managing the risk of b-virus infection...

© Copyright National University of Singapore. All Rights Reserved.

MANAGING THE RISK OF

B-VIRUS INFECTION

FROM MACAQUE-DERIVED

MATERIALS: THE CONTROL BANDING

APPROACH

Dr Rajkumar Ramamoorthy1, Dr Michele M. Bailey2,

Dr Tessy Joseph1, Mr Saravanan Gunaratnam1

1 Office of Safety, Health and Environment, NUS2 Comparative Medicine, NUS


Content

1. Background

2. What are the Occupational Safety & Health

(OSH) concerns when working with Macaque-

derived materials?

3. Risk management approach - Control banding

4. Monitoring

5. Summary

6. References

2


1. Background

1. In institutes of higher learning in Singapore, Principal

Investigator (PIs) and their researchers work with Non

Human Primates (NHPs) including Macaques and

their samples.

2. In NUS, the samples are obtained from sources from

within Singapore and other parts of the world.

Types of work include:

a) Anatomical and histochemical studies

b) Electrophysiological studies

c) Molecular biology studies including tissue culture

d) Material compatibility studies

3

© Copyright National University of Singapore. All Rights Reserved. 4

i. Dedicated researcher

ii. Asst. Professor

iii. Macaque bite

iv. Fatal

Neuroencephalomyelitis

v. Invaluable postmortem

sample

Dr Willam Barnet Brebner

i. B-Virus discovered !!

ii. Safety awareness

triggered

(Pimentel, 2008)


Dr Elizabeth R Griffin

5

i. Dedicated researcher

ii. Macaque body fluid splash

into eyes

iii. Fatal Neuroencephalomyelitis

i. Lab-acquired infection

from Macaque-material

ii. The Elizabeth R Griffin

Research Foundation

iii. B-Virus working group

(http://www.ergriffinresearch.org/)

http://www.ergriffinresearch.org/


B-virus ulcers in rhesus macaque

http://www.bphc.org/whatwedo/infectious-diseases/Infectious-Diseases-A-to-Z/Pages/Herpes-B-Virus.aspx

http://thejunglenook.tumblr.com/post/93351649625/how-big-a-danger-is-simian-herpes-b-to-people-who

http://www.bphc.org/whatwedo/infectious-diseases/Infectious-Diseases-A-to-Z/Pages/Herpes-B-Virus.aspx



B-virus

7

Electron microscopy of the liver sample showing intranuclear viral

capsids with circular profile (Carlson et al., 1997)


1. Zoonotic pathogens from NHPs

2. B-virus from Macaque (endemic)

3. Fatal (80%), if untreated

4. It can survive for hours on an exposed dry

surface

5. Transmission: splashes, needlestick or

aerosols, contaminated equipment etc.

6. There are no vaccines available for prevention

of B virus infection

2. What are the OSH concerns when

working with Macaque-derived

materials?

8


OSH concerns

1. In March 1989, Southwest Foundation

Laboratory identified B-virus contamination in a

batch of primary monkey (Rhesus) kidney cells

(pMK) from a commercial supplier (Wells et al

1989).

2. “The virus can be present in the saliva, feces,

urine, or nervous tissue of infected monkeys

and may be found in cell cultures derived from

infected monkeys. (CDC)”

3. Macaque samples used in NUS- e.g., blood,

brain tissue, whole carcass & cell lines

9


In vivo and in vitro work

10

http://carnivoraforum.com/topic/9328619/1/

1 2 3

A

B

Hazard


B-virus pathology

11

Vesicles at inoculation site

Pruritic rash

Tingling, pain &numbness

Lymphadenopathy

Paresthesias

Fever

Myalgias

Weakness

Abdominal pain

Sinusitis

Conjunctivitis

Asc

en

din

g P

ara

lysis

Resp

irato

ry F

ail

ure

Co

ma

Brain stem

Encephalomyelitis

Exposure Spinal cord

Brain

Persistent Headache

Diplopia

Confusion

Dizziness

Ataxia

Incubation period

is 2 days -5 weeks


B-virus pathology

12

Vesicles at inoculation site

Pruritic rash

Tingling, pain & numbness

Lymphadenopathy

Paresthesias

Fever

Myalgias

Weakness

Abdominal pain

Sinusitis

Conjunctivitis

Persistent Headache

Diplopia

Confusion

Dizziness

Ataxia

Asc

en

din

g P

ara

lysis

Resp

irato

ry F

ail

ure

Co

ma

Brain stem

Encephalomyelitis

Exposure to

periphery allows

Non-CNS

symptoms

Exposure to head

and neck leads to

CNS symptoms


Rationale for developing this

programme and working team

1. Risk of B-virus infection from Macaque-derived

materials

2. AAALAC requirement

3. World class safety standards

4. Safety awareness in staff

13

OSHE- Office of Safety, Health & Environment

IBC- Institutional Biosafety Committee

OH- Occupational Health Clinic

CM- Comparative Medicine (NUS animal facility)

OSHE

OH

CM

IBC


3. Risk management approach

- Control banding

Technique to guide the assessment and

management of workplace risks (NIOSH)

1. A system that makes use of previous knowledge

2. Task‐based advice

3. Prioritized hazards based on levels of risks &

exposure

4. Focused on controls

14

https://www.cdc.gov/niosh/topics/ctrlbanding/


Principles of control banding

1. Effective occupational hygiene practices,

supplemented by using appropriate personal

protective equipment (PPE)

2. Engineering controls, including local exhaust

ventilation & containment

3. Seeking specialist advice

15


The difference…

16

Hazard

Exposure

Control

Keith Tait, Corporate Health & Safety, Pfizer

National Control Banding Workshop, Washington, DC March, 2005

Traditional approach

Hazard

Control

Exposure

Control banding approach


Control banding- key components

Categorise the hazards by linking

1. Hazard category (Eg. Biological)

2. Hazard classification (Eg. Infectious)

3. Associated containment levels (Eg BSL-1)

4. Recommendations for each hazard category (Eg.

administrative and engineering controls)

17


Engineering

control

Hazard

Control Banding when handling

NHP (Macaque)- derived materials

NHP derived materials

Non-Macaque Macaque

Chemically

fixed

Untreated

material

Chemically

fixed

Untreated

material

BSL-1 BSL-2 BSL-1BSL-2

(Enhanced)

• Authorization from IBC/ OSHE

prior to work/ possession (iORC)

• Restricted access and signage

• OH programme

• Class room training

• B-virus exposure kit and post

exposure response procedure

Seeking

expert

advice


Process flow

19

Circular to Deans,

HODs and Directors

Database

Researchers attending the class room

training on safe handling of NHP

(Macaque)-derived materials

BSL-2 (enhanced) practices

Identify researchers handling Macaque-

derived materials through a survey

New researchers

declaring the use of

NHP (Macaque)

derived materials in

the iORC*

Monitoring

* iORC-Integrated Online

Research Compliance System


Survey results: NHP-derived

materials use in NUS

20

60% 30%

PIs using Non-Macaque derived

materials or Inactivated

samples

PIs using Macaque-

derived materials (fresh)

Students

Research Assistants

Research Fellows

Lab Technologists

Safety & Health

Coordinators


Classroom training

Title : SAFE HANDLING OF NON-HUMAN

PRIMATE(MACAQUE) DERIVED

MATERIALS

Trainees : All staff and students handling Macaque-

derived materials

Content :

21

1. Introduction – Biological Hazards of

working with NHP derived materials

2. NUS requirements for handling Macaque-

derived materials

3. Dealing with exposure to Macaque-

derived materials

4. Summary and references


4. Monitoring

1. Regular Safety & Health Management System

(SHMS) audits for PIs

2. Project risk assessment (on iORC) review and

database update

3. Inspections (regular and adhoc)

4. Overall effectiveness of the training- increase in

mean Likert score from 3.46 to 6.23 on a scale

of 1-7

22


Learning gained in the class room training on safe

handling of NHP (macaque)-derived materials

23

Columns represent mean of scores from . Error bars represent SEM.

(N=35). **P≤0.001. Paired t test.

***

3.46

6.23


Compliance by researchers-

current status

1. 100% of the researchers attended training

since the programme launched in October

2016

2. B-virus exposure kit procured by PIs prior to

the commencement of work

24


5. Summary

1. B-virus is a potential zoonotic pathogen present in

Macaque-derived materials which can cause serious

disease in humans.

2. An integrated programme on safe use of Macaque-

derived materials was launched in NUS.

3. Excellent response from the research community

a. 100% of researchers handling Macaque-derived materials

attended the training

b. PIs procured B-virus exposure kits prior to the commencement

of work

c. Increased awareness as observed from training scores.

4. Principles of control banding were useful and this tool

could be extended to other similar programmes.

25


6. References1. Cohen JI, Davenport DS, Stewart JA, Deitchman S, Hilliard JK, Chapman LE; B virus Working Group.

Recommendations for prevention of and therapy for exposure to B virus (Cercopithecine herpesvirus 1). Clin Infect

Dis 2002, 35:1191-203.

2. Carlson CS, O'Sullivan MG, Jayo MJ, Anderson DK, Harber ES, Jerome WG, Bullock BC, Heberling RL. Fatal

disseminated cercopithecine herpesvirus 1 (herpes B infection in cynomolgus monkeys (Macaca fascicularis). Vet

Pathol. 1997, 34:405-14.

3. http://thejunglenook.tumblr.com/post/93351649625/how-big-a-danger-is-simian-herpes-b-to-people-who

4. Fatal Cercopithecine herpesvirus 1 (B Virus) Infection Following a Mucocutaneous Exposure and Interim

Recommendations for Worker Protection. MMWR. December 18, 1998, 47: 1073-6.

5. National Research Council (US) Committee on Occupational Health and Safety in the Care and Use of Nonhuman

Primates. Washington (DC): National Academies Press (US); 2003.

6. Pimentel JD, Herpes B virus-“B” is for Brebner: Dr. William Bartlet Brebner (1903–1932), CMAJ. 2008,178: 734.

7. Rohrman M. Macacine Herpes Virus (B Virus). Workplace Health Saf. 2016, 64:9-12.

8. Wells DL, Lipper SL, Hilliard JK, Stewart JA, Holmes GP, Herrmann KL, Kiley MP, Schonberger LB. Herpesvirus

simiae contamination of primary rhesus monkey kidney cell cultures. CDC recommendations to minimize risks to

laboratory personnel. Diagn Microbiol Infect Dis. 1989, 12:333-5.

9. Epidemiologic Notes and Reports B-Virus Infection in Humans -- Pensacola, Florida. Morbidity and Mortality

Weekly Report, May 22, 1987, 36: 289-90,295-6

10. https://www.cdc.gov/herpesbvirus/transmission.html

11. http://www.ergriffinresearch.org/

12. Weigler BJ. Biology of B virus in macaque and human hosts: a review. Clin Infect Dis. 1992,14: 555-67.

13. Watchman L, Mansfield K, Viral Diseases of Nonhuman Primates in Abee CR, Mansfield K, TardifS, Morris T eds:

Nonhuman Primates in Biomedical Research 2nd ed, Volume 2: Diseases, pgs 7-13

14. https://www.cdc.gov/niosh/docs/2009-152/pdfs/2009-152.pdf

15. https://www.cdc.gov/niosh/topics/ctrlbanding/

16. https://ehs.unl.edu/2013-06_Presentation5.pdf

26


http://www.nap.edu/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2263097/

http://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/pubmed/2556236

https://www.cdc.gov/herpesbvirus/transmission.html

http://www.ergriffinresearch.org/

http://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/pubmed/1313312

https://www.cdc.gov/niosh/docs/2009-152/pdfs/2009-152.pdf

https://www.cdc.gov/niosh/topics/ctrlbanding/


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managing the risk of b-virus infection...

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