Wednesday, May 22, 2013

Rabies


This time at Infection Landscapes we cover the "madness" disease. Rabies is a zoonotic disease that causes encephalitis and, if no vaccine is administered, almost always results in death. While human rabies infection is not common in the developed world, it is a significant cause of death in the developing world where the vast majority of infections are acquired from dogs. The name "rabies" comes from the Latin word for madness. This is an ancient disease having been documented for almost four thousand years. It has always been associated with rage and violence in the afflicted.

The Pathogen: Rabies is caused by the rabies virus, which is the type species for the Lyssavirus genus in the Rhabdoviridae family. Rabies virus is an enveloped, single-stranded negative-sense RNA virus with a helical capsid. The virus is approximately 75 nm in diameter and 180 nm long.


The primary target host cells are neurons. Each stage of the rabies virus infection cycle in the host cell is illustrated in the graphic below (published in Lancet Infectious Diseases Volume 2, Issue 6, June 2002, Pages 327–343).


The virus first gains the peripheral nervous system where it passes along axons in the periphery until it eventually gains the central nervous system, which is the primary site of pathogenesis. The graphic below depicts the pathogenic cycle in animal rabies (published in Lancet Infectious Diseases Volume 2, Issue 6, June 2002, Pages 327–343):


The Disease. Rabies is an extremely serious disease, which almost always results in death if infected individuals do not receive post-exposure prophylaxis before symtpoms begin to appear. The incubation period is highly varied and can range from several days to several years, however for most human infections symptoms typically appear between 2 and 12 weeks following infection. Initial symptoms are often vague and may be comprised of only fever and general flu-like illness. However, this progresses rapidly to include neurologic sequelae.

There are two general forms of clinical rabies in both animals and humans: furious rabies, and paralytic rabies. Furious rabies occurs in approximately 70% of human rabies cases and presents first with a prodrome typified by feelings of great anxiety. Other symptoms during this phase are non-specific and may include headache, myalgia, and fever. Following the prodrome, the neurologic phase progresses with intermittent agitation and aggressive behavior. Hydrophobia is a common symptom due to spasms of muscle structures in the neck. Increased saliva is also a prominent feature of the neurologic phase. Coma then develops in a short time, typically within a few days from the onset of this phase. Other autonomic abnormalities are common and can include pulmonary edema, blood pressure variability, and cardiac arrhythmia. Interestingly, there can also be differences in presentation based on whether the human infection was acquired from a dog or a bat, the latter being associated with seizures and hallucinations. Paralytic rabies occurs in approximately 30% of humans rabies cases, and is much more difficult to identify and diagnose. This form of disease is very similar in clinical appearance to Guillain-Barre syndrome with respect to encephalopathy, paralysis, and electrophysiological findings.

Post exposure prophylaxis (PEP) is critical to administer to any individual suspected of having been inoculated with the rabies virus. There are two primary components to PEP. First, the bite wound, or suspected point of entry, must be thoroughly cleaned using soap and water as soon as possible after exposure. This can help to reduce the number of virus particles that can gain entry into cells. Second, vaccination must be provided as soon as possible following exposure. Rabies is one of the very few infections for which effective immunization can be administered after the exposure. This is due to the extended period of time required for the virus particles to reach the CNS and initiate pathogenesis. As such, PEP can be administered during the incubation period to effectively block pathogenesis. However, while the incubation period is typically a few weeks, it can be as short as a few days for some individuals. As such, it is critical to begin PEP as soon as possible following the exposure. In addition, the number of virions introduced to the infected individual as well as the site of introduction are important determinants of the duration of the incubation period. For example, individuals with multiple or severe bite wounds will typically have a larger inoculum, and those with bites on the hands, face, neck, or head will have a shorter distance for virions to travel before reaching the CNS. In either scenario, the incubation period can be reduced substantially. Children are also at greater risk because they typically experience bites on the face and head more frequently than adults.

A course of tissue culture vaccine should be administered, however it takes 1 to 2 weeks to mount an adequate humoral immune response. As such, the necessary antibodies may not be available in time for individuals with short incubation periods. Therefore, in addition to the tissue culture vaccine, we rely first on passive immunity by administering antirabies immunoglobulin (RIG) in and around all bite wounds. The passive antibodies must be injected at the wound sites, not intramuscularly at some site distal to the wounds.

The document below states the specific recommendations of the Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention (CDC):

Rabies Post-Exposure Prophylaxis Schedule (PDF)


The problem with PEP is that it is expensive and often not available at all, or in part, in those areas of the world with high endemicity of rabies in dogs, particularly South and Southeast Asia and Africa. Thus, even if a rabies exposure is well documented and identified prior to the onset of symptoms, often supplies are inadequate to administer complete and effective PEP.

Epidemiology and the Landscape. Rabies virus is shed in the saliva of symptomatic hosts and, as such, contact transmission via biting is the primary route of infection. Rabies virus only infects mammals and, while all mammals are susceptible to infection, certain mammal species are particularly important as reservoir hosts and vectors for human infection. In particular, dogs, cats, domestic livestock, and bats are important sources of rabies infection to humans. Dogs are by the most important source of human infection, accounting for the vast majority of human infections worldwide (however, almost all human rabies infections in the United States are due to contact with wild animals, particularly raccoons, skunks, and bats). Areas with large populations of free roaming stray dogs have the largest occurrence of rabies in humans. The single most important feature defining the landscape of human rabies infection is the spatial range of stray dogs. This feature is definitive because the range of stray dogs always intersects or is in union with the human social landscape in either its residential or occupational components, or both. Moreover, the spatial range of stray dogs often is in contact with sylvan or peri-sylvan landscapes at its boundaries, thus maintaining both the primary domestic rabies reservoir, through contact between dogs and other sylvan mammals, and the human transmission cycle, through regular contact between dogs and humans. The map below shows the important mammal reservoirs and vectors for rabies virus (published in Lancet Infectious Diseases Volume 2, Issue 6, June 2002, Pages 327–343).
    

Rabies exists in almost every country and landmass on earth with the exception of Antarctica and some remote islands. The regions of South Asia and sub-Saharan Africa experience the vast majority of human rabies each year, with India alone accounting for approximately 20,000 of the total 55,000 annual rabies deaths. The map below produced by the World Health Organization (WHO) shows the global distribution of rabies infection risk for humans: 


The transmission of rabies by bite from sylvan hosts to domestic livestock is another important route of transmission that can result in secondary transmission to human hosts. In addition, airborne transmission is a possible, but rare, route of infection that can occur if the saliva of an infected host becomes aerosolized and is subsequently inhaled by a susceptible host. Such cases have been documented among individuals exploring caves that harbor bats, or among people with bats in the home who were not bitten. However, airborne transmission of rabies is exceptionally rare, at least among documented cases, so it is difficult to know exactly whether or not transmission to humans with no history of a bat bite acquired an aerosolized infection or acquired the infection through the typical biting route, but from a bite that was imperceptible as a bite. Indeed, it is not uncommon to experience a bite from some bat species and be unaware of the incident, especially if the bite was acquired during sleep and is not in a conspicuous position on the body.


Control and Prevention. Control of animal vectors is the primary strategy for the prevention of rabies in humans. This strategy typically targets dogs, as these are the most important animal vector for transmission to humans, and involves two intervention components. The first is the management of stray dog populations to reduce numbers, which may entail culling. The management of stray dog populations is critical because 1) it reduces the reservoir population and the potential effective contacts between stray dogs and humans, and 2) smaller, managed populations of dogs can be more easily administered the second intervention component. The second component consists of canine vaccination. Rabies can be controlled in the canine population if 70% of dogs are vaccinated using inactivated virus vaccine. Immunity lasts for approximately 3 years in the animals.


As mentioned above, in the developed world and in the United States in particular, almost all rabies infections are due to contact with wild animals. Therefore, the best prevention strategy for rabies in these areas is to avoid contact with wild animals. This is a good general practice for many reasons, but it also serves to remove the potential for rabies transmission between infected animals and humans. And we should remember that contact with wildlife is much more likely in an urban landscape than a sylvan landscape for most people. For example, there is a large raccoon population in Manhattan in the heart of New York City and many of these animals have tested positive for rabies. One should be especially wary of any animal that is exhibiting unusual, erratic, or aggressive behavior. If any contact with such an animal does occur, seek medical consultation.

Photo by umbrooklynborn.blogspot.com

60 comments:

  1. Ah, good old rabies. I got the rabies vaccine after being bitten by a dog back home in Mexico. It was when the injections went into the belly button. Fun times. Thanks for this. It's very informative.

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    1. BJ! I was in the basement of my church for a gathering following vacation Bible School. On the floor there looked to appear a banana peel. I reached down to pick it up, and unfortunately, it was not. It was a bat, and it napped me in the index and middle finger. It was caught, and taken to the vet, to have tested. It came back positive for rabies. I had to have injections around the wound site, which were painful, but the remaining series were thru the center of my navel! Having a twisted outie, and the long needle seemed to hit every nerve ending along the way, the vaccine stung, however it was what needed to be done, as I am alive today. When I heard that the rabies shots were done thru the center of the navel, I didn't believe it, only until I had to go thru it myself

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  2. Hi Ren,
    Oh, no! Yeah, I remember the days of abdominal injection for the rabies vaccine. Tough times. :) At least you are vaccinated though, which is quite valuable especially if you travel back and forth much.
    Thanks for reading the blog, glad you found it helpful!
    Cheers,
    Mike

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  3. I really enjoyed reading this article. Growing up in Grenada, you're always told to not interact with any dog you're unfamiliar with (usually stray dogs) because they "might have rabies" but it's usually said as a joke. It was cool to actually read the facts. I also never knew rabies was such a serious infection, again because of how jovial everyone is about it back home. Now I'm really curious to know how much of a problem rabies actually is in Grenada. Personally I've never heard of anyone becoming infected but I'm sure it happens. The Veterinary School at St. George's University has a rabies and stray dogs program. I know they test and adopt stray dogs but I'm not sure if they vaccinate them as well... very expensive, no?

    On another note, this is the first time I'm learning about vaccination after becoming infected. Oh if that was the case for all infectious diseases. Also, why exactly can't someone receive passive immunity (RIG) if they were already vaccinated? Is it because it wouldn't be effective?

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    1. I feel the same way about stray dogs in Queens. I was always afraid of stray dogs and there were a lot of them in my neighborhood growing up. I also knew that if a raccoon or a possum was out during the day that they probably had Rabies.

      I heard about post-exposure prophylaxis for Rabies recently while interning at the DOH. I didn't realize that Rabies could be such a serious disease either.

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    2. Rabies vaccine is inactivated vaccine. Pre-exposure prophylaxis is usually protective up to 5-10 yrs and requires only booster dose on infected dog bite. Immunoglobulins in vaccinated individuals don’t offer anything additional.
      For Post exposure prophylaxis or infected dog bite in unvaccinated individual, it has to be done starting day 0 or day of the bite. Immunoglobulins control the spread of virus and in the meantime vaccination supposedly mounts immunity in the individual. All this is feasible only early in the course of disease.
      After neurologic symptoms of disease set in, nothing works and mortality is 100%.

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    3. Kizzi mentioned post-exposure prophylaxis and noted that we haven't previously learned about vaccination post-infection. I looked into this question and two infections treated similarly: tetanus and HIV. Tetanus is sometimes treated with 2-3 injections of the tetanus vaccine, and HIV is treated with AZT or other antiretroviral drugs within 72 hours of exposure.

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  4. This is a very interesting article and a very interesting disease to discuss. Prior to reading the post I always assumed the majority of rabies infections came from dogs, even in the US. It was interesting to read that the almost all the rabies infections in the US are from raccoons, skunks and bats. I also found it shocking that India made up approximately 20,000 of the roughly 55,000 annual rabies deaths. Although shocking I can imagine that this is due in part because of the expense of PEP (the vaccine given to those who have been bit) and because it is often not available to these endemic areas. I am curious in knowing if the control and prevention efforts are taking place in these endemic areas or the more developed areas in the world. The efforts seem to be targeted toward the endemic areas because it has a focus on managing the stray dog population and canine vaccination but I wonder if these efforts are expensive and not widely practiced because of the cost. It seem imperative that these prevention and control efforts are implemented in India and other endemic areas.

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    1. In response to Janay, I too found the article very informative, and was shocked that the majority of the rabies infections in America come from other animals besides dogs, mainly raccoons. The article touched on a critical point that NYC has a very large raccoon population and most of which are infected with the rabies virus.
      Interestingly enough the majority of annual rabies infections stem from India, about 40% thus the interventions efforts need to be better, or control of the dog population needs to be better enforced. Since PEP clinical treatment is very expensive and not often not an option in areas with high endemicity, maybe better animal control is the answer.

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  5. As I mentioned two weeks ago in my "Anthrax" post, India has a high number of stray animals that are allowed to roam free in the streets as well as in people's homes. Animal control or shelters are almost non existent in rural parts of India. Packs of wild dogs that are mostly rabies infected are extremely prevalent and attack at any time of day. As a precaution, we are told not to venture outside after dusk because dogs infected with rabies have a tendency to hide in bushes or ditches and attack people as they walk by. Even after receiving a rabies bite, most people wait up to 5 hours before going to a hospital for treatment. Most suffer neurological problems as a result.

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    1. Hi Lincy!
      may be you or Dr.Walsh can answer this question, on average when persons in India become infected with rabies, for those who have suffered neurological problems how long on average the reported incubation period for them? Also, why do they wait so long to seek medical attention!? 5 hours is a long time to wait after such an occurrence. Are they well aware of the virus and what it can do? Hows the public health arena and dissemination of information in regards to Rabies?

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  6. One of the most interesting facts that I learned from this is that rabies can be transmuted from not just dogs but also from cats, domestic livestock, and bats. In the United States, most rabies cases are from wild animals such as raccoons, skunks, and bats.

    Another form of transmission I was surprised by was the airborne transmission. Airborne transmission of rabies is transmitted by the saliva of the infected host becomes aerosolized and then inhaled by the susceptible host.

    In manhattan, there is a large raccoon population that has been shown to be positive for rabies. It is important that the population is aware of which animals can be carries of rabies. I never knew that rabies can be transmitted from other wild animals.

    The best preventative measure is to stay away from wild animals.

    How can preventative programs educate the population about other animals besides dogs that transmit rabies?

    I also found it interesting that even after exposure to a rabies bite, that vaccinated can be administered after the bite.

    Information such as this is very important and its nice to know especially if you have traveled.

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    1. Good Question regarding preventative programs. I think the wildlife conservation society (WCS) can play a big part in this. In this age of technology, most people turn to the internet for information. Maintaining up to date information on their website would be beneficial. This would also apply to local parks. For people who live in the city there is minimal contact with wild animals and most of the domesticated animals (dogs) are already vaccinated. New York City should also disseminate information to the public. I think that especially when it comes to the warmer seasons, where people go camping, hiking and hunting, it would be extremely beneficial for these agencies to have TV and Radio ads regarding rabies and other deadly diseases, and also directing people to specific website or phone numbers if they still have questions or need additional information.

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    2. Nicole MastrogiovanniJune 20, 2014 at 3:14 PM

      Difaa, after reading this I also learned the same fact that not only dogs are capable of the rabies virus but also cats and domestic animals such as livestock as well. I completely agree that it is necessary to promote awareness of the other various animals that can have rabies since most of the public is aware of dogs and raccoons but not so much the other types of animals. I think this is especially important for children to be educated on the topic of which animals may have rabies since they are often curious and may want to pet the animals not knowing that those types of animals could be sick and infected with rabies. Therefore, I believe school would be the best option for education of children and teenagers on the topic of rabies and expanding their knowledge on which animals are capable of carrying it and to be on the look out for any of these domesticated animals that look ill and to stay away and call animal control for assistance versus trying to help the animal themselves.

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    3. Harry,
      My concern with camping, hiking, and hunting is that some individuals get adventurous and curious about wild animals. And some may not go to informative websites to acquire more information before doing such activities.

      The best method is exactly what you mentioned. TV and radio ads may be more informative to the population. Some would rather have that information given to them rather then for them to acquire about this information therefore this may be the best method.

      I find it interesting how for specific disorders, diseases, and viruses, it is important to pick the most effective social media method to inform the population.

      Thank you for your thoughtful post.

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    4. With various social media outlets, health departments and various public health programs can now provide information on pre and post-prophylaxis treatment for rabies. Just yesterday, the NYC DOHMH twitted that #Rabies vaccine will be distributed in parts of Brooklyn and Queens to help prevent rabies among raccoons.

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    5. Regarding your comment, Difaa, on transmission of rabies via bats, it's important to recognize that it is both aeresolized rabies virus as well as an unnoticed bite that could be the source of exposure. I can never forget the story of a coworkers daughter that was sleeping in a dorm room that overlooks a park in NYC; it was also inhabited by a few bats that had gone unnoticed for a week or so. Upon discovering them, the advice from the ID docs was that she should receive the post-exposure prophylaxis as there was a chance of having been bitten while they were sleeping. Creepy!
      Again, being aware of this is critical to prevent such a devastating disease. I am not sure if it is common knowledge, and I agree that access to the internet allows everyone access to information that would previously have been unavailable to the general public.

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  7. Nicole,
    That is a great idea. Educating children is a great method. Especially since children share knowledgeable information they learn from school with their parents. This helps educate children and their parents.

    Children are more daring in regards to approaching animals and may not understand the danger they may present. Therefore targeting children is a great idea.

    I personally see children as a “risk factor” since they love to touch everything and do not have proper hygiene practices. Therefore this age group population is a great group to educate.


    Thank you for your great idea.

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  8. While avoiding contact with infected animals is an admirable method of prevention, unfortunately it is not feasible for everybody. Much of the southeastern US is woodland, increasing the rate of contact between sylvan mammals and humans. Other people at increased risk are farmers, national forest and parks services workers, hunters, and tourists who enjoy backpacking through forests here and abroad (especially to areas where rabies is endemic) looking for mystery, adventure, and peace. I did some googling and found that there is also a pre-exposure vaccine available for those at higher risks. Its cost is much less than the cost of the post-exposure vaccine and RIG, about $200-$350 per shot as opposed to $7000+ apparently (http://www.rabiesvaccinecost.com). While I understand why there might be economic reasons against pre-exposure vaccinating in South Asia and sub-Saharan Africa, shouldn’t it be easier for the US? After all the focus on prevention codified in the ACA, I’m certain that a selective vaccination program targeting high risk individuals could be useful. The UN could also partake in international efforts to decrease the disease burden. However, when I googled rabies vaccine prices for dogs, it seems that the cheaper option ($57 per shot at petco) would be the one espoused in the article, a vaccination program targeting stray dogs in countries where such packs roam. It's not as much of a problem in the US but could be in countries such as India.

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  9. Alexandr PinkhasovJuly 23, 2014 at 8:14 PM

    There are two experiences in my life that have taught me of the potential debilitating and deadly outcomes that follow rabies infection. The article underlined that rabies infections, and stray animals are more common in developing counties. My first experience, a few summers ago I would constantly hear something rummaging through the garbage at nights. Knowing that it’s probably a raccoon or cat, I called a rodent-control company to take care of the problem. The professional set a trap and within about a week we caught the rascal (turned out to be a raccoon) that was keeping me up at night. The professional who picked up the cage actually informed me that a large proportion of these animals have rabies, and that it was good that I try to take care of the rodent myself. The second experience is based on a story my parents told me when they visited Costa Rica. In Costa Rica they noticed a large number of stray dogs. A young girl, who was staying in the same resort as my parents, was bit by a small puppy she was petting. According to my father, who is a physician, the girl’s family didn’t take the bite seriously because the size of the dog. My father insisted that the family should seek medical attention. Some time later, when my parents returned home, my father received an email from the girl’s parents thanking him for his advice because they ended up receiving the vaccine and then learned of the severe consequences that could have followed if they didn’t.
    These two scenarios underline a very important concern, and that is that people don’t understand the parameters and severity of the disease. I’ve heard multiple people say “oh, if that animal was infected you would know because if would be acting crazy and have white foam around its mouth”. While these characteristics may be true, they don’t always have to be present in an infected animal. Secondly, people need to understand that a wild animal regardless of its size and age can have the disease. These misconceptions may cause people to not receive medical attention. I believe that as aspiring public health professionals, our focus should be on informing people of the consequences of not seeking medical attention. This Infectious Landscape article is a good venue of information, and does a good job at presenting the information in terms a layman would understand.

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  10. Alexandr PinkhasovJuly 23, 2014 at 8:14 PM

    There are two experiences in my life that have taught me of the potential debilitating and deadly outcomes that follow rabies infection. The article underlined that rabies infections, and stray animals are more common in developing counties. My first experience, a few summers ago I would constantly hear something rummaging through the garbage at nights. Knowing that it’s probably a raccoon or cat, I called a rodent-control company to take care of the problem. The professional set a trap and within about a week we caught the rascal (turned out to be a raccoon) that was keeping me up at night. The professional who picked up the cage actually informed me that a large proportion of these animals have rabies, and that it was good that I try to take care of the rodent myself. The second experience is based on a story my parents told me when they visited Costa Rica. In Costa Rica they noticed a large number of stray dogs. A young girl, who was staying in the same resort as my parents, was bit by a small puppy she was petting. According to my father, who is a physician, the girl’s family didn’t take the bite seriously because the size of the dog. My father insisted that the family should seek medical attention. Some time later, when my parents returned home, my father received an email from the girl’s parents thanking him for his advice because they ended up receiving the vaccine and then learned of the severe consequences that could have followed if they didn’t.
    These two scenarios underline a very important concern, and that is that people don’t understand the parameters and severity of the disease. I’ve heard multiple people say “oh, if that animal was infected you would know because if would be acting crazy and have white foam around its mouth”. While these characteristics may be true, they don’t always have to be present in an infected animal. Secondly, people need to understand that a wild animal regardless of its size and age can have the disease. These misconceptions may cause people to not receive medical attention. I believe that as aspiring public health professionals, our focus should be on informing people of the consequences of not seeking medical attention. This Infectious Landscape article is a good venue of information, and does a good job at presenting the information in terms a layman would understand.

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    1. Alexandr, I found this article along with your post to be very informative. An important point you make that I find to be very true is that most people don’t understand the severity of the disease. I must admit I was one of these people before reading this post. I had always assumed that I would know if an animal had rabies because they would present with white foam around the mouth. Clearly this is true, but not always the case as in every animal affected with rabies. I often travel to Italy, where my parents were born. My parents are from southern Italy and there is a huge population of stray dogs there, similar to what you mentioned about Costa Rica. I would often see a cute stray dog and have no reservations about going up and petting it, but after reading this post I will not continue to do so. Alexandr, I too believe there are many misconceptions about this disease and people need to be properly educated in order to avoid occurrence of this disease. In my future travels, I plan on warning people about the consequences of interacting with stray animals.

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    2. Thank you for sharing your experiences Alexandr, they really highlight how dangerous misconceptions of this disease can be. Growing up, whenever the topic of "rabies" would come up, it was always associated with angry, wild, or belligerent behavior. However, as this article underlines, rabies is much more common that we think. While vaccination of animals is a good public health strategy, I think more needs to be done on the community education side in both developed and developing countries. For example, I had an idea that the raccoons that roamed around Queens Village were rabid, but I didn't know that "wild" behavior was not a required sign of infection. Furthermore, in developing countries where contact with stray animals is more commonplace, community education should be done, starting from elementary school levels, so that a simple an action as petting a stray animal won't lead to serious illness or death.

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    3. Thank you for sharing these two experiences Alexandr, you brought up some interesting points. Growing up in the suburbs of Ohio we are taught to steer clear from raccoons, skunks and possums because they probably have rabies. These critters would scavenge around the neighborhood at night and commonly come onto porches. It did not occur to me until now that our pet cats (unlike NYC apartment pet cats) are indoor/outdoor and also roam around exploring at various times of day and night which put them at risk of coming in contact with wild animals and getting into brawls. We could have been welcoming rabies into our homes via our cute pets. I am glad you brought up the perception of what an infected animal would look like. If you are familiar with the old movie “Cujo” then I believe that would be the portrait of what many people could associate an infected animal with. I agree that we should inform people of the seriousness of seeking medical attention. I also believe we should educate people of the cycle of a rabies infection, what the common and not so common host could be, what cues to be aware of in an infected creature or ourselves. Someone had mentioned in an earlier post about educating young ones in schools as kids are curious likely to approach animals, I think that is a good start.

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  11. Throughout my studies, I found Rabies to be one of the most unique infections within the world of virology. One of the more interesting points regarding Rabies is the virus’ ability to promote its own transmission. Most of the time, Rabies is transmitted via infected saliva penetrating protected barriers through an animal bite. The virus spreads from the bite to the peripheral nerves, ultimately affecting the CNS. Individuals affected by Rabies will present with a clenched jaw, and will have the tendency to want to bite others.

    Individuals will also present with an inability/difficulty to swallow. Because of this, the affected individual will be unable to swallow any fluids including water. The individual will present as “water hungry” due to the dysphagia, rather than a true hydrophobia. This water hunger also contributes to the affected individuals’ feeling of necessity to bite others.

    It was interesting to learn the incubation periods can vary between other mammals, as well as the routes of transmission such as the secondary route through domestic livestock as well as transmission through aerosolized droplets.

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  12. Alexandr, I found this article along with your post to be very informative. An important point you make that I find to be very true is that most people don’t understand the severity of the disease. I must admit I was one of these people before reading this post. I had always assumed that I would know if an animal had rabies because they would present with white foam around the mouth. Clearly this is true, but not always the case as in every animal affected with rabies. I often travel to Italy, where my parents were born. My parents are from the south of Italy and there is a huge population of stray dogs there, similar to what you mentioned about Costa Rica. I would often see a cute stray dog and have no reservations about going up and petting it, but after reading this post I will not continue to do so. Alexandr, I too believe there are many misconceptions about this disease and people need to be properly educated in order to avoid occurrence of this disease in humans. In my future travels, I plan on warning people about the consequences of interacting with stray animals.

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  13. As mentioned above, the rabies virus is enveloped; this plays a major role in both its infectivity and pathogenicity. The envelope is actually taken from the cell membrane of a previous host. Because the envelope is familiar to the host, the virus can enter the cell without activating the host's humoral immunity. Rabies is an enveloped virus so it must remain wet; this may explain why the virus is shed in saliva and transmitted via biting. Even the symptoms of rabies are amazingly self-serving to the virus; when rabies enters the body and is left untreated, it eventually gains access to the central nervous system and produces symptoms such as increased salivation and aggression.

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    1. As I read the information on rabies, I too considered some of the characteristics you mentioned. From my notes in class, I was able to make the connection between rabies being an enveloped virus and its association with a fluid like saliva. The virus' persistence to survive surrounds this need to be wet and is reflected in the host's symptoms. It seems also that the host's body is consumed with the desire of the virus to survive as displayed by "increased saliva." I can see why many writers' imaginations lead them to portray infected characters as zombies being controlled/ possessed by a virus.

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  14. I did not know much about rabies, and the fact that the rabies virus can infect cats and many other mammals surprised me. The blog post mentioned that regions with large population of stray dogs tend to have more rabies cases in human, and I am just wondering why regions with large population of stray cats does not. I believe contact between human and stray cats should not be uncommon, so would it be the case that cats are less likely to acquire rabies infection? I thought of this question because there are many stray cats near my house, and sometimes I feed them with food. However, after reading this blog post, I realized that maybe I should avoid this kind of unnecessary contact. Another thing that I found interesting is about the possibility of airborne transmission. I tend to believe that this is not an effective route of transmission for rabies virus because if its major route of transmission is airborne, the burden of disease would be greater. I also feel the need to educate the public about the potential of acquiring rabies from wild animals as a preventive measure in the United States. If I had not read this article, I would have been unaware of the potential danger from contacting with wild animals.

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  15. I remember going back to Bangladesh, my parents homeland and there was a government advisory to avoid contact with wild dogs because of rabies. It's nice to see that so many advancements have been made in terms of vaccinations. Interestingly I live on Long Island and every week when we put the trash out, many raccoons start circling the garbage and it freaks everyone out. A family friend was once bit by a wild dog and he experienced fevers, headaches at the start only for it to later become something far more debilitating. Seeing the progression of the disease firsthand was overwhelming as there aren't many treatment centers available in 3rd world countries.

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    1. Hi Sayed,
      I can completely relate to your accounts from Bangladesh as I go back every few years. Although there arent as many stray dogs in urban cities, they are definitely plentiful in rural villages, such as the one my grandparents live in. Everytime we would begin eating, a pack of dogs would show up waiting for us to toss them some scraps (the dining room was essentially outside).
      Here in the United States, we often dont realize the severity of acquiring the rabies virus, especially because of how available vaccines are here. As the article mentioned, if left untreated, an individual infected with rabies will surely die. It is a sad reality that Post Exposure Prophylaxis are scarce or unavailable in regions such as South Asia and Africa, where rabies is endemic. This is a similar situation to regions in Africa where Ebola is endemic, but the means to serologically identify the virus/disease are not available.
      I wonder if passive immunity measures are cheaper, and perhaps effective without PEP. In any case, it is nice to see countries such as Bangladesh making efforts to warn the public about a very deadly disease.

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  16. Why is it that dogs are at such high a risk while cats are not? I see stray cats several times a week and they never seem to pose a problem. Are they just not able to transmit the virus, or is it something else?

    Secondly, why not vaccinate against rabies as part of the immunization schedule? ("MMRR"). If it gives lifetime immunity and is compatible with the rest of the vaccines, a vaccination at a young age could prevent many of the infections people experience later in life.

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    1. I thought the same thing, Richard. What is it about the makeup of dogs that allows easier transmission than other animals? Additionally, speaking to your point about not adding it to the immunization schedule- I don't think it would make much sense from an economic perspective since it really is not endemic in the US and in most parts of the world. The mortality rates are still quite low and unlike Measles, mumps or rubella, rabies has never been a dire problem. I believe that there are a number of other vaccines that would take priority.

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    2. I agree with you, David. Granted vaccination might be effective, we have only had 5 cases of animal rabies thus far this year within NYC even given the large raccoon population within the 5 boroughs. Those are only cases in animals, so we would only need to vaccinate if we had a reason to believe that human rabies would become a problem. It seems as though bats are the #1 reservoir in NY state as tested by labs (http://www.wadsworth.org/rabies/monthly/May15nmb.pdf), but not within NYC (http://www.nyc.gov/html/doh/downloads/pdf/cd/animal-rabies-2015.pdf).

      I wonder why the two maps are not consistent with the data presented...is the state not obligated to report on NYC? Are they independent bodies?

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    3. I would postulate that the reason stray dogs are said to be of the highest concern is because dogs are more of an aggressive animals than cats. A stray dog would more likely interact closely (perhaps even aggressively) with a passing human, say if it was hungry, than a cat would.
      As far as making it part of the mandated vaccination schedule I agree with David that it would not be economical. Additionally, I believe that heard immunity is practically impossible to achieve in the case of rabies and that is something we try to achieve with vaccinations.

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  17. Rabies is a problem in Egypt, and stray dogs are the main way the virus transmits.
    I see in the article that India consists of almost half of the deaths yearly in the
    whole world. And since there is prophylaxis vaccine and treatment post exposure to
    infection, and also there are a lot of methods to control stray dogs as the main
    culprit to infection in India, I wonder why a country like India for example did not
    take serious measure to control it. Is it because the vaccine and immunoglobuins are
    controlled by some pharmaceutical patents and cost a lot or there are other
    barriers? And how to overcome these barriers?

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  18. Hello,
    I am writing to request permission to use a copy of the rabies virus graphics on your website for a presentation I am giving on the rabies virus in my microbiology class at Anoka Ramsey Community College. This presentation is required for my microbiology class and is for educational purposes only. Thank you for your consideration.
    Sincerely,
    Larissa Yehle

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  19. Being from Pennsylvania, I have only ever heard about rabies on the news. There are many wild animals out and about, especially bats and raccoons. I have never heard of any stray dogs, but there is a somewhat large stray cat issue in some parts of my town. However, the only stories I have ever heard of was when animals were found to be infected, not humans. Throughout reading this article, I was intrigued by the statistic that approximately 55,000 annual human deaths were caused by rabies. I thought this statistic would be higher considering the assumably rare public health education and vaccines for rabies in the developing world. Because of the sometimes long asymptomatic period of the virus, if an individual is bitten by an animal that they did not know was infected with rabies, they may be less likely to seek medical treatment. However, insufficient surveillance can contribute to this reported low mortality rate. Another piece of information that I learned from this article was the long period in which an animal can be infected but have no symptoms. I always thought that if an animal had the rabies virus, they would immediately start showing symptoms within hours. I guess the movie industry doesn't really know their facts about rabies.

    I really enjoyed reading this rabies article and thankfully I have never had a personal experience involving rabies. However, being a person who loves animals and probably wouldn't think twice about going up to a wild one, I should probably be more cautious!

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    1. Similar to Stacy I love animals and am always ready to make a new Fury friend. Recently I witnessed a rabid skunk in front of Westchester Medical Center after picking up my boyfriend from a late shift at work. We decided it was infected by rabies after noticing its aggressive behavior; boldly walking in plain sight very close to the sidewalk. So Stacy you and I both should probably be more cautious.

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  20. After reading Stacy's comment, I was intrigued and did more reading on Rabies and realized the severity of the issue; especially when looking at current epidemiology. One thing I'd like to hear more about is how often cats are infected with Rabies. In my opinion stray cats are much more temperamental than stray dogs so I'd be interested to hear about prevention efforts for cats as well. I found this great article about rabies surveillance in raccoon in Maryland from Jan 1, 1983 to Sept 30, 1992 where they found 129 confirmed cases of rabies in cats and only 12 cases in dogs (Fogelman, 1993). Another article showed infection in cats was four times that of dogs (Gerhold, 2013). If this trend has remained consistent over the years, I'm very curious to see where prevention is headed. Although TNVR (Trap- Neuter- Vaccinate- Return) Programs are useful, will they really be able to manage the many cat colonies that exist currently in the US (often unreported).

    Gerhold R, Jessup D. Zoonotic diseases associated with free-roaming cats. Zoonoses And Public Health [serial online]. May 2013;60(3):189-195.

    Fogelman V, Fischman H, Horman J, Grigor J. Epidemiologic and clinical characteristics of rabies in cats. Journal Of The American Veterinary Medical Association [serial online]. June 1, 1993;202(11):1829-1833.

    -Brooke Wyatt

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    1. I had never heard of TNR before this blog post. I was somewhat skeptical about it being more effective than simply killing off feral animals. It's interesting though, apparently euthanasia programs actually result in clearing the ecological niche that the feral cat population is inhabiting, and allow for a new population to move in and to explode in size in the community. It winds up being more costly than TNR, which is focused on reproductions. By re-releasing the cats into the wild, they continue to compete for resources in the same habitats, but do not reproduce (or exhibit undesirable reproductive behavior), and thereby more effectively control the feral cat population in communities, apparently. They also apparently are less likely to get diseases, but I couldn't find whether or not that applied to rabies, would be interesting to find out.

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  21. Growing up in a developing country, as it pertains to pets, means that animals live outside and are often more vulnerable to infections. Domestic animals did not get vaccines or experience many of the other protective practices to which many American pet owners typically commit. As a result, we were told that if we were bitten by dog we should head to the hospital immediately and sure enough, we would get a shot. I didn't quite understand why such precautions were taken until I read the information above. I am thankful I never had to deal with the consequences of being bitten by a dog and it believe me it had nothing to do with understanding the dangers of the virus- I was deathly afraid of dogs and equally afraid of needles.
    I have not had too many encounters with raccoons since I moved to Brooklyn, but I often hear people who live in the suburbs complain about them. In fact, I have heard those complaints on the news a few times. I seldom heard complaints about possible rabies exposure, however. Residents often gripe about how they make a mess rummaging through their garbage. I can imagine that that must be quite annoying for them, but it seems the issue of their geographic susceptibility to rabies should be of greater concern.

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    1. I understand your fear of getting bitten by any wild animal. But sometimes you have to understand that we live in the world that is not possible to prevent a lot of things from ever happening to us. The only option you have right now is to avoid getting out during the night while wild animals usually get out of their hiding places and look for their food and are more active. Also you have to stay from the abandoned places where all homeless animals sleep and live. Plus it is not possible to prevent wild animals from entering our private areas because we live in an open area where anything can get to us no matter what we do or try to do to prevent it from biting us. There are always other animals that might gain their entry into our private property only if one of the animal species are controlled by the environmental protective agency.

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  22. I wonder if it might not be so much about the biology of dogs but maybe their social "pack" nature that makes them more susceptible to infecting each other? I know that sometimes dogs play fight, so maybe they can't distinguish playful behavior and aggression, or even overly friendly behavior that might be a result of the rabies virus in infected dogs.

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    1. S.Wallace-I think a majority of rabies comes from dogs because of the potential contact rate with humans (excluding more affluent countries such as the United States). In this article it notes that rabies in dogs is particularly found in South and Southeast Asia and Africa. Dogs are typically strays and aren’t considered “pets” and are not treated the way pets are treated in the U.S. for example. I don’t think it’s the makeup of a dog that make them more susceptible to infection since there are a number of others including cats, domestic livestock, and bats that are important sources of rabies infection to humans. I think the fact that dogs are strays in these countries, free roaming, and like any animal (or human being for that matter) whose life is not of good quality, they will be more susceptible to infection.

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  23. Rabies is always on our minds in the ER when seeing children with dog bites, which unfortunately, is very common. This article was able to put this issue into perspective for me. There are plenty of racoons running around that could be a reservoir in our NY communities! First, it's critical to know that canine vaccines are only effective for three years; not sure if dog owners are aware of this and maintain their pets vaccination status, something that I will now inquire about. I had heard about post-exposure prophylaxis for students exposed to bats in dorm-rooms in NYC and thought it far fetched but now appreciate that, while rare, it is possible to have aeresolized infected saliva. In NY, post exposure cards are sent to the DOH when there is a dog bite for the purpose of tracking outbreaks of rabies. This practice came to mind when we were discussing "Passive Reporting" because it is one of the few practices in the ER setting in which we are actively reporting a potential exposure to the DOH. While the prevalence of rabies may be low in the US it is critical to know about it's presenting symptoms- which are vague and nonspecific at first, with a potential for a long latency to pathogenesis- in our global community with international travel it is important to have this disease in mind so that proper treatment can be initiated. While it's never pleasant to treat a child or adult with the post-exposure protocol, clearly the sequelae of not treating is far worse. As with many other diseases, it is unfortunate that where prevalence of this disease is highest, there is very limited availability of vaccine. Prevention of this horrific disease if transmitted with it's high fatality rates is clearly a concern in certain regions, such as India and South Asia, in which more could be done to prevent the 55,000 deaths reported per year. Thankfully, I have never personally seen a rabies infected human, but clearly more resources need to be available for those with a known exposure in highly endemic regions to prevent rabies disease and death.

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  24. Rabies: the infamous term but when compared to other infectious diseases, the common public is mostly unaware of the true nature of this disease because of its rarity. Similar to general understanding, I have heard of the disease with the common association of dog bites; however, this post provided a great overview of the type of disease, transmission, symptoms, prevention, and treatment methods. As one of the very few infections where effective immunization can be administered after the exposure, this presents great opportunities for effective intervention methods. Although rabies is noted as uncommon, it is interesting to note that this disease has been documented up to 4,000 years ago (that’s a really long time!). In 2015, the New York Times published an article that identified a recent study on rabies, which is now believed to kill 59,000 people a year, or about 160 a day. Learning these statistics seems to show that rabies is definitely a disease that should not go overlooked despite the low prevalence in the US. When I went to visit my family this past summer in Haiti, stray dogs were as common as pigeons in New York City! With the high number of stray animals that were in close encounters with the general population, it provided insight as to why Haiti previously had high incidence rates of rabies when compared to other Caribbean countries. Thankfully with improved control efforts and national vaccination of dogs the number of cases have decreased. With cholera still being a main concern in Haiti, many people did not mention the high risk of rabies.
    Despite the lack of attention I believe that rabies has familiarity with today's society because it was used as inspiration for the zombie genre of television and film. I have watched countless zombie movies such as Dawn of the Dead, 28 Days Later, and as a Walking Dead fan, I am susceptible to associate the transmission methods and some of the symptoms (i.e. fever, muscle spasms, rage, violence) to what is portrayed in entertainment.

    After reading this post, I think I will remove off my bucket list doing another excursion such as exploring a bat cave while traveling...

    Ref:
    http://www.nytimes.com/2015/04/21/health/rabies-deaths-higher-than-previously-thought.html?_r=0
    http://crudem.org/rabies-in-haiti/

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  25. https://www.health.ny.gov/diseases/communicable/zoonoses/rabies/

    Above is a link to how to capture a bat in case it bit you or your pet to test it for rabies. I don't know how rabies treatment availability is in NYC but it fluctuates according to the CDC site.
    Coming from a country with the endemic problem of stray dogs and constant worry of getting rabies, immunization availability was a constant concern especially with the old abdominal shots for 23 days...

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    1. Thanks for posting that link. It was a great resource to find out more information, especially more local information. I didn't know that they used the animal's brain tissue to test it for rabies. I'm sure if NYC has known cases of rabies then it is accessible. I wonder how RPEP is similar to PEP because PEP is very available and used for stuff like needle pricks at hospitals or labs and as HIV medication. This post got me googling places to get vaccines and I came across this booklet (http://www.nyc.gov/html/doh/downloads/pdf/chi/chi29-suppl1.pdf) and it seems like most of the raccoons are located in staten island.

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  26. Very interesting article about a disease that I think more people should know about. At least in terms of the animals that can transmit the disease...I think most people are still under the impression that rabies is transmitted only through stray dogs, because of media and culture. Compared to other countries, there are fewer stray dogs in the U.S.. However, there are plenty of other transmission routes that are actually pretty common, such as bats (in basements or attics), raccoons, and skunks. Since we went over vaccines in class this week, I wonder what is in the rabies vaccine, and how it is made...

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  27. It is informative and interesting to know that rabies is an infection for which immunization can be administered after the exposure due to the duration it takes virus particles to reach the CNS and begin pathogenesis. Discussed in the entry is the importance to administer post exposure prophylaxis soon after the exposure because the incubation period can be a few days. The duration of the incubation period is determined by the number of virons that enters the infected person and the introduction site. I learned that bites on the hands, face, neck, and head have shorter distance for virions to travel before reaching the CNS. As mentioned in other post, it is unfortunate that PEP is expensive and scarce in areas of the world in which rabies is endemic; this makes it difficult to prevent infection.

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    1. After reading your comment, I decided to read more about post-exposure prophylaxis and how it depends on the type of contact with the confirmed or suspect rabid animal. According to the WHO guidelines, these types of contact include: touching or feeding of animals, licks on intact skin, nibbling of uncovered skin, minor scratches, single or multiple transdermal bites or scratches and contamination of mucous membrane with saliva, among others. Given the multiple types of contact that can result in exposure to rabies, it is important for people to have some knowledge of the cause and effects of rabies, especially if they have contact with animals on a daily basis. As mentioned in the post, rabies can be controlled in the canine population if 70% of dogs are vaccinated using inactivated virus vaccine, which if most people aided in this, it could definitely be possible. Sadly this is not the case, especially in countries or areas at high risk of rabies (i.e. large population of free stray dogs). However, campaigns such as the World Rabies Day promoted by the American Veterinary Medical Foundation can go a long way when creating awareness of the importance of understanding that rabies is a public health issue that can be prevented.

      Works Cited: http://www.who.int/ith/vaccines/rabies/en/

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  28. I did not know that the name "rabies" comes from the Latin word for madness. I also hadn't known that if no vaccine is administered, rabies almost always results in death. Furthermore, I was surprised to read that Manhattan has a large raccoon population and that many have tested positive for rabies.

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    1. Manhattan definitely suffers from a raccoon problem. Walk anywhere along Central Park after sundown, and you will definitely run into some. I've seen many, and I had to sneakily run by so as not get away without drawing attention. When I was in undergrad, there was a rabies infected one on campus, and a student was bit by it. In the small microcosm of the school, it was easy to get animal prevention on campus to get rid of the one rabid raccoon. However, in a large city with a large raccoon population, I can imagine that it would be a lot more difficult to find and capture the rabid animal.

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  29. The thought that rabies could be transmitted in the air is terrifying, no matter how exceedingly rare it might be. It is no surprise however that NYC raccoons have rabies because you have to be mad to live in this city! The wild raccoon population in New York is large all over the five boroughs especially in areas where there are parks that provide cover, shelter and other wild animals to eat. The problems is, is where there are large parks, there are usually a lot of people to come into contact with as well. This magnifies the possibility of an encounter with a rabid animal. Additionally, since rabid racoons are not on a top list of threats for most New Yorkers, a lack of awareness might lead to complacency in dealing with them. Racoons are known for going through trash for food and living in basements and garages. When a human is near, they become very confrontational and will attack. I have seen one attempt to bite through a steel trap. More awareness must be given to New Yorkers about rabid raccoons on two fronts. First, the physical bite from a raccoon is sufficient to cause significant injury especially to small children. Compound that with the resulting disease burden and you have insult to the injury. Rabies is not an isolated disease relegated to the developing world or rural areas.

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  30. he thought that rabies could be transmitted in the air is terrifying, no matter how exceedingly rare it might be. It is no surprise however that NYC raccoons have rabies because you have to be mad to live in this city! The wild raccoon population in New York is large all over the five boroughs especially in areas where there are parks that provide cover, shelter and other wild animals to eat. The problems is, is where there are large parks, there are usually a lot of people to come into contact with as well. This magnifies the possibility of an encounter with a rabid animal. Additionally, since rabid racoons are not on a top list of threats for most New Yorkers, a lack of awareness might lead to complacency in dealing with them. Racoons are known for going through trash for food and living in basements and garages. When a human is near, they become very confrontational and will attack. I have seen one attempt to bite through a steel trap. More awareness must be given to New Yorkers about rabid raccoons on two fronts. First, the physical bite from a raccoon is sufficient to cause significant injury especially to small children. Compound that with the resulting disease burden and you have insult to the injury. Rabies is not an isolated disease relegated to the developing world or rural areas.

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  31. This was really informative and interesting! I didn't realize that many people still die from rabies.... also scary to know that animals with rabies are living in NYC. Awhile back I read somewhere that scientists are actually using this virus to help fight against HIV infection. I'm not sure if they made any progress in developing actual medication. It was interesting to read that they use PEP to treat rabies, since it is also used as HIV medication.

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  32. I found it interesting that even though the rabies virus is an enveloped virus -- which tend to be disrupted by drying and must remain wet -- could be passed via inhaled, dried saliva particles. I think this fact reiterates how dangerous the disease is, especially in the developing world (where resources can be limited for treating patients once they are infected with the virus).

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  33. Rabies seems difficult to deal with from both potential prevention/mitigation angles. On the vector side, it seems unlikely that we will be able to cull or vaccinate the urban wildlife population, much less the peri-urban or sylvan one. Rangers have been trying to hunt down the raccoons of central park for decades with basically no success, and they continue to bite people (as the article link with really strange photos below attests).

    On the vaccination side, I've been unable to get a clear answer on exactly why the cost of PEP is so high (around $3,000 for the series, according to the CDC). It must partially be because of the combination of the multiple shots necessary with the relatively infrequency of the need for them. Since the CDC does estimate the cost of rabies infections in the United States alone at at least $245 million per year, it would seem potentially cost effective to figure out some better production/distribution method for both the pre and post exposure vaccinations. I eargerly await the advent of the 3D medication printer.


    http://www.nydailynews.com/new-york/brooklyn-singer-attacked-central-park-raccoons-article-1.1415408
    http://www.cdc.gov/rabies/location/usa/cost.html

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