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  • P.K. Peterson

Rabies Virus—The Most Frightening Germ of All

“It is sometimes as dangerous to be run into by a microbe as by a trolley car.”

- James J. Walsh, M.D., American physician, author


“We have the vaccines, we know they work—how is it possible that so many people still die from this painful, long-known disease?”

- Prof. Louis Nel, Executive Director of the Global Alliance for Rabies Control


In last week’s Germ Gems post, I wrote about my favorite germ, Lactobacillus. I thought it fitting, therefore, to follow this week with the microbe I consider to be the world’s most frightening germ—rabies virus. What makes this germ so scary is that it is extraordinarily lethal, 99+% of cases are fatal, and it causes a horrific death. Yet there is good news—100% of cases are preventable. In this Germ Gems post, I discuss the epidemiology and clinical features of rabies and I summarize what everyone needs to know to avert dying from this disease.

It’s all about lethality. The World Health Organization (WHO) reports that rabies kills 59,000 people globally per year. One aspect of the mortality due to rabies that sets it apart from most other viral infections is that the age of the victim is of little or no consequence. Whether you are young (40% of people bitten by suspect rabid animals are children under 15 years) or a senior citizen, once you develop symptoms of rabies, it’s too late. Of the hundreds of thousands of patients who have been treated for rabies worldwide, only three convincing cases of rabies survivors have been reported­—making rabies virtually 100% fatal.


The contenders. While not as fatal as rabies, several other viral infections have shockingly high mortality rates, for example, Ebola (50%) and Nipah (40 to 70%), and the coronaviruses MERS (35%) and SARS (15%). The mortality due to many other viral infections is much lower including COVID-19 (3%) and influenza A virus (1918 pandemic flu 2.5%). Of course, when you factor in the denominators of many of these infections, they represent a much bigger Public Health threat than does rabies.


Only one other infectious agent, a prion (a misfolded cell protein) that causes Creutzfeldt Jacob Disease (CJD), exacts a mortality as a high as the rabies virus. While uniformly fatal, CJD is an exceedingly rare brain disease (averaging about one case per million per year).


In the 1980s, an outbreak of a variant form of CJD transmitted by ingestion of contaminated beef (“mad cow disease”) provoked mass panic. Fortunately, that outbreak was relatively short-lived. We are now on the lookout for another prion disease caused by infected deer (see my August 31, 2019 Germ Gems post, “Oh Deer! What Could the Matter Be: Chronic Wasting Disease”). So far there have been no documented transmissions from prion-infected deer to humans.


Epidemiology. Rabies is a zoonotic infection, that is, the virus is transmitted from animals to humans. Globally, bites from infected dogs are the main source of human rabies and are responsible for up to 99% of all rabies transmissions to humans. In addition, bites from infected bats, foxes, skunks, racoons, and cats pose a risk for humans. Interestingly, bites by rodents, such as, mice, rats, hamsters, gerbils, and squirrels are not a problem, and neither are those from lagomorphs—rabbits and hares.

Until 1960, dog bites were also the main source of human rabies in the U.S. Since then, a collaboration between Veterinary Medicine and Public Health to vaccinate all dogs against rabies has dramatically changed the epidemiology in America and many other industrialized countries. Bats have now emerged as the main carrier of rabies in the U.S. According to the Center for Disease Control and Prevention (CDC), after two years of no rabies deaths in 2019 and 2020, in 2021 five deaths were reported in the U.S., all of them related to bites by rabid bats. None of these victims received post-bite treatment.


Rabies is present on all continents, except Antarctica, with over 95% of human deaths occurring in Asia and African countries. Only a small handful of countries are considered rabies free— Australia and the Cayman Islands among them. World travelers, therefore, need to be alert to the risk of rabid animals. As I discuss below, there are effective human vaccines and immunoglobulins for treatment after a bite by an infected animal. Every year, more than 29 million people worldwide receive such post-bite vaccination, thereby preventing hundreds of thousands of rabies deaths annually. Tragically, such post-bite treatment is not available or accessible in many impoverished countries—the places where most rabies deaths continue to occur.


Symptoms. The name rabies is derived from the Latin rabies “rage, madness, fury.” The genus name of the rabies virus, Lyssavirus, comes from the Greek word lyssa “violent.” Rabies virus is one of many RNA viruses that targets the nervous system. As the name suggests, rabies is a violent disease characterized by a frenzied madness.

After an incubation period lasting on average 2-3 months, fever with pain and an unusual tingling sensation at the bite wound site develop. As the virus spreads along nerves to the central nervous system, progressive and fatal inflammation of the brain and spinal cord develops.


There are two clinical forms of rabies: “furious rabies” and “paralytic rabies.” The furious form results in signs of hyperactivity, excitable behavior, hydrophobia (fear of water), and sometimes aerophobia (fear of drafts or of fresh air). Paralytic rabies runs a less dramatic course, but eventually also ends with death. Like a large majority of American physicians, I’ve never cared for a patient with rabies, but for training purposes I’ve viewed videos of patients with both forms of the disease which have left a lasting impression—their deaths were horrifying.


What everyone needs to know about rabies. A clinical tipoff that an animal is rabid is an unprovoked bite. Also, occasionally a rabid bat may transmit the virus in its saliva via an aerosol. Therefore, indoor exposures to bats, even without a witnessed bite, is a matter of concern.


If you, a friend, or a family member is bitten by a bat, or another animal known to transmit rabies, immediately wash and flush the bite wound for a minimum of 15 minutes with soap and water. Next, contact your state’s Department of Health or the CDC’s rabies hotline (manned 24 hours a day) for advice about potential treatment and the corralling of the offending animal for observation or for euthanizing them for examination of the brain for the virus.

Post-exposure prophylaxis (PEP). Rabies is a remarkable example of the benefit of vaccination. We have the father of immunology, the French scientist Louis Pasteur, to thank for the life-saving rabies vaccine. (In July 1885 Pasteur was the first to administer a rabies vaccine that saved the life of Joseph Meister, a nine-year old boy who had been attacked by a rabid dog.)


But, “time is of the essence” if you want to avert dying from rabies. The immediate treatment of a bite victim after rabies exposure with rabies vaccine plus administration of rabies immunoglobulin (a regimen referred to as PEP), prevents viral entry into the central nervous system, thus saving lives. Officials at your state’s Department of Health will coordinate your management with your healthcare provider. They will also work with veterinary medicine colleagues to decide what steps should be taken regarding quarantining of potentially rabid animals.


Eliminating the scourge of rabies. In 1960, the U.S. demonstrated the solution to curbing rabies in dogs through rabies vaccination. The WHO’s “Zero by 30” Global Strategic Plan to Prevent Human Rabies aims at preventing all rabies deaths by 2030 through increased awareness, vaccinating dogs to prevent disease at its source, and life-saving post-bite treatment (PEP) for people. In the U.S., the goal of preventing human rabies deaths is similar—in addition to continuing to promote vaccination of all dogs, the aim is to increase public awareness of the role of bats in virus transmission and to inform the public that a life-saving treatment exists. While rabies is close to 100% fatal, with PEP treatment, death is also 100% preventable.

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

 

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