One Health Approach to Control & Eradicate the Rabies: A sincere Contribution of Louis Pasteur
Dr. Deep Narayan Singh, Dr. Ajay Kumar, Dr. Mamta, Dr. Rajneesh Sirohi, Dr. Yajuvendra Singh and Dr. Manisha Tyagi
College of Veterinary Science & Animal Husbandry,
DUVASU, Mathura-281001
Introduction:
Louis Pasteur is the renowned chemist and microbiologist of the 19th century involved in the development of the rabies vaccine. He worked with a researcher’s team in the laboratory, mainly Pierre Paul Emile Roux, and also physicians in the clinical practice approach and the defense of Pasteur’s anti-rabies technique in the Académie Nationale de Médecine, Alfred Vulpian being the most notable. Pasteur’s first studies on rabies are noted in his 1881 publication. But in July 6, 1885, he revealed that he had already immunized 50 dogs against rabies. Meanwhile, he was looking for human immunization. The most polemic of this search involves the second and last Emperor of Brazil, Dom Pedro II, who was a patron of the arts and sciences and followed and supported the work of the great scientist. During the reign of Dom Pedro II, the first Pasteur’s Institute was founded in Rio de Janeiro, nine months before the Parisian, which had the financial support of Dom Pedro. Louis Pasteur and his colleagues injected the first of 14 daily doses of rabbit spinal cord suspensions containing progressively inactivated rabies virus into 9-year-old Joseph Meister, who had been severely bitten by a rabid dog 2 days before. This was the beginning of the modern era of immunization, which had been presaged by Edward Jenner nearly 100 years earlier. The basic “Pasteur Treatment,” based on brain tissue vaccine with the addition of formaldehyde, is still used in many countries of the world where rabies is prevalent. This treatment still involves immunizations given daily for 14-21 days, and it still carries the same risk of neurologic sequelae as in Pasteur’s day. In the United States and other developed countries, more potent, safer, but very expensive, cell culture-based rabies vaccines are combined with hyperimmune globulin for postexposure treatment. The efficacy of such regimens has been well proven. Another era in vaccine development is now beginning–an era based on the practical application of recombinant-deoxyribonucleic acid (DNA) technology and other novel genetic manipulations of rabies and other viruses and microorganisms. These new technologies promise even more potent and safer vaccines, as well as lower costs, improved stability, and easier delivery throughout the world to people at risk.
Rabies and its etiology:
Rabies is a fatal, acute, progressive encephalomyelitis caused by neurotropic viruses in the family Rhabdoviridae, genus Lyssaviru or rabies virus. The virus is found in wild and some domestic animals, and is transmitted to other animals and to humans through their saliva (following bites, scratches, licks on broken skin and mucous membrane). In India, dogs are responsible for about 97% of human rabies, followed by cats (2%), and others (1%). The disease is invariably fatal and perhaps the most painful and dreadful of all communicable diseases in which the sick person is tormented at the same time with thirst and fear of water (hydrophobia). Fortunately, development of rabies can be prevented to a large extent if animal bites are managed appropriately and in time. In this regard the post-exposure treatment of animal bite cases are of prime importance. Rabies is responsible for extensive morbidity and mortality in India. The disease is endemic throughout the country. With the exception of Andaman & Nicobar and Lakshadweep Islands, human cases of rabies are reported from all over the country. The cases occur throughout the year. About 96% of the mortality and morbidity is associated with dog bites. Cats, wolf, jackal, mongoose and monkeys are other important reservoirs of rabies in India. Bat rabies has not been conclusively reported from the country. Numerous and diverse variants of lyssaviruses are found in a wide variety of animal species throughout the world, all of which may cause fatal human rabies. Rabies virus is by far the most common lyssavirus infection of humans. Tens of millions of potential human exposures and tens of thousands of deaths from rabies virus occur each year. India accounts for approximately 20,000 rabies-related human deaths each year out of the 59,000 global deaths.
Vector and Reservoir Host:
Rabies is an ancient zoonotic disease caused by infection with the rabies virus (RABV). While the circulation of RABV in domestic dogs has been appreciated for centuries, the recognition of bat and wild carnivore reservoirs began in the early part of the 20th century. Bats are the ancestral reservoir of RABV and a remarkable diversity of species perpetuate distinct lineages of the virus, despite the fact that circulation in bats is geographically limited to the New World fauna. The circulation of RABV in domestic dogs likely represents a historic shift from a bat reservoir, although the timing and details of such an ancient event have been difficult to resolve from the virus genetic evidence. Since becoming established in the domestic dog population, RABV has undergone repeated host shifts to wild carnivores globally.
Transmission
The normal and most successful mode of transmission is inoculation of saliva from the bite of a rabid animal. Rabies virus is neurotropic and gains access to the peripheral nervous system by being taken up at a nerve synapse at the site of the bite. The virus travels through peripheral nerves to the central nervous system, where most viral replication occurs, before traveling back out through the peripheral nervous system. After reaching the salivary glands, virus can be secreted allowing the transmission cycle to repeat. Exposure of rabies virus to anatomic sites nearer the central nervous system may reduce the incubation period. In addition to saliva, rabies virus may also be found in nervous tissues (central and peripheral) and tears. Infection from non-bite exposures, such as organ transplantation from infected humans, does occur. However, human-to-human transmission does not generally occur otherwise. All mammals are believed to be susceptible to infection, but major rabies reservoirs are terrestrial carnivores and bats. Although dogs are the main reservoir in developing countries, the epidemiology of the disease differs from one region or country to another. All patients with mammal bites should be medically evaluated. Bat bites anywhere in the world are a cause of concern and an indication to consider prophylaxis.
Epidemiology:
Lyssa viruses, have been found on all continents except Antarctica. Rabies virus is classified into 2 major genetic lineages: canine and New World bat. These 2 lineages can be further classified into rabies virus variants based on the reservoir species in which they circulate. Regionally, different viral variants are adapted to various mammalian hosts and perpetuate in dogs and wildlife, such as bats, foxes, jackals, mongooses, raccoons, and skunks. Canine rabies remains enzootic in many areas of the world, including Africa, Asia, and parts of Central and South America. In addition to rabies virus, the Lyssa virus genus includes 14 other viruses that all cause the disease rabies. Non-rabies lyssa viruses are found in Europe, Asia, Africa, and Australia; although they have caused human deaths, nonrabies lyssaviruses contribute relatively little to the global rabies burden compared to rabies virus.
Clinical Observations
Clinical illness in humans begins following invasion of the peripheral and then central nervous system and culminates in acute fatal encephalitis. After infection, the asymptomatic incubation period is variable, but signs and symptoms most commonly develop within several weeks to several months after exposure. Pain and paresthesia at the site of exposure are often the first symptoms of disease. The disease then progresses rapidly from a nonspecific, prodromal phase with fever and vague symptoms to an acute, progressive encephalitis. The neurologic phase may be characterized by anxiety, paresis, paralysis, and other signs of encephalitis; spasms of swallowing muscles can be stimulated by the sight, sound, or perception of water (hydrophobia); and delirium and convulsions can develop, followed rapidly by coma and death. Once clinical signs manifest, patients die quickly in the absence of intensive supportive care.
Diagnosis:
- Diagnosis in animals
A diagnosis of rabies can be made after detection of rabies virus from any part of the affected brain, but in order to rule out rabies, the test must include tissue from at least two locations in the brain, preferably the brain stem and cerebellum. The test requires that the animal be euthanized. The test itself takes about 2 hours, but it takes time to remove the brain samples from an animal suspected of having rabies and to ship these samples to a state public health or veterinary diagnostic laboratory for diagnosis. Approximately 120,000 animals or more are tested for rabies each year in the United States, and approximately 6% are found to be rabid. The proportion of positive animals depends largely on the species of animal and ranges from <1% in domestic animals to >10% of wildlife species. Based on routine public health surveillance and pathogenesis studies, we have learned that it is not necessary to euthanize and test all animals that bite or otherwise potentially expose a person to rabies. For animals with a low probability of rabies such as dogs, cats, and ferrets, observation periods (10 days) may be appropriate to rule out the risk of potential human rabies exposure. Consultation with a local or state health official following a potential exposure can help determine the best course of action based on current public health recommendations.
- Diagnosis in humans
Several tests are necessary to diagnose rabies ante-mortem (before death) in humans; no single test is sufficient. 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. Skin biopsy specimens are examined for rabies antigen in the cutaneous nerves at the base of hair follicles. Definitive antemortem diagnosis requires high-complexity experimental test methods on multiple samples (serum, cerebrospinal fluid (CSF), saliva, and skin biopsy from the nape of the neck), which can be collected sequentially if initial testing is negative and clinical suspicion is high. Additional detailed information on diagnostic testing may be obtained from CDC (Center for Disease control. Rising levels of rabies virus–neutralizing antibodies, particularly in the CSF, is diagnostic in an unvaccinated, encephalitic patient. Rabies is a nationally notifiable disease.
Control & Eradication Program:
CDC is designated as the national rabies reference laboratory for the United States, as well as a World Health Organization collaborating center for rabies and a World Organisation for Animal Health (OIE) rabies reference laboratory. As such, CDC performs public health testing for domestic and international health agencies, for both human and animal rabies diagnosis. Before submitting samples to CDC for rabies testing, the submitter must consult with program staff, obtain approval, and submit appropriate paperwork. Step-by-step instructions can be found at National Centre for Disease Control (formerly National Institute of Communicable Diseases), Delhi, WHO Collaborating Centre for Rabies Epidemiology, organized an expert consultation in 2002 to formulate national guidelines for rabies prophylaxis to bring out uniformity in post-exposure prophylaxis practices. Due to new interventions in this field, it has been further revised over the years.
National Rabies Control Programme was approved during 12th FYP by Standing Finance Committee meeting held on 03.10.2013 as Central Sector Scheme to be implemented under the Umbrella of NHM .The Programme had two components – Human and Animal Components in 12th FYP. Human Component for roll out in the all States and UTs through nodal agency NCDC with total budget of Rs 20 Crores and Animal Health Component for pilot testing in Haryana and Chennai through nodal agency Animal Welfare Board of India(AWBI) under the aegis of MoEF & CC, GOI with total budget of Rs 30 Crores for the Plan period. The Human Health Component has been rolled out in 26 States and UTs (Pilot Project for Animal Health Component by AWBI has been ended with closure of last FY of 12th FYP i.e. with effect from 31.3.2017). This strategy would combine the expertise of FAO, OIE and WHO as well as other major stakeholders including the Global Alliance for Rabies Control (GARC), with the aim of gaining support from countries and funding agencies worldwide to act through existing international health mechanisms including rabies vaccine banks, reporting systems, control tools (such as The Rabies Blueprint, Rabies Stakeholder Consultations, and the Stepwise Approach towards Rabies Elimination), regional frameworks and resources, and collaboration between animal and human health sectors. Past rabies elimination strategies included the reduction of population density through culling, based on the rationale that rabies transmission is density-dependent with disease density increasing proportional to host density. However studies have shown that culling is an ineffective means of elimination and mass vaccination is most efficacious to reduce disease incidence in all species. The Bangladesh canine rabies elimination program focuses primarily on dog bite management and mass dog vaccination to reduce the incidence of human deaths. Since 2011, dog vaccines have been administered in 58 of the 64 districts, combined with local capacity building and knowledge transfer, resulting in a 50% decrease in human rabies deaths, demonstrating the effectiveness of mass vaccination.
Coordinated actions for eliminating human rabies in the Americas began in 1983, with technical cooperation from PAHO on regional programmes and the operation of epidemiologic surveillance system (Siepi). Achievements have been due largely to strong cooperation between the health and the agricultural sectors, as well as with regional and international organisations, public and private agencies and nongovernmental organisations. Since the introduction of the programme, the number of human rabies cases has dropped 95% and declined in dogs by 98%.
Elimination of dog-mediated rabies is feasible given political will, adequate resources and diligent programme management. The progress of elimination strategies must be continuously controlled and evaluated at regional and national levels, in order to monitor subsequent effectiveness and ensure optimisation of the use of financial and human resources. Successful follow-up and evaluation requires data, rendering the need for rabies to be a disease of obligatory notification.
Conclusions:
Rabies continues to be a significant public health hazard underestimated in majority of countries in the world. The government should be emphasized much more for establishment of laboratories and diagnostic center for vaccine production as well as diagnosis of rabbit vectors and affected individuals. There is also urgent need of wildlife rabies control campaigns including controlling dog population. Post-exposure prophylaxis provided has steadily increased over time. Countries of the Region are spending increasing part of their health budget on procurement of modern rabies vaccines and immunoglobulins to meet the increasing demand for rabies post-exposure treatment. Intersectoral sustainable co-operation for rabies surveillance, prevention and control, particularly between the Ministries of Health, Agriculture, Environment, Municipalities, Education and Interior still needs further strengthening.
