Fatal Meningococcal Disease in a Laboratory Worker — California, 2012

Channing D. Sheets, MSEd1, Kathleen Harriman, PhD1, Jennifer Zipprich, PhD1, Janice K. Louie, MD1, William S. Probert, PhD1, Michael Horowitz, MS2, Janice C. Prudhomme, DO2, Deborah Gold, MPH2, Leonard Mayer, PhD3 (Author affiliations at end of text)

Occupationally acquired meningococcal disease is rare (1). Adherence to recommendations for safe handling of Neisseria meningitidis in the laboratory greatly reduces the risk for transmission to laboratory workers (2). A California microbiologist developed fatal serogroup B meningococcal disease after working with N. meningitidis patient isolates in a research laboratory (laboratory A). The California Department of Public Health (CDPH), the local health department, the California Division of Occupational Safety and Health (CalOSHA), and the federal Occupational Safety and Health Administration (OSHA) collaborated on an investigation of laboratory A, which revealed several breaches in recommended laboratory practice for safe handling of N. meningitidis, including manipulating cultures on the bench top. Additionally, laboratory workers had not been offered meningococcal vaccine in accordance with Advisory Committee on Immunization Practices (ACIP) recommendations and CalOSHA Aerosol Transmissible Diseases Standard requirements (3,4). In accordance with OSHA and CalOSHA regulations, laboratory staff members must receive laboratory biosafety training and use appropriate personal protective equipment, and those who routinely work with N. meningitidis isolates should receive meningococcal vaccine.

Case Report

On the evening of Friday, April 27, 2012, a microbiologist aged 25 years had onset of headache, fever, neck pain, and stiffness. The following morning, April 28, he was transported by automobile to the emergency department at hospital A, where he was employed in laboratory A as a researcher. While on the way to the hospital he lost consciousness. Upon arrival, the patient was noted to have a petechial rash, was suspected of having meningococcal disease, and was treated with ceftriaxone. He later had a respiratory arrest. Attempted resuscitation was unsuccessful, and he was declared dead approximately 3 hours after his arrival.

On the day of the patient's death, hospital A notified the local health department and CDPH of the case of suspected meningococcal disease. On April 29, hospital A notified OSHA, which notified CalOSHA that the deceased had worked in a laboratory conducting N. meningitidis vaccine research. Hospital A evaluated potentially exposed emergency department staff members and research laboratory employees; all persons found to have been exposed were immediately assessed for symptoms of meningococcal disease and offered postexposure chemoprophylaxis. Laboratory A voluntarily closed on April 30. No additional cases of meningococcal disease were identified among emergency department or laboratory staff members. The local health department identified other close contacts of the patient and ensured that they received postexposure chemoprophylaxis.

Blood and tissue specimens from the patient were sent to the CDPH Microbial Diseases Laboratory for isolation and serogroup identification. N. meningitidis serogroup B was identified in the clinical specimens by polymerase chain reaction. The patient had worked with N. meningitidis serogroup B isolates in the weeks and days before his death.

Investigation Findings

CalOSHA, OSHA, and CDPH initiated an investigation. Laboratory A was inspected, and employees were interviewed about their training as well as laboratory practices and protocols and were asked to demonstrate how procedures were performed. Multiple breaches in recommended laboratory safety practices were identified (Tables 1 and 2), including manipulation of N. meningitidis isolates on an open laboratory bench (2,5). The inspection team made recommendations for safe handling of N. meningitidis isolates and use of appropriate personal protective equipment. Laboratory A microbiologists working with N. meningitidis isolates had not been offered quadrivalent meningococcal vaccine, as recommended by ACIP (4). At the conclusion of the investigation, OSHA issued three citations classified as serious for failure to protect laboratory workers.

Discussion

Although occupationally acquired meningococcal disease is rare, it is a known risk among microbiologists who work with N. meningitidis isolates (6–8). Investigations of laboratory-acquired cases of meningococcal disease in the United States have demonstrated a many-fold higher attack rate for microbiologists compared with the U.S. general population aged 30–59 years and a case fatality rate of 50%, more than triple the 12%–15% case fatality rate associated with disease in the general population (9). In almost all cases, infected microbiologists had manipulated sterile-site isolates on an open laboratory bench outside of a biosafety cabinet (2,6). Manipulating N. meningitidis isolates outside a biosafety cabinet is known to be associated with a high risk for contracting meningococcal disease (7).

To decrease the risk of transmission to laboratory workers handling invasive N. meningitidis strains (serogroups A, B, C, Y, and W), CDC recommends the use of enhanced biosafety level two (BSL-2) containment practices, where BSL-2 requirements are met and some BSL-3 practices also are adopted (2). Updated recommendations for microbiologists manipulating N. meningitidis strains were published in January 2012 as a supplement to the Biosafety in Microbiological and Biomedical Laboratories guide and include the use of a nonrecirculating biosafety cabinet and the following personal protective equipment: disposable closed front laboratory coat, double gloves, fit-tested N95 filtering facepiece or higher level respiratory protection, and eye protection (2,5). In California, personnel using respirators also must be enrolled in a respiratory protection program (10).

Although this fatal case of serogroup B meningococcal disease was not vaccine-preventable by meningococcal vaccines currently licensed in the United States, licensed vaccines to protect against serogroup A, C, Y, and W-135 disease are available. ACIP recommends meningococcal vaccination for microbiologists who are routinely exposed to isolates of N. meningitidis (3,4). The CalOSHA Aerosol Transmissible Diseases Standard also requires that California employers offer all vaccinations as recommended by applicable public health guidelines for specific laboratory operations (1,4). A serogroup B vaccine (Bexsero, Novartis) was licensed in Europe, Australia, and Canada in 2013 and has received a "breakthrough therapy" designation from the Food and Drug Administration.

Employers should be familiar with laboratory biosafety recommendations and ensure that a laboratory biosafety program is in place. Employers also should ensure that laboratory staff are trained, adhere to recommended biosafety practices and procedures, and are offered recommended vaccines.

Acknowledgments

Linda Guthertz, MA, Heike Quinn, MS, Gillian Edwards, MS, Robin Hogue, Nancy Caton, Margot Graves, Barbara Materna, PhD, Sharon Messenger, PhD, Rita Brenden, PhD, Herschel Kirk, California Department of Public Health. Diane Portnoy, MPH, San Francisco Department of Public Health. Sandra Huang, MD, Alameda County Public Health Department. Occupational Safety and Health Administration.

1California Department of Public Health, 2California Division of Occupational Safety and Health, 3Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, CDC (Corresponding author: Channing Sheets, channing.sheets@cdph.ca.gov, 415-254-2582)

References

1. CDC. Laboratory-acquired meningococcal disease—United States, 2000. MMWR 2002;51:141–4.
2. CDC, National Institutes of Health. Biosafety in microbiological and biomedical laboratories. 5th edition. Washington, DC: US Department of Health and Human Services, CDC, National Institutes of Health; 2009. Available at http://www.cdc.gov/biosafety/publications/bmbl5.
3. California Division of Occupational Safety and Health. Aerosol transmissible diseases. Title 8 C.C.R. Section 5199 (2009). Available at http://www.dir.ca.gov/title8/5199.html.
4. CDC. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices. MMWR 2013;62(No. RR-2).
5. CDC. Epidemiologic notes and reports: laboratory-acquired meningococcemia—California and Massachusetts. MMWR 1991;40:46–7,55.
6. Boutet R, Stuart JM, Kaczmarski ER, Gray SJ, Jones DM, Andrews N. Risk of laboratory-acquired meningococcal disease. J Hosp Infect 2001;49:282–4.
7. Sejvar JJ, Johnson D, Popovic T, et al. Assessing the risk of laboratory-acquired meningococcal disease. J Clin Microbiol 2005;43:4811–14.
8. CDC. Guidelines for safe work practices in human and animal medical diagnostic laboratories. MMWR 2012;61(Suppl).
9. Kimman TG, Smit E, Klein MR. Evidence-based biosafety: a review of the principles and effectiveness of microbiological containment measures. Clin Microbiol Rev 2008;21:403–25.
10. California Division of Occupational Safety and Health. Respiratory protection. Title 8 C.C.R. Section 5144 (1974). Available at https://www.dir.ca.gov/title8/5144.html.