Rabies Guidelines

Download the Rabies Guidelines

1.0 INTRODUCTION

1.1 Purpose of Guidelines

1.2 Pre-travel Health Risk Assessment Overview

1.3 Short cut to expert opinion on Rabies Pre-exposure prophylaxis

Click here to jump to Section 9.2 (Expert Opinion on Rabies Pre-exposure Prophylaxis)

2.0 DETERMINE IF TRAVELLER WILL BE VISITING A RISK AREA

• Rabies is found on all continents except Antarctica and WHOWHO - World Health Organisation estimates nearly 60,000 deaths occur annually¹. The majority of deaths occur in Asia (~60%) and Africa (~36%)¹; however, cases are likely underestimated in many countries.
• See Figure 1 below showing countries where rabies is endemic² and here for an interactive map where information on each region and country can be found.
• Australia and New Zealand are rabies free in terrestrial mammals. The only cases reported are imported from elsewhere.

Figure 1: Endemicity of dog rabies and dog-transmitted human rabies, 2016

Source: World Health Organisation (2017, February 17), Human rabies: 2016 updated and call for data, Weekly Epidemiological Record, 7(91). 77-86.  https://www.who.int/publications/i/item/who-wer9207#

• Other lyssaviruses, which are genetically related to rabies, circulate globally among bats. The bat lyssaviruses (including the Australian bat lyssavirus) cause a similar clinical picture to rabies with equally dismal survival rates (see Figure 2 below)¹.

Figure 2: Diversity of bat associated lyssaviruses¹

© Crown copyright (2018, World Health Organisation Expert Consultation on Rabies, third report. WHO Technical Report Series, No. 1012). Used with the permission. Licensed under the Open Government Licence v3.0. 

3.0 EDUCATE THE TRAVELLER ABOUT THE DISEASE

• Rabies is a zoonotic disease caused by an RNA virus (genus Lyssavirus), which causes acute progressive encephalitis.
• Infection is acquired by exposure to saliva or neural tissue from an infected animal – usually dogs (99%),³ however cats⁴, bats, foxes, racoons and other mammals can also transmit the infection.³
• Humans can be exposed to infection through a mammal’s bite or a scratch that breaks the skin or direct contact of the virus with the person’s mucosa (nose, eye, mouth).⁵
• Incubation of rabies is usually 3 to 8 weeks; however, it can range from 1 week up to several years.⁵ The risk of rabies is higher, and the incubation period is shorter if the individual is bitten/scratched in areas closer to the central nervous system, such as the head and neck, and in areas richly innervated with nerves, e.g. fingers.⁵
• Childhood fatalities are over-represented, with 40% of deaths occurring in those under 15 years of age³.
• Rabies has the highest case fatality rate (~100%) of any infectious disease.¹ Once symptoms of rabies appear, it is almost always fatal; therefore, prevention is the key message for all travellers.
• Without post exposure prophylaxis (PEP), the average probability of developing rabies following a bite by a rabid animal varies by site of bite.⁶ For example after bite to the
  •             head is 55%
  •             upper extremity is 22%
  •             trunk is 9% and
  •             lower limb is 12%⁶

NOTE: The majority of persons bitten by known rabid dogs do NOT acquire rabies

4.0 UNDERSTAND PRE AND POST EXPOSURE VACCINATION

• It is important travellers understand Pre-Exposure Prophylaxis (PrEP) and Post Exposure Prophylaxis (PEP) Rabies vaccination:

4.1 POST exposure

• Post Exposure Prophylaxis (PEP) rabies vaccination is required after an animal exposure
• Vaccines are given, but it may take many weeks to mount a good response so some travellers must also be given Rabies Immune Globulin (RIG) which contains instant antibodies to cover the traveller until their own antibodies develop. RIG is required for category III exposures (and category II bat exposures; see Table 4 below) if no PrEP has been given but is not required if PrEP has been provided except in severely immunocompromised (IC) travellers.¹
• Note RIG is not available in many endemic countries.^7,8 Vaccines are more readily available worldwide than RIG. To check availability of both vaccine and RIG by country see here.⁸ See Table 4 below for classification of injury and management post-exposure.

4.2 PRE exposure

Pre-exposure prophylaxis (PrEP) is giving doses of vaccine prior to an animal exposure to allow the immune system to produce antibodies.  PrEP primes the immune system.

The rationale for PrEP includes:

• RIG is not required (except for those severely immunocompromised).
• Fewer PEP vaccine doses may be required if the traveller has previously received some of a PrEP vaccination-series.

5.0 ADVISE ABOUT HIGH-RISK ACTIVITIES AND RISK GROUPS

5.1 Predicting Risk

• Any visit to a rabies endemic area may result in exposure.
• It is important to understand that it is not possible to accurately predict who may be exposed to infection. Bites and skin abrasions are very common in travellers and often under-reported.⁹
• Activities involving contact with animals increase the risk of a risk exposure.⁹ However, those bitten or scratched are not always interacting directly with animals. Travellers may be bitten or scratched when involved in seemingly non-animal related activities such as riding bicycles or motorcycles, walking in a temple or sitting on a beach.
• In a month of travel, experiencing an animal bite is relatively common whilst the risk of dying of rabies is extremely low¹⁰. See article and logarithmic table here to consider the likelihood of an animal bite that may put a traveller at risk from rabies¹⁰.

5.2 Risk Factors for Rabies Risk Exposures

See Table 1 below for details about demographic factors and activities that increase the risk of exposure to rabies.

Table 1. Risk Factors for Rabies Risk Exposures

5.3 Myths about rabies

There are myths about rabies that go like this ‘Rabies risk is not a big worry ….

• Rabies is not a big worry because it’s only a short trip’ – unfortunately not the case; many persons who are bitten, are bitten on short trips – not because short trips are riskier, but because short trips are more common, and you cannot accurately predict risk.⁹
• Rabies is not a big worry if you don’t pat dogs’ – unfortunately not the case; many of those bitten are not patting animals or did not initiate the contact with the animal: They are just near animals as part of the common activities associated with travel and they are bitten unexpectedly.⁹
• Rabies is not a big worry, because if you get bitten you can just be treated afterwards’ – unfortunately not the case; unvaccinated travellers who are bitten need rabies immunoglobulin (RIG) and this can be very hard to find in many rabies-risk countries.^7,8 Seeking vaccination can cause a great deal of stress and travel disruption. Since rabies is a universally fatal disease, PEP is essential for every traveller who has a rabies-risk exposure.   

6.0 ADVISE TRAVELLER ON WHAT TO DO IF EXPOSED OVERSEAS

• Avoid activities in section 5 above. Recommend travel insurance as any PEP and RIG may require flights or a change of schedule.
• In the event the traveller is bitten, scratched, or their mucosa (eye, nose, mouth) is in direct contact with a potentially infected animal or bat, the traveller should understand and recognise the urgency to take the following actions:

1. 1. Immediate wound management
   2. Rabies vaccine (post-exposure prophylaxis – PEP) may be required (see Section 9)
   3. Rabies immunoglobulin (RIG) may be required⁵ (see Section 9)

Immediate wound management

• It is essential to wash the area well with soap or detergent and water. Flush with copious amounts of water for at least 15 minutes.³
• Application of a virucidal solution such as povidone-iodine is recommended^1,5. Local remedies are discouraged.
• The traveller is strongly encouraged to seek urgent medical attention from health professionals experienced in managing wounds at risk of rabies infection, as human immunoglobulin and vaccination may be required.
• See Table 4 below for categories of exposure and recommendations for PEP.

7.0 ADVISE ON ACTION TO BE TAKEN ON RETURN TO AUSTRALIA OR NEW ZEALAND IF EXPOSED OVERSEAS

7.1 Travellers potentially exposed to Rabies

• If the traveller is exposed to a potentially rabid animal and receives care whilst away, they should be encouraged to record the following information from the local medical provider^5,11, which can then be given to their public health unit on return to Australia or New Zealand.
  • Name and contact details of the clinic providing the care (phone number and email)
  • If RIG was administered
    • Name/Type of RIG (human, equine, monoclonal antibody)
    • Batch number
    • Volume, number of vials used
    • Time and date of administration.
  • If vaccine was administered
    • Name/Type of vaccine used
    • Batch number
    • Route
    • Time and date/s of administration.
  • It is recommended that all travellers who have been exposed and treated with PEP whilst overseas, should seek medical attention on their return.⁵ Travellers should contact their local travel medicine clinic or GP, and will likely be referred to their local public health unit.  Rabies serology may need to be checked to ensure the effectiveness of vaccines, and/or additional vaccine doses may be provided.  If RIG was not given whilst away and less than 7 days have passed since first PEP vaccination, RIG may still be recommended.    State public health provides RIG and rabies vaccine at no cost in Australia whereas in New Zealand a cost may be incurred.

8.0 DECIDE WITH THE TRAVELLER WHERE THE RISK / BENEFIT OF PRE-VACCINATION FALLS

Travel health practitioners are recommended to discuss the following with their patient:

• The risk of rabies when visiting rabies-endemic
• There is difficulty to accurately predict rabies risk, however children, young adults and those travelling to risk areas for long periods or on multiple trips, are at an increased risk of being bitten/scratched by a mammal.
• The myths about rabies risk as outlined above
• The importance of avoiding exposure
• What to do in the event of a bite
• Whether PEP and RIG are likely to be available if the traveller has a rabies-prone exposure (i.e. often it is not readily available).
• RIG is made from either equine or human sources.
• RIG is very expensive and has a short half-life. Low resource countries have limited supplies particularly in remote medical settings.
• Monoclonal antibody RIG is now available in some countries and will likely be more commonly available in the future.
• Even travellers who successfully access rabies vaccine whilst travelling, suffer a great measure of stress and trip disruption in dealing with the risk exposure.
• Check departure date and whether there is time for the rabies pre-vaccination course to be provided
• Whether the traveller is likely to visit these regions in future and thus get more ‘value’ from their PrEP vaccination
• The cost of the vaccine (including costs for administering the vaccine) and the time to attend a clinic for the vaccine.
• The risk of adverse events from the vaccine

In simple terms, where access is likely to be poor, and risk of exposure is high, PrEP should be offered. 

9.0 DECIDE WHICH VACCINE AND SCHEDULE TO USE

9.1 Vaccines

• There are currently 3 human rabies vaccines registered in Australia (Rabipur, Merieux Inactivated Rabies Vaccine (MIRV) and Verorab) however it is likely MIRV will be discontinued now Verorab is readily available.⁵ Currently New Zealand has only 2 registered vaccines (Rabipur¹² and MIRV¹³) with Verorab registration having lapsed.¹⁴  Despite this, Verorab is likely to be available when other vaccines are out of stock.
• All vaccines can be used for both PRE and POST exposure.
• A course should ideally use the same vaccine for each dose, but if necessary, different brands of rabies vaccine can be used interchangeably.⁵
• The dose of rabies vaccines is the same for all ages (infant, children, adult) regardless of whether being used for PRE or POST vaccination.
• Vaccines can be given intramuscularly (IM) or intradermally (ID).
• ID vaccination of MIRV and Rabipur is ‘off label’ in both Australia⁵ and NZ^12,13, however numerous studies show ID administration of rabies vaccines are efficacious in persons under 50 years of age with no immune deficiencies.¹⁵
• Since ID dose is significantly less volume than IM, ID is cheaper to administer if a vial can be used for more than one traveller.
• ID injections should only be provided by suitably qualified and experienced providers, usually in specialised travel medicine clinics. Immunisation providers must follow multidose vial procedures and discard the remaining vaccine 8 hours after opening the vial or at the end of the vaccination session.
• Both IM and ID vaccinations should be given in deltoid (or anterolateral thigh in infants). Buttock injection is not recommended.^1,5

9.2 Pre-Exposure Prophylaxis (PrEP) Vaccine Schedules

1. Australian Rabies PrEP guideline5

There are 4 options for administering pre-exposure prophylaxis, varying by schedule length, number of doses and route of administration. There is no preferential recommendation for choosing a schedule and route of administration. Consideration should include a person’s circumstance and personal preferences.

Three visit schedule

The recommended 3-visit pre-exposure prophylaxis schedule comprises 3 vaccine doses, given at days 0, 7 and 21–28. These can be given by either the intramuscular or intradermal route.

Two visit schedule

The recommended 2-visit pre-exposure prophylaxis schedule given by the intramuscular route comprises

• 2 vaccine doses, given at days 0 & 7.

The recommended 2-visit pre-exposure prophylaxis schedule given by the intradermal route comprises 4 vaccine doses, given as follows:

• 2 x 0.1 mL injections given at different sites on day 0
• 2 x 0.1 mL injections given at different sites on day 7

Australian guidelines recommend rabies virus neutralising antibody (VNAb) levels should be checked 3 weeks (range 2 to 4 weeks) after finishing the ID two visit schedule to ensure levels are ≥0.5IU per ml.⁵  If there is insufficient time for antibody levels to be checked, IM may be preferable to ID.⁵

• Two visit schedules (IM or ID) may be beneficial for those with time or budget constraints when travelling to endemic areas e.g. presenting for travel advice close to their departure time, or those who have difficulty returning for appointments.
• Australian guidelines state that for travellers undertaking the two-visit schedule and likely to have future exposures, an IM booster given at least 12 months from first dose is recommended as antibody levels may wane and be inadequate for future exposures.⁵ In Australia, an IM booster is recommended even if ID vaccinations were given initially.  A booster beyond 12 months should still provide adequate protection.^5,9,15   See section 3 below regarding WHO recommendations (boosters not recommended) and CDC (boosters recommended if ongoing exposure risk).
• Two visit schedules (IM or ID) are not recommended for immunocompromised travellers (as their immune response may not be adequate).⁵
• Two visit ID schedules are not recommended for adults over 50 years (as seroconversion is less likely to occur in those over 50 years of age).^15,16
• Intradermal (ID) injection route is not recommended for those who are
• immunocompromised (immune response may not be adequate).⁵
• taking chloroquine or other anti-malarial medications structurally related e.g. mefloquine, hydroxychloroquine at the time of vaccination or within one month, as the immune response is reduced).¹⁷
• Immunocompromised patients should also have their VNAb titres checked 2-4 weeks after their 3^rd visit IM dose. An additional vaccination (and follow up serology), is recommended if titre is below 0.5IU/ml.  If titre remains below 0.5IU/ml, advice should be sought from specialist immunisation clinics or health authorities.⁵

Table 2. Australian Rabies Pre-Exposure Vaccine Recommendations⁵

*IM booster at least 12 months after first dose visit will improve long term antibody response

Other considerations:

• It is preferable to use the same brand of vaccine for the course, however Rabies vaccines are interchangeable so if necessary, the course can be completed with a different WHO approved vaccine.⁵
• Other live and inactivated vaccines can be co-administered with rabies vaccines provided they are not mixed in the same syringe and are injected at different sites.^5,6
• Whilst pregnancy is not a contraindication to rabies vaccination, a risk assessment for pregnant women travelling to an enzootic area is recommended.¹⁸
• The immune system is not impaired by delay⁶, (and may even work better if there is more time between doses), so doses of vaccine can be given late but not early, e.g. where schedule says day 0 and day 7, doses of vaccine can be given at day 0, then day 8 or even much later say at day 40 but not day 0 and then day 6.
• Where travel of more than one year is planned, a 3-visit PrEP course would mean a booster is not necessary.

Contraindications to vaccines

PrEP

• Persons with anaphylactic or severe allergy to eggs should avoid purified chick embryo cell vaccine (Rabipur)⁵, and instead be offered human diploid cell vaccine (MIRV) or Verorab (cell culture vaccine)
• Persons with rubber or latex allergy are recommended not to be given Verorab⁵.
• MIRV can rarely lead to serum sickness. Thus, for individuals who may require multiple doses over a lifetime e.g. frequent travellers or those at occupational risk, the purified chick embryo cell vaccine (Rabipur) or (cell culture vaccine) Verorab will be more suitable as PrEP and PEP. ^19,20

PEP

• Given the fatality rate if infected by a rabid animal, there are no absolute contraindications to any rabies vaccine. WHO and CDC both state rabies vaccines are inactivated and have been safely administered to persons of all ages including pregnant women.^1,21

2. New Zealand

Schedules practiced by New Zealand travel practitioners are similar to Australian guidelines with both 2 and 3 visit IM or ID schedules included as options.  In addition, a three visit, 2 site ID schedule is an option for immunocompromised travellers.

Serology and boosters are not routine however, a risk assessment is recommended (particularly for those immunocompromised or over 50 years), where a booster may be recommended anytime between 1 and 10 years post primary series (depending on risk and anticipated activities e.g. remote travel) noting however that WHO recommendations do not generally advise any further booster being required. Thus, recommendations are on a case-by-case basis.

See Table 3 for recommended schedules.

Table 3. New Zealand Rabies Pre-Exposure Vaccine Recommendations

3. Other Recommended Vaccine Schedules

The WHO and CDC both support 2 Visit PrEP, however schedules differ in type of administration.

1. World Health Organisation (WHO) recommend either two visit, one site IM (day 0 and 7) or two visit, two sites ID of PrEP (2 ID injections at different sites, day 0 and 7 with total 4 doses (except immunocompromised see below).^1,6
   A systematic review of vaccine potency has shown that current vaccines (>2.5 IU/IM dose), when administered by the ID route for either PEP or PrEP, have efficacy equivalent to or higher than that of the same vaccine administered by the IM route.⁶
   WHO does not advocate boosters unless exposed and needing PEP⁶
   A 3-visit schedule (day 0, 7, 21-28 IM or ID) is recommended for immuncompromised.¹
   WHO also states that evidence suggests that a change in the route of administration (from IM to ID) or in vaccine product (different brands) during a PEP or PrEP course is safe and immunogenic.²¹
2. Centers for Disease Control and Prevention (CDC) recommends two IM doses of PrEP (day 0 & 7) for travellers at risk.²¹ For immunocompromised patients, serology should be performed 2-4 weeks post 2 dose series and if antibody <0.5IU/ml, a booster should be given.
   CDC advocates either a serology test between years 1 & 3 or a pre-emptive booster from day 21 and up to 3 years for individuals at ongoing risk of exposure.²¹

For a comparison of all schedules (Australia, New Zealand, WHO, CDC) see table here

9.3 Post Exposure Prophylaxis (PEP)

• A detailed discussion of PEP is outside the scope of these guidelines however a general understanding is important to inform PRE exposure vaccination
• PEP is recommended for category II and III wounds. The recommended schedule, number of doses, and route (IM or ID) will depend on the country, availability of vaccines and RIG, previous PrEP and patient factors (e.g. immunocompromised). 
• For those who completed a 2- or 3-visit PrEP schedule prior to exposure, shorter schedules will be recommended (but may depend on the country protocol).
• All travellers must seek PEP as soon as possible after exposure. There are no studies showing how long one can safely wait. However, for exposures on the head, neck or fingers the incubation of rabies will be more rapid so it is especially important to have the PEP as soon as possible and preferably within 48 hours of exposure.^1,5
• Immunocompromised, pregnant and lactating women can and should all be vaccinated if exposed (Category II & III).^1,5,6
• Persons who happen to report a rabies risk exposure in the weeks, months or even years prior to presentation should be referred to a specialised travel clinic or public health organisation for assessment as there have been cases of extended incubation periods leading to fatal rabies encephalitis.

9.4 Rabies Immunoglobulin

• For category III exposures (and bat exposures categorised as Category II), the non-immune traveller (no PrEP) should have RIG injected into the wound after cleaning (but no later than 7 days after initial PEP vaccination).¹
• The maximum dose (human RIG – 20IU/kg, equine RIG – 40IU/kg) should be infiltrated into or as close as possible to all wounds (avoiding compartment syndrome).
• For severe and multiple wounds requiring more immunoglobulin than the maximum dose, the RIG can be diluted with sterile saline to ensure infiltration of all wounds.
• If there has been mucosal contamination, rinsing with RIG can be considered.^1,5
• Alternatives to human RIG (HRIG) in some countries include equine RIG and less commonly, a monoclonal antibody. Travellers should be encouraged to ask for written details of all treatment provided (see below).
• For those travellers who have received full PrEP, RIG is not recommended except in those severely immunocompromised.^1,5
• Since wounds from bats are more likely to result in human infection, category II exposures from bats are treated as for category III exposures.⁵

Table 4. Categories of contact and recommended post-exposure prophylaxis (PEP)¹

Source: World Health Organisation (2018), WHO Expert Consultation on Rabies, third report. WHO Technical Report Series, No. 1012. https://apps.who.int/iris/bitstream/handle/10665/272364/9789241210218-eng.pdf?sequence=1&isAllowed=y

Practice point: Those travellers who suffer a rabies risk exposure, even those who successfully access rabies vaccine, often suffer a great measure of stress and trip disruption in dealing with the risk exposure.

In Australia the local public health unit will likely advise what should be done with any RIG that cannot be injected into the wound site. In New Zealand, there are authoritative travellers’ health clinics in Auckland and Wellington that will do the same.

10.0 REFERENCES

1. World Health Organisation (2018), WHO Expert Consultation on Rabies, third report. WHO Technical Report Series, No. 1012. https://apps.who.int/iris/bitstream/handle/10665/272364/9789241210218-eng.pdf?sequence=1&isAllowed=y accessed on June 1, 2023.
2. World Health Organisation (2017, February 17), Human rabies: 2016 updated and call for data, Weekly Epidemiological Record, 7(91). 77-86.  https://www.who.int/publications/i/item/who-wer9207# accessed on June 1, 2023
3. World Health Organisation (2023, September 20), Rabies Key Facts. https://www.who.int/news-room/fact-sheets/detail/rabies accessed on June 1, 2023.
4. Wilde, H., Wacharapluesadee, S., Hemachudha, T., Tepsumethanon, V., Lumlertdacha, B., 2017. Rabies. In: Quah, S.R. and Cockerham, W.C. (eds.) The International Encyclopedia of Public Health, 2nd edition. vol. 6, pp. 236–244. Oxford: Academic Press.
5. Australian Technical Advisory Group on Immunisation. (2022). Rabies and other Lyssaviruses. In Australian Immunisation Handbook. https://immunisationhandbook.health.gov.au/contents/vaccine-preventable-diseases/rabies-and-other-lyssaviruses accessed January 25, 2024.
6. World Health Organisation (2018, April 20), Rabies vaccines: WHO position paper – April 2018, Weekly Epidemiological Record,16 (93) 201-220. https://www.who.int/publications/i/item/who-wer9316 accessed on June 1, 2023.
7. Jentes, E. S., Blanton, J. D., Johnson, K. J., Petersen, B. W., Lamias, M. J., Robertson, K., Franka, R., Briggs, D., Costa, P., Lai, I., Quarry, D., Rupprecht, C. E., Marano, N. & Brunette, G. W. (2013). The global availability of rabies immune globulin and rabies vaccine in clinics providing direct care to travelers. Journal of travel medicine, 20(3), 148–158. https://doi.org/10.1111/jtm.12024
8. Centers for Disease Control and Prevention (2023, March 2). Rabies Homepage, Rabies Status: Assessment by Country https://www.cdc.gov/rabies/country-risk/index.html accessed June 17, 2024
9. Mills, D. J., Lau, C. L., & Weinstein, P. (2011). Animal bites and rabies exposure in Australian travellers. The Medical journal of Australia, 195(11-12), 673–675. https://doi.org/10.5694/mja10.11413 accessed July 15, 2023
10. Steffen, R., Chen, L.H. & Leggat, P.A (2023). Travel vaccines – priorities determined by incidence and impact, Journal of Travel Medicine, 30(7) https://doi.org/10.1093/jtm/taad085
11. New South Wales Health (2023, October 26). Rabies information for Travellers. New South Wales Government. https://www.health.nsw.gov.au/Infectious/factsheets/Factsheets/rabies-travel.pdf accessed February 5, 2024
12. Seqirus (NZ) Ltd, Rabipur Inactivated Rabies Virus Vaccine Powder and solvent for solution for injection (2022, January 18). https://www.medsafe.govt.nz/profs/datasheet/r/rabipurinj.pdf  accessed February 5, 2024
13. Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics, Merieux Inactivated Rabies Vaccine (MIRV) 2.5 IU suspension for injection (June 20, 2022). https://www.medsafe.govt.nz/profs/datasheet/m/merieuxinj.pdf  accessed February 5, 2024
14. Medsafe (2019, May 21). Medicines: Medsafe Product Detail https://www.medsafe.govt.nz/regulatory/ProductDetail.asp?ID=13393 accessed on February 5, 2024
15. Furuya-Kanamori, L., Ramsey, L., Manson, M., Gilbert, B. and Lau, C. L. (2020). Intradermal rabies pre-exposure vaccination schedules in older travellers: comparison of immunogenicity post-primary course and post-booster. Journal of Travel Medicine. Nov 9;27(7) DOI: 10.1093/jtm/taaa006 accessed December 3, 2022.
16. Mills, D. J., Lau, C. L., Fearnley, E. J., & Weinstein, P. (2011). The immunogenicity of a modified intradermal pre-exposure rabies vaccination schedule–a case series of 420 travelers. Journal of travel medicine, 18(5), 327–332. https://doi.org/10.1111/j.1708-8305.2011.00540.x accessed February 5, 2024
17. Endy, T. P., Keiser, P. B., Cibula, D., Abbott, M., Ware, L., Thomas, S. J., & Polhemus, M. E. (2020). Effect of Antimalarial Drugs on the Immune Response to Intramuscular Rabies Vaccination Using a Postexposure Prophylaxis Regimen. The Journal of infectious diseases, 221(6), 927–933. https://doi.org/10.1093/infdis/jiz558 accessed February 25, 2024 
18. Australian Technical Advisory Group on Immunisation. (2022). Rabies and other Lyssaviruses. In Australian Immunisation Handbook.  Table. Vaccines that are not routinely recommended in pregnancy: inactivated viral vaccines https://immunisationhandbook.health.gov.au/resources/tables/table-vaccines-that-are-not-routinely-recommended-in-pregnancy-inactivated-viral-vaccines accessed January 25, 2024
19. Fishbein, D. B., Yenne, K. M., Dreesen, D. W., Teplis, C. F., Mehta, N., & Briggs, D. J. (1993). Risk factors for systemic hypersensitivity reactions after booster vaccinations with human diploid cell rabies vaccine: a nationwide prospective study. Vaccine, 11(14), 1390–1394. https://doi.org/10.1016/0264-410x(93)90167-v accessed July 15, 2023
20. Warrington, R. J., Martens, C. J., Rubin, M., Rutherford, W. J., & Aoki, F. Y. (1987). Immunologic studies in subjects with a serum sickness-like illness after immunization with human diploid cell rabies vaccine. The Journal of allergy and clinical immunology, 79(4), 605–610. https://doi.org/10.1016/s0091-6749(87)80156-2 accessed July 15, 2023
21. Rao, A.K., Briggs. D., Moore. S.M., et al. Use of a Modified Preexposure Prophylaxis Vaccination Schedule to Prevent Human Rabies: Recommendations of the Advisory Committee on Immunization Practices — United States, 2022. MMWR Morb Mortal Wkly Rep 2022;71:619–627. DOI: http://dx.doi.org/10.15585/mmwr.mm7118a2 accessed July 15, 2023

11.0 ADDITIONAL READINGS AND LINKS

Garcia Garrido, H. M., van Put, B., Terryn, S., et al. (2023). Immunogenicity and 1-year boostability of a three-dose intramuscular rabies pre-exposure prophylaxis schedule in adults receiving immunosuppressive monotherapy: a prospective single-centre clinical trial. Journal Travel Medicine. 2023;30(2):taac148. https://doi.org/10.1093/jtm/taac148  accessed January 25, 2024.

Hampson, K., Coudeville, L., Lembo, T., Sambo, M., Kieffer, A., Attlan, M., et al. (2015) Estimating the Global Burden of Endemic Canine Rabies. PLoS Negl Trop Dis 9(4): e0003709. https://doi.org/10.1371/journal.pntd.0003709 accessed June 18, 2023.

Wallace, R., Petersen, B. and Shlim, D. (2023, May 1), Rabies.  In G. W. Brunette and J. B. Nemhauser (Eds.), CDC Yellow Book 2024, Oxford University Press.  https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/rabies#:~:text=Travelers%20with%20a%20sustained%20risk,unless%20they%20have%20an%20exposure. accessed June 18, 2023.

World Health Organisation (n.d.). Rabies – presence of dog-transmitted human rabies 2021. Interactive map. https://apps.who.int/neglected_diseases/ntddata/rabies/rabies.html accessed June 18, 2023.

World Health Organisation. (n.d.). Evidence to Recommendation Table 4: time and dose sparing PrEP. https://cdn.who.int/media/docs/default-source/immunization/position_paper_documents/rabies/rabies-time-dose-sparing-prep.pdf?sfvrsn=fe81e0b4_2 accessed April 6, 2023.

Dated June 27, 2024
Prepared by Frances Daily
Next update scheduled for 27 June 2025