchers' rigorous adherence to biosafety practices whenever they work with live bacteria, and clinicians should routinely ask about patients' occupations and possibly related exposures when they seek treatment, MMWR's editors urged.
Casadaban, who was also diabetic, died in September 2009 after flu-like symptoms worsened over the course of a week into respiratory distress and cardiac arrest.
He had reportedly been working with the bacterium as part of a federal bioterrorism research project.
He was not named in the MMWR report but his identity was given in news reports at the time of his death. It attracted international attention not only because it involved plague but because the attenuated strain involved -- known as KIM D27 -- was not supposed to be dangerous.
Key to solving the mystery of how Casadaban died was that the specific attenuation in KIM D27 is removal of an element known as pgm. It allows Y. pestis to absorb iron from its host. Deprived of iron, the bacterium is rendered nonvirulent -- or at least, that's what the infectious-disease community thought.
In the MMWR report, Kathy Ritger, MD, MPH, of the Chicago Department of Health, and colleagues said that the iron overload characteristic of hemochromatosis may have allowed the KIM D27 strain to overcome the pgm deletion and acquire enough iron to become dangerous.
Postmortem tests revealed that Casadaban had a total serum iron level of 541 μg/dL, more than triple the upper limit of normal (160 μg/dL). Iron saturation was 83.5% and total iron binding capacity was 648 μg/dL, both also well above the reference ranges.
DNA testing showed that the man had two copies of the C282Y mutation in the HFE gene, known to be a cause of hemochromatosis.
"Investigators found no evidence that the researcher knew he had hemochromatosis or that he exhibited any symptoms of this condition," Ritger and colleagues wrote.
As for how Casadaban became infected, the investigators were less sure. "The patient's family members and co-workers were asked about knowledge of any possible exposure events, such as a needle puncture or splash of liquid to the face, and none were reported," they indicated.
But, Ritger and colleagues added, "interviews with laboratory co-workers revealed that the patient inconsistently complied with the laboratory policy to wear gloves while handling Y. pestis KIM D27 bacterial cultures."
Regulations mandate special containment procedures or facilities for research with wild-type Y. pestis, but not for the KIM D27 strain.
An accompanying unsigned editorial noted that Casadaban's death was the first laboratory-acquired fatal plague infection in the U.S. since 1959. That case involved an unattenuated virulent strain.
The MMWR editors indicated that the researcher's diabetes may also have contributed to the severity of the infection.
They wrote that the incident holds lessons both for the research community and for clinicians.
"Researchers working with attenuated Y. pestis and other potentially infectious material should always use at least biosafety level 2 practices, and laboratory managers should ensure that staff adheres to recommended biosafety practices," the editorial said.
"Institutional safety committees should implement and maintain effective surveillance programs to identify and monitor acute illness among laboratory workers, and healthcare providers should routinely inquire about occupational exposures when evaluating patients."
Study authors and the editorialists were all government employees. There was no external funding for the work.
Primary source: Morbidity and Mortality Weekly Report
Source reference:
Ritger K, et al "Fatal laboratory-acquired infection with an attenuated Yersinia pestis strain -- Chicago, Illinois, 2009" MMWR 2011; 60: 201-205.
http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/25051
An undiagnosed genetic disease appears to have been the critical factor in the 2009 death of a University of Chicago researcher from plague, investigators have concluded.
The 60-year-old man, Malcolm Casadaban, PhD, had been working with an attenuated strain of Yersinia pestis, the plague bacterium, as part of his research. The strain was subsequently cultured from his blood after death.
Although a forensic team from state and local health departments and the CDC were unable to determine how exactly Casadaban came into contact with the organism, autopsy results also indicated he had hereditary hemochromatosis, according to a report in the Feb. 25 issue of the CDC's Morbidity and Mortality Weekly Report.Action Points
Note that this case report describes the first reported fatality from a laboratory-acquired infection with an attenuated strain of Y. pestis.
A possible explanation for the outcome in this patient is that hemochromatosis-induced iron overload might have allowed the infecting strain to overcome its iron-acquisition defects and become virulent.
The incident should heighten researchers' rigorous adherence to biosafety practices whenever they work with live bacteria, and clinicians should routinely ask about patients' occupations and possibly related exposures when they seek treatment, MMWR's editors urged.
Casadaban, who was also diabetic, died in September 2009 after flu-like symptoms worsened over the course of a week into respiratory distress and cardiac arrest.
He had reportedly been working with the bacterium as part of a federal bioterrorism research project.
He was not named in the MMWR report but his identity was given in news reports at the time of his death. It attracted international attention not only because it involved plague but because the attenuated strain involved -- known as KIM D27 -- was not supposed to be dangerous.
Key to solving the mystery of how Casadaban died was that the specific attenuation in KIM D27 is removal of an element known as pgm. It allows Y. pestis to absorb iron from its host. Deprived of iron, the bacterium is rendered nonvirulent -- or at least, that's what the infectious-disease community thought.
In the MMWR report, Kathy Ritger, MD, MPH, of the Chicago Department of Health, and colleagues said that the iron overload characteristic of hemochromatosis may have allowed the KIM D27 strain to overcome the pgm deletion and acquire enough iron to become dangerous.
Postmortem tests revealed that Casadaban had a total serum iron level of 541 μg/dL, more than triple the upper limit of normal (160 μg/dL). Iron saturation was 83.5% and total iron binding capacity was 648 μg/dL, both also well above the reference ranges.
DNA testing showed that the man had two copies of the C282Y mutation in the HFE gene, known to be a cause of hemochromatosis.
"Investigators found no evidence that the researcher knew he had hemochromatosis or that he exhibited any symptoms of this condition," Ritger and colleagues wrote.
As for how Casadaban became infected, the investigators were less sure. "The patient's family members and co-workers were asked about knowledge of any possible exposure events, such as a needle puncture or splash of liquid to the face, and none were reported," they indicated.
But, Ritger and colleagues added, "interviews with laboratory co-workers revealed that the patient inconsistently complied with the laboratory policy to wear gloves while handling Y. pestis KIM D27 bacterial cultures."
Regulations mandate special containment procedures or facilities for research with wild-type Y. pestis, but not for the KIM D27 strain.
An accompanying unsigned editorial noted that Casadaban's death was the first laboratory-acquired fatal plague infection in the U.S. since 1959. That case involved an unattenuated virulent strain.
The MMWR editors indicated that the researcher's diabetes may also have contributed to the severity of the infection.
They wrote that the incident holds lessons both for the research community and for clinicians.
"Researchers working with attenuated Y. pestis and other potentially infectious material should always use at least biosafety level 2 practices, and laboratory managers should ensure that staff adheres to recommended biosafety practices," the editorial said.
"Institutional safety committees should implement and maintain effective surveillance programs to identify and monitor acute illness among laboratory workers, and healthcare providers should routinely inquire about occupational exposures when evaluating patients."
Study authors and the editorialists were all government employees. There was no external funding for the work.
Primary source: Morbidity and Mortality Weekly Report
Source reference:
Ritger K, et al "Fatal laboratory-acquired infection with an attenuated Yersinia pestis strain -- Chicago, Illinois, 2009" MMWR 2011; 60: 201-205.
http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/25051
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