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

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

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

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

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

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)

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)

“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.”

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

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

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)

“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

“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

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

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

Science, September 2007

Madison Chamber Photo courtesy of Hillier Architecture

Texas A&M University (2007) Who: 1 student worker infected in Brucella lab exposure incident Agent: virulent Brucella 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

Texas A&M University (2007) Who: 1 student worker infected in Brucella lab exposure incident Agent: virulent Brucella 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

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

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

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

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)

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)

Other Infectious Disease Lab “Mishaps”

Texas Tech University Who: Thomas Butler Agent: Yersinia pestis 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

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

Thank You!