Travel Med Infect Dis. 2013 Nov-Dec;11(6):427-30. doi: 10.1016/j.tmaid.2013.09.006.

Immunogenicity of a modified intradermal pre-exposure rabies vaccination schedule using a purified chick embryo cell vaccine: an observational study.

Lau CL, Hohl N.

WHO Collaborating Centre for Children’s Health and the Environment, Queensland Children’s Medical Research Institute, The University of Queensland, Australia; Travel Medicine Alliance Clinics, Australia. Electronic address: colleen.lau@uq.edu.au.

ABSTRACT:

Background: In Australia, recommendations for pre-exposure rabies vaccination involve 3 doses of vaccines on days 0, 7, and 28 using either 1.0mL intramuscular (IM) vaccines, or 0.1 mL intradermal (ID) vaccines. The use of IM vaccines is limited by their prohibitive cost, and ID vaccines by the recommendation for serology 2 to 3 weeks post-vaccination. A recent study reported the successful use of human diploid cell rabies vaccines (HDCV) with a modified ID schedule (2 x 0.1mL ID on days 0 and 7) – Travellers Rabies Intradermal 2 site (TRID2) – that was affordable, required less time to complete than standard ID schedules, and achieved a seroconversion rate of 94.5%. This study reports the immunogenicity of pre-exposure rabies vaccination using a purified chick embryo cell vaccine (PCECV) with the TRID2 schedule.

Method: Travellers who attended a travel medicine clinic for pre-travel health advice and vaccinations were recruited for the study. Participants were aged 10 to 50 years, given the PCECV using the TRID2 schedule, and rabies serology was performed at day 28 to assess immunity.

Results: Fifty-four travellers were vaccinated, with a seroconversion rate of 94.4% at day 28. Seroconversion rates did not differ between age groups, but older travellers had lower antibody levels.

Conclusions: This study supports the effectiveness of the TRID2 schedule, and found the schedule equally effective with HDCV or PCECV.

SUPPLEMENT:

Rabies is invariably fatal in humans, and is responsible for an estimated 55,000 deaths per year globally [1]. Travellers to endemic areas are at risk of infection if bitten or scratched by infected mammals, and can be protected by pre-exposure vaccination prior to travel or post-exposure prophylaxis after animal contact. A recent study from an Australian travel medicine clinic found that most travellers who were bitten or scratched by an animal had difficulty obtaining post-exposure prophylaxis while overseas, resulting in significant delays in treatment [2].

In Australia, recommendations for pre-exposure rabies vaccination involve 3 doses of vaccines on days 0, 7, and 28 using either 1.0mL intramuscular (IM) vaccines, or 0.1 mL intradermal (ID) vaccines [3]. The use of IM vaccines is limited by the prohibitive cost, and the use of ID vaccines is limited by the time required to have rabies antibody levels tested 2 to 3 weeks post-vaccination, as recommended by the national immunisation guidelines [3]. Worldwide, the cost of IM vaccines coupled with vaccine shortages has stimulated studies using various rabies ID vaccine schedules [4-6].

Mills et al [7] reported the successful use of a modified ID schedule (2 x 0.1mL ID on days 0 and 7) – Travellers Rabies Intradermal 2 site (TRID2) – that was more affordable for travellers and required less time to complete than the standard ID schedule [7]. The study involved the use of human diploid cell rabies vaccines (HDCV) and found a seroconversion rate of 94.5%.

Our study corroborates findings by the Mills et al study that the TRID2 schedule for rabies pre-exposure vaccination provided similar immunogenicity as the standard ID schedule. The Mills et al study used a HDCV vaccine, and this study found that PCECV was also effective for the TRID2 schedule.

The TRID2 schedule provides significant cost savings compared to IM vaccines, more convenient than the standard ID schedule, and allows more travellers to be vaccinated prior to travel. The modified schedule has high immunogenicity in young travellers, and would be particularly useful for backpackers with limited budgets, and families travelling with multiple children.

References:

1. World Health Organisation. Rabies Vaccines. Who Position Paper. Wkly Epidemiol Rec 2010;32:309-20.
2. Mills DJ, Lau CL, Weinstein P. Animal Bites and Rabies Exposure in Australian Travellers. Med J Aust 2011;195:673-5.
3. National Health and Medical Research Council. The Australian Immunisation Handbook 10th Edition. 4.16 Rabies and other lyssaviruses (including Australian bat lyssavirus). Australian Government Department of Health and Ageing 2013.
4. Warrell MJ. Intradermal Rabies Vaccination: The Evolution and Future of Pre- and Post-Exposure Prophylaxis. Current Topics in Microbiology and Immunology 2012;351:139-57.
5. Warrell MJ. Current Rabies Vaccines and Prophylaxis Schedules: Preventing Rabies before and after Exposure. Travel Med Infect Dis 2012;10:1-15.
6. Permpalung N, Wongrakpanich S, Korpaisarn S, Tanratana P, Angsanakul J. Trend of Human Rabies Prophylaxis in Developing Countries: Toward Optimal Rabies Immunization. Vaccine 2013; In press.
7. Mills DJ, Lau CL, Fearnley EJ, Weinstein P. The Immunogenicity of a Modified Intradermal Pre-Exposure Rabies Vaccination Schedule–a Case Series of 420 Travelers. J Travel Med 2011;18:327-32.

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