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Guidelines on managing rabies post-exposure

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 promptly, 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 within the Rabies and Immunoglobulin Service (RIgS) 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 RIgS 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, address, and NHS number if possible
    • date of exposure
    • country of exposure
    • species and current health status of animal involved
    • category of exposure
    • site of exposure
    • whether the patient is immunosuppressed or has any allergies
    • any previous rabies vaccinations or immunoglobulin treatment
  • 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

Date of exposure

  • Risk assessment should be undertaken as soon as reasonable 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. This will include knowing what the animal/country risk was at the time of the exposure
  • 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 RIgS team

Which country?

  • The risk of rabies in each country takes into account the presence or absence of endemic rabies in domesticated cats and dogs (companion animals) and the presence or absence of rabies in wild-life
  • All countries apart from the UK and Ireland are considered high risk for a bat exposure: the UK and Ireland are considered low risk for bat exposures
  • The combined risk of rabies from terrestrial mammals according to geographical location (country, island and territory) and animal exposure is updated regularly. This information is incorporated into the Rabies PET form and the most recent version of the combined country/animal risks can be found on the PHE website

Category 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
CategoryTerrestrial mammalsBats
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No physical contact with saliva

For example:

  • touching, stroking or feeding animals

 

No physical contact (i.e. no direct contact with the bat’s saliva)

For example:

  • touching a bat where the person was protected by a barrier capable of preventing saliva contact, such as a boot, shoe, or appropriate protective clothing
||

Minimal contact with saliva and/or unable to infiltrate wound with HRIG if needed

For example:

  • bruising or abrasions
  • licks to broken skin (i.e. over insect bites or scratches)
  • minor scratches (i.e. not down to the muscle)
  • minor bites (i.e. to covered areas where saliva does not contaminate the wound directly)

Uncertain physical contact (i.e. where there has been no observed direct physical contact (with saliva) but this could have occurred)

For example:

  • handling a bat without appropriate protective clothing (i.e. gloves)
  • a bat becoming tangled in hair
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Direct contact with saliva

For example:

  • severe/deep lacerations (i.e. down to the muscle)
  • major bites (i.e. direct saliva contact with muscle through the wound)
  • contact of mucous membranes with saliva (e.g. licks)

Direct physical contact with bat’s saliva

For example:

  • all bites or scratches
  • contamination of mucous membrane with saliva or bat droppings/urine
  • potential unrecognised contact with bat (i.e. any bat found in the room of a sleeping or intoxicated person or young child)
  • In the UK most bat bites are felt, not seen, and rarely cause an obvious break in the skin, but should still be considered a direct physical exposure (category 3). PHE recommends that all bat bites, even if said to be from a pipistrelle, should be treated

Site of bite/additional useful information

  • The site of the bite should be given if known. If the bite is to the head or neck and treatment with HRIG is required, PET should be started within 24 hours of the contact with PHE
  • If the animal was a terrestrial mammal (wild or domestic), these details are useful:
    • 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 in both the country of potential exposure and the country of origin of the animal

Composite rabies risk

  • Using the combined country/animal risk and the category risk, a composite rabies risk is given a red, amber, or green rating
  • This rating is then used with the past medical history to determine what treatment, if any, is required

Composite rabies risk table

Country/animal riskCategory 1 exposureCategory 2 exposureCategory 3 exposure
No risk Green Green Green 
Low risk  Green  Amber  Amber 
High risk  Green Amber  Red 

Significant past medical history

Immunosuppression

  • Severe immunosuppression is described in chapter 6 of the Green Book as the conditions where the individual should not receive live vaccines
  • Anyone who falls into any of the groups listed should be considered to be immunosuppressed and will require treatment with five doses of vaccine and HRIG for any red or amber exposures, and follow up blood tests at the time of the 4th dose of vaccine

Other relevant history

  • Should include any history of allergy or bleeding disorders. There are no contraindications for rabies vaccination and/or HRIG if the risk assessment indicates it is needed. However, if there is a history of allergy to any of the excipients, the vaccine/HRIG should be given under close medical supervision with the ability to appropriately manage anaphylactic reactions
  • Intramuscular injection is the preferred route of vaccine administration. However for individuals with a bleeding discorder vaccinations should be given by subcutaneous injection to reduce the risk of bleeding

Previous rabies pre-exposure prophylaxis or post-exposure treatment

  • For those without severe immunosuppression the immune status will be based on history of previous vaccination either as part of rabies post-exposure treatment or pre-exposure prophylaxis given before the current exposure. Ignore any treatment given following the current incident being assessed, as this will only affect what further treatment needs to be given
  • Immunosuppressed: see immunosuppression
  • Fully immunised: At least three documented doses of rabies vaccine (on at least two separate days, either as a complete primary pre-exposure course or as part of a four or five dose post-exposure treatment course) or documented rabies antibody (VNA) titres of at least 0.5 IU/ml
    • if within the last six months the patient has completed a rabies post-exposure treatment course (either four doses of vaccine, or two doses if previously fully immunised), no further treatment is required for a more recent exposure
  • Partially immunised: Person who has had an incomplete/inadequate primary vaccination course (i.e. less than three doses of intramuscular pre-exposure prophylaxis, or anything less than three doses of intradermal vaccine over two separate days), or VNA never greater than 0.5 IU/ml
  • Non immunised: Person who has never received pre- or post-exposure immunisation with rabies vaccine.

Treatment recommendations

Treatment based on risk assessment

  • A formal risk assessment based on the composite rabies risk and the vaccine status should be performed; recommended treatment will generally fall into five categories (see table below):
    • no risk and therefore no treatment
    • vaccine only
    • vaccine and HRIG
    • vaccine, HRIG, and blood test with the 4th dose of vaccine—see Immunosuppression
    • observation of animal (domestic cats and dogs only—see section B4 of the full guideline)

Post-exposure treatment based on composite rabies risk and vaccine status

 Post-exposure treatment
Composite rabies risk Non-immunised/partially immunised Fully immunised Immunosuppressed 
Green None None None 
Amber

Four doses of vaccine

day 0, 3, 7, and 21

Two doses of vaccine

day 0 and day 3–7

HRIG and five doses of vaccine

day 0, 3, 7, 14, and 30

Red 

HRIG* and four doses of vaccine

day 0, 3, 7, and 21

Two doses of vaccine

day 0 and day 3–7

HRIG and five doses of vaccine

day 0, 3, 8, 14, and 30

*HRIG is not required more than 7 days after the first dose of vaccine, or more than 1 day after the second dose. HRIG is not required for partially immunised patients (unless immunosuppressed)
HRIG=human rabies immunoglobulin

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 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 ideally be started within two working days of contact with PHE. 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 4 vaccines at the following interval 0, 3, 7, 21 days given by the i.m. route
  • Day 0 is the day of first vaccine NOT necessarily the day of exposure
  • If an individual insists on a particular type of vaccine not held within the PHE supply, this will have to be sourced and paid for privately by that individual
  • 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 fourth and final dose of rabies vaccine PET should not be given before day 21
  • 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 partially immunised, a full course of 4 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

Is rabies immunoglobulin (HRIG) required?

  • The mainstay of rabies post-exposure treatment (PET) is rabies vaccine. Human rabies immunoglobulin (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 more than 7 days  after the first dose of rabies vaccine or to an individual who is already partially or previously immunised. HRIG is not indicated if the person has already received two doses of rabies vaccine
  • 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 maximum dose is 20 IU/kg, adults and children (all ages), and should not be exceeded as it may inhibit the immune response to rabies vaccine
  • The packaging of the HRIG will have the minimum quantity of immunoglobulin in the vial. This should not be used for calculating the dose required. Instead the potency recorded on the vial itself must be used
  • 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, is available on the PHE website, is also available from the RIgS team (0208 327 6204), and is on the individual vial
    • weight of the patient
    • volume that is contained in the vials (vials contain 1–4 ml, 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
  • HRIG acts to neutralise the virus at the site of the wound and to be effective HRIG must be infiltrated around the site of the wound. If it is not possible to infiltrate the whole volume then any excess can be given by intramuscular injection in the anterolateral thigh. Only in the case of mucous membrane contamination should the whole volume of HRIG be given intramuscularly
  • If more than 5 ml (2 ml in children under 20 kg) 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 sent 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/720075/PHE_guidelines_on_rabies_post-exposure_treatment.pdf

Public Health England. PHE guidelines on rabies post-exposure treatment. London: Public Health England, 2018.
First included: May 2016, updated July 2018.