1

Benjamin Fontes, MPH, CBSPABSA Conference, Charleston, SCOctober 16, 2018

OVERVIEW•REVIEW PATHOGEN ENTRY AND POSSIBLE DESTINATIONS IN HOST

•GIVE EXAMPLES OF KNOWN PROBABLE AND POSSIBLE LAIGIVE EXAMPLES OF KNOWN, PROBABLE AND POSSIBLE LAI EXPOSURE ROUTES

•PROVIDE INFORMATION FOR EXPANDED RISK AWARENESS DISCUSSION WITH THOSE EXPOSED TO BIOHAZARDS

•INSPIRED BY ABSA MEMBERS

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LAB ACQUIRED INFECTIONS 1930 -2015•1930 – 2015•7,325 LAIS (SYMPTOMATIC AND ASYMPTOMATIC)7,325 LAIS (SYMPTOMATIC AND ASYMPTOMATIC)•210 FATAL LAI’S• BYERS KB AND HARDING, AL. LABORATORY-ASSOCIATED INFECTIONS. 2017. IN:

WOOLEY, DP, AND BYERS, KB, EDITORS, BIOLOGICAL SAFETY: PRINCIPLES AND PRACTICES, 5TH ED., WASHINGTON, DC: ASM PRESS. P. 59 – 94.• PIKE RM. 1979. LABORATORY-ASSOCIATED INFECTIONS: INCIDENCE, ,

FATALITIES, CAUSES, AND PREVENTION. ANNU REV MICROBIOL: 33: 41 -66.• SULKIN SE, PIKE RM. SURVEY OF LABORATORY-ACQUIRED INFECTIONS. AM J

PUB HLTH. 1951; 41: 769-81.

WHAT IS KNOWN ABOUT EXPOSURE ROUTES?

Percutaneous Facial Mucous Membranes Ingestion

I h l ti *C t tInhalation *Contact

*Contact involves self-inoculation through one of the known exposure routes

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REVIEW OF LABORATORY INFECTIONS:IMPORTANT MESSAGES

•80% OF THE PUBLISHED LABORATORY ACQUIRED INFECTIONS LINKED TO AN UNKNOWN ROUTE OF EXPOSURE.

•AEROSOLS MOST LIKELY ASSOCIATED WITH UNKNOWN INFECTIONSINFECTIONS

•DR. EDWARD SULKIN & DR. ROBERT PIKE

GOLDEN AGE OF BIOSAFETY (1949 – 1979)

THERE CAN BE UNNATURAL ROUTES OF EXPOSURE IN THE LABORATORY SETTING THAT ARE GENERALLY NOT SEEN IN NATURE.

(SULKIN 1960)

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Infections with unidentified route of exposure

7 Non-traditional exposure route

NON-TRADITIONAL EXPOSURE ROUTESGI Pathogens: Salmonella, Listeria, Shigella, Campylobacter, E. coli, etc.

Eye Nasal Cavity

Throat Gut

Thomas, R.J., “Particle Size and Pathogenicity in the Respiratory Tract.” Virulence 4:8, 847-858; November 15, 2013.

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NON-TRADITIONAL EXPOSURE ROUTES

Aerosol Nasal Throat G t

GI Pathogens: Salmonella, Listeria, Shigella, Campylobacter, E. coli, etc.

Aerosol muco-ciliaryescalator

Throat Gut

Aerosol Tracheo- Throat G tAerosol Tracheobronchialmucociliaryescalator

Throat Gut

NON-TRADITIONAL EXPOSURE ROUTESWest Nile Virus, Yellow Fever Virus, Rabies Virus, Influenza Virus, Neisseria meningitidis, Streptococcus pneumoniae

Aerosol Nasal Cavity

Cranial Nerves

Brain

pneumoniae

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NON-TRADITIONAL EXPOSURE ROUTES

A l L Bl d

West Nile Virus, Yellow Fever Virus, Rabies Virus, Neisseria meningitidis, Sabia Virus, EEE, WEE, VEE

Aerosol Lower Lung

Blood stream

Winkler, W.G. 1973. Airborne rabies transmission in a laboratory worker. JAMA 226 (10):1219-1221.Centers for Disease Control. 1977. Rabies in a laboratory worker, New York. MMWR 26(22): 183-184

Thomas, R.J., “Particle Size and Pathogenicity in the Respiratory Tract.” Virulence 4:8, 847-858; November 15, 2013.

RECOGNIZED VS. UNRECOGNIZED EXPOSURES: PEOPLE REPORT WHAT THEY CAN “FEEL”

Feel splashes/splatter to face or skin

Feel needle sticks, lacerations, punctures, cuts, etc.

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WHAT YOU CAN’T FEEL IS (PROBABLY) NOT REPORTED?

Ingestion Inhalation

May also not feel exposure through micro-abrasions

GOLDEN AGE OF BIOSAFETY (1949 – 1979)

THE LABORATORY CAN BE MORE DANGEROUS THAN NATURE DUE TO THE ABILITY TO AMPLIFY AND CONCENTRATE PATHOGENS TO LEVELS NOT SEEN IN NATURE. ALSO, THE GROWTH AND PROPAGATION OF INFECTIOUS AGENTS IN LABORATORY SETTINGS ARE CONDUCTED REPEATEDLY WITHIN THE LABORATORY AS PART OF THE RESEARCH EFFORTTHE LABORATORY AS PART OF THE RESEARCH EFFORT, ENHANCING THE POTENTIAL EXPOSURE.

(LANGMUIR 1960)

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UNKNOWN BIOHAZARDSWHY A CONSISTENT APPLICATION OF GOOD MICROBIOLOGICAL PRACTICES IS CRITICAL• NEW PATHOGENS (MIMIVIRUS)• NEW PATHOGENS (MIMIVIRUS)

• OUTBREAK PATHOGEN STRAINS (E.COLI 0157:H7)

• FIRST “REPORT” OF INFECTION IN HUMANS WITH EXISTING PATHOGEN (KEYSTONE VIRUS 2018 FLORIDA)

• MORBIDITY NEWLY RECOGNIZED IN AN EXISTING MICROORGANISM (MERKEL POLYOMA VIRUS)

• INTRODUCTION OF BIOHAZARDS TO LOW RISK LABS (TRANSFERRIN, MYCOPLASMA, VIRUS IN TISSUES)

• VETERINARY RISKS (VET SCHOOL, CLINICS, FIELD SETTINGS – CRYPTOSPORIDIUM INFECTIONS)

• NON-PATHOGENIC MICROBES ASSISTING WITH PATHOGENICITY OR SPREAD OF DISEASE (FUSOBACTERIUM NUCLEATUM)

• WHEN GOOD GENES GET INTO BAD PLACES (DR. GARY FUJIMOTO)

REFERENCES

• Raoult, D. et al. The Discovery and Characterization of Mimivirus, the Largest Known Virus and Putative Pneumonia Agent. Emerging Infections. 2007;45 (1 July): 95-102.

• Lednicky, J.A. et al. Keystone Virus Isolated From a Florida Teenager With Rash and Subjective Fever: Another Endemic Arbovirus in the Southeastern United States. Clinical Infectious Diseases, Brief Report. 2018; published online June 9, 2018: 1-3.

• Spurgeon, M.E., Lambert P.F. Merkel Cell Polyomavirus: A Newly Discovered Human Virus with Oncogenic Potential. Virology. 2013; January 5;435(1): 118-130.

• Spina, N. et al. Four Laboratory-Associated Cases of Infection with Escherichia coli O157:H7. Journal of Clinical Microbiology. 2005;43(6): 2938-2939.

• Philpott, M.S. et al. A Laboratory-associated Outbreak of Cryptosporiosis. Applied Biosafety 2015; 20(3): 130-136Biosafety. 2015; 20(3): 130 136.

• Kinross, P. et al. Cryptosporidium parvum infections in a cohort of veterinary students in Sweden. Epidemiology and Infection. 2015;143: 2748-2756.

• Fardini, Y. Fusobacterium nucleatum adhesion FadA binds vascular endothelial cadherin and alters endothelial integrity. Molecular Microbiology. 2011; 82(6): 1468-1480.

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GOLDEN AGE OF BIOSAFETY (1949 – 1979)

THE MAJORITY OF LABORATORY PROCEDURES HAVE THE POTENTIAL TO GENERATE AEROSOLS IN THE SIZE RANGE THAT CAN REMAIN SUSPENDED IN AIR AND ALSO REACH THE LOWER LUNG, WHERE THEY CAN EITHER BE INHALEDAND CAUSE INFECTION OR ENTER THE BLOODSTREAM VIA THE ALVEOLI AND CAUSE INFECTION IN ANOTHER LOCATION OF THE BODY.

(REITMAN AND WEDUM 1956 AND KENNEY AND SABEL 1968)

ROUTE OF EXPOSURE TREES

ION

FACIAL MUCOUS ON

Lung (Epithelial

ALA

TI MEMBRANES

CRANIAL NERVES FROM NOSE TO

BRAIN

Mucociliary ALA

TI

Lung (Epithelial cells, other)

Blood (alveoli, lymphatic system)

Contact (from

INH

A MucociliaryEscalators - Gut

INH Contact (from

contaminated surfaces)

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GOLDEN AGE OF BIOSAFETY (1949 – 1979)

FROM DR. ARNOLD G. WEDUM, CONSIDERED THE “FATHER OF BIOLOGICAL SAFETY” IN THE U.S., WE LEARN THE IMPORTANCE OF “CONFINING AEROSOLS AS CLOSE AS POSSIBLE TO THEIR POINT OF GENERATION ”POSSIBLE TO THEIR POINT OF GENERATION.

(WEDUM 1960)

NASAL CAVITY TO BRAIN VIA CRANIAL NERVES

INFLUENZA A VIRUS, HERPES VIRUSES, POLIOVIRUS, PARAMYXOVIRUSES, VESICULAR STOMATITIS VIRUS, RABIES VIRUS, PARAINFLUENZA VIRUS, , , ,ADENOVIRUSES, JAPANESE ENCEPHALITIS VIRUS, WEST NILE VIRUS, CHIKUNGUNYA VIRUS, LACROSSE VIRUS, BUNYAVIRUSES, STREPTOCOCCUS PNEUMONIAE, NEISSERIA MENINGITIDIS, BURKHOLDERIA PSEUDOMALLEI, LISTERIA MONOCYTOGENES, LYMPHOCYTIC CHORIOMENINGITIS VIRUS, NAEGLERIA FOWLERI, EEE, VEE, WEE

• DANDO S J ET AL “PATHOGENS PENETRATING THE CENTRAL NERVOUS SYSTEM: INFECTION PATHWAYS AND• DANDO, S.J. ET AL, PATHOGENS PENETRATING THE CENTRAL NERVOUS SYSTEM: INFECTION PATHWAYS AND CELLULAR AND MOLECULAR MECHANISMS OF INVASION.” 2014. CLINICAL MICROBIOLOGICAL REVIEWS, VOL. 27 NO. 4, 691-726, OCTOBER 2014• BELOOR, J. ET AL, “SMALL INTERFERING RNA-MEDIATED CONTROL OF VIRUS REPLICATION IN CNS IS

THERAPEUTIC AND ENABLES NATURAL IMMUNITY TO WEST NILE VIRUS,” 2018. CELL HOST & MICROBE, 23, 549-556, APRIL 11, 2018.

• VAN RIEL, ET AL, “THE OLFACTORY NERVE: A SHORTCUT FOR INFLUENZA AND OTHER VIRAL DISEASES INTO THE CENTRAL NERVOUS SYSTEM, JOURNAL OF PATHOLOGY; 235, 277-287, 2015.

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INGESTION •DR. THOMAS HAMM (PLEA TO NHP

STAFF NOT WEARING GOGGLES: “S_IT EATERS”

•NASAL LACRIMAL DUCT

•MUCOCILIARY ESCALATORS•NASOPHARYNGEAL••TRACHEAL BRONCHIAL

•3 WAYS YOU CAN INGEST A PATHOGEN

ROUTE OF EXPOSURE TREES

ON

VIA EATING, DRINKING OR

GES

TIO VIA EATING, DRINKING OR

CONTACT

VIA NASAL LACRIMAL DUCT

ING VIA MUCOCILLIARY ESCALATOR

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INGESTION LIKELY UNRECOGNIZED•NOT COGNIZANT OF HAND TO FACE CONTACT

•POOR WORK PRACTICES IN SHALLOW WATER (JIM WELCH)POOR WORK PRACTICES IN SHALLOW WATER (JIM WELCH)

•LACK OF RECOGNITION OF POSSIBLE ROLE OF AEROSOLS FROM CONTAMINATION TO HOST ENTRY

•CAN’T “FEEL” THE EXPOSURE

•COMPETING RISKS OUTSIDE OF LAB•COMPETING RISKS OUTSIDE OF LAB•CDC: 48 MILLION FOODBORNE ILLNESSES ANNUALLY

•MANY SELF MEDICATE AND DON’T REPORT

•OVER 250 FOODBORNE PATHOGENS

ROUTE OF EXPOSURE TREES

us

s Blood Lymph

cial

Mu

cou

Mem

bran

es

Blood, Lymph

CRANIAL NERVES -FROM NOSE TO BRAIN

GUT (f

Fac M GUT (from eye, nose or

mouth)

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HAND TO FACE CONTACT (HFC) ARTICLE• 72% of researchers

touched face at least once • High likelihood of

fi h d d i t• Average of 2.6 HFCs/hr

• HFC found “common” among BSL-2 lab workers

Possibly an overlooked

finger, hand and wrist contamination

• Only 3 of 93 researchers wore eye or face protection in the BSL-2 lab

Johnston, J.D., et al, “The Influence of Risk Perception on Biosafety Level-2 Laboratory Workers’ Hand-To-Face Contact Behaviors,” Journal of Occupational and Environmental Hygiene, Vol. 11, pp 625-632, September 2014

• Possibly an overlooked route of exposure for unknown LAIs

the BSL 2 lab

ROUTE OF EXPOSURE TREES

ous

SKIN

utan

eo

SKIN (Local infections)

BLOOD STREAM

C CO S

Per

c FACIAL MUCOUS MEMBRANES

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PERCUTANEOUS EXPOSURES

Needle sticks, lacerations, punctures bitespunctures, bites

Unhealed wounds

Breaks in skin, cuticles, posion ivy, eczema, dermatitis

Acne, other micro-abrasions

GLOVE - LEAK RATE - FACTSGlove Leak

RatesExam Gloves

Surgical Gloves

Before Use(FDA)

2.5% 1.5%

After Use *21 – 35% **15.2%

**Double gloving: leak rates for inner gloves when double gloved - 1.17% (98 83% Eff i !)

*Boyle, B & Boyle, T, “Loss of Glove Integrity During Laboratory Animal Care Providers Daily Tasks,” Lenape Regional High School, Medford NJ, Science Fair Poster Presentation, 2017

**Makama, J.G. et al, “Glove Perforation Rate in Surgery: A Randomized, Controlled Study to Evaluate the Efficacy of Double Gloving,” Surgical Infections, Vol. 17 No. 4, pp 436-442, March 16, 2016

(98.83% Effective!)

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BIOSAFETY FOUNDATION GAMEDon’t eat, drink or smoke

Confine Aerosols

Eliminate or work

safely with sharps

No mouth pipetting

Disinfection Wear PPE WashHands

Inhalation

Mucous Membranes

Through Skin

Ingestion

HOW RESEARCHERS TYPICALLY ANSWERDon’t eat, drink or smoke

Confine Aerosols

Eliminate or work

safely with sharps

No mouth pipetting

Disinfection Wear PPE WashHands

Inhalation X X

Mucous Membranes X X X XMembranes

Through Skin X x

Ingestion X X X X

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MISCONCEPTIONS (OR MISINFORMATION)?•MY GOWN WON’T PROTECT ME, I ONLY HAVE TO WORRY ABOUT

SHARPS.”

•I CAN’T GET INFECTED WITH SALMONELLA FROM FACIAL CONTACT

•VIBRIO CHOLERAE SHOULD NOT BE CLASSIFIED AS A HUMAN PATHOGEN IN THE USA (WE CAN TREAT IT)

•I’M WORKING WITH ATTENUATED VACCINIA, SO I DON’T NEED AN IMMUNIZATION. MY FIRST EXPOSURE WILL BE MY IMMUNIZATION.

•I DON’T NEED EYE PROTECTION: I’M USING A BIOSAFETY CABINET; I’M ONLY WORKING WITH GI PATHOGENS; I’M ONLY WORKING WITH SMALL VOLUMES OF LIQUIDS

EXPECTED RESPONSESDon’t eat, drink or smoke

Confine Aerosols

Eliminate or work

safely with sharps

No mouth pipetting

Disinfection Wear PPE WashHands

Inhalation X X X X

Mucous Membranes X X X X X XMembranes

Through Skin X X X X

Ingestion x X X X X X

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FOUNDATION GAME AUGMENTED Don’t eat, drink or smoke

Confine Aerosols

Eliminate or work

safely with sharps

No mouth pipetting

Disinfection Wear PPE WashHands

Inhalation X X X X

Mucous Membranes X X X X X X X

Through Skin X X X X X X X

Ingestion x X X X X X X

SUMMARY•ROUTES OF EXPOSURE HAVE NOT CHANGED

•CONTROLLING BIOHAZARDS REMAINS THE AIM

•GOOD MICROBIOLOGICAL WORK PRACTICES WILL HELP PREVENT EXPOSURES

•THE IMMUNE SYSTEM IS DIVINE, EXCEPT WHEN IT’S NOT

•CONSIDER THE PROBABLE, POSSIBLE AND UNRECOGNIZED EXPOSURE ,ROUTES IN RISK ASSESSMENT AND BIOSAFETY TRAINING (ALONG WITH THE KNOWN EXPOSURE ROUTES AND SIGNS & SYMPTOMS OF DISEASE)

•ADDRESS LABORATORIAN MISCONCEPTIONS WITH FACTS

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“WE ARE ALL THE SAME”

“Do what you can;

With what you have;

In the place that you are;

In the time that you have”

Nkosi Johnson“We Are All The Same” by James Wooten

REFERENCES• BYERS K.B. AND HARDING L.H. 2017. LABORATORY-ASSOCIATED INFECTIONS. IN:

WOOLEY, D.P., BYERS, K.B., EDITORS, BIOLOGICAL SAFETY PRINCIPLES AND PRACTICES 5TH ED WASHINGTON DC: ASM PRESS P 59-94PRACTICES, 5 ED., WASHINGTON, DC: ASM PRESS. P. 59 94.

• CENTERS FOR DISEASE CONTROL. 1977. RABIES IN A LABORATORY WORKER, NEW YORK. MMWR 26(22): 183-184

• LANGMUIR, A. D. 1960. EPIDEMIOLOGY OF AIRBORNE INFECTIONS. P 173-181. IN: MCDERMONT, W., EDITOR, CONFERENCE ON AIRBORNE INFECTION. BACTERIOLOGICAL REVIEWS (25)3: 173-382.

• HEYMAN D. L., R. B. AYLWARD, AND C. WOLFF. 2004. DANGEROUS PATHOGENS IN THE LABORATORY: FROM SMALLPOX TO TODAY’S SARS SETBACKS AND TOMORROW’S POLIO-FREE WORLD. LANCET 363:1566-1568.

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REFERENCES• KENNEY, M.T. AND SABEL, F.L. 1968. PARTICLE SIZE DISTRIBUTION OF SERRATIA

MARCESANS AEROSOLS CREATED DURING COMMON LABORATORY PROCEDURES AND SIMULATED LABORATORY ACCIDENTS APPLIED MICROBIOLOGY (16)8: 1146-1150SIMULATED LABORATORY ACCIDENTS. APPLIED MICROBIOLOGY (16)8: 1146-1150.

• MERMEL, L.A., S.L. JOSEPHSON, J. DEMPSEY, S. PARENTEAU, C. PERRY, AND N. MAGILL. 1997. OUTBREAK OF SHIGELLA SONNEI IN A CLINICAL MICROBIOLOGY LABORATORY. J. CLIN. MICROBIOL. 35:163-165.

• MESELSON, M. ET AL, 1994, THE SVERDLOVSK ANTHRAX OUTBREAK OF 1979. SCIENCE 266(5188): 1202 – 08.

• PIKE RM. 1979. LABORATORY-ASSOCIATED INFECTIONS: INCIDENCE, FATALITIES, CAUSES, AND PREVENTION. ANNU REV MICROBIOL: 33: 41 -66.

REFERENCES• PHILLIPS, G.B. 1965. “CAUSAL FACTORS IN MICROBIOLOGICAL LABORATORY

ACCIDENTS AND INFECTIONS.” FORT DETRICK, FREDERICK, MD, MISC. PUBL. 2. AD 615-012N, (NATIONAL TECHNICAL INFORMATION SERVICE, SPRINGFIELD, VA.) IN HARDING, A.L. AND BYERS, K.B. 2006. LABORATORY-ASSOCIATED INFECTION,” P. 53-77. IN FLEMING, D.O. AND HUNT, D.L. (ED.), BIOLOGICAL SAFETY: PRINCIPLES AND PRACTICES, ASM PRESS, WASHINGTON, DC.

• REITMAN, M. AND WEDUM A.G. 1956. MICROBIOLOGICAL SAFETY. PUBLIC HEALTH REPORTS. (71)7: 659-665.

• SKINHOLJ P 1974 OCCUPATIONAL RISKS IN DANISH CLINICAL CHEMICALSKINHOLJ, P. 1974. OCCUPATIONAL RISKS IN DANISH CLINICAL CHEMICAL LABORATORIES. II INFECTIONS. SCAND J CLIN LAB INVEST 33:27-29.

• SULKIN SE, PIKE RM. SURVEY OF LABORATORY-ACQUIRED INFECTIONS. AM J PUB HLTH. 1951; 41: 769-81.

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REFERENCES• SULKIN, S.E. 1960. LABORATORY-ACQUIRED INFECTIONS. P 203-209. IN:

MCDERMONT, W., EDITOR, CONFERENCE ON AIRBORNE INFECTION. BACTERIOLOGICAL REVIEWS (25)3: 173-382.

• THOMAS, R.J., “PARTICLE SIZE AND PATHOGENICITY IN THE RESPIRATORY TRACT.” VIRULENCE 4:8, 847-858; NOVEMBER 15, 2013.

• WEDUM, A.G. 1960. CONTROL OF LABORATORY AIRBORNE INFECTION. P 210-216. IN: MCDERMONT, W., EDITOR, CONFERENCE ON AIRBORNE INFECTION. BACTERIOLOGICAL REVIEWS (25)3: 173-382.

WINKLER, W.G. 1973. AIRBORNE RABIES TRANSMISSION IN A LABORATORY WORKER. JAMA 226 (10):1219-1221.

Overview of a few Laboratory Acquired Infections (LAIs)

Benjamin Fontes, CBSP, MPH – Yale University EHS

Pathogen Exposure Route

Notable impact

Factors Risk Assessment or Risk Management

failures

Reference

Salmonella typhimurium

U ING

SO NASS, IBOA, PWP 1, 2, 3, 4, 5, 6

Salmonella typhimurium

U ING

SO, F NASS, IBOA, PWP 1, 2, 3, 4, 5, 6

Salmonella typhimurium

U ING

SO NASS, IBOA, PWP 1, 2, 3, 4, 5, 6

Lassa Fever virus U AER-L

SI, F NASS, IBOA, PWP 1, 2, 3, 4, 5, 6

Rabies virus U AER-L AER-MM

F PWP 1, 2, 3, 4, 5, 6

Rabies virus U AER-L AER-MM

F PWP 1, 2, 3, 4, 5, 6

Neisseria meningitidis

U AER-L

F NASS, PWP, NIMM 1, 2, 3, 4, 5, 6

Yersinia pestis (attenuated)

U AER-L

F NASS, PWP 1, 2, 3, 4, 5, 6

Sabia virus U AER-L

SI NASS, PWP 1, 2, 3, 4, 5, 6

Samonella typhi and S. agona

U ING

SO, F TERR???

IBOA, PWP 2, 3, 4

Hepatitis B virus U SK

F PWP, NIMM 2, 3, 4, 5

Bacillus cereus U SK

SI NASS, IBOA, PWP 1, 2, 3, 4

Shigella sonnei U ING

SI NASS, IBOA, PWP 1, 2, 3, 4, 6

SARS-CoV U AER-L

SO, F IBOA, PWP 1, 2, 3, 4, 5, 6

Macacine Herpesvirus 1 (B-virus)

U MM

F NASS, PWP 1, 3, 4, 5

Dengue virus SK PWP

2, 3, 4

Vaccinia virus VA

U SK

NASS, PWP, NIMM 2, 3, 4

Vaccinia virus PA

U MM

NASS, PWP, NIMM 1, 2, 3, 4, 5

Vaccinia virus VA

U SK

NASS, PWP, NIMM 1, 3, 4

Shigella dysenteriae

ING TERR

SI SO

IBOA, PWP 1, 2, 3

HIV

SK IBOA, PWP 2, 3, 4

HIV & Hepatitis C virus

SK Multiple F

IBOA, PWP 2, 4, 5

Borrelia burgdorferi

U SK

PWP 2, 4

Francisella tularensis

U AER-L

NASS, PWP 1, 2, 3, 4, 5

Brucella Melitensis

U AER-L

NASS, IBOA, PWP 1, 2, 3, 4, 5

Cryptosporidium parvum

U MM AER-MM AER-L

NASS, PWP 1, 2, 3, 4, 5, 6

TABLE Legend

AER-L aerosol exposure to lung AER-MM aerosol exposure to mucous membranes ING ingestion MM mucous membranes (splash, hand contact) SK percutaneous, skin U unknown route of exposure TERR terrorism

1 pathogen 2 procedures 3 personnel 4 practices (work practices) 5 protective equipment (personal protective equipment

and engineering controls) 6 place (facility design)

NASS no awareness of signs and symptoms NIMM no immunization PWP poor work practices IBOA infected by others actions

LAI laboratory acquired infection F fatal LAI SI secondary infection of others in lab or building SO secondary infection of others outside the institution

Quick Overview of the 6 P’s of Risk Assessment and Risk Management 1-Pathogen Policy that requires registration for possession, use, storage and transfer of biohazards and regulated biological materials including human pathogens. The PI and the IBC must conduct a formal risk assessment of the proposed research with biohazards and a review also of the standard operating procedures developed to work safely with the biohazard. 2-Procedures Identify all of the proposed procedures, supplies and equipment that will be used in the protocol and ensure that this is part of the risk assessment review and assignment of the final biocontainment level and SOPs created for the work. All procedures and all work locations, including animal experiments must be part of this review. Evaluation of sharps risks, aerosol risks, splash and splatter containment, etc. and the commensurate containment needed is part of this process. 3-Personnel A medical surveillance review is required to determine what pre- and post-exposure prophylaxis may be indicated, a review of the signs and symptoms of disease caused by the biohazard and all clinical manifestations must be completed with all involved in the project (researchers to animal handlers, etc.) The PI and IBC must also ensure that all involved have relevant work experience, training, education, awareness and comfort for the proposed research. If needed a competency work practice evaluation should be conducted. Researchers must be reminded to not work with breaks in the skin, to have changes in their health evaluated and to report any potentially related symptoms or illnesses to Occupational Health.

4-Practices The work practices that will be used as part of the SOP to work safely and contain the pathogen must be developed, reviewed and approved by the IBC. These SOPs should be part of the institution’s overall Biosafety Manual to create a site-specific biosafety manual. Some registration forms can guide the PI to develop site-specific work practices. 5-Protective Equipment This part of the Risk Management side of Biorisk Management involves personal protective clothing and equipment and the use of engineering controls. Individuals require training on the use of both. Both must be evaluated to ensure that they are present, adequate, in good condition and used appropriately. 6-Place Facility or lab design is the final part of the Risk Management side and this is the required evaluation by the IBC and Biosafety Officer to ensure that all work locations are appropriate for the proposed research. High traffic areas, large open areas, directional airflow and labs that open directly to public access corridors are some of the factors that must be critically evaluated to ensure that the proposed research will not lead to high risk situations for those performing the work and those outside the lab.

Pathogen LAI Reference Salmonella typhimurium (CDC MMWR) 2011, 2014, 2017

https://www.cdc.gov/salmonella/2011/lab-exposure-1-17-2012.html https://www.cdc.gov/salmonella/typhimurium-labs-06-14/index.html https://www.cdc.gov/salmonella/typhimurium-07-17/index.html

Lassa Fever virus http://www.nytimes.com/2004/02/21/nyregion/jordi-casals-ariet-who-found-lassa-virus-dies-at-92.html Rabies virus 1973 Winkler WG, Fashinell TR, Leffingwell L, et al. Airborne rabies transmission in a laboratory worker. JAMA.

1973;226:1219-21. Rabies virus 1977 Centers for Disease Control and Prevention. Rabies in a laboratory worker, New York. MMWR Morb Mortal Wkly

Rep. 1977;26:183-4. Neisseria meningitidis 2012

http://www.sciencemag.org/news/2012/05/death-california-researcher-spurs-investigation https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6335a2.htm

Yersinia pestis 2009 https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6007a1.htm

Sabia virus 1994 https://www.aiha.org/get-involved/VolunteerGroups/LabHSCommittee/Pages/Sabia-Virus-in-Centrifuge-Incident.aspx http://www.nytimes.com/1994/12/13/science/yale-accepts-blame-for-safety-lapses-linked-to-lab-accident.html

Salmonella agona, Salmonella typhi, 1980

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC273903/

Hepatitis B virus, 1985 Personal communication in Clinical Chemistry laboratory

Bacillus cereus, 2011

http://www.sciencemag.org/news/2011/09/updated-university-chicago-microbiologist-infected-possible-lab-accident https://sites.google.com/site/bioterrorbible/lab-accidents/bio-lab-accidents-2011?tmpl=%2Fsystem%2Fapp%2Ftemplates%2Fprint%2F&showPrintDialog=1

Shigella sonnei, 1996

http://jcm.asm.org/content/35/12/3163.full.pdf

SARS-CoV, 2003, 2004

http://www.who.int/csr/don/2004_04_30/en/ http://www.nytimes.com/2004/04/26/world/new-cases-identified-in-china-s-sars-outbreak.html http://www.cidrap.umn.edu/news-perspective/2003/12/taiwanese-sars-researcher-infected http://www.nejm.org/doi/full/10.1056/NEJMoa032565

Macacine Herpesvirus https://www.cdc.gov/mmwr/preview/mmwrhtml/00056008.htm

1, 1997 Dengue infection, 2014 https://my.absa.org/LAI

Vaccinia virus, CT VA Hospital, 2005

https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5715a3.htm

Vaccinia virus, PA, 2004

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291406/

Vaccinia virus, VA, 2008

https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5829a1.htm

Shigella dysenteriae, 1996

https://jamanetwork.com/journals/jama/fullarticle/417894

HIV needlestick 1988

http://www.nytimes.com/1997/12/18/nyregion/yale-must-pay-12.2-million-to-a-physician-who-got-hiv.html

HIV/Hepatitis C virus 1998, 1990

https://www.ahcmedia.com/articles/20911-the-needlestick-that-changed-her-life https://www.ahcmedia.com/articles/58948-double-deadly-needlestick-transmits-hiv-and-hcv http://www.nejm.org/doi/full/10.1056/NEJM199703273361304

Borrelia burgdorferi 1996

Personal communication, bite of infected nymph tick

Brucella abortus, 2006

http://www.cidrap.umn.edu/news-perspective/2007/07/cdc-suspends-work-texas-am-biodefense-lab http://www.cidrap.umn.edu/news-perspective/2007/09/cdc-details-problems-texas-am-biodefense-lab

Cryptosporidium parvum, 2011

https://absaconference.org/wp-content/uploads/2016/10/ABSA2016_Session17_Philpott.pdf

Francisella tularensis http://www.cidrap.umn.edu/news-perspective/2005/04/inquiry-leaves-boston-tularemia-mystery-unsolved http://massspectrometryconsortium.arizona.edu/sites/default/files/Boston_Univerity_Tularemia_report_2005.pdf