World Rabies Day 2022: A One Health View

Coordinated by the Global Alliance for Rabies Control, World Rabies Day is the biggest event on the global rabies calendar (1), occurring annually on September 28 – the anniversary of Louis Pasteur’s death – since 2007. The event aims to raise awareness and visibility while advocating for global elimination of rabies. Created as an inclusive initiative, it unites people, organizations, and stakeholders across all sectors. With this concept of togetherness and unity in mind, the theme for this year’s World Rabies Day is “Rabies: One Health, Zero Deaths.”

Why do we need World Rabies Day?
 

Rabies is a feared and neglected ancient infectious disease (2). Caused by pathogens in the family Rhabdoviridae, genus Lyssavirus, and distributed globally, this viral zoonosis causes tens of thousands human fatalities and exposes millions annually. All mammals are believed susceptible, but only certain taxa act as reservoirs. Direct access to, replication within, and passage from the central nervous system all serve as a basic viral strategy for perpetuation.

Using a combination of stealth and subversion, lyssaviruses are quintessential neurotropic agents that cause acute, progressive encephalitis. Rabies virus is diabolical in its pathology, transmission, and perseverance in nature – but no treatment exists, so prevention is key. Fortunately, in the many countries leveraging animal vaccination, pre- and post-exposure human vaccination, and public health measures, there are typically only one or two rabies-related deaths per year (2).

Present-day snapshot
 

Every year, rabies causes approximately 59,000 human deaths worldwide; however, it is difficult to estimate the total global burden of disease for all animal species due insufficient testing or reporting of cases in certain regions. In the most recent US research effort, 54 jurisdictions submitted 87,895 animal samples for rabies testing, of which 97.3 percent returned a conclusive test result (3). Of these conclusive results, 5.2 percent tested positive for rabies, representing a 4.5 percent decrease from 2019. Texas, Pennsylvania, Virginia, New York, North Carolina, New Jersey, Maryland, and California accounted for over 60 percent of all animal rabies cases reported in 2020.

Of the total reported rabid animals, 91.3 percent involved wildlife, with raccoons, bats, skunks, and foxes representing the primary hosts confirmed with rabies. Rabid cats, cattle, and dogs accounted for 95 percent of rabies cases involving domestic animals in 2020. No human cases were reported in 2020, but five human deaths caused by rabies were reported in the US in 2021 (4) – the highest annual case count in the last decade.

Raccoons are the most commonly reported rabid animals in the US (5), followed by skunks and bats, but the prevalent species transmitting rabies can vary from state to state (see Figure 1). For example, in Texas, animals defined as high-risk for rabies transmission are skunks, bats, foxes, coyotes, and raccoons. If rabies infection occurs in a species other than the reservoir species for the variant – for instance, a cat infected with a skunk variant or a skunk infected with a bat variant – it is considered a “spillover event.” In evolutionary terms, bats are recognized as the ultimate reservoir of the lyssaviruses (2), but despite more than 17 conspecific members, rabies virus appears to be the only lyssavirus with clear reservoir representation among multiple orders of mammals.

Protecting yourself from rabies
 

When people visualize a rabid animal, most picture foaming-at-the-mouth images from the movie Cujo – but the most typical signs of rabies are unexplained paralysis and a change in behavior (5). For example, a friendly cat might become abnormally aggressive, a normally playful puppy might suddenly become shy and withdrawn, or a nocturnal animal might be out during the day.

Simple steps to follow to avoid exposure to rabies

• Don’t interact with strange animals.
• Never handle downed bats; as a rule of thumb, bats should be avoided altogether.
• Report bites to the proper officials, such the local rabies control authority, animal control officer, game warden, or local health department employee.
• For children, a teacher or parent is a good reporting resource.
• Though many wildlife species appear cute and cuddly, never attempt to feed or interact with them.
• Avoid handling sick, injured, or dead animals.
• If you have children or are an educator, teach them how to correctly behave around animals to avoid being bitten (not pulling animals’ ears or tails, teasing them, bothering them while they sleep, running past them, moving toward unfamiliar animals, or trying to play with a mother’s offspring).

What if I get bitten by an animal?
 

Thankfully, post-exposure prophylaxis (PEP) isn’t nearly as bad as it used to be – and vaccines are widely available. If a bite does occur, wash the wound immediately with soap and water and apply iodine if available and you are not allergic; promptly seek medical attention and guidance from a physician; and take rabies PEP if prescribed by a physician (6). The single most important thing you can do is not ignore an animal bite– remember, PEP no longer involves the scary treatment of vaccinations in the stomach! Now, it consists of a weight-based dose of human rabies immunoglobulin and a series of four vaccinations (five for immunocompromised individuals) in the deltoid area over a one-month period. Sometimes, because animal oral areas also contain a diverse number of bacteria, you may also be given a tetanus vaccination and antibiotics as a precaution.

If you happen to work in a high-risk occupation (like I did at the Texas Department of State Health Services Bureau of Laboratory and Zoonosis Control Division, where I tested animal specimens for rabies), you can get pre-exposure rabies vaccinations (three doses given in the deltoid area over the course of three to four weeks). You are only eligible if you work in a high-risk occupation, such as rabies diagnostic lab worker, spelunker/caver, veterinarian, veterinary technician or assistant, veterinary student, animal control officer, shelter employee, or wildlife worker. However, if you are traveling to a foreign area with enzootic rabies, you should consult with a physician about getting pre-exposure vaccinations (7).

An important, lifesaving reminder is that bat bites are almost impossible to see or identify – you may not even know you have been bitten by a bat due to their tiny, sharp teeth (see Figure 2). As a rule, do not handle bats; avoid them at all costs.

Is there a laboratory test to detect rabies virus?
 

In most instances, rabies is fatal once symptoms are present and specimens are tested postmortem – but there are some methods for antemortem testing in humans (9). In either case, a proper specimen (e.g., brain tissue, cerebrospinal fluid, or another specific specimen) is set up for a fluorescent antibody test (FAb), in which specific rabies antibodies attach to corresponding antigens in the tissue. If the specimen is truly positive, it results in a fluorescent green microscopic view of rabies antigens (see Figure 3). The FAb test is still considered the gold standard, though there are more current, molecular-based rabies tests and traditional classic tests that also do the trick.

What’s next?
 

Made evident by the emergence of SARS-CoV-2 and recent outbreaks of monkeypox arriving on new shores outside Africa, viral pathogens continue to pose substantial – yet somewhat predictable – concerns to human health and welfare worldwide. In contrast to more recently appreciated threats, rabies is one of the oldest described infectious diseases and likely has an even more ancient pedigree that predates most historical accounts (2).

Beyond prevention in humans and domestic animals, rabies is the only zoonosis in which wildlife vaccination – using attenuated or recombinant biologics – has risen from an academic concept to a safe, effective, and economical long-term practice on a broad scale. For example, after the multi-year use of oral rabies vaccine (ORV) distributed in edible baits, western Europe and large parts of southern Ontario successfully eradicated fox rabies (10). There are now numerous success stories regarding ORV use in many countries, including the US. I have had the honor and privilege of working with the inaugural ORV team in Texas from 1993, during which we have eliminated canine rabies from the state (11) – just imagine what could be accomplished globally using this technology aimed at the large-scale vaccination of wildlife and subsequent reduction of mortality from this ancient, diabolical virus (12).

Over the past 10 years, substantial progress has been made on a global scale regarding pathogen discovery, diagnostics, prophylaxis, and the engagement of professionals in academia, government, industry, and international nongovernmental organizations. Further success requires maintaining this cross-disciplinary philosophy – promoting collaboration among both medical and non-medical professions within an updated One Health approach and working toward a common goal to better understand, communicate, detect, prevent, control, and eliminate lyssavirus infections within the next decade (13).