“RABIES: ONE HEALTH ZERO DEATH” -ALL FOR ONE- ONE HEALTH FOR ALL

“RABIES: ONE HEALTH ZERO DEATH” –ALL FOR ONE- ONE HEALTH FOR ALL

Dr Shashi Pradhan

Department of Veterinary Medicine

CoVSc and A.H., N.D.V.S.U. Jabalpur

 INTRODUCTION    

It is a collaborative, multisectoral and transdisciplinary  approach ,All for one one health for all  to control the rabies  all three play important role  like environment health  -human and animals if we want to control rabies we also want to control vector present in environment  like bat, rabid dog.  We have to aware human  regarding rabies and its prevention and pre and post bite vaccination and at last pet should we vaccinated. The rabies virus, which belongs to the Rhabdoviridae family, infects the central nervous system and causes hallucinations, excessive drooling, a fear of water, paralysis, and death in mammals. The most common way for it to spread is by a rabid dog’s bite. Treatment must begin as soon as possible after infection; else, death is very likely. Dogs in India are primarily responsible for the majority of human rabies cases (97%; 20,000 fatalities annually). As bites in children frequently go unnoticed and unreported, over half of rabies cases and fatalities in India are in youngsters under the age of 15.

The Latin word for rabies, “rabere,” also means “to be mad.” Since the dawn of civilisation, the illness has been well known. In the twenty-third century BC, the pre-mosaic Eshmuna code of Babylon contained the first authentic description of rabies. But Louis Pasteur was the one to link the illness to a virus in the 1880s. Despite the fact that rabies is a viral zoonosis that can be prevented through vaccination, it still poses a serious threat to public health in developing nations, as shown by the fact that rabies causes more than 60,000 fatalities each year while only about 15 million people worldwide receive post-exposure prophylaxis (PEP) for the disease.

Rabies in mammals is fatal due to involvement of nervous system (NS) and is caused by a neurotropic, negative sense, non-segmented, single-stranded RNA virus that belongs to the Lyssavirus genus of the Rhabdoviridae family and Mononegavirale order.

The interesting feature of the lyssavirus is presence of seven distinct genotypes. The rabies virus (RABV) genome is approx. 12 kb size, which carries five structural proteins namely, nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and RNA-dependent RNA polymerase (L).

The majority of cases of rabies are fatal, and there is no specific antiviral medication available. This makes rabies significant on a global scale. All continents, with the exception of Antarctica and Australia, are covered by the disease’s distribution. The disease creates urgent public health concerns in Asia and Africa. In the Asian subcontinent, it is primarily high in Bangladesh and India, then fairly common in Nepal, Myanmar, Bhutan, Thailand, and Indonesia. Its prevalence has been reported to range from 20% to 50% in several domestic animal species. Animals’ susceptibility varies widely depending on their species, genetic make-up, age, strain, biotype, or virus dose, as well as their exposure route. Worldwide rabies is endemic, which is a major concern but in countries like USA control programmes have facilitated the process of reducing the number of cases.

In many developing countries, mortality in humans due to rabies infection are low because of under-reporting, cultural beliefs, poor or inadequate rabies diagnostic units and poor knowledge on the mode of transmission and prevention of the disease.

The existence of multiple lyssavirus genotypes in various parts of the world, the majority of which cause disease in people, is a big worry. The presence of the virus at low levels in samples that are readily available, such as saliva and cerebrospinal fluid (CSF), makes it difficult to make an accurate diagnosis of the illness in humans quickly.

The standard method for diagnosing rabies involves finding Negri bodies using Sellar’s staining. Due to its short duration, cheap cost, and excellent sensitivity, the direct fluorescent antibody method (dFAT) is the gold standard test for rabies diagnosis and has been authorised by the WHO. In addition to dFAT, the very sensitive mouse inoculation test is frequently used, particularly in underdeveloped nations.

The development of successful therapy may be dependent on a better knowledge of the fundamental mechanisms underlying the pathogenesis of rabies. The therapeutic approach for rabies in animals and people is a major demanding topic in medicine.

HISTORY

The widespread and deadly sickness known as rabies affects both humans and animals. Around 2300 BC, rabies was first identified in Egypt. Aristotle also accurately characterised rabies in ancient Greece. The Avesta in Persia from the sixth century BC and the Susrutasamhita in India from the first century BC both have descriptions of canine rabies. In 1804 Zinke noticed that the saliva from diseased dogs was contagious. Prior to Pasteur’s discovery in 1885, there were no efficient preventive or curative treatments for animals. Pasteur in 1881 demonstrated the neurotropism of the virus. In 1885, Pasteur discovered and administered a rabies vaccine, prior to the structure and properties of the RABV were understood. In the same year, first time he administered the rabies vaccine to Joseph Meister, who was attacked worsely by rabies-affected animal. That day was the milestone for the beginning of the modern science in the area of infectious diseases targeting control and prevention of diseases.

The first rabies oral vaccination campaign for wildlife was conducted during 1978 in Switzerland, and then subsequently other European countries. A field trial of three oral vaccination campaigns and compulsory vaccination to dogs in the outbreak area was initiated using SAD B19 bait in 1988 and Finland was declared as rabies-free country again in 1991.

ETIOLOGY

The genus Lyssavirus and family Rhabdoviridae are home to the single-stranded RNA virus known as the rabies virus. The virus’s bullet form makes it extremely resistant to cold, dryness, and degradation. It can survive for many years at -70°C or when freeze-dried and maintained at 0-4°C. It is stable between pH 3 and pH 11. Most organic solvents, surface-active agents, quaternary ammonium compounds, proteolytic enzymes, alcohol, ultraviolet and X-ray radiation, and pasteurisation temperature all quickly inactivate viruses by the action of oxidising agents.

 EPIDEMIOLOGY

            Among the viral diseases, rabies is unique and it can affect a wide range of victims including all warmblooded animals. Rabies is prevalent throughout the world except in Islands. Many of the countries are endemic for rabies, except Australia and Antarctica. The countries free from rabies in Asian subcontinent are Bahrain, Cyprus, Hong Kong, Japan, Malaysia, Maldives, Qatar, Singapore, Lakshdweep, Andaman and Nicobar islands of India and Timor-Leste. Countries such as Antigua and Barmuda, Bahamas, Barbados, Belize, Falkland, Jamaica, Saintkitts and Nevis, Trinidad and Tobago, Uruguay of America subcontinent and Albania, E.Y.R. of Macedona, Finland, Gibraltar, Greece, Iceland, Isle of Man, Malta, Portugal, Norway (except Svalbard), United Kingdom and Spain (except Melill + ceuta) have also got rabies-free status. Among the African countries Cape Verde, Congo, Libya Mauritius, Reunion and Seychelles are free from rabies. Oceana group of Islands like Fiji, Cook Islands, Vanuatu, Guam, French Polynesia, New Zealand, New Caledonia, Solomon Islands and Papua New Guinea have also got rabies-free status.

As per the definition of World Health Organization (WHO), a country that has no record of indigenously acquired case of human or animal rabies within two years period due to surveillance and import regulations can claim rabiesfree status. But susceptibility to reintroduction from neighbouring countries does exist in spite of undertaking vaccination programmes in wildlife. Travellers visiting developing nations having sympathy for pet animals find it difficult to avoid feral dogs and cats thereby violate the precautionary measures. Any country maintaining the rabies-free status requires strict continuous monitoring, quarantine of imported animals and regulations to avoid the entrance of virus particularly with the import or introduction of infected animals.

If we consider status of rabies in Asia it is clear that majority of the developing nations of this subcontinent are the fatal sufferer of rabies. As per the WHO global vaccines research forum, over 3 billion people are affected with dog rabies and more than 30,000 deaths occur annually in Asian continent means every 15 min, mortality of one Asian. But the painful fact is that among the rabies induced mortality in human, 15% of mortality occurred in children under 15 years of age.

Rabies is predominant in Bangladesh and India followed by Nepal, Myanmar, Bhutan, Thailand and Indonesia. Nepal is one of the nations in the world, where the number of human rabies deaths is maximal. In Africa, maximum mortality rates are documented in children and underprivileged agrarian people. The most important reason for transmission of rabies in Africa is dog population and urbanization. In Europian continent, though rabies is still exist, but rabies cases in human have been vanished from most of the European nations most likely due to the enforcement of policies regarding vaccination in animals especially in dogs.

India is one of the countries with the largest rabies burden. The Association of the Prevention and Control of Rabies in India (APCRI) conducted a nationwide analysis, which reveals that 18,500 mortalities in human have occurred due to rabies annually. Around 40,000– 70,000 human deaths are still reported worldwide. Andaman and Nicobar and Lakshadweep islands are however free of the disease, while in other parts of the country it is very much prevalent. Prevalence of rabies in different species have been documented as 48% in dogs, 21.9% in cats, 61.4% in cattle and buffalo, 48.7% in goats and 45% in horses (WHO 1998). In the country numerous outbreaks of rabies have well been documented in domestic animals, wherein dog was suspected as the source of infection. The animal reservoirs of rabies vary from geographical region to region.

TRANSMISSION

All mammals are susceptible to rabies and can transmit the RABV, but there is great interspecies variability exists among mammals in the capability of acting as reservoirs. The primary reservoir for rabies is carnivorous mammals throughout the world.

The virus circulates in two cycles namely Urban and Sylvatic. The most frequent way of transmission of the disease is through the bite of infected dog, cats and wild carnivores. In rabies infected dogs, the saliva contains rabies virus 2-3 days before the onset of clinical signs. Cattle, horses, deer and other herbivores can become infected with rabies but they are unlikely to transmit the disease to humans. Transmission may also occur via aerosol. Transmission from person to person is extremely rare, and can happen through transplant surgery.

From CNS RABV reaches the salivary glands via cranial nerves (facial and glossopharyngeal nerves) and then it is excreted in saliva, which is ready to be transmitted. to a new host. Most common way of transmission for rabies (90%) is bite of infected animals like dogs and cats, because of their intimate association with human being. Most of the nations in the world, particularly in Asia and Africa, dog bite are responsible for 85%–95% of rabies cases in human, which is generally occurs to the victims in the form of physical and emotional trauma. Usually RABV gains entry into the body via the wounds or cuts, not through the intact skin. So, spread needs deposition of RABV from the saliva or infected neural tissue into the bite wounds, open cuts in the skin and mucous membranes. The risk of rabies infection by bite is 5%–80%, which is approximately 50 times more than by a licks or scratches, occurrence of which is 0.1%–1%. Percutaneous infection probably occurs during unnoticed skin contact and superficial bite and scratches.

In the last 50 years, few non-bite exposures have been documented in humans. But the number of cases of rabies not being transmitted by animal bite is less. The non-bite exposure includes inhalation of aerosolized RABV into the body system at higher concentration, organ and cornea transplants, and contamination of open wounds, abrasions, mucous membranes with rabies antigen laden saliva or with infectious material such as brain tissue from a rabid animal. Disease transmission through organ transplantation especially corneal transplantation was reported in German patients during 2005. Theoretically, bites from rabies infected humans can transmit the disease but it was less well confirmed. There is only one report of a human with encephalitic rabies biting another human. Relatives and health workers can be of potential risk while having unprotected contact with infected people and direct contact with secretions containing high concentration of virus. Standard barrier precautions should be implemented while caring for an infected patient to minimize any risk of the transmission. Cases have been documented due to airborne exposure in laboratories during vaccine production.

PATHOGENESIS

The RABV causes relatively slow but progressive disease without initial clinical signs which turns fatal after onset of clinical signs. The virus at the injected site remains hidden (eclipse) for variable time (a threshold must exceed to cause disease). The incubation or eclipse period is highly variable from 2 weeks to 6 years (avg. 2–3 months), which entirely depends on the concentration of the virus inoculated, inoculation site and density of innervations. Greatest risk factor is bites on the hands, neck, face and head mainly with bleeding lead to shorter incubation period due to the decreased length and greater number of neurons. It gets attached through G-protein receptors to the target cells (myocytes, local sensory and motor neurons) and amplifies in muscle cells and in macrophages. It may then persist there up to 18 days. Then, through muscle spindles of sensory nerves or neuromuscular junction of motor nerves the virus ascends centripetally along the nerves (3 mm/hour, experimental data) and reaches the CNS to infect the nerve cells. The RABV travels along the course of peripheral nerves (through fast axonal transport system) and the transport is sternly retrograde, that suggests the infection is via both motor and sensory nerves.

Despite severe neurological signs of rabies, the neuropathological findings (under natural conditions) are comparatively mild and degenerative neuronal changes are not uniquely identified. Although rabies is regarded as almost fatal, few cases in humans and dogs have survived after the development of neurological illness.

CLINICAL SYMPTOMS

            Initial symptoms of rabies are usually non-specific and suggest involvement of the respiratory, gastrointestinal and/or central nervous systems. In the acute stage, signs of hyperactivity (furious rabies) or paralysis (dumb rabies) predominate. In both furious and dumb rabies, paralysis eventually progresses to coma and death in all cases, usually due to respiratory failure. Death occurs during the first seven days of illness without intensive care. The stereotypical image of an infected (“rabid”) animal is a “mad dog” foaming at the mouth.

Dogs

            Incubation period lasts from 10 days to 2 or more months. Prodromal phase usually lasts for 2-3 days with apprehension, nervousness, anxiety, solitude and variable fever. Friendly animals become shy or irritable and may snap whereas fractious ones may become more docile and affectionate. Most animals will consistently lick the site of viral inoculation. Pupillary dilatation with or without sluggish palpebral/corneal reflexes may become apparent. Some dogs may develop pruritus at the site of exposure and claw and chew at the area until it is ulcerated. Reflex excitability is enhanced, the animal being started by the least stimulus There is anorexia, irritation in the region of bite, stimulation of the genitourinary tract and a slight increase in body temperature.

Cats

Generally the disease is of furious type with symptoms similar to dogs. Paralysis of the posterior third of the body follows 2 to 4 days after the excitation symptoms appear.

Cattle

Among farm animals, cattle are most commonly affected. Usual incubation period is about 3 weeks, which may vary from two weeks to several months. In the paralytic form, knuckling of hind fetlocks, sagging and swaying of hindquarters while walking, often deviation or flaccidity of the tail to one side are common early signs. Yawning is a very characteristic sign observed in cattle. Within eight hours of yawning the animal starts bellowing, which continues till the paralytic recumbent stage. Decreased sensation usually accompanies their weakness and is one of the best diagnostic criteria in the detection of rabies. It is most evident over the hindquarters. Tenesmus with paralysis of the anus, resulting in the suckling in and blowing out of air occur late in the in-coordination stages just before the animal becomes recumbent. Drooling of saliva is one of the most consistent findings. Bulls in this stage often have paralysis of penis. Death occurs usually 48 hours after recumbency and/or after a course of 6 to 7 days. In furious rabies, the animal has a tense, alert appearance, and is hypersensitive to sounds and movement and is attracted to noise and approach as though about to attack. Animal may violently attack other animals or inanimate objects. These attacks are often badly directed and are impeded by the incoordination of gait. Loud bellowing is usual; sound is characteristically hoarse and actions are exaggerated. Sexual excitement is common. The termination of furious phase is often sudden. These signs may be evident for 24 to 48 hours and then animal collapses suddenly in a paralyzed state, dying usually within a few hours.

Sheep

Clinical picture is similar to cattle. Sexual excitement, attacking humans or each other and vigorous wool pulling, sudden falling after violent exertion, muscular tremor and salivation. Excessive bleating does not occur. Most sheep are quiet and anorectic.

Goats

Commonly aggressive and continuous bleating is common.

Horses

Abnormal postures, frequent whinnying, unexplained aggressiveness and kicking, biting, colic, sudden onset of lameness in one limb followed by recumbency the next day, high stepping gait, ataxia, apparent blindness and violent head tossing. Lameness or weakness in one leg may be the first sign observed, but the usual pattern of death starts with lassitude. Sternal recumbency and lateral recumbency followed by paddling convulsions and terminal paralysis.

Pigs

Excitement and a tendency to attack or dullness and incoordination. Twitching of the nose, rapid chewing movements, excessive salivation and clonic convulsions.

• Backward walking.
• Paralysis and death occurs 12 to 48 hours after the onset of signs.

Man

Classical Rabies

• Most cases go through three stages-:

1. Prodromal Stage

Lasts from 2-10 days and presents in the form of fever, headache, malaise, fatigue, and also localized pain around area of initial infection.

1. Sensory Excitation Phase

Hyper reactivity, hallucinations, disorientation, seizures and bizarre behavior. About 50% of infected individuals developed painful spasms of the pharynx and larynx resulting in a fear to eat or drink. Hydrophobia (fear of water) is pathognomonic feature of rabies. Increased salivation with drooling. This phase persists for 2-7 days.

III. Coma and paralysis phase

Paralysis and respiratory problems.

Dumb rabies

About 20% of cases have only two phases where the patient skips the sensory excitation phase. Coma and paralysis phase are present. Dumb rabies is almost 100% fatal.

TREATMENT

No treatment for rabies is available after the onset of the clinical signs. Treatment consists of thorough wound cleansing for a minimum of 15 minutes using water, soap and a virucidal antiseptic (e.g. povidiene iodine or ethanol) followed by the administration of rabies passive immunization and cell culture or purified embryonated egg rabies vaccine of proven efficacy.

PREVENTION AND CONTROL

Vaccination

• Use of Cell Culture vaccines that will provide stable and long lasting immunity is recommended.
• First vaccination of dogs and cats at the age of 3 months, the booster at the age of 12 months and subsequently, biannual vaccination is prescribed.

Control

• Canine rabies can be eliminated by regular vaccination of dogs.
• Vaccination coverage of 70% has been sufficient to control canine rabies in several settings.
• Oral vaccination of dogs offers a new approach that may significantly improve dog vaccination coverage.
• Three practical methods of dog population management are recognized: movement restriction, habitat control and reproduction control.

Post Exposure Vaccination

• Available vaccines are Human Diploid Cell Vaccine (HDCV); Purified Chick Embryo Cell Vaccine (PCEC); Purified Vero Cell Rabies Vaccine (PVRV) and Purified Duck Embryo Vaccine.
• Intramuscular administration of five injections on day 0, 3, 7, 14 and 28.
• The sixth injection (Day 90) should be considered as optional and should be given to those individuals who are immunologically deficient.
• Date 0 indicates date of first injection.
• The deltoid region is ideal for the inoculation of these vaccines. Gluteal region is not recommended because the fat present in this region retards the absorption of antigen and hence, impairs the generation of optimal immune response.
• Rabies immunoglobulin (RIG) should be given for all class ІІІ exposures, irrespective of the interval between exposure and beginning of treatment.

TARGET ZERO DEATH

Rabies deaths in human are 100% preventable through prompt and appropriate medical care. By vaccinating 70% of dog populations in areas where rabies is present, the number of human cases can rapidly drop to almost zero. India is endemic for rabies, and accounts for more than one third of the world’s rabies deaths.   Vaccinating dogs is the most cost-effective strategy for preventing rabies in people. Worldwide, over 59,000 people die every year from rabies. The National Action Plan for Rabies Elimination in India (NAPRE) is to achieve zero human deaths due to dog-mediated Rabies by 2030.

• ABC for Dogs:-

Most animal bites in India are by dogs, of which about 60% are strays and 40% pets. Also among the people bitten by dogs, most of them belong to lower socio economic strata. Animal Birth Control (ABC) and Rabies Prevention program keeps rabies out of our community and saves millions of dogs from being born into a hard life. While bringing down the number of street dogs in a humane manner the number of cases of human rabies also dramatically declined.

• Anti-Rabies Vaccination for dogs:-

Dog vaccination against rabies is the only way to break the cycle of transmission among dogs and between dogs and humans. It is estimated that by vaccinating 70% of the dogs in infected areas, rabies could be eradicated in dogs and the number of human cases would rapidly drop to zero. For this, free anti-rabies vaccination camps for dogs are regularly organized on the occasion of World Veterinary Day (last Saturday of April), World Zoonosis Day (6th July) and World Rabies Day (28th September) every year.

• Responsible pet ownership:-

Those who pet dogs should take responsibility for annual vaccination of their dogs as well as to get their dogs registered under the local Municipal bodies which would help in surveillance.

• On site Treatment:-

If a dog is found bitten by another rabid or even non rabid dog, on site first aid should be provided.  The bitten animal should be kept under observation for at least 10 days. This would help in identifying rabid cases and controlling them at the source itself.

• Education in Schools:-

It has been observed that rabies affects mainly the people of lower socio economic strata and children between the age of 5 and 15 years. Thus, it becomes very important to make children aware of the disease- its transmission, diagnosis, first aid and treatment. This might help in spreading awareness and also prevention against Rabies.

• Counseling in Hospitals:-

People who had been bitten needs counseling and right information about post exposure prophylaxis as well as about the severity of disease to prevent misinformation driven ignorance which may cost them their life. This would not only save human lives but also make public aware.

• Post bite care and observation:-

Post bite care and Observation thereof is a crucial part as this disease is highly fatal.

• Community Engagement:-

To spread awareness regarding Rabies, to start campaigns against Rabies and vaccination of dogs the engagement of local community is needed.

Government of India along with WHO has started initiatives such as the Surveys conducted by Association for Prevention and Control of Rabies in India (APCRI) which aims to eliminate rabies from India by 2030 and also support rabies surveillance in Humans. Also the government should emphasize on public health educational strategy at the community level within endemic region along with continuous education of veterinary professionals in rabies prevention and control. Collaborations of national and international as well as government and non-government organizations in order to create mass awareness about rabies and also to provide mass vaccination of dogs in an economic way in order to eliminate rabies could prove to be a revolutionary step. Public awareness, health education, dog vaccination and the accessibility and availability of Post exposure prevention are keys for rabies prevention and control.

CONCLUSION

In the majority of early cases, rabies can be ruled out based on the findings of diagnostic testing or the development of the illness. However, it is crucial to take precautions and to think about rabies at the earliest possible time. Additionally, it is important to improve the surveillance for the RABV variants that are now prevalent in rabid animals, especially in wildlife. To understand the role that these animals play in disease transmission, it is currently unknown how common rabies is in wild animals. For the purpose of finding newly introduced RABV variations, on-going monitoring of less common non-reservoir species is crucial. Strict barrier precautions are mandatory as the RABV as such is transmissible through contact of saliva with skin (broken) as well as mucous membrane.

Although it can differ depending on jurisdiction, it is crucial from the veterinarians’ perspective that they notify the right authorities along with the proper reporting of the disease. To further reduce the risk of disease spread and raise public awareness of precautions for people living in rural areas and those working in abattoirs, medical and veterinary professionals must be knowledgeable about the route of rabies transmission. It is crucial that everyone who comes into contact with the patient reports to the doctors and prioritises PEP. The introduction of sequence specific RT-PCR technology has advanced molecular diagnosis, making the diagnosis highly target specific.

Recent biotechnological tools should be used to provide advanced molecular diagnostic approaches for early confirmatory diagnosis and discrimination of distinct RABV genotypes. The pathophysiology and pathogenesis of rabies should be better understood in the near future through additional research, which will open the door to the creation of effective antiviral therapy approaches. Along with this advancement, molecular biology has made it possible to create newer generation vaccinations to stop the spread of rabies among animals and people. It has also been discovered that novel medicines, including as cytokine and siRNA therapies, are effective methods. For people who have a higher risk of exposure to rabies, an appropriate vaccination and monitoring for antibody titers every two years are recommended to ensure effective protection.

Last but not least, it is terrible that children, particularly in developing countries where rabies is widespread, are most at risk of catching the disease from dog bites. Travellers should decide whether to get vaccinated against rabies before entering distant rural areas. In many endemic regions of the world, an evaluation of the risk of being bitten by a rabid dog and local access to rabies immunoglobulins and vaccines are urgently needed. Although the existing oral/bait vaccinations offer protection, they are not entirely effective in all species of wild animals; the vaccines’ field stability should be checked, as well as the recipients’ post-vaccination immunological status. Taking advantages of recombinant DNA technology, novel immune-prophylactic and environmentally stable agents like subunit vaccines, DNA vectored vaccines or DNA vaccines could be developed to nullify the drawbacks of conventional vaccines. Edible vaccine especially for domestic and wild ruminants should be developed to curtail the rabies.

Despite the majority of countries in the world gaining the designation of rabies-free zones, many still have the category of high-risk areas. This demonstrates that by taking preventative measures, rabies may be successfully eradicated from high-risk areas. Controlling rabies is also made possible by the development of modern medicine. In this sense, public knowledge can have a significant impact. High-level political commitment is also crucial in order to implement these proposals.

 All For 1 : One Health for All