Occupational Health Issues in Biological Laboratories Schepens Eye Research Institute Thomas H....

Occupational Health Issues in Biological Laboratories

Schepens Eye Research Institute

Thomas H. Winters, MD, FACOEMChief Medical Officer and President, OEHN

September 6, 2012

Copyright 2012 - Information in this document is proprietary and confidential and not to be distributed without permission and authorization

Exposure Risks Suggested Immediate Actions for

Researcher Exposures Brief Agent Descriptions Importance of Early Reporting Lab Animals and Allergies Case Studies

Slide 2

AGENDA

Exposure Risks

Slide 3

EXPOSURE RISKS and TREATMENT

Slide 4

Range of Exposure

Initial Care for All Exposures• Basic First Aid – Employee to wash area with soap and

water or antiseptic for approximately 15 minutes.

Low Risk High Risk

(Small Animals i.e. Mouse)

(Large Animals

i.e.NHP)

ANIMAL BITES AND SCRATCHES PROCEDURE

1. Return animal to its cage and remove gloves.

2. Try to express the wound for signs of blood.

3. Wash your hands with soap and water for 15 minutes.

4. Report all bites/scratches to your supervisor and the Safety Officer.

5. Write down the data on the animal that you were bitten/scratched by - in case it is needed.

6. Once informed, Safety will report the animal bite to local government officials as required by the City of Boston.

7. You should contact our OEHN Medical Consultant, if you feel the wound is infected or if your incident involved any infectious or toxic agents.

8. In case of a medical emergency, please dial 9-911 and ask for an ambulance.

Slide 5

SCHEPENS EMERGENCY NUMBERS

Safety Office Emergency Number: 617.912.0244 (office) 617.799.2645 (cell)

Animal Facility Emergency Number: 617.912.7441 (office) 617.799.2659 (cell)

Supervisor's First Report of Injury or Illness Formto be completed by injured employee and their supervisor and submitted to Human Resources within y 48 hours of injury/illness.

Slide 6

MOUSE BITE (LOW RISK)

Observe at first – Apply Bacitracin and Bandaid If affected area becomes red / swollen

• Augmentin (875/125 mg) 1 tab PO BID for 7 days• Alternative (if allergic to penicillin): Larithromycin 500mg

PO bid x 7 days• Pregnant Patients:

Augmentin (as prescribed above) or Clindamycin (300mg PO q8 hrs x 7 days) for those women

with PCN allergy Category B agents

Slide 7

MOUSE BITE (DIRTY)

(Biologics, chemicals or toxins involved) Assess risk of biologic, chemical or toxin Observe at first – Apply Bacitracin and Bandaid If affected area becomes red / swollen

• Augmentin (875/125 mg) 1 tab PO BID for 7 days• Alternative (if allergic to penicillin): Larithromycin 500mg

PO bid x 7 days• Pregnant Patients:

Augmentin (as prescribed above) or Clindamycin (300mg PO q8 hrs x 7 days) for those women

with PCN allergy Category B agents Slide 8

RAT BITE: CLEAN INJURY

Concerning agents: Spirillium minus (associated: With Rat Bite Fever) or Streptobacillus Moniliformis

If Superficial (i.e. pinch / redness) -> Observe, bacitracin and bandaid

If deep (i.e. break of skin / bleeding, inflamed or swollen)• L PEP = Augmentin or• Alternative: (if allergic to penicillin) Doxycycline (100 mg

PO BID x 7 days)• Pregnant Patients:

Augmentin or Clindamycin (PCN Allergy) Same dose as above

Slide 9

RAT BITE: DIRTY INJURY

PEP = Augmentin Alternative: (if allergic to penicillin) Doxycycline 100mg PO

BID x 7 days Pregnant Patients:

• Augmentin or Clindamycin• Same dose as above

Risk assessment of chemical or toxin

Slide 10

(Biologics, Chemicals, or Toxins Involved)

RABBIT BITES/SCRATCHES Agents of Concern: Contain few infectious pathogens Rare: Harbor the bacteria for human Tularemia (Rabbit Fever) Occasional cases of zoonotic disease in humans from

laboratory rabbits have included: Pasteurella multocida, Francisella tularensis (tularemia), Q Fever, ringworm and enteric diseases (e.g. Cryptosporidia).

Of greatest concern are scratches that can be inflicted with their strong hind legs and sharp claws or from bites.

Always cleanse wounds immediately with soap and water or antiseptic and seek medical consultation.

Slide 11

Princeton University, Occupational Health; Zoonosisweb.princeton.edu/sites/ehs/biosafety/animalworker/pg4.htmVirginia Tech; Rabbits, Occupational Safety Information; http://www.acc.vt.edu/pages/training/ohs/downloads/rabbit.pdf

NON-HUMAN PRIMATES (NHP) BITES/SCRATCHES Agents of Concern: Herpes B, SIV, HIV, SHIV Found specifically among Old-World NHP Macaques PEP = Valcyclovir 1g PO TID x 14 days NHP should be tested (all body fluids) – Contact Veterinarian

regarding results of analysis. Exposed worker to contact occupational health on the next

business day to confirm that a follow up appointment has been scheduled

Slide 12

Suggested Immediate Actions Following Researcher Exposure Adeno Associated Viral Vector Lentivirus Viral Vector Cyclosporine Pertussis Formaldehyde and/or Paraformaldehyde Streptozotocin (STZ)

ADENO-ASSOCIATED VIRAL VECTORS (AAV)

Slide 14

Transmission Suggested Action

Skin Exposure (Needlestick or scratch)

1. Scrub skin for ~20 minutes using soap and copious amounts of water.

2. Contact OEHN Medical Consultant for additional advice, evaluation and serum sample.

Mucous Membrane Splash to Eye(s), Nose or Mouth

1. Rinse a minimum of 15 minutes in eye wash or flush area with water.

2. Report to hospital emergency room for evaluation.

3. Serum sample should be taken as soon as possible.Splash Affecting Garments

Remove garments that may have become soiled or contaminated and place them in a double red plastic bag.

After Every Incident Contact OEHN Medical Consultant and Perform Other SASP Animal Safety Protocol

LENTIVIRUS VIRAL VECTOR

Slide 15



Immediately go to the sink and thoroughly wash the wound with soap and water. Decontaminate any exposed skin surfaces with an antiseptic scrub solution.

Mucous Membrane Splash to Eye(s), Nose or Mouth

Exposure should be irrigated vigorously.

Splash Affecting Garments

Remove garments that may have become soiled or contaminated and place them in a double red plastic bag.


CYCLOSPORINE

Slide 16

Mode of Transmission Suggested Action

SkinWash repeatedly with plenty of water. If there is irritation.


Wash with plenty of water for 15 minutes.

Mucous membrane Splash to Eye(s), Nose or Mouth


Inhalation (unlikely)Transfer patient to fresh air. In severe cases apply oxygen if available.


PERTUSSIS

Slide 17


Inhalation In case of complaints, contact your OEHN Medical Consultant.


Immediately wash with water and soap and rinse thoroughly.


Rinse opened eye for several minutes under running water.

Ingestion Immediately, contact your OEHN Medical Consultant.


Retain the product label to show to Dr. Winters.

FORMALDEHYDE AND/OR PARAFORMALDEHYDE

Slide 18


SkinWash repeatedly with plenty of water. If there is irritation.


Wash with plenty of water for 10-15 minutes.


If patient is conscious, give him plenty of water and induce vomiting.

Inhalation Transfer patient to fresh air. In severe cases apply oxygen if available.


STREPTOZOTOCIN (STZ)

Slide 19


Skin Immediately flush with plenty of water, remove contaminated shoes and clothing, seek medical attention immediately


Wash with plenty of water for 10-15 minutes.



Inhalation Transfer patient to fresh air. In severe cases apply oxygen if available.


Brief Agent Descriptions Lentivirus Herpes Simplex (HSV-1) Herpes B LCMV

21

LENTIVIRAL VECTOR

By the end of this segment you will be able to describe the following information about Lentivirus: • ID• Mode of Transmission• Signs and Symptoms• Treatment• Post Exposure Prophylaxis

LENTIVIRUS: ID and TRANSMISSION

ID: • Use of the HIV virus as a viral vector has required the

reengineering of the virus to achieve safe gene transfer• Since HIV normally targets CD4 cells, replacing the HIV

envelope gene with vesicular stomatitis virus glycoprotein (VSV-G) expands the infectious range of the vector and modes of transmission

Transmission:• No lentivirus vector infection known to humans.• Remote possibility of replication competent lentivirus

(RCL)

22

23

LENTIVIRUS: SIGNS AND SYMPTOMS

Problems include what to monitor and for what length of time due to the potential for long latent periods

Replication competent lentivirus Possible Oncogene

24

LENTIVIRUS: POST EXPOSURE PROPHYLAXIS

Post exposure prophylaxis is the use of antiretroviral drugs to inhibit the growth of the virus after exposure.

Two-or-more drug class PEP regimen based of the level of risk for HIV transmission. • Truvada for 7 days• Expanded regiment add Rategravir

Because PEP is potentially toxic, exposures that pose a negligible risk for transmission should not be treated.

HERPES SIMPLEX VIRUS (HSV 1)

By the end of this segment you will be able to describe the following information about Herpes Simplex Virus (HSV 1): • ID and Reservoir• Mode of Transmission• Signs and Symptoms• Visual Identification• Prophylaxis• Post Exposure Treatment

HSV: ID AND RESERVOIR

Herpes Simplex Virus (HSV) • ID:

Herpesviridae• Reservoir:

Humans

HSV-1: MODE OF TRANSMISSION

Mode of transmission for HSV-1:• Contact with saliva of carrier.• Infections on hands of HCS (i.e. dentist) from patients

shedding HSV results in herpes whitlow.• Transmission during birth usually via infected birth canal;

less often in utero or postpartum• Both Type 1 and Type 2 may be transmitted to sites via

oral-genital, oral-anal or anal-genital contact, however: Usually sexually transmitted HSV is Type 2

HSV: SIGNS AND SYMPTOMS

Signs and Symptoms for HSV-1:• Primary infection may be mild and inapparent occurring in

early childhood.• 10% of primary infections overt.• Fever and malaise lasting one week or longer.• May be associated with:

Gingivostomatitis with vesicular lesions in oropharynx. Severe keratoconjunctivitis. Generalized cutaneous eruption

complicating chronic eczema

HSV: VISUAL IDENTIFICATION

Reference: http://www.microbes-edu.org/etudiant/dermatoses2.html

Herpes vesicles and herpetic whitlow

Eye Infection

http://www.microbes-edu.org/etudiant/dermatoses2.html

HSV: PROPHYLAXIS AND POST EXPOSURE TREATMENT Prophylaxis for HSV-1 :

• No antiviral medications are effective against primary infection.

• Acyclovir may be used prophylactically to prevent or reduce incidence of recurrences.

Post Exposure Treatment:• Acyclovir has been shown to reduce shedding of virus,

reduce pain and accelerate healing time.

HERPES B

By the end of this segment you will be able to describe the following information about Lentivirus: • ID• Mode of Transmission• Signs and Symptoms• Treatment• Post Exposure Prophylaxis

Slide 31

HERPES B: ID

The primary infectious agent from non-human primates is Herpes B virus, or Cercopithecine herpes virus 1.

Herpes B is commonly found among macaque monkeys, including rhesus macaques, pig-tailed macaques, and cynomolgus monkeys.

HERPES B: MODE OF TRANSMISSION

Transmission

Skin: Scratch or bite from non-human primates or contact with infectious tissues or fluids of non-human primates. The ocular, oral, or genital secretions of monkeys, as well as the CNS tissues and CSF of monkeys, are potentially infectious.

Mucous membrane Splash to Eye(s), Nose or Mouth:

Direct contact with Herpes B virus positive secretions

Respiratory tract: Inhalation of aerosolized particulates (very rare).

HERPES B: SIGNS AND SYMPTOMS

Early manifestations:• Tiny blisters, vesicles or ulcers at or near the exposure site• Severe pain or itching at the exposure site• Swollen lymph nodes near the area of exposure that drain

the area (neck for head and neck)

HERPES B: SIGNS AND SYMPTOMS (cont.)

Intermediate manifestations:• Fever• Numbness or other unusual sensations• Discomfort at or near the exposure site• Muscle weakness or paralysis in the exposed extremity• Signs of conjunctivitis, eye redness, irritation or tearing• Meningo-encephalitis symptoms

HERPES B: VISUAL IDENTIFICATION

Herpes B: Post Exposure Prophylaxis

Drug of first choice Alternative drug

Valacyclovir, 1 g po q8h for 14 days Acyclovir, 800 mg po 5 times per day for 14 days

If post exposure prophylaxis is indicated, it should begin within hours of exposure with the drugs shown in the following table:

38

LYMPHOCYTIC CHORIOMENINGITIS VIRUS (LCMV) By the end of this segment you will be able to

describe the following information about LCMV: • ID• Mode of Transmission• Signs and Symptoms• Treatment• Post Exposure Prophylaxis

39

LCMV: ID

Arenaviridae are enveloped viruses containing two single-stranded RNA segments designated small and large.• The Arenaviridae family contains a single genus: Arenavirus,

consisting of 18 species • LCMV is the prototype virus of the family Arenaviridae.

LCMV is a rodent-borne viral infectious disease

40

LCMV: MODE OF TRANSMISSION

Direct contact with infected rodent saliva, blood, urine, feces, bedding and nesting materials

Inhalation of droplets Transplacental spread – pregnant women No human to human spread

41

LCMV: SIGNS AND SYMPTOMS

Flu-like illness Abdominal pain Altered mental status Thrombocytopenia Elevated aminotransferase levels Coagulopathy Graft dysfunction

Myalgia Fever or leukocytosis within three weeks after

transplantation. Diarrhea Peri-incisional rash Renal failure Seizures

42

LCMV: GENERAL LAB RESTRICTIONS

Agent LCMV: Armstrong strain

BL BL2, BL2-N (mice) is recommended on CDC BMBL and precedents, however PI will perform work at BL3 and BL3-N

NIH RG/CDC BL

BL2/ABL2 for body fluids; culture or mouse studies with lab-adapted strains.BL3 if high potential for aerosol generation, hamster work, production quantities, high concentrations, human samples, infected transplantable tumors.

Stipulations Follow ABSL3/BSL3 SOPs; inform women of child bearing age of the risk to the fetus if pregnant.

Special Hazards

Pregnancy risk: potential transmission to fetus.Aerosol transmission rodent urine, feces, saliva

NIH Citation N/A

Precedent BL2 and BL2-N: 07-270, 08-284, 94-091

43

LCMV: DIAGNOSIS AND TREATMENT

Diagnosis:• Clinical diagnosis difficult• Diagnosis is through serology

Virus isolation has been difficult, PCR. Treatment:

• Requires hospitalization and supportive treatment based on severity.

• Anti-inflammatory drugs, such as Corticosteroids, may be considered under specific circumstances, NSAIDs

44

LCMV: POST EXPOSURE PROPHYLAXIS

None

Importance of Early Reporting

Importance of Early Reporting

Some of the primary reasons that it is important to report a potential exposure early are to:• Analyze the root cause of the exposure • Implement appropriate surveillance• Provide strategic post exposure prophylaxis which is

sometimes available• Provide optimal care to the exposed worker.• Administer vaccines, if appropriate.• Analyze the root cause of the exposure.

Lab Animalsand Allergies

Slide 47

ANIMAL ALLERGENS - HAZARDS

The most prevalent biological hazards, in terms of frequency of occurrence, are simple allergens associated with the use and care of laboratory animals.

Approximately one third of laboratory animal workers have occupational allergy to animal danders, and a third of these have symptomatic asthma.

Sensitization generally occurs with the first 3 years of employment, and risk factors include atopic background, as well as job description as it relates to the intensity of exposure.

Health surveys of people working with laboratory animals show that up to 56 percent are affected by animal-related allergies.

In a survey of 5,641 workers from 137 animal facilities, 23 percent had allergic symptoms related to laboratory animals.

These figures do not include former workers who became ill and could not continue working.

Slide 48Laboratory Hazards and Risks; By: Vince McLeodPublished: September 9 2011; http://www.labmanager.com/?articles.view/articleNo/5083/article/Laboratory-Hazards-and-Risks

http://www.labmanager.com/?articles.authors/authorNo/8/Vince%20McLeod

http://www.labmanager.com/?articles.authors/authorNo/8/Vince%20McLeod

ANIMAL ALLERGENS – HAZARDS (cont.)

Lab Animal allergens frequently results in significant morbidity, at times even necessitating a change in occupation.

Animal allergens may lead to:• Decreased productivity• Increased workloads for others• Increased health and worker’s compensation costs for the

employer.

Slide 49

ANIMAL ALLERGENS - SOURCES

Slide 50

Animal Allergen MWa (kD) Source Biological function

Mouse (Mus musculus)

Mus m 1 (prealbumin) Mus m 2 Albumin

19

16

Hair, dander, urine Hair, dander Serum

Lipocalin-odorant binding protein

Unknown Serum protein

Rat (Rattus norvegicus)

Rat n 1A/Rat n 1 B (α2u-globulin)

Albumin

16-21 Hair, dander, urine, saliva

Serum

Lipocalin-pheromone binding protein

Serum proteinRabbit (Oryctolagus cuniculus)

Ory c 1

Ory c2

17 Hair, dander, saliva

Hair, dander, urine

Unknown

Bush RK, Wood RA, Eggleston PA. 1998. Laboratory animal allergy. J Allergy Clin Immunol 102:99-112.http://dels-old.nas.edu/ilar_n/ilarjournal/42_1/all-laa.pdf

MINIMIZING ANIMAL ALLERGENS

Identify and characterize allergen hazards.

Identify allergen exposure sources.

Characterize allergen sources.

Characterize worker exposure to allergen sources.

Characterize air movement (for aeroallergens).

Identify exposure control options.

Slide 51Controlling Exposure to Laboratory Animal Allergens, D.J. Harrison; Vol 42. No. 1, 2001; http://dels-old.nas.edu/ilar_n/ilarjournal/42_1/all-exp.pdfhttp://or.ucsf.edu/ehs/9399-DSY/12399

http://dels-old.nas.edu/ilar_n/ilarjournal/42_1/all-exp.pdf

MINIMIZING ANIMAL ALLERGENS (cont’d)

Select appropriate exposure control(s), based on total costs, ethics, applicable compliance requirements, and so forth.

Implement exposure controls.

Monitor control performance.

Maintain control systems.

Use well-designed air handling and waste management systems

Routinely use dust/mist masks, gloves, and gowns

Slide 52Controlling Exposure to Laboratory Animal Allergens, D.J. Harrison; Vol 42. No. 1, 2001; http://dels-old.nas.edu/ilar_n/ilarjournal/42_1/all-exp.pdfhttp://or.ucsf.edu/ehs/9399-DSY/12399

http://dels-old.nas.edu/ilar_n/ilarjournal/42_1/all-exp.pdf

MINIMIZING ANIMAL ALLERGENS (cont’d)

A laboratory can further reduce exposure with generally available equipment, such as • Laminar flow caging, and procedures,

Frequent wet washing of vivaria and Careful maintenance of ventilation systems.

• Periodic medical screening of all laboratory animal workers with questionnaires and allergy skin testing in

• Training programs to reduce personal exposure.

Slide 53R.K. Bush, R.A. Wood and P.A. Eggleston, “Laboratory Animal Allergy,”J. Allergy Clin. Immunol., (July 1998). http://www.ncbi.nlm.nih.gov/ pubmed/9679853.

http://www.ncbi.nlm.nih.gov/pubmed/9679853



Case Studies: Recent Exposures

HERPES B INFECTION IDENTIFIED IN MA – MARCH 2012 1 confirmed case and 1 suspected case of Herpes B infection identified in

Massachusetts laboratory workers March 28, 2012, Boston Public Health Commission (BPHC) notified of a

confirmed case of Herpes B virus infection. April 2, a second suspected case in a person exposed to the same rhesus

monkey, was reported. On March 27, researcher visited a local hospital and reported symptoms

including fever (102 F°), rigors, headache, and mild photophobia. • The patient was started on a course of ganciclovir and remained

hospitalized. On March 24, the a second person visited a local hospital, reporting a

headache, and was admitted and treated with ganciclovir. Laboratory results for Herpes B testing are pending. She was prescribed a course of valacyclovir and discharge

Slide 55

During this training we discussed the following topics: The exposure risks posed to animal researchers. Immediate actions that researchers should take

after certain exposures. A brief description of agents you may encounter. The reasons why it is important to report any

exposure to appropriate personnel as soon as possible.

Minimizing allergic reactions to lab animals.Slide 56

SUMMARY

QUESTIONS?

Slide 57

mailto:[email protected]?subject=Questions%20about%20Section%20I

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