One of the longest rivals of mankind itself, the deadly illness rabies still poses a threat in the modern day. Known to humans for over 4,000 years, little progress has occurred over the centuries. Besides the remarkable invention of the post-exposure vaccination (PREP), which was created in the 19th century, rabies had otherwise been at a stalemate with humanity until recently.
The problem with post-exposure vaccination is the time constraint; one must receive the vaccine within 48 hours, or else it proves ineffective. However, oftentimes, people either cannot access resources in the given time frame or they aren’t aware they’ve been infected until symptoms occur. The species to transmit rabies most frequently in the United States are bats, and unfortunately, most aren’t aware they’ve been bitten. Bats tend to have bites that are only a few inches in size. In other countries (specifically third world countries), stray dogs tend to transmit rabies the most. In most of these countries, there aren’t adequate resources and most people cannot receive PREP. Worldwide, there’s over 60,000 deaths from rabies but only 2-3 happen in the United States. Once symptoms appear, rabies is almost 100% fatal with only one case documented where a person was able to fight off rabies while within a coma.
Rabies itself is a rather simple illness to understand. In order to contract rabies, the virus RABV has to be transmitted through direct contact (broken skin, eyes), and it’s oftentimes transmitted through saliva. After infection, the virus will move slowly, creeping up towards the central nervous system damaging nerves along the way. There are four stages of rabies: incubation, prodromal phase, acute neurological phase and finally, coma. Incubation is the time period before the virus makes it to the central nervous system. There are no symptoms present during this phase, and if caught early enough, can be prevented by the pre-exposure vaccination. The prodromal phase happens next, and at this point, RABV has traveled through nerve cells and is entering the brain and spinal cord. The immune system will begin to react, and flu-like symptoms (fever, etc) will begin to occur. This phase lasts about 2-10 days, and by this point, it’s too late for pre-exposure vaccination to be effective. Then, the acute neurological phase occurs. This is when extensive damage to the brain and spinal cord happens. There are 2 types of acute neurological phases for rabies: paralysis and furious. ⅔ people will have ‘furious’ rabies, where they are aggressive, oftentimes have seizures and are delirious. It lasts only a few days to a week. The others have paralysis, where they are unusually weak and will end up paralyzed, however this can last up to a month. The final stage is coma, when the body eventually collapses from weakness. This is the final stage of the infection, and death is the end result.
However, recently scientists have begun looking into cures and have identified a possible successful treatment: utilizing monoclonal human antibodies (mAbs). Antibodies recognize and counteract specific antigens (or proteins) that are on an illness. The clinical trials have currently been focused on rats, and other rodents. The monoclonal human antibodies are an antibody created in the lab, mixing a human antibody with a rat antibody, and creating a special mixture. In this case, the mAbs used were RVC20/RVC50. In the trials, the rats are injected with a strain of RABV. Usually, rats die around 10-13 days after exposure to the rabies virus, however scientists found that when utilizing mAbs, the rats have been able to be cleared of rabies even after the symptomatic stage. When given to rats at 6 days after exposure (when symptoms have already begun), the rats have been found to be completely eradicated of rabies with a 100% success rate. The later it’s injected, the lower the success rate becomes. However for the most part, even at 8 days after exposure, most cases are successful with mAbs. Many rats have been able to live over 100 days after exposure!
Scientists have found that the ways to inject the cure should be mixed, and should not just be one method. Intracerebroventricular infusion is a method that bypasses the blood brain barrier (a barrier that blood forms that keeps ‘bad’ things out of the brain) and allows for high drug concentrations to enter central brain compartments. Intramuscular administration is a technique used to deliver medication deep into the muscles. When both of these methods of injection were used, scientists found that it was much more effective than just using one method of injecting alone. The scientists would do one intramuscular administration, and continuous intracerebroventricular infusion, which proved extremely effective. Higher doses are not necessarily more effective, as long as enough is used, the results will be the same.
The rats were found to have normal weight, normal motor function and normal cognitive function through many different tests. Some of them included the open field test, where mice would be placed in a field and their behavior would be observed, or the rotarod test, which measures motor function. Although there still may be quite a bit of time for the treatment to be perfected and widespread, the discovery of the cure is already quite an achievement. In fact, the cure is already being put into use in places such as India right now. As scientists work to make the cure more cost efficient so that it’s able to be offered to all, humanity should be ecstatic and thankful to these scientists for their contribution to the betterment of humanity.
Works cited:
de Melo, G. D., Sonthonnax, F., Lepousez, G., Jouvion, G., Minola, A., Zatta, F., Larrous, F., Kergoat, L., Mazo, C., Moigneu, C., Aiello, R., Salomoni, A., Brisebard, E., De Benedictis, P., Corti, D., & Bourhy, H. (2020). A combination of two human monoclonal antibodies cures symptomatic rabies. EMBO Molecular Medicine, 12(11), e12628. https://doi.org/10.15252/emmm.202012628