By Jay Prakash Yadav and Maninder Singh*

Introduction:

Rabies is a highly fatal but vaccine-preventable viral zoonosis (diseases which are naturally transmitted between vertebrate animals to humans and vice-versa), caused by genus Lyssavirus of the Rhabdoviridae family. The virus is a bullet shaped enveloped infectious particle (180 nm x 75 nm in size), having 12 Kb negative sense single-stranded RNA genome. The disease is prevalent throughout the world and endemic in many countries except in Australia and Antarctica, with over 95% of human deaths occurring in the Asia and Africa regions. It affects all warm-blooded animals including dog, cat, domestic, and wild animals. In up to 99% of human cases, domestic dogs are responsible for rabies virus transmission.  The disease is spread to human and animals through bites or scratches of rabid animals, usually via saliva. Once clinical symptoms appear, rabies is virtually 100% fatal. The incubation period (time between infections to the appearance of clinical signs of the disease) of the disease varies from 1 week to 1 year (avg. 2–3 months). The disease predominantly affects poor and vulnerable populations who live in remote rural areas and the children of 5–14 years are frequent victims. Direct Fluorescent Antibody Test (dFAT) is considered to be gold standard by World Organization for Animal Health (OIE) and World Health Organization (WHO) for the detection of rabies virus in brain tissues. Live attenuated or inactivated viruses, DNA and recombinant vaccines are commercially available for prevention of disease in animals and humans. Every year on 28th September ‘World Rabies Day’ is celebrated to raise awareness about rabies and bring together partners to enhance prevention and control efforts worldwide. This year’s theme ‘Rabies: One Health, Zero Deaths’ will highlight the connection of the environment with both people and animals. Rabies is included in WHO new 2021–2030 road map and is targeted for the global elimination of dog-mediated human deaths by 2030.  

History:

Rabies has terrified civilizations ever since it became obvious that the bite of a rabid animal insured an inevitably horrible death. The origin of the word rabies is either from the Sanskrit “rabhas” (to do violence) or the Latin “rabere” (to rage). The ancient Greeks called rabies “lyssa” (violence). The first written record of rabies causing death in dogs and humans is found in the Mosaic Esmuna Code of Babylon in 2300 B.C. where Babylonians had to pay a fine if their dog transmitted rabies to another person. In the first century A.D., the Roman scholar Celsus correctly suggested that rabies was transmitted by the saliva of the biting animal. He incorrectly suggested a cure for rabies by holding the victim under water. The first real treatment for rabies came in the 1880s. A French chemist named Louis Pasteur was dabbling with chicken cholera when he noticed that virulent cultures exposed to the elements no longer caused disease. He also noted that chickens given this weakened or “attenuated strain” were immune to inoculation with fresh, virulent cultures. Pasteur next tried an attenuated vaccine against anthrax in cattle. It worked! He then turned his attention to rabies, the scourge of the world. His initial animal studies were very promising, but Pasteur wanted more time to purify his attenuated vaccine before trying it on himself. On July 6, 1885, a 9 year old boy named Joseph Meister was mauled by a rabid dog. A local doctor treated his wounds and told the family that the only person who could save Joseph was Louis Pasteur. After much pleading, Pasteur agreed only after consulting with a couple of real doctors who said Joseph was a “dead boy walking”. Joseph received 13 inoculations in 11 days and made a complete recovery. The word leaked out and patients came streaming in the world over. Nine years later, at the time of Pasteur’s death, over 20,000 people had been given his post-exposure prophylactic vaccine. To raise the awareness about rabies prevention and to highlight progress in defeating this horrifying disease, every year 28th September is celebrated as ‘World Rabies Day’ to mark the death anniversary of Louis Pasteur, the man who first developed rabies vaccine.

Epidemiology:

Rabies is estimated to cause 59,000 human deaths annually and the disease is spread in more than 150 countries and territories. Among total cases of rabies, 95% of rabies cases occur in Africa and Asia. Due to underreporting and uncertain estimates, this number may likely to be increase. Dogs play a major source of the vast majority of human rabies deaths, contributing up to 99% of all rabies transmissions to humans. India is endemic for rabies accounting for 36% of the world’s rabies deaths. The true burden of rabies in India is not fully known; although as per available information, it causes 18,000–20,000 deaths every year. About 30–60% of reported rabies cases and deaths in India occur in children under the age of 15 years as bites that occur in children often go unrecognized and unreported. Rabies deaths in humans are 100% preventable through prompt and appropriate medical care. Vaccination of dogs is the most cost-effective strategy for preventing rabies in people.

Clinical Symptoms:

The incubation period for rabies is typically 2–3 months but sometimes it may vary from 1 week to 1 year, depending upon factors such as the location of animal bite and viral load at bite site. Initial symptoms of rabies include a fever with pain and unusual or unexplained tingling, pricking, or burning sensation (paraesthesia) at the wound site. As the virus spreads to the central nervous system through nerves, progressive and fatal inflammation of the brain and spinal cord develops.

There are broadly two forms of the disease: 

  1. Furious form: This form results in signs of hyper-excitability, hydrophobia (fear of water), and sometimes aerophobia (fear of air). In this form, death occurs after a few days due to cardio-respiratory arrest. 
  2. Paralytic (or dumb) form: In this form of rabies, there is flaccid muscle weakness in the early onset of infection, starting at the site of the bite or scratch, followed by gradual muscle paralysis. Later on coma slowly develops, and eventually death occurs. 

Diagnosis:

Laboratory diagnosis of rabies is carried out as follows:

    1. Staining: Staining an impression smear of tissue specimen (brain) by Seller’s stain and
      examination of slide for the presence of Negri bodies.
    2. Direct Fluorescent Antibody Test (dFAT): This test is considered to be gold standard for rabies diagnosis. It is based upon microscopic examination of tissue specimens treated with antirabies serum tagged with fluorescent dye (usually fluorescein isothiocynate conjugate). This test is considered to be highly specific for detection of rabies infection.
    3. Immunoperoxidase reaction: This staining technique has been shown to be as specific as FAT. It is based upon detecting rabies antigen in autopsy specimen of brain tissue.
    4. Virus isolation: Intracerebral inoculation of suckling mice with suspected tissue suspension is a sensitive technique for isolation of rabies virus. This technique could be coupled with FAT or microscopic examination of infected mouse brain tissue. The use of cell culture (neuroblastoma cells) could be effective for rabies virus isolation. 
    5. Serological tests: Different serological techniques, such as enzyme-linked immunosorbant assay (ELISA), mouse neutralization test and fluorescent focus inhibition test are useful in the detection of rabies antibodies. 
    6. Molecular tests: Different polymerase chain reaction (PCR) based assays are used for the detection of rabies antigen in suspected tissue specimens. 

      Prevention and Control:

      To prevent the transmission and control of the disease, following strategies need to be followed: 

      1. Eliminate stray dog population: Stray dogs play an important role in the transmission of rabies. Controlling the dog population through castration (surgical sterilization) will help in reducing dog bite cases.  
      2. Vaccinate your pets: Rabies is a vaccine-preventable disease. Vaccinating dogs/cats is the most cost-effective strategy for preventing rabies in people. Pet owners need to vaccinate their animals (dogs and cats) at the age of 12–16 weeks followed by booster dose after 3–4 weeks of primary dose, and then annual vaccination. 
      3. Awareness about rabies and preventing dog bites: Educating the community (both children and adults) and pet owners about dog behaviour and bite prevention will help in decreasing both the incidences of human rabies and the financial burden to treat dog bite cases. 
      4. Immunization of people:
        1. Pre-exposure immunization: It is recommended for laboratory workers handling live rabies viruses, veterinarians, wildlife rangers, animal disease control staff, travelers visiting high remote areas with high incidence of rabies, and animal lovers. Such persons need to vaccinate themselves with three doses of vaccine at 0, 7, 21/28 days. 
        2. Post-exposure prophylaxis (PEP): It is the immediate treatment of a bite victim after rabies virus exposure. This prevents entry of virus into the central nervous system. PEP consists of:
          • Immediate and thorough flushing and washing of the wound for a minimum of 15 minutes with soap and water followed by application of antiseptics such as povidone iodine. It will help in removal and destruction of rabies virus at the bite site. Starting the treatment soon after an exposure to rabies virus can effectively prevent the onset of symptoms and death.
          • A course of potent and effective rabies vaccine that meets WHO standards on day of 0, 3, 7, 14, and 28 days post bite, and the administration of rabies immunoglobulin (RIG), if necessary.

      Depending on the severity of the contact with the suspected rabid animal, administration of recommended PEP is as follows:

      Categories of contact with suspect rabid animal

      Post-exposure prophylaxis measures

      Category I – touching or feeding animals, animal licks on intact skin (no exposure)

      Washing of exposed skin surfaces, no PEP

      Category II – nibbling of uncovered skin, minor scratches or abrasions without bleeding (exposure)

      Wound washing and immediate vaccination

      Category III – single or multiple transdermal bites or scratches, contamination of mucous membrane or broken skin with saliva from animal licks, exposures due to direct contact with bats (severe exposure)

      Wound washing, immediate vaccination and administration of rabies immunoglobulin

       

      1. One Health Approach: Collaboration, communication, and coordination between different health science professionals (veterinarians, physicians, agriculturist, epidemiologists, social science professionals, data analyst etc) and policy makers is required to develop integrative policy framework to reduce the incidence of rabies and global elimination of  dog-mediated human rabies deaths by 2030

       

      References:

      World Rabies Day 2022, World Health Organization. https://www.who.int/news-room/events/detail/2022/09/28/default-calendar/world-rabies-day-2022

      Rabies in India, World Health Organization.https://www.who.int/india/health-topics/rabies

      Rabies, World Health Organization.https://www.who.int/news-room/factsheets/detail/rabies#:~:text=Immediate%2C%20thorough%20wound%20washing%20with,and%20vaccination%20campaigns%20are%20critical.

      Singh, R., Singh, K.P., Cherian, S., Saminathan, M., Kapoor, S., Manjunatha Reddy, G.B., Panda, S. and Dhama, K., 2017. Rabies–epidemiology, pathogenesis, public health concerns and advances in diagnosis and control: a comprehensive review. Veterinary Quarterly, 37(1): 212-251. 

       

      *Department of Veterinary Public Health and Epidemiology, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University, Rampura Phul, Bathinda- 151103, India

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