Introduction

Rabies is one of the deadliest zoonoses, caused by the virus of the Lyssavirus genus (family Rhabdoviridae).

Spreading in almost every continents of the world, with more than 150 endemic countries, rabies claims nearly 60,000 human lives annually and it is estimated that every 10 minutes, a person dies from rabies infection. Most of the human rabies victims were children, <15 years of age, in the Africa and Asia. Every year, more than 15 million people worldwide receive a post-bite vaccination. Recent increases in human rabies deaths in parts of Africa and Asia suggest that rabies is re-emerging as a serious public health issue. More than 95% of human rabies deaths resulted from exposure to infected dogs (http://www.oie.int). Despite the almost 100% mortality, rabies is a vaccine preventable diseases. Effective vaccines, available commercially for both humans and dogs, can be used for both pre- and post-exposure prophylaxis.

Immunology of Rabies Vaccination

Currently available rabies vaccines can protect against all strains of the rabies viruses and provide good cross-protective immunity against the viruses in phylogroup I, but not II and III, of the Lyssavirus. Currently, there are inactivated vaccine, recombinant canarypox virus expressing the rabies glycoprotein available for the use in domestic animals. In addition, live vaccinia vector expressing the rabies glycoprotein (oral vaccine) is also available for certain wildlife species including raccoon and coyotes. The goal of rabies vaccination is to induce viral neutralizing antibodies (VNA) against the glycoprotein before the virus gain access to the host nervous system. Although a level of protective VNA cannot be truly established, a minimum level of 0.5 IU/ml is used as a correlate of protection. In general, protective immunity should be achieved by day 14 of a post-exposure immunization regimen, regardless of concurrent administration of rabies immunoglobulin (RIG) and irrespective of age. In vaccinated animals, an antibody titer gradually increases and peaks approximately at 28 days following initial vaccination. Unlike other vaccines, anti-rabies VNA rapidly declined within 60 days and vaccinated animals turned seronegative (<0.5 IU/ml) by 180 days post vaccination. Therefore, veterinarians should be aware of this timeframe, when planning for booster vaccination and serological determination for pets traveling from rabies endemic zone to other countries.

In contrast to serum neutralizing antibodies, immunological memory in vaccinated pet persisted longer, possibly lifelong, and can be reactivated upon vaccination booster or natural exposure. In healthy dogs, the duration of immunity (DOI) for rabies vaccine lasted longer than 7 years and revaccination was not necessary for maintaining the immunological memory or protective immunity in animals. This information supports an extended booster interval in owned adult pets, as recommended by several veterinary professional organizations, including WSAVA. Rabies vaccine is considered a core vaccine for rabies endemic countries. The 2016 WSAVA vaccination guidelines recommended to give one dose of rabies vaccine to puppies at 12 weeks of age. In high-risk areas, a second dose may be given at 2–4 weeks later. For initial adult vaccination, a single dose is recommended. Revaccination (booster) should be given at 1 year of age. Subsequently, the time of following booster is determined by the vaccine licensed DOI, and country’s statute. In supporting the biological relevance of immunological memory, dogs and cats with an out-of-date rabies vaccination exhibited similar anamnestic responses to the animals with regular vaccine status, regardless of the time since last vaccination or numbers of previously received rabies vaccines. Thus, post-exposure management of any previously vaccinated dogs or cats, regardless of vaccination status (regular vs overdue), should be similar. The updated protocol for post-exposure management in rabies-exposed animals is available from the provided reference.

Factors affecting the effectiveness of rabies vaccination and control in the endemic area.

Several factors, including animal size, age, breed, blood sampling time and vaccine (company, batch), significantly affect the levels of antibody responses in vaccinated dogs. Young (<1 yr) and old (>7 yr) dogs usually had lower antibody responses to rabies vaccination. Although maternal-derived immunity (MDA) has been one of the major interfering factors for vaccination in young animals, the interfering effect of MDA on rabies vaccination is not prominent. By 3 months of age, the level of MDA should have decreased, and active immunization will succeed in most puppies. In addition, host health and immunological status, proper vaccine handling, and delivery techniques are all critical for effective rabies immunization. Successful rabies vaccination and control program depend on both vaccine efficacy and coverage. Neither of these will reach 100%. In the endemic areas, achieving 70% herd immunity against rabies in the dog population will be crucial for controlling disease transmission and elimination of dog-mediated human rabies. Continuing education of health and veterinary professionals in rabies prevention and control, strengthening of public awareness and community engagement are essential for successful rabies control.

Rabies control and eradication require multi-sectoral coordination and collaboration. In 2015, the WHO-FAO-OIE have set the tripartite collaboration with a goal for elimination of the dog-mediated human rabies by 2030. The global frameworks have been agreed and now being implemented. Success will depend on implementation of the five pillars of rabies elimination (STOP-R): socio-cultural, technical, organizational and political approaches.

References

1.  Fooks AR, Cliquet F, Finke S, Freuling C, Hemachudha T, Mani RS, et al. Rabies. Nat Rev Dis Primers. 2017;3:17091.

2.  OIE. Manual of Diagnostic Tests and Vaccines for Terrestrial Animals2013. Available from: http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.01.17_RABIES.pdf.

3.  National Association of State Public Health V, Compendium of Animal Rabies P, Control C, Brown CM, Slavinski S, Ettestad P, et al. Compendium of Animal Rabies Prevention and Control, 2016. J Am Vet Med Assoc. 2016;248(5):505–17.

4.  WHO. Rabies vaccines. WHO position paper. Wkly Epidemiol Rec. 2007;82(49- 50):425–35.

5.  Tepsumethanon W, Polsuwan C, Lumlertdaecha B, Khawplod P, Hemachudha T, Chutivongse S, et al. Immune response to rabies vaccine in Thai dogs: a preliminary report. Vaccine. 1991;9(9):627–30.

6.  Schultz RD. Duration of immunity for canine and feline vaccines: a review. Vet Microbiol. 2006;117(1):75–9.

7.  Day MJ, Horzinek MC, Schultz RD, Squires RA. WSAVA Guidelines for the vaccination of dogs and cats. J Small Anim Pract. 2016;57(1):E1–E45.

8.  Moore MC, Davis RD, Kang Q, Vahl CI, Wallace RM, Hanlon CA, et al. Comparison of anamnestic responses to rabies vaccination in dogs and cats with current and out-of-date vaccination status. J Am Vet Med Assoc. 2015;246(2):205–11.

9.  Kennedy LJ, Lunt M, Barnes A, McElhinney L, Fooks AR, Baxter DN, et al. Factors influencing the antibody response of dogs vaccinated against rabies. Vaccine. 2007;25(51):8500–7.

10.  WHO. Global framework to eliminate human rabies transmitted by dogs by 2030. Available from: www.who.int/neglected_diseases/news/Global_framework_eliminate_human_rabies_transmitted_dogs_2030/en.