345 Disease Podcast Rabies

The Neglected Disease Podcast is discussing rabies and its global impact. Rabies is a disease that is often overlooked and not talked about, but it has significant harmful effects. Rabies is a virus that affects mammals and is transmitted through bites or scratches. The virus has a long incubation period and once symptoms occur, it leads to neurological distress, hydrophobia, and aggression. Without treatment, rabies is fatal. Rabies cases have decreased globally, but it remains a problem in India and Africa. Rabies is one of the neglected tropical diseases recognized by the World Health Organization. Developed countries have successfully eradicated rabies, but it still poses a major threat to people in developing countries. Treatment for rabies is available through vaccines, but early diagnosis is crucial. There are still unknowns about the virus, including how it differentiates and why some people develop different forms of the disease. Despite the grim nature of rabies, there are pr Welcome to the first episode of the Neglected Disease Podcast. I'm one of the hosts, Ashley, and I'm joined by Corey. Would you like to tell us more about the podcast? Of course. We will discuss diseases that deserve more attention and their impacts around the world. Today, we start with rabies. Corey, how many people casually throw around the word rabies without realizing the impact it still has on the world? Well, Ashley, most people have heard of rabies, but they don't know the specific scientific details behind it and how impactful it still is. Rabies is a disease that most people do not discuss or are concerned about in everyday life and is not often the center of media attention. Exactly. The goal of this episode is to give an in-depth look at rabies and hopefully bring more awareness to its global harmful effects. To start, rabies is of the genus Lizavirus and is part of a family of viruses known as rhabdovirus. The prefix lisa means rage and was named after the Greek god of rage. The name rabies originates from the Sanskrit word rabhas, which means violence. The genome is a negative single-stranded RNA and is rod-shaped, looking like gel cap pills under a microscope. The majority of lisaviruses are found in bats, which may indicate the origin of rabies. Coincidentally, rabies has been thought to be the origin of the vampire folklore. This is due to the exposing of the roots of teeth and because of dehydration. Also because of spasms occurring and there is exposure to light and because of the urge to bite people being another sign of the virus being present. However, this lore remains contested. Regardless, rabies has claimed humanity from the beginning of recorded history. As dogs and other animals became domesticated, they brought rabies with them. The first record of rabies was in the Codice of Eshnunna, which validated a large punishment on the owner if their dog infected someone with rabies. Even during the medieval and early modern times, owning dogs as pets was discouraged. There was a social stigma around the common person owning a dog and they often had to pay heavy fines if they wanted to keep their pet. This continued until Louis Pasteur developed his rabies vaccine in 1885. Since then, rabies cases have decreased throughout the world. However, rabies remains a problem in India and Africa, where there are over 59,000 cases per year. Actually, I'm curious, what animals can be a host of rabies? Any animal can be the host of rabies. Rabies is transmitted by a bite from an infected animal. Typically, dogs are seen as the main mode of transmission to humans. But any mammal can transmit the disease and infect it. Bats are a key mode of transmission in the United States. But worldwide, dogs are estimated to be responsible for 99% of all rabies cases. Wow, yeah. Most people understand that you can infect it with rabies through saliva, which is most commonly transmitted from the bite of an infected animal. However, what most people don't realize is that the incubation period of the disease varies depending on the location of the bite. The closer the bite is to the brain, the shorter the incubation period. Any other ways people can get infected? Well, the most common way people can get infected is through the bite of an infected animal. But people may also get infected by scratches. If an animal licks their paws or claws while infected, this causes the virus to be present on the claws, which introduces the virus to a wound. However, this is a relatively rare mode of transmission. Another rare method is an organ transplantation. This is extremely rare, occurring only about 18 times. The organ donor becomes infected with rabies and then dies of some other cause while still in the incubation period. I think this is terrifying. Imagine thinking you just received a life-saving transplant only to die weeks later from the horrible illness. The CDC doesn't even screen for rabies, since it's so rare and would be a waste of resources. Isn't that insane? That is pretty astounding. Even 18 cases is a lot for a procedure where safety is so important. Once someone becomes infected, what occurs during the incubation period? The incubation period is normally 1 to 3 months, but it can be as long as 8 years. This is an extremely large range in which the virus can remain hidden within an individual. It just depends where the victim gets bit. While the incubation period is occurring, rabies is slowly multiplying in the muscle tissue near the site of the wound, undetected. Eventually, rabies travels through the motor neurons up into the central nervous system, and then the onset of visible symptoms occurs. And what exactly are the symptoms? The first symptom after the incubation period is prodrome, which is numbness or tingling and flu-like symptoms. At this point, no neurological distress is present. Encephalitis is then caused by the virus replicating fast in the brain, leading to the acute neurological period characterized by confusion, hydrophobia, and hallucinations. The hydrophobia occurs due to the virus invading the salivary glands to use as a vector to spread the disease. When the virus invades the salivary glands, it leads to painful throat spasms in the presence of water. The consumption of water will lead to a dilution of the virus. As a result, the historical name of rabies was hydrophobia. This onset of symptoms often manifests simultaneously with behavioral changes, most often leading to an increase in aggression. If people do not receive treatment for rabies, they will die within a few days, most often caused by cardiorespiratory arrest resulting from the degradation of neurons. Fortunately, the patient is usually fully conscious during this entire process. This is a pass for encephalitic rabies, which accounts for 80% of cases. However, paralytic rabies, which accounts for only 20% of cases, are symptoms that are much different. Yeah, with paralytic rabies, it is much longer and more suffering occurs. Muscles gradually become paralyzed, starting at the infected wound sites, and eventually a coma develops with death following after. What is unfortunate is that these symptoms are not as obvious as encephalitic rabies, which leads to the under-reporting of cases. What is curious about these two forms of rabies is that scientists are unsure how people develop one or the other. They have no idea what causes people to develop encephalitic or paralytic rabies. This is kind of scary considering the symptoms are so different. Luckily, even though these symptoms are terrifying, most developed countries have successfully eradicated rabies. These countries include Australia, Japan, and the United Kingdom. Surprisingly, the United States is not one of these countries that has successfully eradicated rabies, but most cases occur in wildlife with only one to three human cases reported per year. Even though rabies does not affect developed countries much, it has a major impact on people in developing countries. This is one of the reasons rabies is one of the 17 neglected tropical diseases designated by the World Health Organization. Places that account for the most rabies cases are India and sub-Saharan Africa, which often struggle to provide medicine to many people who reside there, especially for rare diseases. Unlike most diseases, though, it is unlikely that outbreaks will occur because of the method of transmission. Normally, only one person is infected after an encounter with a rabid animal, and rarely anyone is infected through contact with humans. Even though outbreaks are not likely to occur, rabies is still present for more than 60,000 deaths each year, which is very alarming. Obviously, people who get infected with rabies need to receive treatment fast. However, rabies can affect the fitness of its host indirectly and directly. It affects the host indirectly because of the injury and a possible secondary infection of the wound. However, the more severe consequences come from rabies affecting the host directly. Without treatment, rabies has a guaranteed 100% death rate. Nevertheless, if a person is treated early in the disease, before it reaches the brain, then there is little effect on fitness and a 0% chance of mortality. Why do people need to be diagnosed with rabies, which leads us to a discussion on the pathology of rabies. How's it done, Ashley? Well, rabies is identified through negri bodies in the brain. Negri bodies are oval-shaped objects found in nerve cells in a rabies-infected brain. However, negri bodies are only found in 50% of victims, so it may be used as a diagnostic tool, but it's not perfect. Negri bodies are also only identified during an autopsy. Most of the diagnostic methods are through symptoms and spinal fluid. However, most people get treated preventively if they are bit by an animal that could be infected with rabies, such as a bat. Wow, so you get bit in the middle of the night and may not even notice you have rabies until you show symptoms? Yup. Aside from the lack of pathologies, there are also some unknowns of the disease. Corey, want to inform the listeners? Surprisingly, there are only two unknowns that we could uncover about the virus. Since rabies research has occurred for so long, as previously mentioned, scientists are unsure how the virus differentiates and why some people develop encephalitic rabies and others develop paralytic rabies. Other than this, the only other unknown is how the disease began. Every resource reference stated that rabies has been mentioned for thousands of years throughout history. However, no one can put a specific time period as to when the virus first appeared. We've talked a lot about the depressing side of rabies and how horrible the symptoms of it can be. Corey, let's end on a high note and talk about the treatments for this horrible disease. There is a rabies vaccine that's often used as a preventative measure if someone is bitten by an animal that could carry rabies. Firstly, the wound should be cleaned thoroughly after exposure. Second, the rabies vaccine is given on days 0, 3, 7, and 14, with day 0 being the day of infection. Along with the first rabies vaccine given on day 0, one dose of rabies immunoglobulin should be given along with it. Rabies immunoglobulin is a medicine made up of antibodies to the rabies vaccine virus that would help prevent the disease. When the vaccine is given in the sequence, it is 100% effective at preventing rabies. Unfortunately, if the symptoms of rabies do start to set in, then the vaccine is no longer effective. Currently, there is no consistent, effective treatment for symptomatic rabies. Treatment usually eases the suffering and mitigates pain. There was once a promising treatment nicknamed the Milwaukee Protocol that involved inducing a medical coma in the patient and then giving them antiviral drugs, usually ketamine and amantadine. This treatment ended up creating the first known rabies survivor, saving the life of Jenna Gies. However, it only has saved 5 out of 36 patients and also entails a large financial price, so its use is not widespread and its effectiveness is still debated among doctors today. Not the best high note in the world, but it's better than nothing. Yeah, although a 13% survival rate is better than zero, neither of those are great options. Clearly, rabies is a horrible disease that causes many people to suffer. The disease itself has many economic and social costs that need to be addressed when discussing the rabies virus. The largest death toll for rabies occurs in the poorest areas of the world. In these regions, dog meat consumption is popular and facilitates the transmission of rabies. Another possible way to get rabies is consuming the neural tissue of infected animals. Even though we know a tremendous amount of information about rabies, it's hard to determine worldwide deaths, and we have to rely on an estimation because many cases go unreported. One economic impact that many people do not think about is livestock losses due to rabies, which can harm economies. If livestock contracts rabies, then it's no longer useful and unable to serve its purpose. In the eyes of the economy, that animal essentially becomes worthless. Through the loss of livestock in time recovering from vaccines, over $5 billion annually are lost, showing the immense economic toll rabies has. Now that we've discussed the economic costs, what does research for rabies look like? Currently, there are an average of 13 rabies-related research papers published yearly, mainly in the United States, France, and China. Rabies research currently looks at vaccine efficiency and development of treatments. One such positive discovery was a possible new treatment. Dr. Brian Schaefer discovered that an anti-LISA virus human monoclonal antibody called F11 may be used to treat rabies even after the onset of infection. What are monoclonal antibodies? Monoclonal antibodies are antibodies that are cloned from a specific white blood cell, in this case, a white blood cell with rabies antibodies. And how does that prevent or stop rabies after infection? F11 activates CD4 T-cells, which help mitigate the viral load in the brain. This is needed as the T-cells the brain utilizes are often able to be destroyed by rabies. Usually, CD4 T-cells cannot enter the brain due to the blood-brain barrier, but F11 is able to bypass that due to a specific FCRY receptor binding in the brain, allowing for CD4 cells to replicate. Although this has yet to be tested on a human, F11 is nonetheless a promising treatment for disease with no known treatments. And Corey, what do you think we, as well as our listeners, could do to help prevent rabies, and if possible, maybe even eradicate it? On a personal level, to help stop the spread of rabies in your areas, you should make sure your pets are up to date on vaccinations. Prevent your pets from roaming in areas you don't know, and make sure to neuter your pets if you do not have the resources to fully look after more. This will reduce the number of unwanted animals that may not be up to date on vaccinations. Additionally, make your property unattractive to wild animals by capping off chimneys and closing lids to trash cans. Finally, please do not touch or pet wild animals unless you are trained to do so. I know many people on the Internet think that wild animals look friendly, but you have a high chance of getting bit or scratched, increasing the transmission of rabies. Any advice on a global scale, Ashley? It is a lot harder to prevent disease transmission on a global scale than it is on an individual scale, but I think informing others of rabies as a neglected tropical disease may bring more awareness to larger organizations that can help areas such as Sub-Saharan Africa and India by providing prevention methods, vaccinations, and more. Rabies will likely never be eradicated on a worldwide level. However, there are just too many possible hopes. All mammals may get rabies, so that's a lot of animals that are at risk. Vaccines may work, but don't forget that bats are natural carriers, so they do not show infection. For these reasons, it's best that the focus is on prevention rather than flat-out eradication. Well, that's all we have about rabies for today. Hope that this podcast was able to educate you on this disease. Definitely. We hope that you now see rabies in a more informative light and how important it is nowadays, even with the prevention. Thank you for listening. Thank you for listening.