![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
Abstract
Rabies being the most lethal zoonotic, vaccine-preventable viral disease with worldwide distribution of reservoir wild animals presents unique challenges for its diagnosis, management and control. Although vaccines available are highly effective, which had played the key role in controlling rabies in North America, western Europe and in a number of Asian and Latin American countries, the requirement of multiple doses along with boosters, associated cost to reduce the incidence in wild animals and prophylactic human vaccination has remained a major impediment towards achieving the same goals in poorer parts of the world such as sub-Saharan Africa and southeast Asia. Current efforts to contain rabies worldwide are directed towards the development of more safe, cheaper and efficacious vaccines along with anti-rabies antibodies for post-exposure prophylaxis. The work presented here provides an overview of the advances made towards controlling the human rabies, particularly in last 10 years, and future perspective.
Financial & competing interests disclosure
This work was supported by Department of Biotechnology (DBT), Department of Science and Technology, Council of Scientific and Industrial Research, Indian Council of Medical Research, India and NATP-World Bank. S Singh is a Ramalingaswami Fellow, supported by DBT, India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Rabies, a zoonosis, is a fatal progressive encephalitis caused by the infection of the members of the Lyssavirus genus. All mammals are susceptible to rabies but animals from the orders of Carnivora and Chiroptera are primary reservoirs, that is, dogs, foxes, jackals, coyotes, skunks, raccoons, mongoose and bats.
Annually about 60,000 people die of rabies. Most of the human rabies cases result from rabid dog bites (>98%), especially in Asia and Africa or bat bites, especially in Americas, Europe and Australia. Very rarely saliva, body fluids and organ transplants originating from infected individuals or bites of other reservoir animals have been reported as a cause of rabies.
Rabies is a 100% preventable disease if proper prophylactic vaccination is provided as a part of the pre-exposure prophylaxis (PrEP) or along with anti-rabies serum (rabies immunoglobins [RIGs]) as a part of the post-exposure prophylaxis (PEP). No one immunized with PrEP and PEP vaccines has died of rabies following coming in contact with a rabid animal.
The complications associated with overwhelming replication of Lyssavirus in CNS are supposed to cause rabies-related death. The nerve tissue vaccine that was widely used up to about a decade ago in many parts of the world though highly effective had serious side effects such as demyelinating allergic encephalitis. Now, it has been replaced with more effective and safer cell culture vaccines in most parts of the world.
Despite the availability of effective rabies vaccines, the reach of vaccines to the patients in the poorer regions of the world had been limited by a combination of factors such as cost, availability, access to preventive medical care, awareness/ignorance and misconceptions about rabies.
To effectively control the disease, various awareness programs and vaccination programs including that for the reservoir animals are desired. A number of such programs are in place and many more are being formulated for the endemic areas by local governments, philanthropic institutions and other stakeholders such as WHO.
The animal vaccination program could greatly benefit from the availability of oral rabies vaccines. Some oral vaccines have been successfully used/tested in wild animals. Concerted efforts are required to make them available globally, particularly to poorer countries where rabies is endemic.
Development of a safe, single-dose vaccine and the cost reduction of the existing vaccine can significantly reduce the economic burden of rabies vaccination programs worldwide besides improving the PrEP or PEP compliance and eventually success of rabies control programs.
Vaccines under development such as subunit vaccines, attenuated live virus vaccines have the potential to eliminate the need of boosters and reduce the dosage required for PEP or PrEP to one, while development of plant-based edible-vaccines could significantly improve the reach and reduce the associated cost of vaccine delivery and administration.
Future rabies intervention efforts should include the development of strategies/small molecules to slow down/stop the replication/spread of virus allowing the PEP to take effect. Development of anti-viral drugs or interfering RNA that may delay the viral replication/spread should be made priority. Although it has tremendous potential to bring down mortality from rabies, the efforts in this direction have been scanty.
Future vaccine development efforts need to include targeting of the members of the phylogroup II and III of Lyssavirus genus to make the vaccine ready for any such eventuality that may see zoonosis of these Lyssavirus members or in a rare case emergence of some recombinant viruses. Available rabies vaccines and those under various stages of development primarily target viruses from phylogroup I of Lyssavirus genus and are presumed to be ineffective against the infection of the members of phylogroup II and III.