Rabies vaccines: WHO position paper—Recommendations

doi:10.1016/j.vaccine.2010.08.082

Vaccine

Volume 28, Issue 44, 18 October 2010, Pages 7140-7142

https://doi.org/10.1016/j.vaccine.2010.08.082 Get rights and content

Abstract

This article presents the WHO recommendations on the use of rabies vaccines excerpted from the recently published Rabies vaccines: WHO position paper. This document replaces the WHO position paper entitled Rabies vaccines WHO position paper published in the Weekly Epidemiological Record in December 2007. Footnotes to this paper provide a limited number of core references; their abstracts as well as a more comprehensive list of references may be found at http://www.who.int/immunization/documents/positionpapers/en/index.html. Grading tables which assess the quality of scientific evidence for key conclusions are also available through this link and are referenced in the position paper.

In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This updated paper reflects the recent recommendations of WHO's Strategic Advisory Group of Experts on immunization, or SAGE.

Section snippets

Pre-exposure prophylaxis

Pre-exposure prophylaxis is recommended for anyone who will be at continual, frequent or increased risk of exposure to the rabies virus, either as a result of their residence or occupation (for example, laboratory workers dealing with RABV and other lyssaviruses, veterinarians and animal handlers). Travellers with extensive outdoor exposure in rural high-risk areas where immediate access to appropriate medical care may be limited should also be vaccinated regardless of duration of stay.

Post-exposure prophylaxis

The indication for post-exposure prophylaxis depends on the type of contact with the suspected rabid animal:

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category I – touching or feeding animals, licks on intact skin (that is, no exposure);
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category II – nibbling of uncovered skin, minor scratches or abrasions without bleeding;
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category III – single or multiple transdermal bites or scratches, contamination of mucous membrane with saliva from licks, licks on broken skin, exposures to bats.

For category I exposures, no prophylaxis is required;

Coordinated efforts towards rabies control

As demonstrated in industrialized countries and in most of Latin America, eliminating rabies from dog populations significantly reduces human exposure to the disease. Mass vaccination of dogs is the single most cost-effective intervention to control and eliminate canine rabies. However, successful rabies control also depends on measures such as managing the dog population, mainly by promoting responsible dog ownership; compulsory notification of rabies in humans and animals; ensuring the

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Reducing the cost of post-exposure rabies prophylaxis: efficacy of 0.1 ml PCEC rabies vaccine administered intradermally using the Thai Red Cross post-exposure regimen in patients severely exposed to laboratory-confirmed rabid animals
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What is an acceptable delay in rabies immune globulin administration when vaccine alone had been given previously?
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WHO position paper. Weekly Epidemiology Record...

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2023, Comparative Immunology, Microbiology and Infectious Diseases
Rabies is a zoonotic disease caused by rabies virus of the genus Lyssa virus and family Rhabdoviridae. It affects all mammals and is prevalent throughout the world and endemic in many countries except in Islands like Australia and Antarctica. It is highly fatal, but preventable. Disease causes threat to public health because rabid dogs bite humans, resulting in thousands of deaths every year. Around 59,000 people die every year from rabies in the world. Dogs play a vital role in most of the human exposure in rabies endemic areas. Transmission of virus occurs through the bite of an infected dog. Disease is manifested by fatal nervous symptoms leading to paralysis and death. Direct fluorescent antibody technique is the gold standard for the diagnosis of the disease in animals and humans. Prevention of rabies involves the vaccination of dogs and humans before or after an exposure. This review describes the etiology, pathogenesis, diagnosis, its prevention and control strategies.
Alternative strategies to increase the immunogenicity of COVID-19 vaccines in kidney transplant recipients not responding to two or three doses of an mRNA vaccine (RECOVAC): a randomised clinical trial
2023, The Lancet Infectious Diseases
An urgent need exists to improve the suboptimal COVID-19 vaccine response in kidney transplant recipients (KTRs). We aimed to compare three alternative strategies with a control single dose mRNA-1273 vaccination: a double vaccine dose, heterologous vaccination, and temporary discontinuation of mycophenolate mofetil or mycophenolic acid.
This open-label randomised trial, done in four university medical centres in the Netherlands, enrolled KTRs without seroconversion after two or three doses of an mRNA vaccine. Between Oct 20, 2021, and Feb 2, 2022, 230 KTRs were randomly assigned block-wise per centre by a web-based system in a 1:1:1 manner to receive 100 μg mRNA-1273, 2 × 100 μg mRNA-1273, or Ad26.COV2-S vaccination. In addition, 103 KTRs receiving 100 μg mRNA-1273, were randomly assigned 1:1 to continue (mycophenolate mofetil+) or discontinue (mycophenolate mofetil-) mycophenolate mofetil or mycophenolic acid treatment for 2 weeks. The primary outcome was the percentage of participants with a spike protein (S1)-specific IgG concentration of at least 10 binding antibody units per mL at 28 days after vaccination, assessed in all participants who had a baseline measurement and who completed day 28 after vaccination without SARS-CoV-2 infection. Safety was assessed as a secondary outcome in all vaccinated patients by incidence of solicited adverse events, acute rejection or other serious adverse events. This trial is registered with ClinicalTrials.gov, NCT05030974 and is closed.
Between April 23, 2021, and July 2, 2021, of 12 158 invited Dutch KTRs, 3828 with a functioning kidney transplant participated in a national survey for antibody measurement after COVID-19 vaccination. Of these patients, 1311 did not seroconvert after their second vaccination and another 761 not even after a third. From these seronegative patients, 345 agreed to participate in our repeated vaccination study. Vaccination with 2 × mRNA-1273 or Ad26.COV2-S was not superior to single mRNA-1273, with seroresponse rates of 49 (68%) of 72 (95% CI 56–79), 46 (63%) of 73 (51–74), and 50 (68%) of 73 (57–79), respectively. The difference with single mRNA-1273 was -0·4% (-16 to 15; p=0·96) for 2 × mRNA-1273 and -6% (-21 to 10; p=0·49) for Ad26.COV2-S. Mycophenolate mofetil- was also not superior to mycophenolate mofetil+, with seroresponse rates of 37 (80%) of 46 (66–91) and 31 (67%) of 46 (52–80), and a difference of 13% (-5 to 31; p=0·15). Local adverse events were more frequent after a single and double dose of mRNA-1273 than after Ad26.COV2-S (65 [92%] of 71, 67 [92%] of 73, and 38 [50%] of 76, respectively; p<0·0001). No acute rejection occurred. There were no serious adverse events related to vaccination.
Repeated vaccination increases SARS-CoV-2-specific antibodies in KTRs, without further enhancement by use of a higher dose, a heterologous vaccine, or 2 weeks discontinuation of mycophenolate mofetil or mycophenolic acid. To achieve a stronger response, possibly required to neutralise new virus variants, repeated booster vaccination is needed.
The Netherlands Organization for Health Research and Development and the Dutch Kidney Foundation.
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Preventable public health challenge: Rabies suspected exposure and prophylaxis practices in southwestern of Turkey
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Citation Excerpt :
Annually 26,400–61,000 people die due to rabies worldwide, which can be prevented via appropriate approaches. Canine reservoirs are dominated of most cases that occur in Africa and Asia and they are also one of the main contributors in many countries of the eastern Mediterranean [3]. Rabies is a mandatory notifiable disease in many eastern Mediterranean countries such as Turkey where rabies is still prevalent [4,5].
Rabies is found in many countries of the eastern Mediterranean and is one of the most important zoonotic diseases in the world. The study aims to describe rabies suspected exposures (RSE) and rabies prophylaxis practices in Antalya-Turkey between 2010 and 2013.
All 2513 RSE cases presenting to a rabies vaccination center in Antalya, southwestern Turkey, were retrospectively investigated.
The mean age of the RSE cases was 30.04 ± 19.63 years with male predominance (63.6%). The vast majority was from urban areas (91.7%), and a postexposure rabies vaccination program was applied to 79.7% of participants. Dogs were the primary source of RSE cases (61.2%). The 39.2% of animals were under observation, and 9.53% of them died. Forty-two animals (1.7%) were laboratory confirmed rabid; 61.9% of them were cows. The rabid animal rate in the rural area was significantly higher than the urban area (18.2% versus 0.2%; p = 0.001).
This study includes a large number of RSE cases and prophylaxis practices in southwestern Turkey. Most RSE cases had dog or cat contact. As most RSE cases were in urban areas; more focused efforts should be made for elimination and vaccination of feral dog and cat population in Turkey.
Safety and immunogenicity of SURE RAB™, an inactivated cell culture derived rabies vaccine: A comparative, phase III clinical trial
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Rabies is a viral zoonotic disease widespread across the world. In India, various cell culture vaccines are available for pre and post exposure prophylaxis (PEP) but are not sufficient to meet the rising demand. The present study evaluated the safety and immunogenicity of Rabies vaccine Human I.P. (Brand name: SURE RAB™) in PEP and demonstrated its non-inferiority to already approved rabies vaccine (Brand name: VERORAB).
It was a phase-III randomized, open label, comparative, single centre clinical trial in post exposure subjects. Safety and immunogenicity were evaluated at Day 0, 14 and 45 ± 7 post vaccination. Day 14 serum samples were analyzed by Enzyme Linked Immunesorbent assay (IgG ELISA, Bio-Rad) and Day 0, 14 and 45 ± 7 serum were tested by Rapid Fluorescent Focus Inhibition Test (RFFIT). Paired t-test was applied to compare the results of Rabies virus neutralizing antibody (RVNA). The severity of adverse reactions was measured on a scale of excellent, good, fair and bad; p-value (p < 0.05) was considered as statistically significant.
All the subjects achieved a protective titer value between 0.5 and 9.0 IU/ml by Day 14 tested by ELISA and significant rise in the antibody titer in all the groups when tested after 45 days. Statistically significant p-value (p < 0.001) observed with RFFIT test indicated biological potency of rabies vaccine. Adverse events and safety was comparable statistically between three groups (p = 0.886) and Group I + II combined versus Group III (p = 0.495).
The study results conclusively demonstrate that SURE RAB™ is comparable to VERORAB in terms of safety and immunogenicity and can be used for PEP in rabies.
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2020, Acta Tropica
Rabies is the most dreaded neglected zoonosis worldwide. It affects mostly developing countries with limited access to post-exposure prophylaxis and a low coverage of dog vaccination.
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Monte Carlo simulations of a series of interconnected probabilities were used to estimate the burden of rabies. The data was collected from cross-sectional surveys of 8775 households of which 4172 were in the District of Bamako and 4603 in the region of Sikasso. Further data was collected in health centres and from the respective veterinary services.
We estimate that in the year 2016 133 [95% Confidence Interval (95%CI) 87-186] people died and that 5’366 [95%CI 3’510-7’504] years of life (YLL) were lost and in 2017 et 136 [95%CI 96-181] people died and that 5530 [IC 95% 3’913-7’377] YLLs were lost. The loss of income was estimated at 3.2 million USD [95%CI 2,1-4,5] en 2016, and 3,3 million USD [95%CI 2,3-4,4] in 2017. This represents the highest financial loss from rabies, followed by the cost of postexposure prophylaxis (PEP) of 86’848 $USD and 89’371 $ USD respectively. From the whole cost of rabies in Mali, 92% of the cost in 2016 and 94% of those in 2017 were attributable to premature mortality and the cost of help seeking. The proportion of cost of PEP was 3% in 2016 and 2017 of the total cost of disease. The cost related to dog vaccination changed from 3% to 1% in the same time period.
This study shows that despite the possibility of preventing human rabies by PEP, its burden remains important in Malian communities. Rabies control by mass vaccination of dogs is hardly done and access to PEP is difficult. However, Rabies elimination by mass vaccination of dogs has been demonstrated to be feasible. Hence a coordinated regional effort between countries by funding dog mass vaccination and full access to PEP can eliminate rabies in West Africa.

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Conference reportRabies vaccines: WHO position paper—Recommendations

Abstract

Section snippets

Pre-exposure prophylaxis

Post-exposure prophylaxis

Coordinated efforts towards rabies control

Vaccine

Vaccine

Vaccine

Conference report
Rabies vaccines: WHO position paper—Recommendations