Life Sciences Institute & Singapore Institute for Clinical Sciences (Brenner Centre)

1. Overview of Laboratory Acquired Infections Life Sciences Institute & Singapore Institute for Clinical Sciences (Brenner Centre) SAFETY DAY 2009

2. Contact Info Scott Patlovich, MPH, CBSP Senior Safety & Health Manager Office of Safety, Health, & Environment Office: 6516 8802 oshsjp@nus.edu.sg

4. Definition of LAI • Laboratory acquired infection (LAI) = an infection obtained through laboratory or laboratory-related activities as a result of work with infectious biological agents, which may be either symptomatic of asymptomatic

5. History of LAIs • Four hallmark studies by Pike and Sulkin collectively identified 4,079 LAIs resulting in 168 deaths between 1930 – 1978 • 159 causative agents identified, although >50% were caused by 10 most common organisms • Many more LAIs likely unreported during this time period

6. (1930-1978) Source: Pike, 1976 & 1978

7. History of LAIs • Harding and Byers literature search of LAIs for 20 years following Pike and Sulkin publications found 1,267 overt infections with 22 deaths • Harding and Byers also reported: • <20% of LAIs from known exposure or documented accident in the lab • Only 7 documented secondary infections from LAIs (1979 – 1999)

8. Despite Controls, LAIs Continue • 1979 Pike concluded “the knowledge, the techniques, and the equipment to prevent most laboratory infections are available” • Yet, laboratory acquired infections continue to occur…(even today)

9. “The conventional wisdom is that laboratory-acquired infections are kept under control by stringent CDC guidelines first introduced in 1984, at a time when investigations of pathogenic bacteria were just starting to bloom. The reality is that no one knows what the reality of laboratory-acquired infections is.”

10. Biosafety Guidelines & Regulations • CDC/NIH. Biosafety in Microbiological and Biomedical Laboratories, 5th Edition. (2007) http://www.cdc.gov/OD/ohs/biosfty/bmbl5/bmbl5toc.htm • World Health Organization. Laboratory Biosafety Manual, 3rd Edition. (2004) http://www.who.int/csr/resources/publications/biosafety/Biosafety7.pdf • Ministry of Health Singapore. Biological Agents and Toxins Act [BATA]. (2006) http://www.biosafety.moh.gov.sg/bioe/ui/pages/links/abt_bata.htm

11. Biosafety Controls • Practices, procedures, and facility controls described in biosafety level criteria (BSLs) • Risk grouping of infectious biological agents • Emphasis on risk assessment, training, SOPs, disinfection, waste management, immunization, post-exposure prophylaxis, biosecurity, etc. • LAIs are not exclusive to BSL-3 or BSL-4 laboratories – many occur in BSL-2 laboratories

12. Potential Routes of Transmission • Inhalation – infectious aerosols, droplets • Ingestion – mouth pipetting; eating, drinking • Percutaneous inoculation – needlesticks and other contaminated sharps; animal bites; exposure to previously broken or damaged skin • Mucous membrane exposure – infectious materials in contact with eyes, nose, mouth (splashes, contact from contaminated surfaces)

15. “Laboratory A” (2002) Who: 1 unvaccinated worker at private lab (“laboratory A”) processing environmental samples following October 2001 anthrax mailings Agent: virulent Bacillus anthracis Route of Exposure: Cutaneous Source: Positive environmental sample not properly handled, plus individual had pre-existing fresh cut on neck from shaving Result: cutaneous anthrax disease including black eschar on neck Other findings: 70% ethanol used for storage vials when 10% bleach prescribed in SOPs; gloves not used to handle vials; wipe samples of lab surfaces indicated only vials were possible source of contamination

16. “Laboratory A” (2002) Who: 1 unvaccinated worker at private lab (“laboratory A”) processing environmental samples following October 2001 anthrax mailings Agent: virulent Bacillus anthracis Route of Exposure: Cutaneous Source: Positive environmental sample not properly handled, plus individual had pre-existing fresh cut on neck from shaving Result: cutaneous anthrax disease including black eschar on neck Other findings: 70% ethanol used for storage vials when 10% bleach prescribed in SOPs; gloves not used to handle vials; wipe samples of lab surfaces indicated only vials were possible source of contamination

18. Boston University (2004) Who: 3 researchers suspected with pneumonic tularemia Agent: Live Vaccine Strain of Francisella tularensis (LVS stock contaminated with wild-type (Type A) virulent form of organism) Route of Exposure: Inhalation Source: Undetermined; several procedures occurring during time period (i.e. centrifuging, vortexing, colony counts not in a BSC) OSHA fine: US$8100 (for improper use of PPE) Other outcomes: City of Boston Public Health Department to survey lab; first ever City of Boston IBC review panel to review all biomedical research in city; construction of new BSL-4 labs highly controversial with public

19. Boston University (2004) Who: 3 researchers suspected with pneumonic tularemia Agent: Live Vaccine Strain of Francisella tularensis(LVS stock contaminated with wild-type (Type A) virulent form of organism) Route of Exposure: Inhalation Source: Undetermined; several procedures occurring during time period (i.e. centrifuging, vortexing, colony counts not in a BSC) OSHA fine: US$8100 (for improper use of PPE) Other outcomes: City of Boston Public Health Department to survey lab; first ever City of Boston IBC review panel to review all biomedical research in city; construction of new BSL-4 labs highly controversial with public

20. Science, September 2007

21. Madison Chamber Photo courtesy of Hillier Architecture

22. Texas A&M University (2007) Who: 1 student worker infected in Brucella lab exposure incident Agent: virulentBrucella spp. Route of Exposure: Mucous membrane exposure (eyes) Source: Improperly trained student worker entered Madison containment chamber to clean unit after aerosolization procedure CDC fine: US$1 million (plus lost grant dollars during lab shutdown) Other outcomes: Failure to properly report cases resulted in cease & desist order from CDC on all infectious disease lab work for nearly one year; significant reputational damage to university

23. Texas A&M University (2007) Who: 1 student worker infected in Brucella lab exposure incident Agent: virulentBrucella spp. Route of Exposure: Mucous membrane exposure (eyes) Source: Improperly trained student worker entered Madison containment chamber to clean unit after aerosolization procedure CDC fine: US$1 million (plus lost grant dollars during lab shutdown) Other outcomes: Failure to properly report cases resulted in cease & desist order from CDC on all infectious disease lab work for nearly one year; significant reputational damage to university

24. Vaccinia Virus (2007) Who: 1 unvaccinated worker at a Virginia academic institution Agent: Vaccinia Virus (live viral component of smallpox vaccine) Route of Exposure: Unknown currently Source: Recombinant stock likely to be contaminated with “Western Reserve” strain of virus Secondary Infections: 102 possible contacts identified; no secondary infections occurred

25. Vaccinia Virus (2007) Who: 1 unvaccinated worker at a Virginia academic institution Agent: Vaccinia Virus (live viral component of smallpox vaccine) Route of Exposure: Unknown currently Source: Recombinant stock likely to be contaminated with “Western Reserve” strain of virus Secondary Infections: 102 possible contacts identified; no secondary infections occurred

26. Recent Vaccinia LAI’s Source: US Centers for Disease Control & Prevention

28. Emory University (1997) Who: 1 worker at the Yerkes Regional Primate Research Center at Emory University in Atlanta, Georgia engaged in behavioral research on hormonal influences in Rhesus macaques Agent: Cercopithecine Herpes Virus 1 (B-virus) Route of Exposure: Mucous membrane exposure (right eye) Source: Splash of bodily fluid from macaque to unprotected eyes (no safety glasses/goggles worn at time of exposure) Result: Fatality of 22-year old female (approx. 6 weeks following exposure) Other findings: No report of exposure until after onset of symptoms of disease; post-exposure treatment not adequate Note: infected macaques are often asymptomatic (no lesions)

29. Emory University (1997) Who: 1 worker at the Yerkes Regional Primate Research Center at Emory University in Atlanta, Georgia engaged in behavioral research on hormonal influences in Rhesus macaques Agent: Cercopithecine Herpes Virus 1 (B-virus) Route of Exposure: Mucous membrane exposure (right eye) Source: Splash of bodily fluid from macaque to unprotected eyes (no safety glasses/goggles worn at time of exposure) Result: Fatality of 22-year old female (approx. 6 weeks following exposure) Other findings: No report of exposure until after onset of symptoms of disease; post-exposure treatment not adequate Note: infected macaques are often asymptomatic (no lesions)

30. Other Infectious Disease Lab “Mishaps”

31. Texas Tech University Who: Thomas Butler Agent: Yersiniapestis What: Apparent loss of 30 vials containing bacteria How Much: 69 counts including illegal transportation, tax fraud, embezzlement, fraud, lying to federal officials Outcomes: 2 years jail time & US$38,000 fine

32. LAIs – Lessons Learned • Prevention of LAIs can be achieved through: • Risk assessment! Risk assessment! Risk assessment! • Establishment of SOPs (controls) appropriate for infectious organisms used • Immunization, when available • Education and training • Use of appropriate precautions including engineering, administrative, and PPE controls • Understanding of disease signs & symptoms • Prompt injury/accident/illness reporting

33. Thank You!