9/28/2022 The Big Effects of a Small Bite!
![]() Would you go to the doctor if an animal bit you? Probably not. How would your opinion change if you knew that rabies causes encephalitis, or swelling of the brain, and almost always results in death once symptoms are present? Today is World Rabies Day, an observance day that aims to raise awareness and promote the elimination of rabies on a global scale. Coordinated by the Global Alliance for Rabies Control (GARC), the theme for 2022 is "One Health, Zero Deaths." World Rabies Day is observed on September 28th of every year to commemorate the death of Louis Pasteur. Pasteur developed the first effective vaccine against rabies in humans in 1885. The Centers for Disease Control and Prevention and the GARC aim to eliminate dog-mediated human rabies by 2030. ![]() More About Rabies and Symptoms Rabies is a zoonotic disease caused by the Rabies Virus, also known as RABV, a negative-stranded RNA virus. It belongs to the genus Lyssavirus and is a member of the Rhabdoviridae family because of the virion's bullet shape. Rabies can cause around 60,000 human deaths every year around the globe. In the United States, bats, raccoons, and foxes carry the RABV. However, dogs are the primary carriers globally, with dog bites causing causing the overwhelming majority of human rabies infections and deaths. According to Dr. Amy Gilbert, a research biologist at the USDA and team leader for applied research to assist wildlife rabies management, "death is by lethal and progressive encephalitis, and one of the hallmarks of rabies is acute progressive deterioration." Both humans and animals rapidly deteriorate once symptoms begin to show. Dr. Gilbert noted that other zoonotic viruses also cause encephalitis. However, a unique to rabies is that "the reservoir host is susceptible to fatal infection", and “there are no asymptomatic wildlife carriers”, which is not present in many other zoonotic diseases.” The Centers for Disease Control reports that symptoms may not appear for weeks or even months once exposed to rabies. Common symptoms appear flu-like at first until developing into cerebral dysfunction, anxiety, agitation, and more. People can also experience delirium, hydrophobia, and insomnia, but the disease is typically fatal once these signs occur. Although rabies has a more extended incubation period, there have been less than 20 cases of human survival after the appearance of clinical rabies symptoms, so people must act quickly after a possible exposure has occurred. ![]() Schematic diagram of bullet shape structure of RABV showing different proteins. Liu, X., Nawaz, Z., Guo, C., Ali, S., Naeem, M. A., Jamil, T., Ahmad, W., Siddiq, M. U., Ahmed, S., Asif Idrees, M., & Ahmad, A. (2022). Rabies Virus Exploits Cytoskeleton Network to Cause Early Disease Progression and Cellular Dysfunction. Frontiers in veterinary science, 9, 889873. https://doi.org/10.3389/fvets.2022.889873 Fun Fact:Hawaii is the only state in the United States that is rabies free! ![]() What Causes Rabies in Humans? RABV enters the body through a bite or scratch from an infected animal. This wound exposes a person's muscle tissue to the infected animal's saliva, which contains RABV particles. The location of the wound, typically in muscle tissue, allows the virus to spread. In 1996, a study showed that the muscular form of the nicotinic acetylcholine receptor (nAChR) binds RABV allowing it to enter the muscle cell. A review of the rabies neuroinvasion mechanism suggests that RABV buds off muscle cells followed by entry into the central nervous system. The access occurs via neuromuscular junctions, specialized synapses between nerve terminals and muscle fibers. The RABV entry into nerve cells follows viral replication and a new round of infection and spread. There are a few instances of rabies transmission through corneal or solid organ transplants, but but most virus transmission occurs through bites or scratches from rabid animals. The Biology of RABV A recent review shows that RABV comprises complex genomic RNA and nucleoproteins within a lipid envelope. It is the most prominent of the 17 species of lyssaviruses. RABV structure resembles a bullet. Studies show that rhabdoviruses encode five different structural proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and an RNA-directed RNA polymerase (L). The N protein protects the RABV genome from RNAse and is the major component of the nucleocapsid. It encapsulates the RNA to form a ribonucleoprotein complex or RNP. The RNP then interacts with P and L proteins to form the nucleocapsid. The P protein function in the replication and transcription allows the RABV to invade the host interferon-mediated antiviral response. It is also the non-catalytic part of the L polymerase protein. The M protein links the nucleocapsid to the viral envelope. The M protein also aids in budding, apoptosis, and intercellular membrane redistribution of the virus. The virus G protein must attach to cellular receptors and enter the cell via endocytosis to establish infection. Once inside the cell, the virus uncoats and releases its helical nucleocapsid into the host cell's cytosol. RABV is a negative sense RNA virus. The viral polymerase transcribes the negative strand to five positive-strand monocistronic mRNAs before protein synthesis. More information on RABV structure and replication is reviewed here. A way to identify RABV on a cellular level is the presence of Negri bodies. Negri bodies are composed of RABV proteins and RNA Rabies Vaccination Rabies vaccination is unique because it can be administered pre- and post-exposure in humans. Pre-exposure vaccination is available for those traveling to RABV-endemic regions or people at enhanced risk of coming in contact with RABV, such as spelunkers, researchers, veterinarians, and individuals who handle wild animals. Post-exposure vaccination is available because possible exposure, via bite or scratch, is easily identifiable. The virus' incubation period is long enough to allow the vaccine to develop a protective immune response within the recipient. Both types of vaccinations involve multiple vaccine doses administered according to a regimen, or schedule, but there are different post-exposure recommendations for persons who have or have not had pre-exposure vaccination, or persons who may have immunocompromising conditions. Dr. Gilbert discussed differences in the vaccines given to humans and wildlife. Wildlife vaccines are "oral, and a primary difference is that the vaccines for wildlife are live, not inactive." She added, "the products used for animals in the United States are live but can never cause rabies because they are recombinant." A recombinant vaccine is a vaccine produced by genetically modifying the viral genome. Dr. Gilbert said, " In animals, vaccines are given before to prevent infection. There is no benefit to vaccinating them once they are infected and showing signs and symptoms." If 70% or more of the dog population gets vaccinated, the rabies infection rate will rapidly decrease, reducing the human infection rates and exposure drastically. Dog vaccination is a critical element of rabies control for human and animal populations, but these vaccinations must be appropriately tracked, registered, documented, and followed up. Rabies Is a Neglected Disease It is very likely that every person reading this article has heard of rabies and has some understanding of its transmission from animals, but rabies is a neglected tropical disease. Compared to other zoonotic diseases, rabies is neglected, despite its significance and impact. The condition is endemic in locations on almost every continent. While many countries are now canine rabies-free, the disease is prevalent in bat populations in most countries in the Americas and other lyssaviruses are found in bat populations throughout the Old World. One reason why rabies might still be a neglected zoonotic disease in developing countries is the lack of laboratory diagnosis and surveillance for both human and animal rabies in developing countries where the disease is endemic. Due to the lack of simple and cost-effective laboratory methods for diagnosis, rabies' burden and public health impact are uncertain and likely underestimated. Even though rabies is almost always fatal once symptoms become apparent, there is a low commitment to controlling rabies due to various factors. Dr. Gilbert said, "rabies is a neglected disease because it primarily impacts the poorest and most under served communities." She added, "a cycle of neglect is created in these locations with limited reporting, which leads to low prioritization of the problem, and this cycle continues." This neglect has led to "advocacy efforts to start pre-exposure campaigns in communities heavily impacted by rabies." There is no effective therapy for rabies once clinical symptoms set in. How to Spread Awareness In the United States, people do not commonly talk about rabies or its effects on many developing countries. Although many people do not believe rabies concerns them, the One Health concept highlights the dynamic between the health of animals, the environment, and humans. In this respect, people should consider the health of those around them and those worldwide who suffer from diseases that more advanced countries no longer worry anymore. Dr. Gilbert believes World Rabies Day should be used to "raise awareness on rabies facts, and get people to remember that rabies is still around even though there are few human deaths in the US." She added, "we know that many people are exposed and receive post-exposure treatment each year." The first step in changing people's minds about rabies is simply getting people to walk into a doctor's office after a possible exposure. People can call their local health department if they are concerned about a possible RABV infection because they will have information on potential concerns about rabies spread in a particular area. ![]() One Health Vaccinations benefit wildlife, domestic animals, and public health. Dr. Gilbert said, "rabies is one of the best examples of One Health we have." She also noted that, "each case of rabies on averages leads to one or two additional cases, but explosive outbreaks are uncommon." One Health approaches focus on controlling rabies at its source in animals, for the benefit of public health, agriculture, and natural resources. This approach will help lower the economic costs of living with rabies. The One Health system benefits developing countries by creating a more economical rabies prevention and control method compared to approaches that focus only on reactive post-exposure prophylaxis. One Health approach has been successful in Bhutan, Bangladesh, and Sri Lanka and is currently used in Nepal. Bangladesh lowered their rabies deaths by 1300 within three years, and Sri Lanka reduced their rabies-related deaths to less than 50 in a year. As the prevalence of rabies control programs grows, countries can look to these programs that use a One Health approach to design effective animal rabies control programs in their own country. With One Health in mind, many countries will be able to eliminate rabies within their communities while supporting the coexistence of humans, domestic animals and wildlife.” Comments are closed.
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