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Fatal Laboratory-Acquired Infection with an Attenuated Yersinia pestis Strain --- Chicago, Illinois, 2009

Fatal Laboratory-Acquired Infection with an Attenuated Yersinia pestis Strain --- Chicago, Illinois, 2009
Weekly
February 25, 2011 / 60(07);201-205





On September 18, 2009, the Chicago Department of Public Health (CDPH) was notified by a local hospital of a suspected case of fatal laboratory-acquired infection with Yersinia pestis, the causative agent of plague. The patient, a researcher in a university laboratory, had been working along with other members of the laboratory group with a pigmentation-negative (pgm-) attenuated Y. pestis strain (KIM D27). The strain had not been known to have caused laboratory-acquired infections or human fatalities. Other researchers in a separate university laboratory facility in the same building had contact with a virulent Y. pestis strain (CO92) that is considered a select biologic agent; however, the pgm- attenuated KIM D27 is excluded from the National Select Agent Registry (1). The university, CDPH, the Illinois Department of Public Health (IDPH), and CDC conducted an investigation to ascertain the cause of death. This report summarizes the results of that investigation, which determined that the cause of death likely was an unrecognized occupational exposure (route unknown) to Y. pestis, leading to septic shock. Y. pestis was isolated from premortem blood cultures. Polymerase chain reaction (PCR) identified the clinical isolate as a pgm- strain of Y. pestis. Postmortem examination revealed no evidence of pneumonic plague. A postmortem diagnosis of hereditary hemochromatosis was made on the basis of histopathologic, laboratory, and genetic testing. One possible explanation for the unexpected fatal outcome in this patient is that hemochromatosis-induced iron overload might have provided the infecting KIM D27 strain, which is attenuated as a result of defects in its ability to acquire iron, with sufficient iron to overcome its iron-acquisition defects and become virulent (2). Researchers should adhere to recommended biosafety practices when handling any live bacterial cultures, even attenuated strains, and institutional biosafety committees should implement and maintain effective surveillance systems to detect and monitor unexpected acute illness in laboratory workers.

Case Report

On September 10, 2009, the researcher, a man aged 60 years with insulin-dependent diabetes mellitus, was evaluated at an outpatient clinic for fever, body aches, and cough of approximately 3 days duration. A clinic physician suspected influenza or other acute respiratory infection and referred the patient to an emergency department (ED) for further evaluation; however, the patient did not seek further care at that time. On September 13, the patient was brought by ambulance to a Chicago hospital ED because of fever, cough, and worsening shortness of breath. Paramedics recorded an oxygen saturation level of 92%, and oxygen was administered via mask.

Upon arrival at the ED, the patient was noted to be alert and able to converse, with a temperature of 100.9oF (38.3oC), pulse of 106 beats per minute, respiratory rate of 42 breaths per minute, and blood pressure of 106/75 mm/Hg. Examination revealed distant breath sounds, abdominal distention, peripheral cyanosis, and trace pedal edema; no lymphadenopathy, rash, or jaundice was noted. A chest radiograph revealed normal lung fields; however, the patient continued to have labored breathing and required supplemental oxygen. Blood chemistries showed renal failure (creatinine: 6.5 mg/dL; blood urea nitrogen: 73 mg/dL), incipient acidosis (bicarbonate: 17 mEq/L; PaCO: 31mmHg; pH: 7.36), and elevated liver function enzymes (aspartate aminotransaminase [AST]: 794 IU/L; alanine aminotransaminase [ALT]: 160 IU/L). Complete blood count showed severe leukocytosis (white blood cells: 79.2 103/mL) with a left shift (22% band forms) and hemoglobin level and platelet count within normal limits. Extracellular bacteria were noted on a peripheral blood smear.

The patient initially was treated with diuretics for suspected congestive heart failure and later with intravenous antibiotics (vancomycin and piperacillin/tazobactam) once infection was suspected. At approximately 12 hours after presentation, the patient had worsening respiratory distress and was intubated. He died 1 hour later of cardiac arrest, despite resuscitation attempts.

The patient had last worked in the laboratory on September 4. On September 10, he notified his supervisor about his illness to explain his absence from work. Whether the patient himself suspected his symptoms were consistent with plague is not known; however, existing laboratory policy called for laboratory workers with illness consistent with plague to report to the university's occupational health clinic (or to the ED). The patient's occupation was not documented in the records of either the outpatient clinic he visited or the hospital ED.

On September 14, blood cultures drawn the previous day yielded gram-negative bacilli (four of four bottles), gram-positive cocci (three of four bottles), and yeast (one of four bottles and presumed to be a contaminant). On September 15, the clinical laboratory identified the gram-positive cocci as nutritionally variant streptococci (NVS). An autopsy performed the same day identified no signs of pneumonia, bowel perforation, or endocarditis, which is often associated with NVS infection. Efforts to identify the slow-growing, gram-negative organism were under way when, on September 16, an ED physician learned that the patient had worked in a laboratory that conducted research on select biologic agents and notified the hospital clinical laboratory. On the morning of September 18, 16S ribosomal DNA sequencing performed by the hospital clinical laboratory narrowed the identity of the gram-negative bacilli to either Y. pestis or Y. pseudotuberculosis. That same day, hospital infection control staff members notified CDPH of the suspected Y. pestis case.

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Fatal Laboratory-Acquired Infection with an Attenuated Yersinia pestis Strain --- Chicago, Illinois, 2009

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