EMD 545 b Biosafety Biosecurity and the Evaluation

EMD 545 b Biosafety, Biosecurity, and the Evaluation of Biohazards Course Lecture #1

Lecture #1 Outline • • Course intro, objectives, syllabus review Texts, handouts, microbiology assessment Student Interests (goals of course) Biosafety (then and now) Biohazards: here, there, everywhere Profession of Biosafety, resources Laboratory Acquired Infections

Course Objectives • Illustrate science and profession of biosafety • Examine the application of biosafety in various settings • Provide a foundation in the principles of biohazard containment and control

Course Syllabus • Lectures – 1 st half of course • Tours – Building HVAC system, cooling tower – Biohazard containment facility – Animal facility tour – Guest speakers • Bioaerosol or “project” sampling location – Selected by student teams

Course Syllabus • Projects – Risk assessment exercise (major) – Regulatory Policy comparison (minor) – Bioaerosol/env. micro sampling (major – team) – Facility commissioning exercise (minor – team) • Completed by group in class session – Point/counterpoint challenge (major – team) • Final Exam (major) – Open book(s), open notes and handouts

Texts • Biosafety: Principles and Practices, 4 th Ed. • CDC/NIH Biosafety in Microbiological and Biomedical Laboratories, 5 th Ed. • NIH Guidelines for Research Involving Recombinant DNA Molecules (April 2002) • Handouts (hard copies, email, or online) • Previous coursework or experience in Micro or Molecular Biology?

Students • Introductions • Student Interests – What do YOU hope to get out of the class? • Course Goals!!

Biosafety • The consistent application of safety measures to minimize or prevent exposure to the person handling the agent, lab and building occupants, the community and the environment. – Key Safety Measures: • good microbiological work practices • safety and containment equipment • facility design consideration

Biohazard • Biohazard n (1967): a biological agent or condition (as an infectious organism or insecure laboratory conditions) that constitutes a hazard to man or his environment; also a hazard posed by such an agent or condition. • Webster’s 9 th New Collegiate Dictionary, Miriam. Webster Inc. Publishers, Springfield, MA USA, 1985

Biohazard Settings/Biosafety Applications • Where?

Biohazard Settings/Biosafety Applications • Research, including: – human & animal pathogens, select agents (bioterrorism) – toxins of biological origin – r. DNA research, Human Gene Transfer, plants, animals, large scale – shipping, transport, import, export, permits – training (BBP, TB, infection control, shipping, Biosafety, BSL-3, work practices, BSC’s) – field work, work abroad (feral animal, insects, arthropods)

Biohazard Settings/Biosafety Applications • Clinical/Hospital Settings (helping sick people) – micro labs, in- and out-patient facilities, infirmaries – infection control, standard precautions, airborne precautions (TB, measles, varicella, flu) – social workers, divinity and law school volunteers, students

Biohazard Settings/Biosafety Applications • Buildings/IAQ – fungi, SBS, cooling towers, HVAC, floods, leaks, allergens • Emergency Response – police, fire, plant maintenance personnel, public health officials – biohazard spills, exposures, incident review • Environmental Issues – mosquito control program, anthrax sampling (mailrooms) – food sanitation • Other – clean air device monitoring (biosafety cabinets, other hoods) – facility design, renovation, construction, and commissioning

Biohazard Settings/Biosafety Applications • Cruise ships, airplanes, trains, buses, other crowded conditions • Homeless shelters, prisons, schools • Farms, agricultural settings (zoonotic agents) • Hunting (gutting/dressing wildlife) • Bioterrorism (local area response) • Production of medical products, vaccines, drugs, biologics • Outbreak investigations, war, refugee camps • Other? ? ?

OEHS Biosafety • “We don’t make the jobs you do…. . • We make the jobs you do safer. ”

Biosafety: Historical Perspective (Seymour Block) • Homer (Odyssey XXII)- burned sulfur for fumigation, 800 BC • Hippocrates- involvement of fomes/fomites in disease process, 4 th century BC • Bible – move campsites daily, care of wastes, strict dietary/cleanliness – rules/regulations regarding lepers • (ISOLATION) – burn or boil clothing and equipment • Aristotle - advised Alexander the Great (boil water, bury excreta)

Biosafety: Historical Perspective (Seymour Block) • Susruta (Hindu physician)- cleaning/fumigation of OR before and after operations, 500 AD • Great plagues- burn victims clothes, burned bodies on 10 foot poles, unique PPE worn by physicians (perfume in beak), full body coverage, Middle Ages • Girolamo Fracastoro- referred to “seeds” or “germs” of disease. Identified 3 sources of contagion (contact, fomites, air). 1478 -1553 • Venice Magistry of Health- fumigated cargo and mail from ships, 1438

Biosafety: Historical Perspective (Seymour Block) • Leeuwenhoek- studied effect of chemicals on “little animals” under microscope, 1676 • Cotton Mather- 1 st in America to vaccinate against smallpox (with smallpox, Jenner used Cowpox), 1720 • James Lind- hygiene as sea (disinfection, filtration of water, cleaning and ventilation of sick bay, special clothes for physicians), 1757 • Nicholas Appert- Canning method for food preservation, 1810 • John Pringle- sanitary trench disposal of waste in warfare

Biosafety: Historical Perspective (Seymour Block) • Oliver Wendell Holmes (1843), Ignaz Semmelweis (1847) Identified spread of puerperal fever to patients from medical staff. Introduced hand washing to thwart spread. • Agostino Bassi (lawyer)- suggested use of germicides, patient isolation, and decontamination of clothes and excreta (1835) • Louis Pasteur- Flame sterilization of surgical tools, heat sterilization of bandages before use on wounds, risk assessment enters forefront with his quote “Chance favors the prepared mind. ” (1880’s)

Biosafety: Historical Perspective (Seymour Block) • Joseph Lister- antiseptic use on open wounds (phenol), poured directly into wounds, lowered infection rate from 90 - 15%, (1860’s - 1880’s) • Robert Koch- sterile technique, pure culture, use of solid media, tested over 70 disinfectants, (1881) • Dakin- 0. 5% hypochlorite used to disinfect wounds in WWI • WWII-1 st war with less deaths from disease than from battle wounds (disinfectants in common use)

Pertinent Biosafety Events • 1918 - Flu pandemic • 1928 - Discovery of antibiotics • 1930’s - present - Biowarfare research continues (Japan’s Unit 731, many other examples before and after) • 1930’s- U. S. Malaria Control Division (later CDC&P) • 1940’s- Invention of Electron Microscope – Can now see viruses! • • • 1950’s -present- Viral Hemorrhagic Fever outbreaks 1967 - Marburg virus outbreak in lab 1966 -1968 - development of Biohazard Symbol 1969 - Lassa Fever LAI’s at Yale 1970 - OSHA, EPA created (OSHA General Duty Clause)

Pertinent Biosafety Events • 1974 - Classification of Etiologic Agents on Basis of Hazard (Biosafety Levels 1 - 4) • 1976 - NIH r. DNA Guidelines • 1976 - Ebola outbreak • 1978 - Smallpox LAI, England • 1979 - Laboratory Safety Monograph (NIH) • 1979 - Anthrax release from military research lab, Sverdlosk, Russia (>60 deaths) • 1980 -1984 - CDC/NIH Biosafety handbook, WHO text • 1981 - 1 st HIV cases reported

Pertinent Biosafety Events • 1986 - EPA Medical Waste Requirements • 1988 -1994 - needles/syringes found on beaches on east coast, Medical Waste Tracking Act established • 1988 -1992 - resurgence of TB cases, MDR-TB observed • 1988 -1991 - OSHA Bloodborne Pathogens Standard • 1990 - 1 st Human Gene Transfer trial initiated (ADA) • 1993 - Hantavirus outbreak, Southwest USA • 1994 - Publication of Richard Preston’s, The Hot Zone • 1994 - Sabia LAI, Yale • 1995 - Hendra virus, Australia/Avian flu, Hong Kong • 1996 - Mad Cow Disease (BSE)

Pertinent Biosafety Events • • • 1997 - Influenza A Virus (H 5 N 1) in poultry, Hong Kong 1999 - West Nile Virus, 1 st time ever in U. S. 1999 - 1 st HGT death, UPenn OTC Protocol 1999 - Nipah Virus, Malaysia (high mortality rate) 2001 - Anthrax letters shipped via US Mail 2002 - HGT Trials suspended after 2 nd case of leukemia caused by integration of “defective” retroviral vector in host chromosome • 2003 - SARS Virus • 2004 – Bird Flu (H 5 N 1) concerns return • 2004 – SARS LAI’s, Tularemia LAI’s (BU)

Pertinent Biosafety Events • 2004 – TB Infections, Washington State (associated w/ Madison Aerosol Chamber). • 2004 – Occular Vaccinia, Pennsylvania (route of exposure unknown). • 2005 – Vaccinia infection from needlestick, Connecticut (animal research experiment) • 2006 – Brucella infections – Texas A&M (associated w/ Madison Aerosol Chamber). 3 additional seroconversions to C. burnetii identified. • 2007 – Significant non-compliance w/ Select Agent Regulations identified at Texas A&M (SA Research shut down). • 2007 – U. S. Federal hearings on oversight of BSL 3 and BSL 4 laboratories.

Laboratory Acquired Infections (Harding & Byers) – Infections acquired through lab or lab related activities (symptomatic or asymptomatic) • LAI’s came with golden age of Microbiology – Typhoid – Brucellosis – Tetanus 1885 1887 1893

LAI’s (1930 - 2001) Harding & Byers • • Sulkin & Pike 1930 - 1978 4, 079 LAI’s 168 fatalities • • Brucellosis Q-Fever Hepatitis Typhoid Fever Tularemia Tuberculosis Dermatomycosis VEE • • Harding & Byers 1979 - 2001 1, 267 over LAI’s 22 fatalities • • M. tuberculosis Q Fever Hantavirus Arboviruses Hepatitis B Virus Brucella Salmonella Shigella

LAI’s 1930 - 2001 (Harding & Byers) • Total: 5, 346 LAI’s • 190 deaths – underreporting likely – many more sub-clinical infections? • Percentage that knew route of exposure similar from 1930 - 1978, and from 1979 1999! • Name that percentage?

Secondary Infections (LAI’s) (Harding & Byers) – The transfer of an occupationally acquired infection to another person outside of the work environment. • Uncommon (8 reported 1979 - 2001) • (2) Brucella- sexual transmission • (2) Salmonella- microbiologist prepared dinner for family (one death) • (1) Leptospira interrogans- through breast milk • (2) Bordetella pertussis- to family members • (1) B-Virus – spouse of injured animal care worker

Laboratory Acquired Infection (LAI) Summaries • PA Vaccinia LAI ocular infection (2004) – Route unknown • Breach in aerosol containment/poor work practices – Failure to consistently wear gloves – Absence of face protection while working outside of primary containment – Failure to confine all procedures to biosafety cabinet – Inadequate decontamination of contaminated work surfaces – Possible hand to eye to contact during experiments – Lack of awareness of signs/symptoms of disease

Laboratory Acquired Infection (LAI) Summaries • Vaccinia infection from needlestick (2005) – – – Inadequate oversight, training Insufficient risk assessment, poor SOP utilized Poor work practices • • – – – Transport of needles by hand to sharps container outside of room Recap of contaminated needles by hand Poor exposure response (delay in skin washing) No report of exposure (State reportable infection!) Secondary bacterial infection (required hospitalization)

Laboratory Acquired Infection (LAI) Summaries • Texas A&M Brucella infection (2006) – Use of Madison Aerosol chamber • • • – – No recognition of signs/symptoms of Brucella infection Untrained, unregistered researcher • – Insufficient Risk Assessment for Agent and Operation Poor training of staff on use of chamber No secondary containment of device or animals removed from device (aerosols from hair of animals) 3 Additional Q-Fever Infections (asymptomatic) unreported No immediate report of Select Agent infections to CDC (10 month delay)

Laboratory Acquired Infection (LAI) Summaries • BU Tularemia infections (2004) – 3 cases – not identified by institution • • Discovered by personal physicians or ER No recognition of signs/symptoms of disease – Attenuated BSL 2 (non Select Agent strain? ) • If r. DNA – in violation of NIH Guidelines! – Lowering containment from BSL 3 to BSL 2 must be authorized by NIH OBA • • Inadequate risk assessment performed Inadequate containment, PPE, work practices – Some procedures conducted on open bench

Laboratory Acquired Infection (LAI) Summaries • Monkey B-Virus Infection (fatal), Georgia, 1997 (Yerkes Regional Primate Center) – Ocular exposure during transport of non-human primate • Insufficient training identified – No agent-specific training on hazards associated w/ NHP’s – No emergency/exposure response training provided • Insufficient personal protective equipment – No face protection provided • Inadequate barrier (open cage) used for transport

Biosafety Profession • Resources: – American Biological Safety Association www. absa. org – Centers for Disease Control & Prevention www. cdc. gov – National Institutes of Health www. nih. gov – World Health Organization www. who. org

Biosafety Profession • Certified Biological Safety Professional (CBSP) - Exam Task List – Disinfection, decontamination, sterilization – Work practices and procedures – Risk assessment/hazard identification – Regulatory aspects, standards & guidelines – Program Management – Equipment Operation and Certification – Facility Design

Biosafety Profession • Also requires knowledge of: – immunology, molecular biology, epidemiology – microbiology, cell biology – animal care and use, cell culture techniques – immunizations, risk management – aerobiology

Biosafety Profession • Sources of information/training – ABSA Professional Development short courses • offered at annual conference and spring seminar • local chapters and affiliates of ABSA – Duke University MPH and DRPH degrees – NIH Biosafety Training Program (BSL 3/BSL 4) – Occ. Health/Public Health/Env. Health programs throughout U. S. and world – Short courses (Harvard SPH, Eagleson Institute, Canada, AIHA, ASM, APIC, NSC, CSHEMA, etc. ) – Mentors (other biosafety officers, laboratorians, biosafety committee members, university courses (learning is ongoing!)