Protocol for Management of Bites by Macaque Primates used in Medical Research

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Charles River Laboratories hold both Asian and Mauritian macaques for medical research objectives. Mauritian macaques either wild or from closed colonies, do not pose any risk for Herpes B virus infection caused by Macacine herpesvirus1. This is also referred to as herpes B, monkey B virus, herpesvirus simiae, and herpesvirus B. Cynomolgus macaques originating from Mauritius are considered to be free of Herpes B infection and no incidence has ever been recorded. Cynomolgus and rhesus macaque colonies in South-east Asia are not considered to be completely free of this virus. Individual animals are tested at source, and must be serology negative before shipment to Charles River Laboratories. However, over the years, very occasional incidences of seroconversion have been identified during post-arrival screening.

In humans Herpes B virus most frequently presents as an ascending encephalomyelitis with an untreated mortality of 80% and survivors may sustain permanent brain damage. A few cases have presented early with vesicular lesions and/or pain at the bite site. CNS disease presents with headache, fever, limb stiffness, nausea and vomiting. Secondary transmission may occur. Transmission is by bite, handling monkey tissues or secretions, and possibly from aerosols or penetrating injuries sustained whilst handling cages. Asian macaques may pose a risk. An Advisory Committee on Dangerous pathogens has published recommendations under the title ‘Working safely with Simians: Management of infection risks’. (see Appendix A) [SR1]

HealthLink360 is a health charity located close to Charles River Laboratories and holds the contract for the provision of first line medical care for staff bitten by macaques.

In certain circumstances HL360 staff may not be available and NHS Lothian Management has agreed that RIDU on call staff will provide a backup service. The fee for providing this service will be charged by invoice issued by HL360 as the main contractor and a subsidiary invoice will be issued by the RIDU Travel Clinic which is met by HL360 on an agreed basis. A member of Charles River staff will phone switchboard and bleep the ID Registrar on call if HealthLink360 staff are unable to deal with their query. If the ID Registrar is unavailable the Charles River injured member of staff should make their way to WGH RIDU for assessment with a covering letter. A copy of this protocol is kept in Ward 42/43 at the Western GeneralHospital

When a bite occurs

Charles River Labs will issue a Non-Human Primate (NHP) Incident Report (see Appendix B) outlining the nature of the incident, the identification of the animal and markers associated with level of risk. The risk will normally be assessed by an appropriate health professional either at HealthLink360 or at WGH RIDU.

Immediate Care after a bite

  1. First Aid - First aid should begin immediately. The exposed area should be cleansed thoroughly by washing and gentle scrubbing the area or wound with a concentrated solution of detergent, povidone-iodine or chlorhexidine and water. Povidone-iodine (Betadine or Videne) will normally be used.
  1. The washed area should then be irrigated with running water for 15-20 minutes.
  1. a specimen for PCR testing should not be obtained from the wound area prior to washing the site. This is because it could force virus more deeply into the wound, reducing the effectiveness of the cleansing protocol.
  1. After the site is cleansed, a serum specimen taken within 24 hours of injury should be obtained from patients with penetrating wounds if the macaque is non-Mauritian.
  2. If the primate colony in is non-Mauritian and B virus is a possibility, the injured person should be treated with an anti-viral agent whilst the result of viral tests are obtained on the primate.
  3. valacyclovir—1g by mouth every 8 hours for 14 days,

or

  1. acyclovir—800 mg by mouth 5 times daily for 14 days
  1. Any sign of ill health, particularly skin lesions or itching, pain or numbness near the site of the wound should be reported.
  1. For those whose tetanus immunisation status is uncertain, and individuals born before 1961 who may not have been immunised in infancy, a full course of immunisation is likely to be required. If no booster has been given in the last 5 years a booster dose of Revaxis should be given.
  1. Human tetanus immunoglobulin 250 IU by intramuscular injection should be given in a different site to the vaccine to those with incomplete primary tetanus immunisation or if the wound is considered high risk, irrespective of immunisation status. The Green Book ,Immunisation against Infectious Disease provides UK guidance and the latest update is available on line. under the section on Management of Patients with Tetanus prone wounds.
  1. All patients who have a skin break should be started on a prophylactic oral antibiotic. This will normally be co-amoxiclav 625mg tid for 7 days. If the patient is allergic to penicillin the choices are:
  2. clindamycin 300mg qid plus levofloxacin 500mg once daily or co-trimoxazole 960mg bid
  3. doxycycline 100mg bid
  4. moxifloxacin 400mg daily
  1. Patients will be referred to RIDU by HL360 if the skin break is not confined to the dermal layer and involves deeper structures. RIDU will then obtain a surgical opinion where necessary.
  1. If the patient arrives directly at Accident and Emergency at RIE, contact should be made with the ID Consultant on call to confirm the appropriate course of action.
  1. The exposed person should be followed up for 7 weeks by HealthLink360 nursing staff. At 24-48 hours after injury a bacteriology swab will be taken and sent in transport medium, and for wound dressings changed. Once the wound/s has/have healed follow up may be by phone call with the patient being discharged from follow-up at 7 weeks. If wound healing causes concern, the patient will be referred to RIDU for further assessment.
  1. A confidential summary letter will be sent to the senior administrator of Human Resources at Charles River Laboratories.
  1. As soon as the serology result taken from the monkey is available a copy should be forwarded to HealthLink360.
  1. If during follow up virus B is cultured or any signs in the monkey suggest infection patients should be referred to the Infectious Diseases Unit Consultant. This may precipitate intravenous treatment as follows:

With no CNS symptoms:

  1. acyclovir—12.5–15 mg/kg intravenously every 8 hours, or
  2. ganciclovir—5 mg/kg intravenously every 12 hours

With CNS symptoms

  1. ganciclovir—5 mg/kg intravenously every 12 hours
  1. Subsequent treatment with oral acyclovir 800mg five times daily indefinitely is likely to be recommended if virus B infection is suspected to prevent reactivation of the virus.

Might be worth adding links to CDC website / Green book / DOH document as References:

Dr Michael E Jones

MB,ChB, FRCP(Edin, Glasg, Lond), FFTM RCPS(Glasg)

Consultant in Infectious Diseases

Regional Infectious Diseases Unit, Western GeneralHospital, Edinburgh

Dr. Sandeep Ramalingam

MD, PhD, FRCPath

Consultant Virologist

Department of Laboratory Medicine, Royal Infirmary of Edinburgh, Edinburgh

Dr John Bremner

MBBS, BSc, MSc, FRCPath

Consultant Virologist
Department of Laboratory Medicine, Royal Infirmary of Edinburgh, Edinburgh

Revised 19/05/14

[SR1]There is no Appendix attached with this document