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Throughout the weekly Padlet assignments, I was able to learn about rabies -- not only from a biological and medical standpoint, but also from a societal one. While I had previous knowledge about the high virulence of the disease, I was very unaware of the global distribution of rabies infections and deaths. The most revealing aspect I learned about rabies through my research was how it disproportionately affects countries with lower economic power, particularly Eastern Asian and African countries. While there are very successful rabies mitigation and management techniques (e.g. wildlife and dog vaccination programs and post-exposure vaccination) like those used here in the US, these techniques aren't adopted by many countries due to social and economic limitations.

Another surprising fact about rabies that I came across in my research was that there are a handful of people who have been able to survive rabies infections and go on to lead relatively normal lives. I always operated under the assumption that a confirmed rabies case was a death sentence. And while the survival rate of rabies is still incredibly low, I was surprised to learn that it was not a 0% survival rate. However, the medical advancements made to enable surviving rabies are particularly intensive, including putting the patient in a medically-induced coma.

Throughout my research, I was able to learn some interesting features of rabies evolution that could have fit in well with this Padlet assignment. For example, rabies has shown evolution towards increased virulence following host-shifts when the origin and host species are more distantly related (explained a bit more in my Week 4 - Virulence post). Similar trends may be present in other zoonotic diseases. I think further exploring the different evolutionary constraints on the pathogenic organisms would be very interesting and topical for this class!

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Animal control interacting with a fox suspected of having rabies. 

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Rabies has a devastating physical impact on hosts, including animal and human populations. However, the effect of rabies reaches beyond just physical sickness and into larger societal and economic impacts. Rabies disproportionately affects less wealthy countries and marginalized communities, including in Eastern Asia and Africa. Though the spread of rabies is easily maintained through education, wildlife and canine vaccination programs, and access to post-exposure vaccines for people, many countries do not have such programs in place due to economic limitations.

The limited rabies containment in certain countries has larger social and economic effects, including on tourism. Past travel advisory warnings against travel to countries with high rabies occurrence have negatively impacted tourism. This could lead to increased social stigma against already vulnerable countries that have high rabies occurrence. The lack of rabies interventions is further complicated by educational disparities by socioeconomic income, with lower socioeconomic classes receiving less quality education and therefore being more resistant to paying for rabies vaccination programs.

While some societies, such as here in the United States, have been economically privileged enough to change behaviors (increasing education, vaccination programs and requirements, etc.) to minimize rabies effects, other societies are not as privileged. While we as a society continue to learn more about the physical effects of rabies and strive for more medical advancements, we are still severely lacking in addressing the global and economic disparities that contribute to rabies proliferation. Going forward, more attention should be shed on groups such as the United Against Rabies organization that aims to eliminate rabies infections ad deaths for all populations, regardless of country of origin and outside social factors.

https://www.peertechzpublications.com/articles/APM-2-107.php#:~:text=It%20cause%20many%20economic%20loses,totaling%20%245.5%20billion%20per%20year.
https://www.who.int/news/item/28-09-2019-rabies-elimination-an-opportunity-for-social-justice
https://www.frontiersin.org/articles/10.3389/fvets.2021.699352/full

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A map showing the prevalence of dog-mediated rabies by country. 

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The leadership and governmental responses to rabies varies widely by country. For example, the United States government has implemented initiatives to virtually eradicate rabies in humans. These initiatives include animal control, vaccination programs for dogs, public outreach, and wide availability of post-exposure vaccines for people.

However, the leadership in other countries such as India has much room for improvement in response to rabies. It's been proposed that the lack of containment of rabies in these countries may be due to a disconnect between policy and research. While there are complex economic and social factors at play, the leadership of these countries could benefit from implementing nationwide programs such as vaccination for canines, wildlife culling, increased access to post-exposure prophylaxis, and public outreach.

https://www.cdc.gov/rabies/location/usa/surveillance/human_rabies.html#:~:text=The%20number%20of%20human%20rabies,availability%20of%20modern%20rabies%20biologics.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339964/#:~:text=Key%20interventions%20for%20rabies%20control,population%20and%20other%20animal%20reservoirs.

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Jeanna Giese, the first person to survive rabies infection without vaccination, gets her college degree 6 years after her battle with rabies. 

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It used to be thought by the healthcare community that contraction of rabies was a death sentence. The mortality rate of rabies is virtually 100% when post-exposure vaccines are not admitted. However, medical advances have been able to combat rabies as a death sentence.

The largest medical advancement against rabies was the invention of the rabies vaccine by Louis Pasteur in 1885. Post-exposure vaccination has been able to essentially eliminate rabies cases in countries with high healthcare levels such as the United States and in Western Europe.

While vaccinations are highly effective in preventing rabies infection in exposed individuals, medical advancements in treating rabies after the onset of symptoms is lagging much further behind. As of 2017, there have only been 29 reported cases of people surviving rabies without a prompt post-exposure vaccination. These survivals have been enabled by healthcare standards such as the Milwaukee method, which involved placing the patient in a chemically-induced coma and administering antivirals, ketamine, and amantadine. However, even with these methods, the probability of surviving a rabies infection is slim-to-none for most patients.

In order to lessen the human impact of rabies, it is essential to provide more equitable healthcare to affected countries regardless of their economic status. This includes greater access to post-exposure vaccination and prevention strategies such as vaccinating stray dogs. It is also essential to continue medical research into how the rabies virus affects the human body and therapies that are able to treat it where vaccination was not possible.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266186/#:~:text=As%20we%20know%20rabies%20has,bite%20of%20a%20rabid%20animal.

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Rabies patient exhibiting neurological symptoms as the virus impacts the nervous system. 

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Virulence is defined as the amount of harm done to a host by a pathogen post-infection. Rabies is extremely virulent, with virtually 100 % of infected individuals dying within several days of the onset of symptoms. Rabies symptoms including blockage of airways, hydrophobia, seizures, and paralysis are almost always fatal.

It remains unknown if this virulence has changed significantly over evolutionary time. However, Mollentze et al. (2020) did show increased rabies virulence following cross-species transmission events when the species were more distantly related. This relationship between species relatedness and rabies virulence could explain constraints on cross-species transmission events.

Sources:
https://www.pnas.org/doi/10.1073/pnas.2006778117
https://www.who.int/news-room/fact-sheets/detail/rabies#:~:text=Rabies%20is%20a%20vaccine%2Dpreventable%2C%20zoonotic%2C%20viral%20disease%20affecting,rabies%20is%20virtually%20100%25%20fatal.

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Global map by country from the World Health Organization showing the A. number of rabies deaths due to canine bites and B. per-capita death rates.

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While rabies was originally thought to have originated from Old-World bats in Africa, recent analyses point to a potential Palearctic origin. The most recent common ancestor of lyssaviruses that cause rabies occurred approximately 7,080 to 11,631 years ago. Since then, rabies (Rabies lyssavirus) has spread all across the globe except Antarctica and Australia (though Australia is home to its own type of lyssavirus with similar effects).

Each year, rabies kills almost 60,000 people. These deaths occur disproportionately in African and Asian countries, as shown in the above map. This is due to global differences in animal control and vaccination rates for canines and access to quality healthcare.

https://apps.who.int/rabies/epidemiology/en/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620125/#:~:text=Current%20theories%20agree%20that%20the,the%2016%20known%20viral%20species.
https://pubmed.ncbi.nlm.nih.gov/28036390/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC115054/#:~:text=Using%20dated%20isolates%2C%20the%20average,888%20to%201%2C459%20years%20ago.

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A depiction of a rapid dog from the Middle Ages in Europe

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The presence of rabies, and its danger to human life, has been known and recorded throughout ancient times. The earliest known report of rabies comes from ancient Babylonia, approximately 2300BC, describing a fine that a dog owner needed to pay if their pet transmitted rabies to another person.

While the nature of the disease to transmit between animals and humans (i.e. a zoonotic disease) was acknowledged in these ancient records, it was first demonstrated experimentally by George Zinke in 1804. He was able to transmit rabies between a rapid dog to a different dog, a hen, and a rabbit.

Louis Pasteur was able to, for the first time, prevent death by rabies in 1885, when he used a series of inoculations containing samples of a spinal cord of a rabies-infected rabbit on a young boy who had been bitten by a rapid dog. At the time, microscope technology was not advanced enough to visualize rabies and see that it is causes by a virus. The virus was seen and identified as rabies for the first time in 1962 using new electron microscopy technology.

https://jnnp.bmj.com/content/73/1/82
https://www.tuckahoevet.com/post/a-history-of-rabies
https://www.pasteur.fr/en/institut-pasteur/history/troisieme-epoque-1877-1887

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Rabies virus in the bloodstream, artist depiction

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Rabies is a viral disease that first causes fever and headaches in people, but quickly progresses to life-threatening symptoms such as cerebral dysfunction, disorientation, delirium, and brain death. Rabies is fatal in 99% of cases, and death typically occurs within 2-10 days after first symptoms present. Rabies is caused by the virus Rabies lyssavirus, and it is transmitted to humans via contact with infected animals.

Rabies lyssavirus is in the Mononegavirales order and Rhabdoviridae family.