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During June 2025, following the release of information about a recent human rabies case, a surge in rabies post-exposure treatment requests have been received by the UK Health Security Agency (UKHSA)’s Rabies and Immunoglobulin Service (RIGS), as well as by issuing centres across the country. This has resulted in a high demand for provision of rabies vaccine and human rabies immunoglobulin (HRIG).

Based on UKHSA experience from routine activities and this recent incident, interim recommendations have been developed to ensure HRIG is used in the most efficient and clinically beneficial way for those at greatest risk of rabies following an exposure.

Individuals carrying out rabies post-exposure risk assessments should use the interim recommendations for the use of HRIG outlined below alongside the UKHSA Guidelines on managing rabies post-exposure.

Role of human rabies immunoglobulin and existing indications

HRIG is used after high-risk exposures to give rapid protection by neutralising the rabies virus at the wound site until the rabies vaccine becomes effective.

The existing UKHSA post-exposure treatment guidance is for HRIG to be given for Category 3 exposures as well as to severely immunosuppressed individuals. When indicated, HRIG at a maximum dose of 20 International Units per kilogram (IU/kg) body weight should be infiltrated in and around the cleansed wound.

Every effort should be made to administer HRIG at the wound site rather than intramuscularly, as the benefit of intramuscular administration away from the site of the wound is likely to be negligible. However, operationally it is recognised that in many cases HRIG tends to be given intramuscularly rather than being infiltrated into or around a wound.

HRIG is no longer required once an active antibody response to the rabies vaccine has started to develop. Therefore, HRIG is not indicated more than 7 days after the first dose of vaccine, or more than one day after the second dose of vaccine.

Prioritisation of HRIG usage

The mainstay of rabies post-exposure treatment (PET) is rabies vaccine and the approach to assessment of rabies vaccination required post-exposure has not changed. 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).

As outlined in the World Health Organization (WHO) Expert Consultation on Rabies, Third Report, 2018:

When access to RIG cannot be guaranteed for all people with a category III exposure, it may be used sparingly and prioritized for those at greatest risk, with consideration of additional high-risk factors. Vaccine should be administered regardless of the availability of RIG.

Considering the risk factors laid out in the WHO Expert Consultation on Rabies, criteria for prioritising the use of HRIG have been developed. Rabies vaccine will continue to be offered as post-exposure treatment to all individuals with a red or amber composite rabies risk, as per existing UKHSA rabies post-exposure treatment guidance.

HRIG usage for 4 key groups is shown in Table 1. The first 3 groups are those who will continue to receive HRIG based on a body weight calculation of 20 IU/kg.

Group 1 includes those individuals who may not make an effective response to rabies vaccine, the severely immunosuppressed, whereby HRIG will provide a degree of initial passive protection but response to vaccination course must be checked by serology at time of the day 30 dose.

Group 2 includes children under 16 years with a bite or severe laceration in a high-risk country. Globally, children are estimated to represent almost half the rabies cases each year as they often play with animals, are more likely to be bitten on the head or neck, and they may not always report a bite or scratch.

Group 3 includes those who have had an exposure to a confirmed rabid animal. For Groups 1 to 3, as much HRIG as is anatomically possible (but avoiding risk of compartment syndrome) should be administered into and around the wound. Any remaining dosage (based on calculated dose for body weight) for these groups only may be administered intramuscularly.

HRIG for Group 4 is focussed on administration at the wound site. For these patients, the usual dose calculated as per body weight is replaced by a single vial of HRIG, which will be issued with instructions to infiltrate the HRIG into and around the wound. HRIG will not be given for healed wounds or those more than one month old, as HRIG infiltration at the site of the exposure will no longer be possible. Careful consideration should always be given to the volume of HRIG that can be administered in each specific anatomical site to avoid risk of compartment syndrome. HRIG can be diluted with saline if additional volume is required to administer to multiple severe bites or lacerations.

Table 1. Interim recommendations for use of HRIG

Group	Scenario for HRIG issue	Dose of HRIG to be used	Other information
1	Severely immunosuppressed patients (as per categories in UKHSA rabies post-exposure guidance) with a Category 2 or 3 exposure in a high-risk country	Maximum of 20 IU/mg of body weight infiltrated into and around the cleansed wound, or remaining dose given as intramuscular administration	If necessary, restart course of 5 doses of rabies vaccine with HRIG. Use calculator on UKHSA risk assessment form to calculation volume (ml) of HRIG required. The quantity of HRIG on the packaging is the minimum content of the vial, and must not be used for calculating the dose
2	Category 3 bite or severe laceration to children in a high-risk country (Red composite rabies risk)	Maximum of 20 IU/mg of body weight infiltrated into and around the cleansed wound, or remaining dose given as intramuscular administration	Administer within 7 days of starting rabies vaccine course. Use calculator on UKHSA risk assessment form to calculation volume (ml) of HRIG required. The quantity of HRIG on the packaging is the minimum content of the vial, and must not be used for calculating the dose
3	Category 3 bite or severe laceration from an animal with confirmed rabies (Red composite rabies risk)	Maximum of 20 IU/mg of body weight infiltrated into and around the cleansed wound, or remaining dose given as intramuscular administration	Administer within 7 days of starting rabies vaccine course. Use calculator on UKHSA risk assessment form to calculation volume (ml) of HRIG required. The quantity of HRIG on the packaging is the minimum content of the vial, and must not be used for calculating the dose
4	Category 3 bite or severe laceration in a high-risk country, not already covered in Groups 1 to 3 (Red composite rabies risk)	1 vial to be used for infiltration into and around cleansed wound, to a maximum dose of 20 IU/mg body weight	HRIG can be diluted with saline if additional volume is needed for multiple bites

Scenarios where HRIG will not be used

HRIG should not be given intramuscularly for any patients, except for those in Groups 1 to 3 (severely immunosuppressed patients or children or those with a exposure from a confirmed rabid animal). This includes administration where a mucous membrane exposure is reported.

Unless exposures in Groups 1 to 3, HRIG should not be administered for fully healed wounds.

Unless exposures in Groups 1 to 3, HRIG should not be administered for those exposures that occurred more than one month prior to current presentation.

HRIG should not be administered for Category 2 exposures including scratches (aside from severely immunosuppressed individuals).

As per existing guidance, HRIG is not required:

• more than 7 days after the first rabies vaccine dose or  where an individual is previously immunised with rabies vaccine
• if a patient has received another rabies immunoglobulin product, such as equine RIG or rabies monoclonal antibody product
• for primate or rodent exposures, even those considered Category 3 exposures

Review of HRIG prioritisation guidance

These interim recommendations will be reviewed on a quarterly basis or more rapidly in the event of changes to demand or supply. A broader review of rabies post-exposure treatment guidance is planned later in 2025.

References

1. Medley AM, Millien MF, Blanton JD, Ma X, Augustin P, Crowdis K and others. ‘Retrospective cohort study to assess the risk of rabies in biting dogs, 2013 to 2015, Republic of Haiti’ Tropical Medical Infectious Diseases 2017: volume 2, issue 2, page 14

2. UKHSA. ‘Guidelines on managing rabies post-exposure’ (January 2023)

3. UKHSA. ‘Immunisation against infectious diseases (the Green Book), Rabies, Chapter 27’ (19 May 2023)

4. WHO. ‘’ (WHO Technical Report Series, number 1012)