Earlier this month, the Centers for Disease Control and Prevention (CDC) issued a stark reminder about the dangers of rabies in their Morbidity and Mortality Weekly Report (MMWR). After two consecutive years with no rabies deaths in the United States, there were five deaths in 2021, including a 7-year old child. Four of the recent deaths (three adults and a child) were all attributable to bat exposures. One of the adults submitted the suspect bat for testing and although the bat tested positive for rabies the individual refused vaccination. A second adult was bitten by a bat and received the vaccine regimen, but due to an underlying autoimmune disease the vaccine failed and he succumbed to rabies. The two other bat-exposure victims weren’t aware of the danger that bats can carry rabies and didn’t seek medical treatment or vaccination. The fifth case was due to a dog bite in the Philippines. Why this person did not seek vaccination is unknown, and after returning to the U.S. the victim developed rabies and died.
This recent spate of rabies cases is a grim reminder that this zoonotic disease is still prevalent among some animal species in North America. In addition to bats, common rabies carriers include skunks, raccoons, and foxes. Consequently, any scratch, bite, lick, or direct contact with these animals should be assumed to be potentially dangerous unless the animal is captured and shown to be rabies-free. Other common wild animals such as rodents (squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice) or lagomorphs (rabbits and hares) are not known to carry rabies or to pose any rabies risk to humans. In contrast, domestic pets such as cats and dogs can transmit rabies if they haven’t been properly vaccinated. Therefore, bites or scratches by felines or canines should also be considered a risk unless the animal’s vaccine status is known.
The rabies virus (Rabies lyssavirus) has an RNA genome and an unusual bullet-shaped structure (Figure 1). The virus is found in the saliva of infected animals and infection is most commonly the result of bites (note that bat bites can be very small and hardly noticeable). Alternatively, infected animals will often have viruses on their claws due to grooming activities that spread their virus-laden saliva. Because of the virus-contaminated claws, even scratches from infected animals can transmit the virus to unsuspecting people. Once in the skin and muscles, the virus replicates and infects the nearby nerve cells. Using the nerves as a conduit, the virus slowly makes its way to the brain, a process that can take weeks, months, and sometimes even years to occur. Upon reaching the brain, the virus replicates rapidly causing extensive damage that results in the first symptoms appearing. The initial symptoms are generally hyperactivity, excitable behavior, mental confusion, and hydrophobia (fear of water), followed by increasing muscle paralysis. Once symptoms appear there is no treatment and death is inevitable. Death usually occurs within 1-2 weeks post symptoms due to respiratory failure resulting from the virus-induced muscle paralysis.
Rabies is a terrible illness, and the only fortunate thing is our ability to prevent disease in persons who have been exposed to the virus. Because of the relatively long incubation period, rabies is amenable to post-exposure vaccination, but vaccination should be done as soon as possible after exposure. For most viruses that cause symptoms within a few days, post-exposure vaccination won’t work as antibodies take a week or more to develop. However, the lag between infection and rabies virus reaching the brain is long enough that antibodies can be elicited by vaccination before the virus reaches its target. These antibodies prevent damage to the brain so that no injury occurs and no symptoms develop.
The rabies virus vaccine is a “killed” or “inactivated” type of vaccine. The vaccine consists of whole rabies viruses that are chemically treated to make them noninfectious. These “dead” viruses are harmless but still retain their shape and immunogenicity which allows them to generate an antibody response when injected into people. Unlike the horror stories of early rabies vaccines (requiring 20 or more abdominal injections), the current vaccine is administered intramuscularly in the arm just like other common vaccines (in the thigh for small children). The recipient is given the first vaccine injection on the day of rabies exposure (day 0) or as soon as possible after the exposure. There are then three subsequent injections on days 3, 7, and 14 (immunocompromised individuals get an additional injection on day 28). Also on day 0, the patient will receive a shot of human rabies immune globulin (HRIG), preferably at the site of the bite or scratch. HRIG is a preparation of antibodies that neutralize the rabies virus as an attempt to stop or curtail virus replication and spread before the vaccine-induced antibodies reach effective levels. Prompt administration of HRIB plus vaccination after a known or suspected exposure is nearly 100% effective at preventing disease and death. So while rabies remains endemic in North America, no one should have to suffer from this horrid disease. Continual education of the public is critical to ensure that everyone understands the rabies risk, knows the likely sources of this disease, and appreciates the need for immediate medical attention after a possible exposure. Let’s hope that 2022 returns to a zero human rabies year.