Rabies:A fatal Disease
Rabies otherwise ‘rabere’ in Latin means ‘to be mad. This is one of the oldest known diseases in history with cases dating back to 4000 years ago. The first official documentation of rabies appeared in the pre-mosaic Eshmuna code of Babylon in the twenty-third century BC. However, it was Louis Pasteur in 1880’s who identified a virus as the cause of the disease. Rabies is a zoonotic (transmitted from animals to human) viral infectious disease. This infection is transmitted to human by the animals already suffering from it. The animals which are mainly reported as causes of rabies are; dogs, raccoons, skunks, bats, and foxes. Rabies or “Hydrophobia” is a disease which makes the dogs sick. In many eastern and western countries dogs are vaccinated against it, but it is not controlled yet. Rabies exposure occurs usually through biting a human or another infected animal. Transmission can also occur through saliva touching an open wound or touching mucous membranes. Rabies affects the brain and spinal cord (central nervous system) with initial symptoms like; flu, fever, headache, but the infection can progress quickly to hallucinations, paralysis, and eventually death. Rabies is a preventable viral zoonosis by vaccines still it remains an important public health issue in the developing countries which is evident from the fact that globally this devasting disease is responsible for more than 70,000 people/year human deaths, while approximately 15 million people receive rabies post-exposure prophylaxis (PEP) annually. Despite of global vast attempt and implementation of extensive control schemes and public health awareness programmes, still over 95% of the mortality happens in Asia and Africa, where canine rabies is enzootic (WHO 2013). In India, about 20,000 human deaths occur each year by the bite of rabid dog. For most of human history, a bite from a rabid animal was uniformly fatal. In the past, people were so scared of rabies that after being bitten by a potentially rabid animal, many would commit suicide. Pasteur’s rabies vaccine from 1885 has led to such intense prophylaxis in developed countries, that in the United States, for example, there have only been about two rabies deaths per year for the past two decades; less developed countries are not so lucky. Based on severity of mortality in humans, rabies stays in seventh position among the infectious diseases present in the globe.
Etiology:
Rabies virus is the “type species” of the Lyssavirus genus of Rhabdoviridae family that are bullet-shaped and composed of two parts cause rabies. The first part is considered more structural and is a viral envelope while the second part is more functional and contains the ribonucleocapsid core. The virus is most commonly spread through the bite of an infected mammal, including domestic and wild ones, but transmission can occur from saliva through broken skin or mucous membranes. Other routes of infection include inhalation of the virus in an aerosolized form, ingestion, transplacentally, and even through organ transplants. In the developing world, stray dogs are the most likely animal to transmit rabies. The virus has also been found in cows, cats, ferrets, and horses.
Epidemiology:
In Asia and Africa, the disease raises a burning public health issues. According to the WHO global vaccines research forum, over 30,000 people die every year due to rabies in Asia. One Asian dies every 15 minutes where 15% are likely to be the children under 15 years. More than 3 billion people in developing countries in Asia are exposed to dog rabies. According to WHO, high death rate was experienced in India in 2004 and lowest in Cambodia and Magnolia. In 2006-2007, more than 3,000 rabies cases were reported which reduced to 205 in the year 2008 in China. In India, about 15 million people are bitten by dogs every year and in 1985, it has been reported that 25,000-30,000 deaths are due to rabies annually, but due to preventive measures, the death rate reduced to 20,585 per year. Nepal has one of the highest reported per capita rates of human rabies deaths in the world. Rabies is an important public health problem in Bangladesh also where nearly 100,000 people being bitten by dogs in 2009 and 3,000 died of rabies. Rabies causes at least 24,000 deaths per year in Africa. The high death rates reported in poor rural communities and children. Its prevalence has been documented from 20% to 50% in different species of domestic animals. The susceptibility of animals varies greatly depending upon the animal species, genetic makeup, animal’s age, strain, biotype or dose of the virus and 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. Under-reporting of rabies in endemic developing countries has resulted in the disease being ignored by medical professionals and subsequently poor assistance from international community and donor agencies. A serious concern about lyssavirus is the occurrence of multiple genotypes in several areas of the world and most of the genotypes cause disease in humans. It is problematic to diagnose the disease rapidly in human due to the presence of virus at low levels in samples that are accessible viz., saliva and cerebrospinal fluid (CSF).
Pathophysiology:
The common mode of transmission of rabies in man is by bite of a rabid animal or the contamination of scratch wounds by virus infected saliva. . After a rabid animal bites someone, the virus is deposited in the muscle and subcutaneous tissue. For most of the incubation period (which is usually one to three months), the virus stays close to the exposure site. Following viral transmission, the rhabdovirus travels through the peripheral nervous system targeting the central nerves, which then leads to encephalomyelitis. In humans, first symptoms seem like any other nonspecific viral syndrome (fever, malaise, headache). These benign symptoms may then progress to anxiety, then to agitation, and then to frank delirium. One very consistent symptom after a rabid bite is tingling at bite site within first few days. Interestingly enough, after the virus has spread from peripheral nerves to central nervous system (CNS), it then travels back to the peripheral nervous system, particularly affecting highly innervated areas (e.g., salivary glands). The “frothing” is due to hypersalivation, and victims can suffer from intense pharyngeal muscle spasm at the mere sight, taste, or sound of water. This is called “hydrophobia.” Once clinical features are seen, rabies is universally fatal.
Autopsy studies have revealed that the brain usually is swollen, congested and has an acute inflammatory process.Though rabies is characterized by fatal outcome and severe neurologic signs, but gross pathological changes in the CNS are relatively less or absent due to mild inflammatory reaction. The intracytoplasmic Negri bodies are detectable in the neurons infected with rabies, which are consisting of aggregates of nucleocapsids.
History and Physical
The clinical signs of rabies are confused with other neurological sings caused by other neurotropic etiological agents. Rabies infection has variable and lengthy incubation period in humans and animals generally last up to 20 to 90 days. In 75% of dogs, the early signs (2–5 days duration) progress to paralytic or dumb forms. This is very risky while attending the dumb form of cases. Paralysis as well as mortality happens in both clinical forms at 4 to 8 days after the appearance of clinical signs.
There are five stages of rabies following inoculation: Incubation; Prodrome; Acute Neurologic Illness; Coma; and death.
Incubation is the period defined as an inoculation to the first onset of symptoms and can range from days to years.
The prodrome phase includes nonspecific symptoms similar to flu-like illnesses with gastrointestinal symptoms, myalgias, and fevers being some of the possible symptoms.
The third stage of rabies is when neurologic symptoms occur. These are classified into one of three categories: encephalitic (also considered “furious”), paralytic (also considered “dumb”), and a rare non-classic form. It is also documented that cats are more likely to develop furious rabies than dogs.
The fourth stage of rabies is the coma stage and usually begins within ten days of stage 3. Patients may have ongoing hydrophobia, develop prolonged apnea periods, and have flaccid paralysis.
Following the onset of stage five, without supportive care due to cardiopulmonary failure, most patients experience death within two to three days. Even with supportive therapy, virtually zero patients survive rabies.
In some cases, no signs are observed and rabies virus has been identified as the case of sudden death. The disease should be differentiated from canine distemper, canine, equine and bovine encephalitis, hepatic encephalopathy, thiamine deficiency (cats), poisoning due to lead and organochloride compounds, benzoic acid, strychnine poisoning, pseudorabies, spongiform encephalopathy and listeriosis.
Prevention and treatment:
Vaccine
There is no effective treatment for rabies. Prevention is the mainstay of treatment including programs involving domestic animal vaccination, education, and monitoring. Rabies can be prevented before the latent symptoms can develop, consists of giving a person an injection of rabies immune globulin and another injection of rabies vaccine as soon as possible after the bite or exposure to saliva from an infected animal. Human rabies immune globulin is used or injected at the bite area immediately because it attacks the virus and slow down or stop viral progression through the nerves. Timing and the ability of the patient to respond by making a good immune response is a key to patient survival. Untreated or inappropriately treated rabies is almost always fatal because treatment is supportive only to limit the patient’s pain. An effective new rabies treatment regime that gives the protection from the disease is developed by the scientists. The treatment regimes are; Post-exposure prophylaxis and Pre-exposure prophylaxis.
If a person is bitten by an animal wound care is the first step in the treatment of any individual with a feared rabies exposure. Appropriate wound care alone has been noted to be almost 100% effective if initiated within three hours of inoculation. Recommendations include scrubbing the wound and surrounding area with soap and water (solutions include 20% soap solution, povidone, and alcohol solutions), and swabbing deeply for puncture wounds, with irrigation. After cleaning the wound thoroughly the application of a virucidal agent such as benzalkonium chloride or povidone-iodine is recommended. Treatment is then initiated based on if the patient was previously immunized or not. For patients with previous immunization, a typical treatment may be with human diploid cell vaccine or purified chick embryo cell vaccine at a dose of 1 mL injected intramuscularly on the day it occurs (day 0) and on day 3. Post-exposure prophylaxis involved one dose of rabies immune globulin and five doses of rabies vaccine 1 mL given intramuscularly on days 0, 3, 7, and 14 (and on day 28 if the individual is immunosuppressed). Rabies immune globulin contains antibodies from blood donors who were given rabies vaccine. The rabies vaccine works by stimulating a person’s immune system to produce antibodies that neutralize the virus.
Recommendations:
Rabies is a fatal viral zoonotic disease and a dangerous public health problem. Public health education workshops should be organized to educate people about responsible pet ownership and routine veterinary care. The majority of animal and human exposures to rabies can be prevented by raising awareness concerning: rabies transmission routes, avoiding contact with wildlife, and following appropriate veterinary care. Human rabies prevention is most important and can be prevented either by eliminating exposures to rabid animals or by providing exposed persons with prompt local treatment of wounds combined with the administration of human rabies immune globulin and vaccine. Many countries having the status of high-risk areas but most of the countries around the globe gained the status of rabies-free territories. This shows that rabies can be successfully ruled out from the high-risk areas by taking preventing measures. Public awareness in this regard can play major role. To accomplish these recommendations, high-level political commitment is also simultaneously essential. Local governments should initiate and maintain effective programs to ensure vaccination of all dogs, cats, and ferrets .
By-Dr Ajeet Kumar Singh
Veterinary Surgeon
Founder and director of Global Veterinary Clinic and Surgery Centre Gorakhpur
