Updates On Control & Eradication of Rabies in India
Dr.R.P.Diwakar
Assistant Professor, Department of Veterinary Microbiology, CVSc&A.H., ANDUAT, Kumarganj. Ayodhya (UP)-224229 India
HISTORY OF RABIES:
A scientist Georg Gottfried Zinke demonstrated that rabies was caused by an infective agent. In 1804, he found that the disease might be passed from a rabid dog to a healthy one. Then, the disease might be transmitted from that dog to rabbits and hens by injecting them with the dog’s saliva. By the 1880s, Pasteur took an interest in rabies. Pasteur realized that if medulla spinalis samples from infected rabbits were air-dried, the virus contained within samples became less virulent – attenuated.
By this discovery, Pasteur to concoct the primary rabies vaccine, and he showed it to be effective in dogs. Next, he turned it up to 11 by treating 9-year-old Joseph Meister. Pasteur and Meister’s physician treated the boy with an emulsion of rabbit medulla spinalis containing the attenuated rabies virus. After a lengthy regimen of injections, the boy was declared healthy and rabies-free 3 months later. Pasteur went on to treat some 350 patients for rabies from different countries like Europe, Russia and America.
INTRODUCTION:
Rabies is one among the oldest recognized diseases affecting humans and one among the foremost important zoonotic diseases in India.
Rabies is primarily a disease of terrestrial and airborne mammals, including dogs, wolves, foxes, coyotes, jackals, cats, bobcats, lions, mongooses, skunks, badgers, bats, monkeys and humans. The dog has been, and still is, the most reservoir of rabies in India. Other animals, like monkeys, jackals, horses, cattle and rodents, seem to bite incidentally on provocation, and the fear of rabies leads the victim to seek post exposure prophylaxis. The amount of cases involving monkey bites has been increasing within the previous couple of years. Monkeys are valuable to rabies, and their bites necessitate post exposure prophylaxis.
Dog-mediated human rabies disproportionately affects poor rural communities, particularly children, with the bulk (80%) of human deaths occurring in rural areas, where awareness and access to appropriate post-exposure prophylaxis is restricted or non-existent.
IN HUMAN:
Domestic dogs are foremost common reservoir of the virus, with 99% of human deaths caused by dog-mediated rabies.
IN ANIMAL:
Transmission of animal rabies is analogous thereto of human rabies, with virus-laden saliva from infected animals entering the body through wounds or by direct contact with mucosal surfaces. Following access to the muscle cells at the wound site, peripheral nerves and subsequently the central systema nervosum, the virus travels retrogradely from the CNS via peripheral nerves to various tissues, most significant the salivary glands, from which it is shed, completing the transmission cycle.
Though the main burden of human rabies is attributed to dog-mediated transmission, a wildlife (sylvatic) cycle of rabies also exists, with wild animals (e.g. bats, raccoons and foxes) serving because the maintenance host of the virus.
Dog rabies is characterized by …
Biting without provocation
Eating abnormal items like sticks, nails, faeces.
Running for no apparent reason
Vocal changes
Excessive salivation
ABOUT OF VIRUS:
Rabies virus belongs to the Order Mononegavirales, viruses with a nonsegmented, negative-stranded RNA genomes. This group, viruses with a definit “bullet” shape are classified within the Rhabdoviridae family, which incorporate a minimum of three genera of animal viruses, Lyssavirus, Ephemerovirus, and Vesiculovirus. The genus Lyssavirus includes rabies virus.
The rabies genome encodes five proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and polymerase (L). Two other viral proteins, the phospoprotein and the large protein (L-protein or polymerase) are associated with the RNP.
VIRAL MULTIPLICATION:
The virus penetrates the host cell and enters the cytoplasm by pinocytosis. The virions aggregate within the large endosomes (cytoplasmic vesicles). The viral membranes fuse to the endosomal membranes, causing the discharge of viral RNP into the cytoplasm (uncoating). Because lyssaviruses have a linear single-negative-stranded RNA (RNA) genome, messenger RNAs (mRNAs) must be transcribed to allow virus replication.
A viral-encoded polymerase (L gene) transcribes the genomic strand of rabies RNA into leader RNA and five capped and polyadenylated mRNAs, which are translated into proteins. Translation, which involves the synthesis of the N, P, M, G and L proteins, occurs on free ribosomes within the cytoplasm. Although G protein synthesis is initiated on free ribosomes, completion of synthesis and glycosylation, occurs within the endoplamsic reticulum and Golgi body. The intracellular ratio of leader RNA to N protein regulates the switch from transcription to replication. When this switch is activated, replication of the viral genome begins. The primary step in viral replication is synthesis of full-length copies (postive strands) of the viral genome. When the switch to replication occurs, RNA transcription becomes “non-stop” and stop codons are ignored. The viral polymerase enters a single site on the 3’ end of the genome, and proceeds to synthesize full-length copies of the genome. These positive strands of rabies RNA function templates for synthesis of full-length negative strands of the viral genome.
The assembly process, the N-P-L complex encapsulates negative-stranded genomic RNA to make the RNP core, and therefore the M protein forms a capsule, or matrix, round the RNP. The RNP-M complex migrates to an area of the plasma membrane containing glycoprotein inserts, and the M-protein initiates coiling. The M-RNP complex binds with the glycoprotein, and the completed virus buds from the plasma membrane. Within the central nervous system (CNS), there is preferential viral budding from plasma membranes. Conversely, virus in the salivary glands buds primarily from the cell membrane into the acinar lumen. Viral budding into the salivary gland and virus-induced aggressive biting-behavior in the host animal maximize chances of viral infection of a new host.
Fig.No.1 Showing Virus Transmission/Replication in animal and man
SYMPTOMS:
The timeperiod for rabies is 2-3 months however; it can range from 7 days to 1 year. The incubation period depends on factors inclusive of: location and severity of bite wound, the quantity of virus inoculated within the wound and degree of innervation at the site of the bite wound.
As the virus spreads from muscle cells at the location of inoculation through the peripheral nerves to the central systema nervosum, progressive, fatal inflammation of the medulla spinalis and subsequently, brain (encephalitis) develops.
Two forms of rabies:
• Furious (classical or encephalitic) form
• Paralytic form.
Furious rabies accounts for about 80% of the total number of human cases; manifesting as signs of hyperactivity, hypersalivation, periods of agitation alternating with lucidity, hydrophobia and sometimes aerophobia. After a few days, the infection invariably leads to coma and death by cardio-respiratory arrest.
Paralytic (or dumb) rabies accounts for about 20% of the total number of human cases. This form of rabies runs a less dramatic but longer course than the furious form. There is flaccid muscle weakness within the early onset of infection, starting at the site of the bite or scratch, followed by gradual paralysis. Death by respiratory failure is usually preceded by the development of a coma. The paralytic form of rabies is often misdiagnosed, contributing to the underreporting of the disease.
LABORATORY TECHNIQUES FOR DIAGNOSIS OF RABIES:
Diagnosis is totally, on the basis of clinical symptoms and signs, and a corroborative history of or evidence of an animal bite, death of an animal, and incomplete or no vaccination following exposure. The facility for laboratory diagnosis and confirmation of rabies, be it in humans or in animals, is available premortem in only a few institutions in India. The standard premortem test is a fluorescent antibody test (FAT) to demonstrate the presence of viral antigen. The standard postmortem test is biopsy of the patient’s brain and examination for “Negri bodies”.
The gold-standard diagnostic procedure is to detect rabies virus antigen in infected tissues, preferably brain smears or touch impressions collected from a biopsy, by fluorescent antibody test (FAT). FAT is suggested by WHO and in 95-99% of cases, gives reliable results on fresh specimens within a few hours. Other methods for detection of lyssavirus antigens like direct rapid immunohistochemistry tests are proven to have sensitivity and specificity like to the FAT. WHO recommends further development of direct rapid immunohistochemistry tests as an alternate to the FAT for improved decentralized laboratory-based surveillance in endemic areas.
Diagnostic procedures for antigen detection
Cell-culture isolation techniques
Enzyme-linked immunosorbent assay (ELISA)
Virus identification using monoclonal antibodies
Tests for the determination of rabies antibodies
TREATMENT:
Rabies is an fatal disease, with only a few documented survivors. There’s no effective curative treatment for rabies once clinical signs have appeared.
All cases of suspected rabies exposure should be treated immediately to stop the onset of clinical symptoms and death. Post-exposure prophylaxis (PEP) consists of wound treatment, the administration of rabies vaccines based on WHO recommendations, and if indicated, the administration of rabies immunoglobulin.
Recommended post-exposure prophylaxis for rabies infection
CONTROL AND ERADICATION OF RABIES FROM INDIA:
For control of human rabies is depends upon the effective and verifiable control of the disease within the puppy population, being the foremost common reservoir of the virus and explanation for 99% of human cases. Dog-mediated human rabies is totally preventable using biologicals and tools that would be accessible even in low-resource settings. Public awareness, health education, dog vaccination and therefore the availability and accessibility of PEP are key for rabies control .and eradication.
Rabies vaccine banks have begun to support countries in their control efforts, providing incentive for them to interect in and leverage investments. A vaccine bank for dog vaccination in Asia has been set up by OIE, and by WHO in South Africa. National mass dog vaccination campaigns are the foremost cost-effective strategy for preventing rabies. A minimum of 70% of the dog population must be vaccinated in order to break the cycle of transmission in dogs and to humans. Preventing human rabies through control of domestic dog rabies is a realistic goal for large parts of Africa and Asia where rabies is a significant public health issue, and is justified financially by the future savings of discontinuing post-exposure prophylaxis for people.
The elimination of rabies however, requires several other components in addition to mass vaccination, including the effective engagement of communities and policymakers, dog population assessment and management and surveillance capacity and legislation.
MANAGEMENT OF STRAY DOG POPULATION:
India has approximately 25 million dogs, with an estimated dog: man ratio of 1:36.2 The dogs fall under 4 broad categories: pets (restricted and supervised); family dogs (partially restricted, wholly dependent); community dogs (unrestricted, partially dependent); and feral dogs (unrestricted, independent). Most dogs in India, perhaps 80%, would fall into the last 3 categories.
The population of stray dogs in India was kept under check by civic authorities, by impounding and euthanizing unclaimed dogs. Because of pressure from animal welfare activists, this approach was replaced by a policy of animal birth control, also referred to as the Animal Birth Control (ABC) Programme, controlling the stray dog population.
WHO strategies for dog rabies control and eventual elimination
- Animal-Birth-Control programs.
- Oral vaccination of domestic carnivores. WHO has stimulated studies on oral vaccination of dogs (OVD.)
- Continual education of health and veterinary professionals in rabies prevention and control
- Public health educational strategies at the community level within endemic regions
HOW TO ERADICATE - To first reduce then eradicate deaths from rabies, collaborative efforts will be required from multiple stakeholders, including veterinarians, public health officials, legal authorities and other health care services.
- There must be strict implementation of the legal provisions for licensing and regular vaccination of pet dogs.
- Public health educational programs are needed to create awareness.
- Modern tissue-culture vaccine and the administration of human rabies immune globulin
- The facilities for the surveillance and diagnosis of animal rabies must be improved in quality and offer wider coverage, and human rabies must be made a compulsory reportable disease.
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