Guidelines on timing of rabies boosters based on antibody levels
Updated 7 June 2022
Applies to England
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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 human deaths 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 1 (EBLV1) was found for the first time in serotine bats (Eptesicus serotinus) in southern England in 2018, and European Bat Lyssavirus 2 (EBLV2), a rabies-like virus, has been found in Daubenton’s bats (Myotis daubentonii) across the UK. A soprano pipistrelle (Pipistrellus pygmaeus) tested positive for lyssavirus antigen in 2020, but there was insufficient RNA to type the virus.
Further Information, guidance and the risk assessment forms for post-exposure treatment and pre-exposure prophylaxis are available on the rabies pages of the UKHSA website.
Purpose and scope
This guidance provides a practical guide for assessing the need for pre-exposure rabies vaccine booster doses based on the results of rabies serology testing. It is aimed at duty doctors at Colindale, health protection teams and other health professionals who may be involved in the assessment and need for rabies pre-exposure vaccine booster doses. It should not be used for assessing the need for post-exposure treatment, or managing a case of possible rabies, both of which are covered in separate documents. (See the Rabies post-exposure treatment: management guidelines).
Requests for pre-exposure vaccine are outside the scope of this document and should be managed as:
- vaccines prior to travel – refer caller to the National Travel Health network and centre (NaTHNaC) or, for complex queries, the advice line: 0845 602 6712
- vaccines for those with occupational risk (see Green Book chapter 27) – who are the responsibility of their employer and will no longer be provided through UKHSA
Vaccine will only be provided from UKHSA for those who regularly handle bats on a voluntary basis (that is, not part of their employment). Requests should be made using the pre-exposure risk assessment form which should be returned by secure e-mail to Ig.clerks@nhs.net
Current practice in England and Wales
The requirement for booster doses is dependent on an individual’s indication for pre-exposure prophylaxis (PrEP) and the likely frequency of ongoing exposures. In those who may have frequent unrecognised exposures to the virus, such as bat handlers, a single reinforcing dose of vaccine should be given one year after the primary course has been completed. Further booster doses should then be given every 3 to 5 years or based on serology. Laboratory staff routinely working with rabies virus should have rabies antibody testing every 6 months, with boosters provided if required.
Routine booster doses are not recommended for most travellers. A single booster dose of vaccine can be considered, following a risk assessment, in those who have completed a primary course more than one year before and are travelling again to a high risk (enzootic) area. A complete pre-exposure primary course is considered to be either 3 doses over 21 to 28 days, or an accelerated 3-dose course (over 7 days) plus an additional dose of vaccine at one year.
Antibody testing to guide PrEP boosters is not offered on the NHS, although some individuals opt to pay for antibody testing. Currently there are no specific guidelines on how to interpret the antibody levels, although antibody titres of at least 0.5 IU/ml are considered protective (World Health Organization, 2018).
Review of response to rabies pre-exposure prophylaxis (PrEP)
In 2016, a review of the British experience of testing of laboratory workers for rabies antibody was published (Mansfield and others, 2016). The paper describes the results of 280 workers who had periodic rabies antibody testing for occupational purposes.
The results indicated that although some individuals can maintain antibody levels greater than 0.5 IU/ml for many (more than 10) years, there are some ‘poor responders’ who quickly lose their measurable rabies antibody (although presumably still maintain their cellular immunity).
Antibody test results taken one year after the primary course of PrEP or a booster was the best predictor of future antibody responses, and it was calculated that there was a 27% reduction (CI 25 to 28%) per 2-fold change in time since the last vaccination or booster. This rate of decline could be used to calculate the need for future boosters or blood tests (see Table 1).
Table 1
| Antibody result at least one year after last dose of vaccine | Recommendation |
|---|---|
| More than 10 IU/ml | Test again 10 years later or give booster vaccination in 10 years |
| More than 3 IU/ml | No booster required, test again or give booster 5 years later |
| More than 2 IU/ml | No booster required, test again or give booster 3 years later |
| More than 1 IU/ml | No booster required, test again or give booster one year later |
| Less than 1 IU/ml | Booster vaccination and then retest one year later |
Recommendations
For laboratory workers handling lyssavirus containing material, provide booster vaccination one year after primary pre-exposure vaccination. Maintain current recommendations for serology every 6 months. Antibody levels should be maintained above 1 IU/ml for this group and boosters provided if levels fall below 1 IU/ml.
For those who may have frequent unrecognised exposures to lyssaviruses, such as bat rehabilitators, a primary course of PrEP with a booster at one year is recommended and then either regular boosting or blood tests or boosters as per the recommended schedule in Table 1.
For those at infrequent risk of exposure but who are likely to have an unrecognised exposure (that is, recreational cavers, veterinarians investigating suspect rabies cases and non-compliant imported pets, engineers maintaining rabies laboratory equipment or those entering rabies laboratories but not directly working with virus as defined in the Green Book, chapter 27) a primary course of PrEP is recommended followed by testing and boosting as per the recommended schedule in Table 1.
If the person is severely immunosuppressed (as defined in Green Book, chapter 6), seriously consider whether it is appropriate that the patient should be handling bats at all. These individuals should be advised that bat lyssavirus infections are fatal in humans, and if they are exposed to bat lyssavirus, it is possible that they may not respond to post-exposure vaccine, and that it may not be possible to treat them and they could die from rabies. The individual requires careful counselling and should be made aware of the potential risks.
If vaccination is still required and the individual is aware of the potential risks if they are exposed, then antibody levels may be required 2 weeks after the last dose of vaccine to ensure an adequate immune response.
If the individual becomes severely immunosuppressed (as defined in Green Book, chapter 6) at any point after receiving a primary course of PrEP, or after having an antibody test or booster, they should seriously consider whether it is appropriate that the patient should be continuing activities which potentially exposes them to lyssaviruses at all.
These individuals should be advised that lyssavirus infections are fatal in humans, and if they are exposed to lyssaviruses, it is possible that they may not respond to post-exposure vaccine, and that it may not be possible to treat them and they could die from rabies.
The individual requires careful counselling and should be made aware of the potential risks. If relevant, their employer must be made aware of their susceptibility and potential risks in the workplace.
If vaccination is still required and the individual (and employer) is aware of the potential risks if they are exposed, then antibody levels may be required 2 weeks after the last dose of vaccine to ensure an adequate immune response.
In individuals who are tested for occupational purposes or considered severely immunosuppressed following a full pre-exposure primary course and have an antibody test result of less than 1 IU/ml with a particular course of rabies vaccine, consider offering an alternative licenced vaccine as a booster, if available, and retest 4 weeks later.
If an alterative vaccine is not available, consider offering another dose of the same vaccine and retest 4 weeks later.
References
Mansfield and others (2016) ‘Rabies pre-exposure prophylaxis elicits long-lasting immunity in humans’. Vaccine: volume 34, pages 5,959 to 5,967
‘Rabies vaccines: World Health Organization position paper’ Weekly Epidemiological Record (WER) April 2018: volume 93, pages 201 to 220
Further documents relating to rabies, rabies pre-exposure prophylaxis and rabies post-exposure prophylaxis are available on the rabies page of the duty doctor pack on the Intranet and at Rabies: risk assessment, post-exposure treatment, management.