Copyright © 2009 by Limsoon Wong

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

SAFETY DAY 2009

Overview of

Laboratory Acquired Infections

Contact Info

Scott Patlovich, MPH, CBSPSenior Safety & Health Manager

Office of Safety, Health, & Environment

Office: 6516 8802oshsjp@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

Source: Pike, 1976 & 1978

(1930-1978)

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 currentlySource: Recombinant stock likely to be contaminated with “Western

Reserve” strain of virusSecondary 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 currentlySource: Recombinant stock likely to be contaminated with “Western

Reserve” strain of virusSecondary Infections: 102 possible contacts identified; no secondary

infections occurred

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 UniversityWho: 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!