Safety Program for Macaque Monkey Handlers

Why the Risk of Infection Is Low

Based on the Paper Published by the B Virus Working Group in January, 1990 (Holmes et al.)

1. Around the world, despite the thousands of monkey inflicted bites, scratches and exposures occurring annually, less than a total of 40 human B virus infections have been reported in the world’s English-language literature.

2. Between 1987 and 1994, despite the thousands of specimens obtained for B virus studies, only eight confirmed cases of human infection were detected.

3. Only 2-3% of seropositive animals shed virus at any given time.

Based on the Experience of One US Research Facility Housing Approximately 500 Macaques (90% Cynomolgus and 10% Rhesus)

4. Newly acquired Cynomolgus monkeys obtained from the island of Mauritius have not been known to be infected.

5. Monkeys are tested for seroconversion one month prior to shipping by the vendor and every six months in the animal lab.

6. Only one monkey in the years 1994 through 1996 seroconverted.

7. Only 8 injuries were recorded in 1996: 4 bites, 1 scratch and the rest involved injuries from cages and scalpel blades during necropsy.

Why the Anxiety Is High

Read about the four cases of symptomatic B virus infection in humans that occurred in Pensacola, Florida in March 1987. (Annals of Int. Med., 6/1/90) Two of these people died and the other two were asymptomatic in 1990 while continuing acyclovir. The two who died were bitten by monkey X which was ill at the time with conjunctivitis and diarrhea. A brief report of these cases can be found on the world wide web in the 1987 CDC Guidelines.

"Three risk factors for human infection were identified: nonuse of mechanical or chemical restraints for monkeys before handling, nonuse of available protective gear, and direct viral inoculation through the application of topical medication."

THERE IS NO REASON TO BE AFRAID OF MACS AND THERE IS NO REASON TO BE ALARMED.... LETS EDUCATE OURSELVES TO THE TRUTH SO THAT WE CAN CALM OUTSIDERS INSTEAD OF BEING FEARFUL OURSELVES. PLEASE.........

Questions & Answers

1. Is it possible to remove the source of infection, that is, to ensure that all monkeys in the lab are virus-free?
It is one of our national strategies to develop domestic monkey colonies that are free of B virus. However, all it takes is one animal to get infected and this can happen at any time. A monkey colony with a history of 100% negative serology is reassuring, but the guidelines should still be followed.

2. What is the purpose of the serum specimen drawn from all new monkeys handlers and placed in frozen storage?
These serum specimens are held in reserve in case they are needed to help in the interpretation of a patient’s serum antibody levels following an exposure or illness. About half of the human population possess antibodies to human herpes simplex virus that cross-react with B virus. By using special techniques, the lab can reduce but not entirely eliminate the frequency of false positive results.

3. Should anti-viral therapy be started before obtaining the results of cultures?
No, wait the two to seven days for culture results.

4. What are some of the problems associated with starting anti-viral therapy?
Interpretation of the two-week post-exposure antibody titers may be difficult after a course of anti-viral treatment. If treatment is begun, should the patient be hospitalized to receive full dose IV therapy? When should therapy be discontinued?

5. Does the location of the wound have any effect on the risk of infection?
It has been suggested that bites to the head and neck are more dangerous because of their proximity to the central nervous system. A B virus infection occurring after these bites would be less likely than distal bites to present with early warning signs such as extremity paresthesias.

6. Will monkeys that are shedding B virus be symptomatic?
It has been estimated that, similar to human herpes simplex virus, only about one third to one half of those shedding virus would be symptomatic.

7. Can B virus cause an asymptomatic infection in humans?
There is no serological evidence that B virus can cause an asymptomatic infection in humans.

8. How fast do macaque monkeys develop antibodies after an oral inoculation with B virus?
Antibodies can be detected 8 to 12 days after exposure and peak antibody levels are seen 30 to 40 days after exposure.

Publication of Guidelines for the Prevention and Treatment of B Virus Infections in Exposed Persons

Cercopithecine herpesvirus 1 (B virus) infection is widespread among Macaca genus primates; the virus is the biologic counterpart of herpes simplex virus in humans. B virus infection in humans is recognized as a rapidly ascending encephalomyelitis with a fatality rate of approximately 70%. The need for guidelines in prevention and treatment of human B virus infection was recognized in 1987 after a cluster of four symptomatic infections occurred among persons in Florida. CDC and the National Institutes of Health consulted primate veterinarians and herpesvirus experts to develop guidelines for preventing B virus infection in persons who work with macaques (1). Recommendations intended to minimize the risk for infection of laboratory workers exposed to B virus-contaminated primary rhesus monkey cell cultures were published in 1989 (2). Guidelines for primate handlers were expanded in 1990 in response to the recognition of filovirus infection in quarantined primates (3).

Human infections with B virus remain an uncommon result of macaque-related injuries, and optimal diagnostic and therapeutic approaches are unclear. However, the increase in the use of macaques for research on simian retrovirus infection and hepatitis has expanded the number of potential incidents of human exposure. In January 1990, Emory University and CDC sponsored a B virus working group intended to formulate a rational approach to the prevention, detection, and management of human B virus infections. Written guidelines were developed based on information from published and unpublished cases, knowledge of the behavior of herpes simplex virus, and expert opinion.

These guidelines (4) are intended to assist institutions in which macaques are handled in developing and enforcing effective standard operating procedures and quality-control interventions and to enable local physician consultants identified by the institutions to evaluate and treat persons with potential B virus exposure. Such institutions should keep a copy of these guidelines in bite/wound kits at the work site. Institutions also should provide copies of these guidelines to injured employees referred for medical evaluation; to the emergency rooms, clinics, or offices where injured employees will seek care; and to employees to give to their personal physician. More information on the guidelines is available from B Virus Guidelines, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC, Mailstop G-19, 1600 Clifton Road, NE, Atlanta, GA 30333.

References

1. CDC. Guidelines for prevention of Herpesvirus simiae (B virus) infection in monkey handlers. MMWR 1987;36:680-2,687-9.

2. Wells DL, Lipper SL, Hilliard JK, et al. 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.

3. CDC. Update: Ebola-related filovirus infection in nonhuman primates and interim guidelines for handling nonhuman primates during transit and quarantine. MMWR 1990;39:22-4,29-30.

4. Holmes GP, Chapman LE, Stewart JA, et al. Guidelines for the prevention and treatment of B-virus infections in exposed persons. Clin Infect Dis 1995;20:421-39.

Another Safety Program for Macaque Monkey Handlers