• Bella Rawson

Rabies: A Forgotten Disease

Words in bold can be found in a Glossary at the bottom of this article.


Just under two years ago, I was sat facing a blank screen in a very cold classroom, the threat of deadlines hanging over my head. For one reason or another, I thought it would be a great idea to add EPQ to my ever growing list of things I wanted to accomplish whilst in Sixth Form, and with that came the annoyed emails from the Head of Department asking where the hell my proposed essay title was.


For anyone unsure, an EPQ is equivalent to half an A-Level and consists of a 5,000 word research project into a topic of your choosing. It can also take the form of a more creative way of expression, such as a dance or sculpture, but given the less than impressed comments from art teachers in the past, I wasn't about to take that route.


By the time it came to beginning the course, I was pretty dead set on being a vet. It should've followed naturally that I would explore something that was related. Unfortnately, my brain didn't seem to recognise this rational line of enquiry, and instead thought it'd be a great idea to start research why bananas have the health benefits they do. Seriously - I'm not kidding.


I ended up realising that what I was actually interested in (rather than the eating habits of primates and levels of potassium they should consume) was disease. Specifically, infectious ones, although at that point I was pretty much interested in anything that caused complete shut down of the body.


I started researching what would become an 8,000 word essay on the feasability of eradicating rabies, starting by narrowing down what diseases I was fascinated by and which ones just didn't quite cut it. Of course, the 5,000 words limit never really entered my head at that point, but that's a whole different story for a whole different day.


What I learned during seven months of browsing, reading, and emailing was that there was a disease that killed nearly 60,000 people around the globe, and countless more animals in the process, but was largely ignored by the media. And, when it was covered, tended to be sensationalised like those mildly ridiculous Stephen King books.


Today, I want to break down what rabies actually is, because when I talk to people about it I'm usually met with a 'oh the frothy thing', or the more usual 'that's still a thing?' We are woefully miseducated about a disease that has the potential to be completely eradicated, and unless you are a vet or somebody who's spent their life studying infectious disease, you're probably not too clued up on the subject.


I should probably preface this with the fact that I'm in no way a credible scientist, vet, doctor, or anything that's mildly a professional job. I'm an eighteen year old who got interested by a subject, spent months researching it, and then wrote a report. I'mby no means an expert, and I would never claim to be, but I do know a thing or two about the disease, and I want to help clear up the many misconceptions that I, too, had before I dropped the idea of researching bananas.


In case you're interested in reading more, or simply want to fact check what I'm saying in preparation for a huge rant about my misinformation, I'm leaving my references in a foot note at the bottom of this article, along with a slight prayer that no respected scientist stumbles across this and calls it a complete load of tosh.

Overview


Rabies was first identified as a fatal disease for both humans AND animals in the 16th century, and since then the disease has been symbiotic with death. Cases have a mortality of near 100% once symptoms have appeared [1], and with 59,000 annual deaths, it's the leading cause of death from all known zoonoses [2] - even though it's completely preventable!


We know that the disease can infect and be transmitted by any mammal, although the typical stereotypes tend to portray canids as the main carriers. In truth, in recent years it's the domestic cat that has been most commonly infected! [3]


For the science nerds among us, the virus has a distinctly 'bullet like' shape, and contains a single stranded, negative sense RNA genome. It's permissive temperature ranges between 36 and 37.5 degrees [4] Celcius, and dog bites account for 99% of all cases in humans. [1]


Speaking of which, the first thing people, in my experience, think of when they hear the word 'rabies', is a dog frothing at the mouth, perhaps having seizures or behaving in a way that it is uncharacteristic. But, the thing is, this actually happens in very few cases, and indeed even when it does occur, the image isn't usually as horrific as you might think.


Broadly, rabies has two forms: Furious rabies, which is most common, and paralytic rabies, which occurs in around 20% of cases. [4] The distinction is important, because with paralytic rabies signs it's entirely possible that an infected organism doesn't show any symptoms at all until the very late stages. However, both forms have the same pathogenesis, and broadly encompass similar symptoms.


Symptoms


In general, inflammation of the spinal cord and encephalitis (brain inflammation) are the most common signs of rabies when a post mortem is conducted. The reason that rabies is always fatal once symptoms appear (save for 15 known cases) is that symptoms only appear when the virus has lodged itself in the Central Nervous System, at which point no drug or treatment will be able to attack it without fundamentally damaging your nerves in the process. Once the virus has reached the brain, it can hijack certain cellular functions to send messages to the salivary glands of the mammal, allowing it to reproduce easily in the tissues. This then means that the virus can spread through the saliva, typically through biting, and infect other mammals. [5]


The Centre for Disease Control in the USA produced a lovely document a few years ago outlining the major symptoms of the disease, but copy and pasting it here would land me in a lot of trouble! So, instead I've gone for a pretty boring table that illustrates the surprising similarity in the presentation of the disease in humans vs in dogs!


(as a side note, Wix doesn't offer the ability to insert tables so I had to try and remember year 9 HTML code and did some "furious" (haha!) Googling! Can't figure out how to stop the furious rabies text from splitting though so if anyone's got any bright ideas....)


Anyway, as you can see, the disease presents fairly similarly across both species, but you'll note that 'foaming at the mouth' doesn't make an appearance. Typically, it's categorised under 'hypersalivation', because the foam is over-produced saliva, and it's a point of confusion for people (see: me) when first learning about the disease because it never explains that anywhere!


Pathogenesis


I talked briefly about how the disease spreads through the body, but I wanted to go a little more in depth. Google the term 'pathogenesis of rabies' and you'll probably be greeted with a myriad of complicated diagrams and weird looking cells. It took me forever to figure it out and put it into words that my A-Level Biology head could actually understand, and though I'm guessing most people don't care all that much about how the virus invades cells, an article about rabies and what it is probably wouldn't be complete without at least a mention of it!



Here, I'm going to attempt a nice bullet point list to summarise the key points.


1) the virus is inoculated into the new host via the bite of an already infected animal


2) the virus produces virions (replicates) in the muscle


3) virus invades the Central Nervous System at a neuro-muscular junction


4) it travels through the peripheral nervous system and replicates in the ganglia and motor neurones


5) it travels to the brain and causes inflammation


6) the virus enters the salivary glands and continues to replicate


[6]


The rabies virus really is a beautiful example of adaptive evolution, especially when you consider how it has evolved to enter and replicate within the salivary glands. Over time, it has followed the Darwinian principal of 'survival of the fittest' (even though, technically, a virus isn't alive) and 'learnt' that it is most effectively transmitted through animal bites. Whilst it's a bit weird to say that I love the virus, I think it's pathogenesis and it's evolution is a stunning example of how viruses have fought an age old war and figured out how to come out on top. If you want more information on how viruses hijack cells in general and how the rabies virus would generally replicate, check out the BBC iPlayer documentary 'The Secret Life of the Cell'!


Vaccine

We've talked about symptoms, we've talked about what it does to the body, but I'd like to circle back to the introduction to this short article's introduction, where I mentioned that the disease is entirely preventable.


In 1885, the world reknowned microbiologists Louis Pasteur and Emile Roux developed the first known vaccine for the disease, which when used resulted in the development of rabies virus neutralising antibodies within the body and conferred protection for an unknown period of time.


I'm always astonished when I ask people who they think invented the rabies vaccine - no one I know has ever got it right. And yes, I'm aware that pasteurisation was arguably his biggest discovery, but Louis Pasteur remains one of the greatest scientists of all time, and his general biographies tend to begin with the information that he was the first person to develop vaccines for rabies and anthrax. I feel kind of sorry for him that more people don't know about that incredible achievement. [7]


The fact that a vaccine exists yet worldwide rabies deaths are almost 60,000 is an incredibly sad fact, and speaks to the reason why it is characterised as a neglected disease. Public Health England have described it as having "the highest case fatality rate of any infectious disease in the world" and the World Health Organisation have established a 2030 goal for complete eradication; yet the vaccine is expensive, this is illustrated in the divide between the success of eradication schemes in high and low income countries.


The disease has been eliminated completely from the United Kingdom, and is no longer present in domestic animals in the United States, however these achievements arose from stringent vaccination and neutering of animals, something that isn't within the budget for lower income countries such as Myanmar. If this is something you might be interested in reading more on, my entire EPQ was on this subject, and there's a list of further reading resources at the bottom of this article.


In Summary

I hope this article has been interesting and informative - I certainly enjoyed writing it! I've tried to keep things as simple as possible and as such only a small amount of the information I have gathered over the years is contained in the text. I think if I were to write everything, no one would read it!


Rabies is a fascinating disease that has been neglected for centuries, and in Western culture isn't talked about because it is of little threat to our daily lives. However, cross the globe and visit countries where the disease is endemic, and you'll soon realise just how dangerous it is; many people live in fear of dogs, leading to mass culling that is ultimately ineffective at preventing its spread (this is know as the vacuum principle and is a whole different kettle of fish! I'm in the middle of writing a blog post about it so stay tuned if you're interested!)


In the mean time, Iif you want to read more about rabies and the difficulties we have globally in eliminating it, then I've referenced all the sources I've used for this post below, and hyperlinked them for easy access. Thank you for reading and I hope it's given you something to think about!


Glossary


References



All information correct at the time of writing on 17th May 2020.

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