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PHE guidelines on rabies post-exposure treatment

Introduction

  • Rabies is an acute viral encephalomyelitis caused by several members of the Rhabdoviridae family. It transmits through infected saliva via bites or scratches from rabid animals (in particular dogs). It is almost invariably fatal once symptoms develop
  • Rabies still poses a significant public health problem in many countries in Asia and Africa where 95% of all human deaths from rabies occur. Post-exposure treatment (PET) using rabies vaccine with or without rabies immunoglobulin (HRIG) is highly effective in preventing disease if given correctly and promptly after exposure
  • The UK has been free of rabies in terrestrial animals since 1922. However, European Bat Lyssavirus 2 (EBLV2), a rabies-like virus, has been found in Daubenton's bats (Myotis daubentonii) across the UK
  • Further information, guidance and the risk assessment form are available on the rabies pages of the PHE website

Risk assessment

  • Individual risk assessment of potential rabies prone exposures should be undertaken as soon as possible, so that post-exposure treatment (PET) can be initiated if required. Although treatment should be started promptly, initiating rabies PET is not a medical emergency, and can often wait until the next day. In complex cases, treatment can be initiated and further advice sought from consultants at the PHE Rabies and Immunoglobulin Service/Virus Reference Department on the next working day
  • All risk assessments should be completed using the rabies post-exposure risk assessment form and either directly uploaded into HPZone, or emailed to the Rabies and Immunoglobulin Service by secure email. The form can be encrypted using the button on the form, and the password sent in a separate email

Post-exposure risk assessment: does the person need PET?

  • The following information is required to complete the risk assessment:
    • patient name, date of birth, age and address
    • date of exposure
    • species and current health status of animal involved
    • country of exposure
    • type of exposure
    • site of exposure
    • any previous rabies vaccinations
  • This should be recorded in the rabies post-exposure form which can be found in HPZone and on the PHE website
  • All enquiries should be recorded, even if vaccine and/or immunoglobulin are not issued

Patient details

  • Complete the patient details as indicated. The PET form also acts as the prescription if vaccine or immunoglobulin is issued. It is a legal requirement for these cases to record the date of birth (4 digits for the year), age if under 18 years old and the patient's address

Relevant medical history

  • There are no absolute contra-indications to rabies post-exposure treatment. However, in certain circumstances i.e. immunosuppression special follow up may be required, and further advice should be sought in hours from PHE Rabies Service, Colindale. Advice about precautions in giving treatment if there has been a previous hypersensitivity reaction are given in the Green Book

Date of exposure

  • Risk assessment should be undertaken as soon as possible following exposure, so that PET, if required, can be started promptly. The incubation period for rabies is typically 1–3 months, but may vary from <1 week to >2 years. Due to the potentially long incubation period for rabies there is no time limit for giving PET and all potential exposures should be risk assessed
  • If the exposure is more than one year ago, human rabies immune globulin (HRIG) is not generally indicated and specialist advice should be sought from the PHE Rabies Service, Colindale

Has the person been previously vaccinated against rabies?

  • Immune status for rabies will be based on history of vaccination and whether the person is immunocompetent and will determine the PET required. Immunity should be assessed as follows:

Fully immunised

  • At least three documented doses of rabies vaccine (either a complete primary pre-exposure course or as part of a five dose postexposure course) or documented rabies antibody (VNA) titres of at least 0.5 IU/ml
  • If the patient has recently completed a rabies post-exposure course of treatment (either 5 doses of vaccine, or 2 doses if previously fully immunised) within the last 6 months, no treatment is required for a more recent exposure
  • If vaccination was more than 10 years ago, treat as fully immunised (2 doses of vaccine only) and check antibody levels 1 week after last dose. If exposure to a known rabid animal, or multiple severe bites to head and neck, then start PET and seek specialist advice from PHE Rabies Service, Colindale on further management
  • If the person is immunosuppressed (as defined in Green Book, chapter 6), treat as though nonimmune and consider testing antibody levels 1 week post vaccination

Partially immune

  • Person who has had incomplete/inadequate primary vaccination course, or virus neutralising antibody never >0.5IU/ml

Non immune

  • Person who has never received pre- or postexposure immunisation with rabies vaccine

Which country? (no risk/low risk/high risk for terrestrial rabies)

  • A country may be considered free from rabies when:
    • the disease is notifiable
    • an effective system of disease surveillance is in operation
    • all regulatory measures for the prevention and control of rabies have been implemented including effective importation procedures
    • no case of indigenously acquired rabies infection has been confirmed in man or any animal species during the past 2 years; however, this status would not be affected by the isolation of a bat lyssavirus such as European bat lyssavirus (EBL1 or EBL2)
    • no imported case in carnivores has been confirmed outside a quarantine station for the past 6 months
  • The risk of rabies from terrestrial mammals according to geographical location (country, island and territory) is updated regularly. This information is incorporated into the Rabies PET form, the most recent version of which can be found on the PHE website
  • All countries should be considered as high risk countries for bat exposures, including the UK

Nature of exposure?

  • The assessment of exposure needs to take into account the risk of direct physical contact with saliva, neural tissue and other body fluids. The assessment will be different for terrestrial mammals and bats

Terrestrial mammals

CategoryTerrestrial mammal: categories of exposure (adapted from WHO)
I Touching or stroking animals
II Licks of the skin or other contact with saliva (e.g. feeding animals)
Minor scratches, bruising or abrasions without bleeding
Minor bites without breaking of the skin (covered areas of arms, trunk and legs)
All bites, licks and scratches from rodents and primates
III Single or multiple transdermal bites or scratches, licks on broken skin
Major bites (multiple or on face, head, finger or neck)
Contact of mucous membranes with saliva (e.g. licks)

Bats

CategoryBats: categories of exposure (adapted from WHO)
I No physical contact:
i.e. no direct physical contact with the bat's saliva or neural tissue, or the person was protected by a barrier capable of preventing such contact, such as a boot, shoe, or appropriate protective clothing
II Uncertain physical contact: (may be common with bat exposures):
i.e. where there has been no observed direct physical contact (with saliva) but this could have occurred, a young child found in a room with a bat, or in the UK a grounded or aggressive bat found in a room of a sleeping (or intoxicated) person*
III Direct physical contact with bat's saliva or neural tissue
Single or multiple transdermal bites or scratches and bruising
Minor bites without breaking of the skin (covered areas of arms, trunk and legs)
Major bites (multiple or on face, head, finger or neck)
Contamination of mucous membrane with saliva or bat droppings/urine

*Bat species found in houses and attics in the UK are unlikely to be infected with rabies-related viruses. Healthy bats avoid contact with humans, therefore bats behaving normally (i.e. flying into a room, but not grounded or acting aggressively) do not constitute a risk. However, as the risk cannot be completely excluded, bat bites occurring in attics of houses in the UK should be treated.

Additional useful information

  • If the animal was a terrestrial mammal (wild or domestic), these details are needed:
    • is rabies known or suspected to be present in the species in the locality?
    • is there an owner known and contactable?
    • was the animal behaving normally at the time of the incident?
    • had it been immunised against rabies?
    • if the animal was a dog or a cat did it become ill while under observation?
    • if the animal has died, does laboratory examination of the animal's brain confirm rabies
    • is the animal non-indigenous or imported? If imported it is important to determine the risk of rabies (no risk/low risk/high risk) in both the country of potential exposure and the country of origin of the animal

Treatment recommendations

Treatment based on risk assessment

  • A formal risk assessment based on the collected information should be performed; Recommended treatment will generally fall into five categories (see algorithms below):
    • no risk and therefore no treatment
    • vaccine and HRIG
    • vaccine only
    • vaccine and blood test 1 week after last dose
    • observation of animal (domestic cats and dogs only)

Summary of risk assessment treatment following exposure to terrestrial animals

Summary of Risk Assessment Treatment following exposure to terrestrial animals

Summary of risk assessment treatment following bat exposure

Summary of Risk Assessment Treatment following bat exposure

What treatment has already been given?

  • If treatment has already been started find out details of what has been given, route of administration and timing. Consider whether:
    • treatment is appropriate to exposure
    • which vaccine (type and name of vaccine if known)—is this compatible with vaccines given in the UK?
    • what vaccine schedule and route has been used—is this compatible with the UK schedule?
    • has human rabies immunoglobulin (HRIG) been given—if not is this indicated and is there still time to give this?
    • finally—how soon does the patient need their next treatment?
  • If no treatment has been started, post exposure treatment should be started within two working days. However for high risk exposures, such as severe and multiple bites to the head and neck or from a confirmed rabid animal, treatment should be started as soon as possible

Is vaccine required?

  • The UK schedule is 5 vaccines at the following interval 0, 3, 7, 14, 28–30 days given by the i.m. route
  • Day 0 is the day of 1st vaccine NOT necessarily the day of exposure
  • If a dose is missed, or timing has been compromised, the next vaccine should be considered as the missed dose, and subsequent intervals readjusted
  • If a person is travelling and has difficulty in achieving the specified interval for PET, it is most important to deliver the first 3 vaccines with plus/minus one day
  • The 5th final dose of rabies vaccine PET should not be given before day 26
  • In a patient who is partially immune, a full course of 5 doses of rabies vaccine should be given, but there is no need to issue HRIG
  • In a patient who is fully immune at the time of exposure the UK schedule is 2 vaccines at day 0 and day 3–7. If the last dose of vaccine was more than 10 years ago, antibody testing should be arranged through RIgS to ensure that there is an adequate antibody response. A collection pack and prepaid envelope will be sent to the GP surgery for collection. The sample (10 ml clotted blood or serum sample) should be collected one week after vaccination, the request form completed and sample and form sent to APHA for testing. The results will be returned to RIgS who will advise if further treatment is needed

Is rabies immunoglobulin (HRIG) required?

  • The mainstay of rabies postexposure treatment (PET) is rabies vaccine. Human rabies immune globulin (HRIG) may provide short term immunity in the first 7 days post initiation of treatment
  • The total antibody level induced by active immunisation (vaccine) is many orders of magnitude greater than can be provided by passive immunisation (HRIG). For this reason HRIG is not given after 7 days post-initiation of rabies PET vaccination or to an individual who is already partially or previously immunised
  • HRIG is manufactured from non-UK human blood products. The final formulation is a liquid and the potency of the material is assessed in international units (IU/ml). The recommended dose is 20IU/kg, adults and children (all ages)
  • The preparations of HRIG available for dispensing do vary in potency and volume. It is therefore CRITICAL to know the following:
    • the potency of the current batch in use; information about potency of batches in current use is encoded into the rabies PET form and is also available from Rabies clerk (0208 327 6204), or Immunisation Department (0208 327 7472)
    • weight of the patient
    • volume in vials (vials contain 1–4 mls, depending on batch and manufacturer)

Administering vaccine and immunoglobulin

  • Vaccine is given in the deltoid muscle by intramuscular injection. Each sequential dose should be given in alternate deltoids. Suggest start in nondominant arm
  • All immunoglobulin (HRIG) is given at the site of the wound, infiltrated around the site of the wound. If this is difficult or the wound has completely healed, then this can be given by intramuscular injection in the anterolateral thigh (this advice is based on the most recent WHO position paper on rabies vaccine (Aug 2010) and may contradict advice in the rabies immunoglobulin product leaflet, which has not been updated)
  • If more than 5 ml (2 ml in children under 20kg) of HRIG needs to be administered it should be in divided doses, at different sites
  • Vaccine and HRIG should NEVER be given at the same anatomical site

How soon should treatment be started?

  • Although treatment should be started promptly, initiating rabies PET is not a medical emergency. In most cases rabies vaccine/HRIG can be mailed out for administration the next day. However for head and neck bites, treatment should ideally be started within 12 hours of reporting

full guidelines available from...

www.gov.uk/government/uploads/system/uploads/attachment_data/file/520305/PHE_clinical_rabies_service_April_2016.pdf

Public Health England. PHE guidelines on rabies post-exposure treatment. London: Public Health England.
First included: May 2016.