World Rabies Day is an international awareness campaign coordinated by the Global Alliance for Rabies Control, a non-profit organization with headquarters in the United States.
It is a United Nations Observance and has been endorsed by international human and veterinary health organizations such as the World Health Organization, the Pan American Health Organization, the World Organization for Animal Health and the US Centers for Disease Control and Prevention. World Rabies Day takes place each year on September 28, the anniversary of the death of Louis Pasteur who, with the collaboration of his colleagues, developed the first efficacious rabies vaccine. World Rabies Day aims to raise awareness about the impact of rabies on humans and animals, provide information and advice on how to prevent the disease in at-risk communities, and support advocacy for increased efforts in rabies control.
The first World Rabies Day campaign took place on 8 September 2007 as a partnership between the Alliance for Rabies Control and the Centers for Disease Control and Prevention, Atlanta, USA, with the co-sponsorship of the World Health Organization, the World Organization for Animal Health and the Pan American Health Organization [Briggs D, Hanlon CA. World Rabies Day: focusing attention on a neglected disease. Vet Rec. 2007 Sep 1;161(9):288-9.]. In 2009, after three World Rabies Days, the Global Alliance for Rabies Control estimated that rabies prevention and awareness events had taken place in over 100 countries, that nearly 100 million people worldwide had been educated about rabies and that nearly 3 million dogs had been vaccinated during events linked to the campaign.
A 2011 review by a network of international government agencies, academics, NGOs and vaccine manufacturers identified World Rabies Day as a useful tool to assist with rabies prevention, targeting at-risk communities, animal health workers, public health practitioners, governments, key opinion leaders and experts. In the years following the review, World Rabies Day has also been used by governments and international agencies as a day on which to announce policies, plans and progress on rabies elimination. For example, in 2013, the Food and Agricultural Organization of the UN, the World Health Organization and the World Organization for Animal Health first called for the global elimination of canine-mediated rabies in a joint statement released on World Rabies Day.
It has been included in the Association of Southeast Asian Nations Rabies Elimination Strategy. At the first Pan-African Rabies Control Network meeting in 2015, the 33 African countries represented there recommended consideration of World Rabies Day as an opportunity for rabies advocacy. In the Philippines World Rabies Day has been observed at the national and local government levels since 2007, and is part of its National Rabies Prevention and Control Program.
World Rabies Day was created to be an inclusive day of education, awareness and action to encourage groups from all levels, the international to the local, to increase the spread of rabies prevention messages. Its objectives include raising global awareness about rabies and how to stop the disease, and educating people in rabies-endemic countries to prevent rabies.
It is centralized with an online platform where World Rabies Day events can be registered and resources can be downloaded to support and promote the outreach of educational messages about rabies in person, in print and online. The campaign also aims to bring together all relevant partners in an effort to address rabies prevention and control. Health workers, scientists and personnel in communities at risk of rabies are encouraged to access a bank of awareness resources through the website of the Global Alliance for Rabies Control for use in local educational initiatives.
As rabies is a disease that crosses borders, especially in wild animal populations, the campaign encourages the transnational collaboration of rabies control and prevention organizations. It also promotes a One Health approach to rabies prevention, part of a worldwide strategy for expanding interdisciplinary collaborations and communications in all aspects of health care for humans and animal health. The WRD logo (pictured above) represents the complexity of rabies, which can infect human beings, wildlife and domestic animals.
The advocacy work of the World Rabies Day campaign includes promoting government involvement in rabies prevention and control programs, increasing the vaccination coverage of pets and community dogs, and improving the educational awareness of how to prevent rabies in all levels of society. It also promotes the utilization of an integrated model of disease management, the Blueprint for Rabies Prevention. The Food and Agricultural Organization of the UN considers that World Rabies Day plays an important role in advocating the prevention and control of rabies among policy makers, especially in countries where rabies is still neglected.
Current rabies vaccine status is licensed rabies vaccines for human use are based on inactivated purified rabies virus grown either in tissue culture or in embryonated duck or chicken eggs. Nerve-tissue grown vaccines, which are less costly but are also less immunogenic and, even more importantly, can have serious side-effects, are no longer recommended by the World Health Organization (WHO) and their use has largely been discontinued.
Rabies vaccines can be given intramuscularly (IM) or at a 5–10-fold lower dose intradermally (ID). A number of different regimens are approved for use in humans. For PrEP the vaccine is given typically three times on days 0, 7, and 21 or 28. Efforts are underway to change this to a two times point 2-dose regimen for which individuals are vaccinated into two sites on days 0 and 7. After exposure to a rabid animal, previously vaccinated individuals need to receive a boost; they do not require treatment with RIG.
Unvaccinated individuals exposed to a rabid animal should receive, as soon as possible, thorough wound cleaning. Depending on the severity of exposure the wound should be infiltrated with RIG used at 20 mg/kg for human serum and 40 mg/kg for equine serum. Left-over serum that cannot be infiltrated into the wound due to space limitations should not be injected into a distant site. Individuals should then start vaccination. The vaccine can be given IM into one site on days 0, 3, and 7 followed by a fourth dose anytime between days 14–28. As an alternative IM regimen, the vaccine can be given to two sites on days 0 and 3 followed by one site injections on days 7 and 21. ID immunization should be given into two sites on days 0, 3, and 7.
As already pointed out, egg- or tissue culture-grown rabies vaccines are safe, and if given correctly, highly effective in preventing disease and death. Nevertheless, they are costly. In the US PEP costs upwards of $3,000 and can cost as much as $40,000. It is far less expensive in developing countries where the vaccine, if given ID, costs about $10–15 while equine RIG for a 60 kg human would add another $20. Further costs through miscellaneous medical supplies, fees for health care providers, travel, and loss of wages further increases the overall expense, which in developing countries commonly exceeds the weekly or even monthly income of a family.
The outcome, avoidance of PEP upon exposure to a rabid animal, is predictable and fatal.
ne could envision the development of separate vaccines for rabies PEP and PrEP as they have different goals. A vaccine for PEP needs to induce VNAs as fast as possible to prevent rabies virus from spreading into the central nervous system. A PrEP vaccine on the other hand should induce sustained VNA titers and robust memory B and CD4+ T helper cell responses that allow for rapid VNA recall after a boost. Any type of new rabies vaccine, whether it is used for PEP, PrEP, or both, would have to be as safe and efficacious as our current vaccines.
As rabies is fatal in more than 99.9% of humans that develop the disease, 80–90% vaccine efficacy, which is viewed as adequate for many of our current vaccines, such as influenza vaccines, which in some years are effective in less than 50% of recipients, is not acceptable for a rabies vaccine. Many vaccines work well in some people but not in others. Some vaccines show striking regional differences, for example the high efficacy rotavirus vaccines show in the US and Europe, is not being recapitulated in Africa. The variability in human immune responses to vaccines is not fully understood and it is assumed that both genetic and environmental factors, including the microbiome and concurrent infectious disease burden, play a role. Needless to say, immune responses to a new rabies vaccine would have to be consistent throughout different human populations.
A new rabies vaccine would have to cost less than currently licensed vaccines. Low cost is especially crucial for a PrEP rabies vaccine, which would need to cost no more than $1–3 in order to be cost-neutral to the alternative of treating exposed individuals with PEP. This takes into account that even after PrEP, a boost should be administered after exposure to a rabid animal. It does not take into account that cost-neutrality is influenced by the incidence of exposure to potentially rabid animals, which varies from country to country and even from region to region. For example, Kenya reported from 2002 to 2012 336 dog bites/100,000 persons, in 2008 and 2009 Iran reported ~ 600 dog bites/100,000 individuals. In Africa and Asia, the incidence of exposure to rabies virus through bites or licks by rabid dogs seems to be especially high in travelers with an estimated incidence of 0.4%.
Novel PrEP rabies vaccines should induce protective VNA titers after a single immunization. Current rabies vaccines stimulate long-lasting B cell memory; anamnestic responses have been observed for more than a decade following immunization.
The same would be expected of a new PrEP vaccine although admittedly such studies would have to be conducted post-licensure. A new PEP rabies vaccine should be more immunogenic and induce neutralizing antibodies faster and at higher levels to reduce the number of vaccine doses preferentially to one and the need for RIG. In either case new rabies vaccines to facilitate their use in developing countries would have to be formulated so that they are stable at ambient temperatures. Production and purification procedures should be simple to eventually allow for their local production in less developed countries.
Novel vaccine delivery methods such as biodegradable ‘bio-needles’ based on silicon or starch polymers might not only increase thermostability of the vaccine but also reduce cost by avoiding the use of syringes, needles, and vials, and, as was shown with silicon microneedles that were tested with an inactivated influenza virus vaccine in mice, may even increase immunogenicity.
The use of controlled release antigen delivery systems is being explored to allow for single immunization regimens, in which the vaccine is release over an extended period of time or at predefined intervals to circumvent the need for booster immunizations. Such methods still phase technical challenges and have thus far neither reached clinical testing for any vaccine nor have they been explored for rabies vaccines.
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