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Rabies is an infectious viral disease that infects the nervous system of humans and other warm-blooded animals. It is a zoonosis - an animal disease that can spread to humans – transmitted by saliva through bites and scratches of infected mammals. The disease primarily circulates among domestics, feral, and wild animals, such as dogs, cats, monkeys, bats, foxes, raccoons, and skunks, although all mammals are at risk. Worldwide, dogs are the main source of human rabies death, contributing up to 99% of all rabies transmissions to humans.
Rabies occurs in more than 150 countries and territories, and causes many deaths every year, mainly in developing countries such as Africa and Asia.
The causes of rabies are RNA viruses that belongs to the genus lyssavirus from the family of Rhabdoviridae, order Mononegavirales. Rabies virus (RABV) is the type species that is responsible for most cases in human beings and animals. It is the causative agent of rabies, posing a severe threat to human and animal health.
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RABV causes an acute, fatal neurological infection for humans and other mammals or animals, the virus transmitted through the saliva of rabid animals via a bite or scratch. The infection occurs with the virus traveling along neurons to the central nervous system (CNS), where viral replication happens that leads to symptoms and systemic spread. The disease is nearly 100% fatal, once symptomatic. (Brunker & Mollentze, 2018)
In most cases rabies is transmitted via the bite of rabid animals which releases infectious virus by their saliva. The virus moves into a body through transdermal inoculation such as wounds, or direct contact with infectious material for example, saliva, cerebrospinal liquid and nerve tissue.
The virus cannot penetrate intact skin. After entering the virus binds to cell receptors. Viruses may either replicate within striated muscle cells or they directly infect nerve cells. The patient shows no clinical signs, until this replication.
The virus then travels via retrograde axoplasmatic transport mechanisms to the central nervous system where, both motor and sensory fibres are involved depend on the animal infected. Once the virus has reached the CNS, rapid virus replication takes place. This replication causes pathologic effects on nerve cell physiology. The virus is then moves from the CNS via anterogradeaxoplasmic and flow within peripheral nerves. The movement causes infection of some of the other adjacent non-nervous tissues, such as secretory tissues of salivary glands. At the time of clinical onset, the virus is widely disseminated throughout the body. With shedding of infectious virus by saliva, the infection cycle of rabies is completed.
RABV virus has also been reported to bud directly into the intercellular space, which along with hypersalivation and the aggressive behaviour often associated with infection, promotes onward transmission of the virus to new hosts. Cause of death as a result of infection with RABV has not been irrefutably established. Overwhelming virus replication in the nervous system leads to many systemic complications, including multiorgan failure. Experimental studies show strong evidence for upregulation of interferons, cytokines, and chemokines in the CNS in response to infection with rabies virus. (R Fooks, etal., 2014)
Chain of Infection (including the relation between the host, agent, and environment)
The causative agent for rabies is neurotropic RNA virus of the genus Lyssavirus and the species of rabies virus (RABV). All species of mammals are infected by RABV, but only a few species are important as reservoirs for the disease. Two epidemiological cycles maintains the rabies infection, which are urban and sylvatic cycles. In the urban rabies infection cycle, dogs are the main reservoir host. This cycle mainly occurs Africa and Asia. The sylvatic (or wildlife) cycle happens in the northern hemisphere. In some parts of the world, urban and sylvatic cycles can present simultaneously.
Despite being 100% preventable, canine-mediated especially dog-mediated rabies is one of the most important zoonosis with the estimation of 70,000 human deaths per year. It affects people mostly in rural areas. Rabies has important social costs due to high human mortality rate and high economic consequences because of the losses in livestock and the cost of the implementation of preventive and control measures in both animals and humans. (OIE, 2014)
Transmission of RABV usually begins when infected saliva of a host (particularly Carnivora and Chiroptera (bats)) is passed to an uninfected animal. The RABV most commonly transmits through the bite and virus-containing saliva of an infected host. Though transmission happened rarely via other routes such as contamination of mucous membranes (i.e., eyes, nose, mouth), aerosol transmission, and corneal and organ transplantations. (Plotkin, 2000)
Humans usually get rabies from the bite of a rabid animal. It is also possible for humans to get rabies when infectious material from a rabid animal (host), such as saliva, gets directly in contact with their eyes, nose, mouth, or a wound. Besides, inhalation of aerosolizedRABV is also a potential non-bite route of exposure. Other contact, such as petting or touching a rabid animal or contact with the blood, urine or faeces of a rabid animal, does not constitute an exposure to the infection of rabies. (Brunker & Mollentze, 2018) The human-to-human transmission of rabies virus occurred by cornea transplantation or any other organs transplantation, where the donor infected with rabies. The virus spread from the donor to the transplant recipient.
Statistics of the disease in Malaysia (for the recent 10 years)
The records of rabies in human were first kept in Malaysia on 1926, although the occurrence of rabies cases has known to start at the year of 1884. Most cases are found near Thailand border where rabies is highly endemic. On analyzing history of rabies cases in Malaysia, the first major outbreak of rabies happens on 1945 in former Province of Wellesly (now SeberangPerai in PulauPinang state) and Perak (KG, 1998) . This case prompted a National Rabies Control Programme of compulsory vaccination of all dogs and a rigorous programme of destruction of stray dogs.
Malaysia declared rabies free in April 1954 by the success of this control programme. However, small outbreaks of rabies in animals and humans continue happens in Perlis, Kedah, Kelantan and Selangor. In 1955, the first immune belt programme is introduced with the vaccination and culling of dogs, and monitoring the dog-bite human cases in areas spanning a 50km to 80km radius from Thailand border in Perlis, KedahKelantan and northern Perak (H., 2015). After the last rabies case in 1998, World Association for Animal Health declare Malaysia rabies free in 2012 with no deaths occur for more than 20 years. (H., 2015)
Recently, in July 2015, rabies virus has been resurfaced in Malaysia with an outbreak in Perlis, Kedah and Penang. Perlis was the first state to be hit by rabies after approximately 15 years as Perlis is the nearest state to Thailand. The infection is then spread to Kedah and Penang. In August 2015, Perlis, Kedah and Penang are declared rabies-infected hot spots with a high number of dogs infected. (H., 2015)
| Location | Susceptible | Cases | Destroyed | Vaccination |
|---|---|---|---|---|
| Perlis | 1838 | 6 | 302 | 1838 |
| Penang | 3946 | 3 | 2224 | 1722 |
| Kedah | 4567 | 1 | 2047 | 4597 |
| Total | 10351 | 10 | 4573 | 8157 |
Table 1 above show the statistical difference between the number of susceptible dogs, rabies cases, and number of dogs destroyed and vaccinated in three different states Perlis, Penang and Kedah. According to this data presented by World Organization for Animal Health (OIE), Kedah has the highest number of susceptible and also vaccinated dogs compared with Perlis and Penang. Meanwhile, the highest cases of rabies has occurred in Perlis with 6 cases. The number of dogs destroyed is at the highest in Penang with 2224 destroyed dogs. The apparent morbidity was 0.10% and proportion of susceptible dogs lost through death and culling was 44.18% from the final report submitted to OIE on 28/10/2015. From this it is clear that the incidence of rabies in Malaysia is less than 0.10%, making eradication easy with concerted efforts at mass vaccination of all dogs.
In continuation from the major outbreak of rabies cases in Malaysia in 2015, four rabies deaths occur in a span of one month in 2017, involving three children (below 10 years old) and an old man aged 52 in Serian, Sarawak. Most recently in 2018, 30 areas in Serian, SriAman, Kuching and Sarikai, Sarawak are declared rabies-infected areas. Death toll climbs to nine in May and more than 72,000 dogs get vaccinated in Sarawak.
Rabies is a preventable disease which causes tens of thousands of deaths worldwide every year. It is important to improve the health systems due to tropical diseases such as rabies on poor and disadvantaged populations. Health and well-being for all people at all ages is the third United Nations Sustainable Development goal, which includes ending the burden of rabies by 2030 and achieving universal health coverage by ensuring equal and affordable access to high-quality health services for all around the world. Rabies, a zoonotic disease, is a good indicator of a successful health system and a model for “one health” collaboration. The launch of the Global Rabies Framework in 2015 celebrated the proof of concept that rabies can be eliminated in various settings and the shared goal of reaching zero human deaths worldwide from rabies by 2030 (WHO, 2018).
The countries that shaded in grey are free from dog-mediated rabies for almost 2 years. The countries that eliminates the rabies cases are Canada, Western Europe, the United States of America, Japan and some Latin American countries, Australia and some Pacific island nations (WHO, 2018). On the other hand, the countries where dog rabies is endemic are Asia, Africa, Central Asia and the Middle-East, and Latin America and the Caribbean. Asia has the highest human deaths that estimated 35,172 deaths (59.6% of global deaths) and losses of approximately 2.2 million disability adjusted life years (DALYs) occur per year due to dog-mediated rabies (Hampson K, 2015). India accounts for the most deaths in Asia (59.9% of human rabies deaths) and globally (35% of human rabies deaths).
In Africa, an estimated 21 476 human deaths occur each year due to dog-mediated rabies (36.4% of global human deaths), with a loss of 1.34 million DALYs (Hampson K, 2015). Apart from that, the disease burden due to dog-mediated rabies is estimated to be 1875 human deaths and 14 310 DALYs in Central Asia and 229 human deaths and 1875 DALYs per year in the Middle East (Hampson K, 2015). While as in Latin America and Caribbean, 66 deaths are estimated in the year of 2016. The numbers of cases of human and dog rabies have decreased significantly in this region from 2013 to 2016, as a result of sustained control (WHO, 2018).
Recently, many prevention methods are being taken worldwide to reduce the rate of rabies infection. One of success story is from Goa, India which has a population of approximately 2.4 million and an estimated 150 000 dogs. Since 2013, the projects have been done for rabies infection prevention such as, 50 000 dogs have vaccinated annually and build awareness of rabies in schools and communities with an education team and signal rabid dogs for removal. According to statistics, human deaths from rabies per year in Goa decreased from 24 to 5 deaths, and no cases have been reported thus far in 2017 (WHO, 2018). This compelling example gives significant evidence that rabies elimination is feasible with existing tools. Sustained commitment, collaboration and support from all parts of the world to implement control measures remain the key to reaching zero human deaths due to rabies infection by 2030, worldwide.
There are many potentially harmful biological agents such as viruses, bacteria, fungi or parasites, and some types of toxic substances that causes disease to living organisms especially humans. In order to handle these pathogens precautions and practices are organized into biosafety levels based on the risks connected with the biological agents. There are three levels of biosafety that are highly followed in laboratories when handling with biological agents. Biosafety Level 1 (BSL-1) is the lowest level of precaution that causes minimal risk from pathogens. This level does not causes harmful diseases and will not affect healthy adults. Biosafety Level 2 (BSL-2) is for moderate biological hazard. BSL-2 involves biological agents that are associated with human diseases which causes moderate hazard to living organisms mostly humans, and environment. However, Biosafety Level 3 (BSL-3) is for serious biological diseases that are fatal due to the hazardous biological agents.
Rabies caused by lyssavirus specifically rabies virus, has the highest fatality rate of any currently recognized infectious disease. Therefore, rabies has been placed at risk group 2 and Biosafety Level 2 (Table 2) (WHO, 2018) . Safety and precautions are important when working with RABV. In general, BSL-2 safety practices are adequate for laboratory practices such as preparation and processing of samples, handling animals, and necropsy and collection. Personal protective equipment such as laboratory coats or gowns, disposable gloves, eye protection, are important when dealing with BSL-2 agents in laboratories. Meanwhile, some activities may require large quantities or highly concentrated viruses or other infectious materials thus, for these practises that increases the risk of exposure, BSL-3 safety precaution should be practised (WHO, 2018).
Pre-exposure rabies vaccination is recommended for individuals working with rabies agents to reduce the risk of being exposed. Usage of Imovax Rabies, Human Diploid Cell Vaccine (HDCV) and Purified Chick Embryo Cell Vaccine (PCECV) lessen the risk of exposure to rabies infection. Apart from that, practices after exposure in laboratories should be taken to reduce the risk level up to 90% ((ROHP), 2012). Post exposure prophylaxis of rabies infection using HDCV and PCECV is very effective on reducing the risk of infection of rabies. When skin is exposed (Needle stick or scratch) to the RABV, wash the wounds immediately and thoroughly for 15 minutes, and the use antiseptic scrubs to clean and decontaminate the surface of the skin ((ROHP), 2012). Cover the wound with waterproof dressings. These immediate precautions may prevent the workers or individuals from getting rabies infection.
Rabies has threatened the world with its infection fatality, although it is 100% curable. Effective control measures need to be taken to eradicate and prevent the rabies from infection. Control measures can be classified into two framework: Socio-cultural framework and Technical framework. Socio-technical framework includes public awareness and education, responsibility of pet owners, and animal welfare. Meanwhile, technical framework involves vaccination to rabid animal, disease surveillance, and dog population management and animal movement control.
It is stated that more than 95% of rabies infections are due to dogs, thus prevention and controls need to be combatted from animal source. In countries such as Asia, with dog-mediated rabies, mass vaccination program should be done to vaccinate the dogs against rabies, as required by laws. Oral Vaccination Campaign (ORV) should be held to provide vaccination to rabies-potential dogs according to international standards. Latin America was managed to successfully run vaccination campaign by the support of public health sector and involvement of communities on eradicating rabies (WHO, 2018). The World Organization for Animal Health (OIE) plays vital role in vaccinating the potential-infectious dogs worldwide.
OIE created an anti-rabies dog vaccine bank in 2012 with financial support from European Union, Canada, Germany, France, Australia and Japan. The vaccine bank delivers vaccine to financially inactive countries mostly of Asia and Africa. Recently on August 2018, 20.1 million anti-rabies vaccines have been delivered (OIE, 2014). OIE delivered 5.4 million among them directly to 20 countries around the world (OIE, 2014). Indeed, in the framework of the Tripartite Alliance on rabies control, the WHO has decided to place its procurement orders for canine vaccines through the OIE Rabies Vaccine Bank (WHO, 2018).
For the individuals with high rabies exposure for example traveling to rabies infected countries, working on rabies virus in laboratory or living in a rabies endemic residence pre-exposure, prophylaxis measures are necessary. Pre-exposure vaccination is needed for the exposed individuals to make them immune to the rabies virus. The vaccination consists of a series of 3 intramuscular injections provided on days 0, 7, and 21 or 28 with human diploid cell rabies vaccine (HDCV) or purified chick embryo cell (PCEC) vaccine (WHO, 2018).
Post exposure prophylaxis is also important on controlling the virus from spreading. Rabies virus spreads from the bite, scratch from the rabies-infected animals, and contact with them. First-aid moves are important for preventing infection. Wash the part of scratch or contact with mild soap and povidone iodine and for almost 15 minutes. For the unvaccinated people, Rabies Immune Globulin (RIG) should be injected on the wound area where the saliva may contaminated the wound tissues (WHO, 2018). It is better when after the exposure to seek health care and consultant for further prevention and treatment to control the virus from spreading. In laboratory, laboratory manager and employees should make sure PEP is instituted in the facility. The ordered PEP such as, wearing gloves and eye protection when handling rabies virus, should keep in practice to avoid rabies infection.
An effective education on rabies and how to prevent it should be given to the public. In order with that, some programmes to prevent dog bites are conducted to reduce the risk of rabies, save the costs of pre and post exposure prophylaxis and wound care, eliminate the trauma of dog bites and restore healthy dog–human relationships.
The education programmes has successfully affects the children’s behaviour to prevent bites according to Meta-analysis (OIE, 2014), although the quality of the evidence is low. Education to prevent dog bites is most effective when involving live dogs. The general public should be advised to avoid direct contact with wildlife animals in general and also with animals that are behaving abnormally and are sick in particular. Anyone bitten by potential-infected animal, particularly in areas where wildlife rabies is endemic, should seek medical attention, immediately. In countries that have been declared free of terrestrial rabies, it is important that the public be aware that anyone potentially exposed to types or signs to rabies should receive prompt post and pre exposure prophylaxis (WHO, 2018).
Understanding Rabies: Transmission, Epidemiology, and Control Measures. (2024, Feb 08). Retrieved from https://studymoose.com/document/understanding-rabies-transmission-epidemiology-and-control-measures
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