Rabies Disease, Transmission and Prevention: Just What Do You Know About Rabies?

Sept. 23, 2019

Bats infected with rabies are now the leading cause of rabies deaths among people in the United States, while rabid dogs that American travelers encounter overseas are the second-leading cause of rabies fatalities, the Centers for Disease Control and Prevention (CDC) announced in a June 12, 2019 Vital Signs report. Rabid bats have been responsible for roughly 70% of  rabies deaths in the U.S. since 1960. Despite this, in the age of Ebola outbreaks, resurgences of vaccine-preventable diseases like measles, and raging antimicrobial-resistant microbes, rabies often flies under our microbial radar, despite being a major public health threat.

Rabies is without a doubt one of the most diabolical diseases and anxiety-inducing diagnoses that a physician can encounter. When one suspects rabies virus exposure, it sets off a smart bomb of anxiety in the central nervous system that spreads like wildfire to the brain, much like an actual rabies virus infection. After 25 years of working with this terrifying yet fascinating disease, I recognize well this panicked state in people when faced with the prospect of a rabies exposure or diagnosis.

A Tale of Texas Rabies: Outbreaks and Solutions 

I began working with the rabies virus in 1994 at the Texas State Department of State Health Services (DSHS) Zoonosis Control Division. At that time, Texas was experiencing 2 simultaneous canine rabies epizootics (epidemics in animals). The epizootics were caused by a canine rabies virus variant (genotype) known as Texas Fox – Domestic Dog Coyote. The 2 epizootics began in Texas in 1988, one involving coyotes and dogs in South Texas and the other gray foxes in West-Central Texas. The South Texas epizootic resulted in 2 human deaths and led to several thousand people receiving post-exposure rabies prophylaxis. In 1994, the public health threat created by these 2 expanding epizootics prompted the governor to declare rabies a public health emergency in Texas. 
 
In February 1995, the Texas DSHS initiated the Oral Rabies Vaccination Program (ORVP) as a multiyear program to create zones of vaccinated coyotes (followed in 1996 with gray foxes) along the leading edges of the epizootics to halt the spread of the virus. The ORVP is a cooperative national and international program led by DSHS. The aerial distribution of vaccine occurring each year involves approximately 75 separate flights by King Air aircraft from the Dynamic Aviation Group, Inc. and annually results in a total flight distance equaling approximately 1.5 times around the world. Since 1995, the program has been responsible for the distribution of over 49.75 million individual doses of Raboral V-RG, an oral rabies vaccine, over approximately 696,900 square miles of Texas. The Texas ORVP has achieved a level of success that could not have been anticipated during early development work done in 1993 and 1994. The South Texas and West-Central Texas ORVP zones have combined into a barrier strategy to prevent reintroduction of the virus and continue to protect the public's health. Simply put, we have eliminated canine rabies from Texas since 2005–a remarkable public health feat. My role in the ORVP led to the establishment of a regional reference rabies laboratory for rabies virus typing which continues to this day.
 
Rodney Rohde about to board a Canadian Twin Otter aircraft (left) to distribute doses of the oral rabies vaccine Raboral V-RG (right) over south and west-central Texas.
Source: courtesy Rodney Rohde

My experience has taught me 2 important lessons about rabies, its control and its treatment: 1) Rabies exists among us but its part in the ecosystem is poorly understood and 2) addressing the low level of health literacy about rabies by the public is the best approach to both decreasing rabies prevalance and improving public health measures. Here are answers to some of the most frequently asked rabies virus questions I’ve received from both scientists and nonscientists alike.

How Do Rabid Animals Behave?

Animals may not “act” rabid. When many people visualize a rabid animal, they picture the foaming-at-the-mouth movie images of Cujo. However, the typical signs of rabies are unexplained paralysis and a change in behavior. For instance, a friendly cat may become very aggressive, a normally playful puppy may become shy and withdrawn, and a nocturnal animal may be out during the day. There is a plethora of other clinical signs that a rabid animal may or may not exhibit, such as not eating, eating strange (non-food) objects, pawing at the mouth, appearing to be choking, having difficulty swallowing, chewing at the site of the bite, having seizures, and exhibiting hypersensitivity to touch or sound, to name a few.

How Many Cases of Human Rabies Occur Annually?

Most references cite 60,000 annual cases of rabies in people worldwide. It’s difficult to assess the annual number of human rabies deaths worldwide due to underreporting in developing countries, particularly Asian and African countries; however, it is estimated to be in the tens of thousands. These cases are primarily transmitted by rabid dogs; the CDC states that exposure to rabid dogs is still the cause of over 90 percent of human exposures to rabies and 99 percent of human deaths worldwide. But remember, this is global. In the U.S., bats are now responsible for 7 out of 10 human rabies deaths.
Total human rabies deaths (top) or per-100,000 people (bottom) illustrate the global burden of dog-transmitted human rabies.

How Long is the Rabies Virus Incubation Period?

The rabies incubation period can vary in length. Although the incubation period can range from days to years, the average duration is 3 to 8 weeks. This range is why it is important to promptly receive post exposure prophylaxis (PEP) – but also why a person should still pursue PEP even if time has lapsed since the bite (possibly because they didn’t initially consider the possibility of rabies). If the incubation period in this person’s case is on the protracted end, PEP may still work.

How is Exposure to Rabies Virus Managed?

Post-exposure prophylaxis (PEP) isn’t nearly as bad as it used to be. If a bite of a potentially rabid animal occurs, immediately follow these steps: 
  • Wash the bite wound with soap and water (use iodine if available and you are not allergic). 
  • Promptly seek medical attention and guidance from a physician.
  • Take rabies PEP if prescribed by a physician. 
The physician may also prescribe antibiotics and a tetanus vaccination depending on the nature of the bite and the circumstances of the bitten person. Note that the PEP regimen no longer features the much-feared extensive series of vaccinations in the stomach! Current PEP protocol consists of a dose of human rabies immune globulin and a series of 4 vaccinations (5 vaccinations for immunocompromised individuals) in the deltoid area over a month period.

Is There a Rabies Virus Vaccine?

The rabies vaccine can also be used as pre-exposure prophylaxis for humans. Pre-exposure vaccinations are given primarily to people at increased risk for rabies exposure. Pre-exposure vaccines can also be given to people at lower risk of exposure if they will be in an area where post-exposure prophylaxis is difficult to obtain. Importantly, these vaccinations do not eliminate the need for additional vaccinations after a rabies exposure, but they reduce the amount of treatment needed compared to a person who has not received the pre-exposure vaccinations.
 
The rabies pre-exposure vaccination regimen consists of 3 vaccinations given over 3-4 weeks. Examples of people who should consider getting the pre-exposure vaccinations include rabies research lab workers, rabies biologics production workers, veterinarians and staff, veterinary students, animal control personnel, pest management professionals and wildlife workers. Travelers visiting foreign areas with enzootic rabies where post-exposure prophylaxis may be delayed should also consider getting pre-exposure vaccinations.

How is Rabies Virus Tested in the Laboratory?

Rabies is nearly always fatal, and testing is thus typically performed on postmortem specimens. However, antemortem testing can be performed for humans. In either case, a proper specimen is needed (e.g., brain tissue, cerebrospinal fluid, or other specific specimens). 

The specimen is analyzed with a fluorescent antibody test in which rabies-specific antibodies will attach to rabies antigens in tissue. If the specimen contains rabies virus, the result is a fluorescent green microscopic signal highlighting the presence of rabies antigen. This test is still the gold standard. However, there are more current and specific (molecular-based) rabies tests as well as additional classic tests (e.g., negri body detection, serological, etc.). Rabies testing is typically performed by and/or coordinated through the local or state public health laboratory.
In a rabies test, if the specimen is truly positive, the result is a fluorescent green microscopic view of rabies antigen.
Source: courtesy Rodney Rohde

Shoud I Be Bat Wary?

Bats are a special concern when it comes to rabies. Bat bites are not always visible. Therefore, in situations in which a bat is physically present and there is a possibility of an inapparent exposure, the bat should be captured and submitted to a rabies laboratory for testing. If the bat cannot be captured or rabies cannot be ruled out by laboratory testing, PEP may be recommended for people with a reasonable probability of an exposure, and domestic animals may be recommended to either get booster vaccinations AND confinement or euthanasia. 

Scenarios that may indicate a reasonable probability of exposure to rabies include:
  • A child touches a live or dead bat.
  • An adult touches a bat without seeing the part of the bat’s body that was touched.
  • A bat flies into a person and touches bare skin.
  • A person steps on a bat with bare feet.
  • A person awakens to find a bat in the same room.
  • A bat is found near an infant, toddler or a person who has sensory limitations or is mentally challenged.
  • A person puts their hand in firewood, brush, a crevice or a dark space (e.g., a closet), then sees a bat close to that hand.
Puncture wound of a bite from a silver-haired bat (A, arrow) and skull of silver-haired bat (B).
Source: Reprinted with permission from Elsevier (The Lancet, 2001, Vol 357, pp 1714)

Globally, rabies remains a disease of public health significance. Rabies (or rabies-related viruses) exists in every continent except Antarctica. Australia is free of dog-associated rabies; however, Australian bat lyssavirus (rabies is a lyssavirus) exists. The estimation is that more than 99% of rabies case fatalities occur in developing countries, particularly Africa and Asia, with India accounting for the most reported deaths in Asia. The low number of cases in humans in the United States compared with that in many developing countries can be attributed partially to access to medical care and rabies biologics, which are nearly 100% effective if administered promptly and properly. Annually, an estimated 40,000 people in the United States and 15 million people worldwide receive PEP. It is imperative for all of us who work in professional public health, animal health, and healthcare to continue to raise rabies awareness.
 
Further Reading: You can learn more about rabies at the rabies in the Americas (RITA) conference this October 27 through November 1, 2019 in Kansas City, MO.

The above represent the views of the author and does not necessarily reflect the opinion of the American Society for Microbiology.

Cover image of rabiesvirus credit.

Author: Rodney Rohde

Rodney Rohde
Dr. Rodney Rohde, Ph.D., is the Associate Director of the Translational Health Research Initiative at Texas State University.