RABIES: ALL FOR ONE -ONE HEALTH FOR ALL

 Prof (Dr) Md Moin Ansari

University Professor & Head

Department of Veterinary Surgery and Radiology

Bihar Veterinary College,

Bihar Animal Sciences University, Patna-800014, Bihar, India.

 Abstract

Rabies is a viral zoonotic neuro-invasive disease and continues to be a major problem in developing nations like India with 20,000 mortality every year. Rabies disease most often transmitted through the bite of a rabid animal. In India, approximately 90 per cent of the rabies cases were encountered due to dog bite and the most vulnerable risk group includes children below the age of fifteen. The most common wild reservoirs of rabies are raccoons, skunks, bats, and foxes. Domestic mammals can also get rabies. Cats, cattle, and dogs are the most frequently reported rabid domestic animals. World Rabies Day is being celebrated to commemorate the death anniversary of Louis Pasteur who developed first anti- rabies vaccine. In this prospective, World Rabies Day has been celebrated to create awareness among public, health professionals, Veterinarians, researchers, stakeholders, champions partners at community, local, national, and global levels to accomplish these goals by mobilizing awareness and resources in support of human rabies prevention and control of this dreadful zoonotic disease around the world including India. This year, September 28 is World Rabies Day. established in 2007, with the aims to raise awareness about the world’s deadliest infectious disease and help the world come together to fight the disease. The theme for 2023’s World Rabies Day is “Rabies: All for One, One Health for All,” and focuses on: continuing to work towards eliminating rabies around the world, embracing the One Health approach to rabies control, which means collaborating across human, animal, and environmental sectors and focusing on the “Zero by 30” goal to reduce rabies deaths in people to zero globally by 2030 will highlight the connection of the environment with both people and animals. The World has a vaccine, medicines, tools, and technologies to break the cycle of one of the deadly zoonotic diseases. Global Strategic Plan for the elimination of dog mediated human rabies death by 2030 (zero by 30).

Key words: Rabies, one health, zero death, prevention, dog

“Although notable progress had been made in various aspects of rabies, there is still a splintering of efforts in research and control and a great need to bring these efforts together”

-George M.B.,1991

Introduction

World Rabies Day is an opportunity to reflect on how rabies impacts your community and other communities around the world. Rabies is still present in many parts of the world. The theme for 2023’s World Rabies Day is “Rabies: All for One, One Health for All,” and focuses on: continuing to work towards eliminating rabies around the world, embracing the One Health approach to rabies control, which means collaborating across human, animal, and environmental sectors and focusing on the “Zero by 30” goal to reduce rabies deaths in people to zero globally by 2030 will highlight the connection of the environment with both people and animals. The World has a vaccine, medicines, tools, and technologies to break the cycle of one of the deadly zoonotic diseases. Rabies is a viral zoonotic neuro-invasive disease, caused by a plethora of lyssa viruses, belongs to the order Mononegavirales, viruses with non-segmented, negative-stranded RNA genomes, of which the classical rabies virus is the most important in domestic or wild animals. The arrangement of 5 proteins designated as N, P, M, G, L and the RNA genome determine the structure of the rabies virus. The term is derived from the Latin rabies, “madness”. This, in turn, may be related to the Sanskrit rabhas, “to rage”. The Greeks derived the word lyssa, from lud or “violent”; this root is used in the genus name of the rabies virus, Lyssavirus. In Ancient Greece, rabies was supposed to be caused by Lyssa, the spirit of mad rage.  In the laboratory it has been found that birds can be infected, as well as cell cultures from birds, reptiles, and insects. Rabies virus which infects the central nervous system causes acute encephalitis (inflammation in the brain) in all warm-blooded hosts and the outcome is almost always fatal. Once a rabies infection is established, there’s no effective treatment.

Rabies continues to be a major problem in developing nations like India with 20,000 mortality every year. Rabies disease most often transmitted through the bite of a rabid animal. In India, approximately 90 per cent of the rabies cases were encountered due to dog bite and the most vulnerable risk group includes children below the age of fifteen. The most common wild reservoirs of rabies are raccoons, skunks, bats, and foxes. Domestic mammals can also get rabies. Cats, cattle, and dogs are the most frequently reported rabid domestic animals. Animals with rabies suffer deterioration of the brain and tend to behave bizarrely and often aggressively, increasing the chances that they will bite another animal or a person and transmit the disease. Most cases of humans contracting the disease from infected animals are in developing nations. Rabies has a long history of association with dogs. The first written record of rabies is in the Codex of Eshnunna (1930 BC), which dictates that the owner of a dog showing symptoms of rabies should take preventive measure against bites. Most rabies cases reported to the Centers for Disease Control and Prevention each year occur in wild animals. India has the highest rate of human rabies in the world, primarily because of stray dogs, whose number has greatly increased since a 2001 law forbade the killing of dogs. An estimated 20,000 people die every year from rabies in India, more than a third of the global total. Ending human deaths from dog mediated rabies by 2030 will require an active role from India, which has a high concentration of the disease but is also empowered by its rich technical expertise and resources to drive cooperation of other countries in the region.

Stages and Clinical Signs of Rabies:

Three stages of rabies are recognized in dogs and other animals.

1. Prodromal stage: The first stage is prodromal stage which last by 1-3 days period characterized by behavioral changes.
2. Excitative stage: It is this stage that is often known as furious rabies, which lasts 3 to 4 days due to the tendency of the affected animal to be hyper-reactive to external stimuli and bite at anything near.
3. Paralytic or dumb stage: The third stage is the paralytic or dumb stage and is caused by damage to motor neurons. Incoordination is seen due to rear limb paralysis and drooling, and difficulty swallowing is caused by paralysis of facial and throat muscles. This disables the host’s ability to swallow, which causes saliva to pour from the mouth. This causes bites to be the most common way for the infection to spread, as the virus is most concentrated in the throat and cheeks, causing major contamination to saliva. Death is usually caused by respiratory arrest.

Rabies has also occasionally been referred to as Hydrophobia (“fear of water”) throughout its history. It refers to a set of symptoms in the later stages of an infection in which the person has difficulty swallowing, shows panic when presented with liquids to drink, and cannot quench their thirst. Any mammal infected with the virus may demonstrate hydrophobia. Saliva production is greatly increased, and attempts to drink, or even the intention or suggestion of drinking, may cause excruciatingly painful spasms of the muscles in the throat and larynx. Since the infected individual cannot swallow saliva and water, the virus has a much higher chance of being transmitted, since it multiplies and assimilates in the salivary glands and is transmitted through biting. Hydrophobia is commonly associated with furious rabies, which affects 80% of rabies-infected people. The remaining 20% may experience a paralytic form of rabies that is marked by muscle weakness, loss of sensation, and paralysis; this form of rabies does not usually cause fear of water.

In animals the first symptoms of rabies may be nonspecific and include lethargy, fever, vomiting, and anorexia. Signs progress within days to cerebral dysfunction, cranial nerve dysfunction, ataxia, weakness, paralysis, seizures, difficulty breathing, difficulty swallowing, excessive salivation, abnormal behavior, aggression, and/or self-mutilation. In human, first symptoms of rabies may be very similar to those of the flu including general weakness or discomfort, fever, or headache. The rabies virus attacks the central nervous system of the host, and in humans, it can cause a range of debilitating symptoms- including states of anxiety and confusion, partial paralysis, agitation, hallucinations, and, in its final phases, a symptom called “hydrophobia,” or a fear of water. The symptoms eventually progress to delirium, and coma. Death usually occurs 2 to 10 days after first symptoms. In human, the incubation period (the time between initial contact with the virus and onset of the disease) generally ranges from two to eight weeks. In rare cases, it can vary from 10 days to 2 years. The incubation period is shorter in children and in people exposed to a large dose of the rabies virus.

Diagnosis:

 Tests are performed on samples of saliva, serum, spinal fluid, and skin biopsies of hair follicles at the nape of the neck. Saliva can be tested by virus isolation or reverse transcription followed by polymerase chain reaction (RT-PCR). Serum and spinal fluid are tested for antibodies to rabies virus. The reference method for diagnosing rabies is the fluorescent antibody test (FAT), an immunohistochemistry procedure, which is recommended by the World Health Organization (WHO).

Differential Diagnosis:

 The differential diagnosis in a case of suspected human rabies may initially include any cause of encephalitis, in particular infection with viruses such as herpesviruses, enteroviruses, and arboviruses such as West Nile virus. The most important viruses to rule out are herpes simplex virus type one, varicella zoster virus, and (less commonly) enteroviruses, including coxsackieviruses, echoviruses, polioviruses, and human enteroviruses. Epidemiologic factors, such as season, geographic location, and the patient’s age, travel history, and possible exposure to bites, rodents, and ticks, may help direct the diagnosis.

Control and Eradication of rabies:

 Almost all human exposure to rabies was fatal until a vaccine was developed in 1885 by Louis Pasteur and Émile Roux. Their original vaccine was harvested from infected rabbits, from which the virus in the nerve tissue was weakened by allowing it to dry for five to ten days. Similar nerve tissue-derived vaccines are still used in some countries, as they are much cheaper than modern cell culture vaccines. Rabies in humans can be eradicated through ensuring adequate animal vaccination and control, educating those at risk, and enhancing access of those bitten to appropriate medical care. Once a rabies infection is established, there’s no effective treatment. Though a small number of people have survived rabies, the disease usually causes death.

Fortunately, the annual World Rabies Day campaign, first observed in 2007. World Rabies Day is being celebrated to commemorate the death anniversary of Louis Pasteur who developed first anti- rabies vaccine. In this prospective, World Rabies Day has been celebrated to create awareness among general public, health professionals, Veterinarians, researchers, stakeholders, champions partners at community, local, national, and global levels to accomplish these goals by mobilizing awareness and resources in support of human rabies prevention and control of this dreadful zoonotic disease around the world including India. Key interventions for rabies control include vaccination for high-risk individuals, surveillance of human cases, post-exposure prophylaxis following animal bites, vaccination and/or culling of the canine population and other animal reservoirs. Almost all the human deaths attributed to rabies are due to rabies transmitted by dogs in countries where dog vaccination programs are not sufficiently developed to stop the spread of the virus.

This year, September 28 is World Rabies Day. established in 2007, with the aims to raise awareness about the world’s deadliest infectious disease and help the world come together to fight the disease. The theme for 2023’s World Rabies Day is “Rabies: All for One, One Health for All,” and focuses on: continuing to work towards eliminating rabies around the world, embracing the One Health approach to rabies control. Under the One Health Initiative, World Health Organization (WHO), Office International des Epizooties (OIE), Food and Agricultural Organization (FAO), and Global Alliance for Rabies Control (GARC) are working on simultaneous campaigns to eliminate canine rabies through the vaccination of dogs, the treatment of human rabies exposures with wound washing and post-exposure prophylaxis, and the improvement of education about rabies prevention where it is needed most. Because pet animals can get rabies from wildlife and then could spread it to humans, preventing rabies in pet animals is also an important step (Educate. Vaccinate. Eliminate) in preventing human rabies cases. “The elimination of rabies in India is a daunting task, but not an impossible one,” says Dr. Reeta Mani, Associate Professor of India’s National Institute of Mental Health and Neurosciences (NIMHANS). “Control of canine rabies through vaccination and dog birth control is imperative, although with 25 million stray dogs in the country this is a formidable task.” While the sheer size of India’s dog population is a significant obstacle, Dr. Mani also points out recent positive developments: “Collaborative efforts between the medical, veterinary, and public health sectors have already made a significant difference. We have seen improved rates of pre-exposure vaccination (PrEP) for vulnerable populations, such as children, and improved awareness of the need for post-exposure prophylaxis (PEP) after a bite.” Within recent years, India has overcome polio, yaws, and maternal and neonatal tetanus. Through a collaborative approach it is possible that this generation will also see the end of rabies in India. The World has a vaccine, medicines, tools, and technologies to break the cycle of one of the deadly zoonotic diseases.

 ONE HEALTH (OH) APPROACH

 One Health (OH) is a new phrase, but the concept was originated as far back as to the time of Aristotle in 500 BC and Hippocrates of Cos in 340 BC. Aristotle wrote the ‘Historia Animalium’ to elaborate on the natural zoonotic history of animals. Researchers including Louis Pasteur and Robert Koch and physicians such as William Osler and Rudolph Virchow demonstrated the collaborative links between animal and human health. More recently, the term ‘One Medicine’ was developed and promoted by veterinary epidemiologist and parasitologist Calvin W. Schwabe (1927–2006) in 1984. In 2003, the term ‘One Health’ draw the attention across the globe since it was mentioned in Washington Post by Dr. William Karesh to describe the outbreaks of Ebola haemorrhagic fever in Africa. He said, ‘Human or livestock or wildlife health can’t be discussed in isolation anymore. According to Weiss, 2003, there is just OH and the solutions require everyone working together on all the different levels. This was followed by a series of conferences across the glove with the theme of ‘One World – One Health. One Health is defined by the OH Commission as “the collaborative effort of multiple disciplines to obtain optimal health for people, animals, and our environment.” In another definition, the One Health Initiative Task Force (OHITF) defines one health as “the promotion, improvement, and defense for the health and well-being of all species by enhancing cooperation and collaboration between physicians, veterinarians, and other scientific health professionals and by promoting strengths in leadership and management to achieve these goals.” The OH approach, employing disease surveillance, management, and eradication through collaboration between veterinarians dealing with livestock and wild animal populations and ecologists examining ecosystem biodiversity and public health experts, may have yielded a more rapid resolution to the outbreak. Collaboration between veterinary, medical, and public health professionals to understand the ecological interactions and reactions to flux in a system can facilitate a clearer understanding of climate change impacts on environmental, animal and human health.

Rabies, brucellosis, bovine tuberculosis, leptospirosis and anthrax are important zoonoses widely prevalent in India and other developing countries. Among these zoonoses, rabies is of utmost public health significance due to its lethality. Rabies is a viral zoonotic disease of mammals. Approximately, 55,000 people are reported to die of rabies every year throughout the world. Rabies is mainly transmitted by roaming dogs, and the rabies virus is also believed to be harbored by them. Gangs of stray dogs often inflict injuries during fight with fellow members, some of which are also rabid. The newly infected victims develop signs and symptoms of various incubation times and thus, in turn, transmit the virus to other stray dogs at different times. In this way, the transmission of the virus is sustained in an area, region, state or country. Despite being a classic preventable zoonotic disease with an almost 100 % case fatality ratio rabies remains one of the notoriously under reported and neglected disease in the modern world.  Each and every case of human rabies is not only a tragic event for the family and community, however, the tools to prevent such terrible deaths have been available ever since rabies can be prevented and managed efficiently by “OH Approach” which involves inter-sectoral collaboration from human, animal, and environmental health disciplines at local, national, and global levels to a make program successful by a comprehensive, strategic, and targeted control and prevention approach with collaborative efforts of veterinarians, clinician, epidemiologist, laboratory scientists and  nursing  experts can help generate public awareness about prevention of Rabies along with Government who can formulate policies. With this background the strategic action plan has four priority deliverables instrumental to the success of the plan viz: dog mass vaccination (DMV- is the most important component), access to timely post-exposure prophylaxis, robust human and dog disease surveillance and community mobilization. Increasing awareness of rabies prevention and control in communities is an integral part of any successful rabies control and or elimination programme. Rabies is 100 % vaccine preventable. Optimizing the supply and access to safe, efficacious and affordable dog and human rabies vaccines and rabies immunoglobulin is key to achieving zero human rabies death. Veterinarians can help in managing the biting canine/dog and help in its monitoring by adopting Animal Birth Control (ABC) Programme. They can also play a key role in rabies prevention by vaccinating anti-rabies vaccine (ARV) to stray dogs in urban and peri-urban areas. Municipal corporations certainly also work hand in hand with veterinary service providers for registering the number of stray dogs in an area and their neutering or sterilization. Anti-rabies vaccines are outstandingly effective, no one should die of dog-transmitted infection. Eliminating rabies in dogs is now feasible and would dramatically reduce human mortality. The high current economic burden of human prophylaxis would then be largely relieved. World Rabies Day (WRD) 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. As the world is celebrating the World Rabies Day on Tuesday’ 28 September’ 2021, efforts and aims to focus on 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 provide supports for implementation efforts in rabies control. The importance of wildlife as reservoirs of human diseases has also been widely recognized for most of the parasitic zoonoses, including American and African trypanosomiasis, leishmaniasis, giardiasis, cryptosporidiosis, balantidiasis, fascioliasis, opisthorchiasis, clonorchiasis, paragonimiasis, schistosomiasis, echinococcosis, taeniasis, diphyllobothriasis, sparganosis, dipylidiasis, trichinellosis, toxocariasis, strongyloidiasis, and Ancylostoma caninum and A. braziliense infections. The OH approach has successfully replaced the disease cantered approach to zoonoses with a system-based approach that aligns multiple disciplines, working locally, nationally, and globally, to attain optimal health for people, domestic, and wild animals and the environment. For vector-borne diseases, effective vector control is an integral part of any intervention strategy. Integrated pest management is a comprehensive approach used to prevent and control various pests that can transmit diseases. Rodent traps should be maintained and monitored, and potential vector nesting materials and breeding sites should be eliminated. Use of insecticides and pesticides should be part of a whole plan, not the only tactic used to control pests. In case of Bird Flu or Avian Influenza caused by H5N1 Influenza virus, veterinarians should promptly demarcate the area of infected zone and start culling and burial activities along with municipality workers. OH, professionals including doctors and nurses professionals should generate awareness about bird flu in the local population and ensure their cooperation by telling them not to consume eggs and meat in the immediate vicinity. In case of possible bioterrorism attack by Bacillus anthracis spores, similar collaborative approach is needed between veterinarians and one health promulgators. Leptospirosis is another zoonotic disease caused by Leptospira spp., a spirochaete, which urgently needs a OH viewpoint. Rodents, rice fields and rainfall are epidemiologically play very significant role for spread of the infection. Various sectors like Health sector, agriculture and others need to be integrated via OH to diagnose cases accurately, properly control rodents and stop spread of the infection. Still others, such as the novel coronavirus that causes COVID-19, have the potential to cause global pandemics. COVID-19, caused by SARS-CoV2 or novel Coronavirus is also a zoonosis. It spread in December 2019 via bats and pangolins to man, in Hubei, China. Now it is spreading rapidly from man to man as a full- fledged pandemic. World Health Organization, NGO’s and national governments are working together for formulation and implementation of stringent OH approach for successful application of OH approach in COVID-19. Preventive measures like social distancing, frequent hand washing and wearing face masks while venturing outside are relevant and significant.

Global Strategic Plan for the elimination of dog mediated human rabies death by 2030 (zero by 30).

1. Washing bite wounds and scratches for 15 minutes with soap and water, povidone iodine, or detergent may reduce the number of viral particles and may be somewhat effective at preventing transmission. It is an effective way of preventing infection, while both pre-exposure and post-exposure vaccinations for humans exist. Global elimination of the disease is feasible through mass vaccinations of dogs, which transmit 95% of rabies cases to humans.
2. Visit your veterinarian with your pet animals on a regular basis and keep rabies vaccinations up to date for all cats, ferrets, and dogs.
3. Maintain control of your pets by keeping cats and ferrets indoors and keeping dogs under direct supervision.
4. Spay or neuter your pets to help reduce the number of unwanted pets that may not be properly cared for or vaccinated regularly.
5. Call animal control to remove all stray animals from your neighborhood since these animals may be unvaccinated or ill.
6. Keeping pets up to date on their rabies vaccination will prevent them from acquiring the disease from wildlife, and thereby prevent possible transmission to family or other people.
7. Understanding rabies risk and knowing what to do after contact with animals can save lives.
8. If find an injured animal, don’t touch it; contact local authorities for assistance.
9. If anybody meets a rabid animal, rabies in humans is 100% preventable through prompt appropriate medical care.
10. If anybody is bitten, scratched, or unsure, contact to a healthcare provider about PEP protocol.
11. PEP consists of a dose of human rabies immune globulin (HRIG) and rabies vaccine given on the day of the rabies exposure, and then a dose of vaccine given again on days 3, 7, and 14. The vaccine should be given at recommended intervals for best results. Rabies prevention is a serious matter and changes should not be made in the schedule of doses.
12. For people who have never been vaccinated against rabies previously PEP should always include administration of both HRIG and rabies vaccine.
13. The combination of HRIG and vaccine is recommended for both bite and non-bite exposures, regardless of the interval between exposure and initiation of treatment.
14. People who have been previously vaccinated or are receiving pre-exposure vaccination (PrEV) for rabies should receive only vaccine.
15. PrEV for those people who work with rabies in laboratory settings and animal control and wildlife officers are just a few of the people who should consider rabies pre- exposure vaccinations.
16. If anybody is traveling to a country where rabies is widespread, you should consult your doctor about the possibility of receiving PrEV against rabies. Although pre-exposure vaccination does not eliminate the need for additional therapy after a rabies exposure, it simplifies management by eliminating the need for rabies immune globulin and decreasing the number of doses of vaccine needed.
17. Pre-exposure prophylaxis may also protect people whose post-exposure therapy is delayed and provide protection to people who are at risk for unapparent exposures to rabies.
18. For primary vaccination, three 1.0 mL injections of HDCV or PCEC vaccine should be administered intramuscularly (deltoid area), one injection per day on days 0, 7, and 21 or 28.
19. For booster doses, people who work (continuous risk) with rabies virus in research laboratories or vaccine production facilities are at the highest risk for unapparent exposures. Such persons should have a serum sample tested for rabies antibody every six months. Intramuscular booster doses of vaccine should be administered to maintain a serum titer corresponding to at least complete neutralization at a 1:5 serum dilution by the rapid fluorescent focus inhibition test (RFFIT).
20. For people who is works as laboratory workers (frequent risk) such as those performing rabies diagnostic testing, veterinarians and staff, and animal-control and wildlife officers in areas where animal rabies is enzootic. Such people should have a serum sample tested for rabies antibody every 2 years; if the titer is less than complete neutralization at a 1:5 serum dilution by the RFFIT, the person also should receive a single booster dose of vaccine.
21. For Veterinarians, veterinary students, and terrestrial animal-control and wildlife officers working in areas where rabies is uncommon to rare (infrequent exposure group) and at-risk international travellers fall into this category and do not routine pre-exposure booster doses of vaccine after completion of primary pre-exposure vaccination.

Prognosis:

Vaccination after exposure, PEP, is highly successful in preventing the disease. In unvaccinated humans, rabies is almost always fatal after neurological symptoms have developed.

Conclusion

The one health approach continues to be a highly integrated efforts in research, which involves inter-sectoral collaboration from human, animal, and environmental health disciplines at local, national, and global levels to a make program successful by a comprehensive, strategic, and targeted control and prevention approach with collaborative efforts of veterinarians, clinicians, epidemiologists, laboratory scientists and nursing experts have a very important role to play in generate public awareness about preventive measures of zoonotic infections in animal reservoirs and enable early outbreak detection to ensure safe health and a better world.

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Rabies All For 1 : One Health for All

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