Introduction
Throughout history, everyone feared it. It used to kill millions of people and even today, 55,000 people die from the disease every year. The symptoms seem unreal: fear and inability to drink water (hydrophobia), fear of air (aerophobia) and paralysis. It makes the victim seem lifeless and deranged. No wonder then, it was used as inspiration for zombies in fiction.
Rabies is a viral disease that infects mammals. First recorded in Mesopotamia, in 2000 BC and it has been terrorising humanity ever since. It is caused by the simple lyssavirus, named after the Greek goddess of madness. 99% of rabies infections in humans come from an infected dog bite, though a small minority can come from other mammals such as bats. It is a neurological disease and primarily attacks the central nervous system, which consists of our brain and spinal cord. Once symptoms show, rabies is fatal, with only a handful of people surviving it after experiencing symptoms.
So how does rabies infect our body? And, if we cannot cure it, is there a way we can prevent it?
Rabies and the Immune System
As mentioned before, humans get rabies from an infected animal bite (mostly dogs). Lyssavirus, from the saliva, is injected deep into our tissue and into our nerves. This is exactly where it wants to be. Lyssa uses the microtubules in nerves as a “highway” to travel to the brain and will easily pass through synapses. It does this by latching onto a specific protein and using that as the “car” to travel up the nerve highway. This is unique to rabies and makes it one of the most ingenious viruses. The normal behaviour of a virus is that it will enter a cell and convert it into a “virus factory” that produces lots of new viruses and will kill the cell. As it does this, the cell, recognising what is happening, releases special proteins called interferons that tell the immune system to attack the virus. This acts as the first line of defence against viruses. This does not happen in the case of Rabies. It can bypass this defence as when it enters a nerve cell, it does not kill it.
As rabies passes through lots of nerve cells to reach the brain, no symptoms are felt. This is known as the incubation period which usually lasts 1-3 months, although it can vary significantly. How long the incubation period is depends on how close the bite is to the brain and how many viruses enter the bite.
During the incubation period, a person can be given post-exposure prophylaxis (or PEP) which consists of the rabies vaccine and rabies immunoglobulin. The rabies vaccine saves 250,000 people every year. However, if no PEP is given rabies will reach the brain and wreak havoc.
When the rabies virus enters the brain, the first symptoms start to show. Only now does the immune system recognise the threat of the virus and will start to deploy the cytotoxic t-cells. These will kill cells infected with viruses but must be activated via antigens. However, the immune system encounters a very peculiar problem with the lyssavirus. White blood cells are not careful in what they do and often inflict damage on civilian cells as a side effect of trying to kill the pathogen. This is something that simply cannot happen in the brain as dead nerve cells can lead to an array of conditions and death. Furthermore, some white blood cells can cause inflammation in the brain which is also dangerous due to the skull. This means white blood cells are generally restricted from passing into the brain and will only enter the brain if they are invited by nerve cells. The rabies virus uses this feature to its advantage. It causes infected nerve cells to kill any cytotoxic T-cells in the brain, essentially “muting” the immune response.
Prognosis
Now, the rabies virus is free to multiply and spread into more nerve cells in the brain. This eventually leads to encephalitis; swelling of the brain. This is what causes paralysis as well as other symptoms such as aggression and hallucination. Another horrific symptom experienced is hydrophobia. Rabies affects the area of the brain responsible for involuntary reflexes, such as swallowing. If a person tries to drink water, their throat will fully shut so they cannot swallow. This inability to swallow also leads to another frightening symptom, frothing of the mouth. After wreaking havoc in the brain, the virus leaves and moves to the rest of the body, infecting every organ. It also enters the salivary glands causing them to create saliva filled with lots of rabies viruses. Soon, every organ starts to fail as the encephalitis of the brain causes pressure to build up on the brain stem which is responsible for breathing and circulation. Eventually, the patient will fall into a coma and sadly pass away.
Rabies as a Neglected Tropical Disease
Unfortunately, rabies disproportionately affects those in less economically developed countries (LEDCs). This is because many people in LEDCs live hundreds of kilometres away from hospitals, have poor infrastructure and sanitation or are simply uneducated on the severe effects of rabies. This is why rabies is considered a neglected tropical disease (NTD) as it primarily affects those in LEDCs and there is not much awareness or investment in rabies compared to other diseases such as HIV, tuberculosis, or malaria where measures exist.
There are measures to help those suffering from rabies in LEDCs. Many villages now have community outreach programs that educate people about rabies and how to spot and act around a rabid dog. They also encourage children to tell their parents if they are bitten as over 40% of all rabies cases come from children under 15. Also, pets are being vaccinated to prevent them from passing the disease onto humans as well.
So, will there be a day when we finally defeat rabies as a species? Will there be a day when thousands of people are liberated from the virus? Well, with all the current efforts being undertaken, the WHO hopes to eradicate dog-mediated rabies by 2030 and as an overwhelming majority of rabies cases come from dogs, it is safe to say we will confine rabies to the history books.