Rabies

Rabies, commonly referred to as hydrophobia, is a zoonotic viral disease. Despite the availability of vaccines, rabies remains overwhelmingly fatal once clinical symptoms become apparent. BioVenic has been actively engaged in rabies diagnostic research, prevention, and treatment strategies for the past two decades to tackle this significant challenge.

Fig. 1 Schematic diagram of the structure of rabies virus.¹

Cause and Effect

Rabies is a viral infection that affects the nervous system, caused by the rabies virus which belongs to the genus Lyssavirus in the Rhabdoviridae family. Rabies virus is a neurotropic virus. The virus particles are 160 nm-240 nm long and 70 nm in diameter. They are bullet-shaped, have a double-layered lipid outer membrane, and have glycoprotein protrusions on their surface. The inner part of the outer membrane is the matrix protein, and the center of the virus is the nucleocapsid composed of unsegmented single-stranded negative-sense RNA and five structural proteins.

If left untreated, rabies is almost always fatal. It is a neurological disorder that affects animals, causing coma, respiratory failure, and ultimately death. The time from onset of symptoms to death can vary, but it typically ranges from days to weeks. Apart from the devastating impact on human health, rabies also has economic consequences.

Pathogenesis

Rabies virus specifically binds to acetylcholine receptors and ganglioside receptors at the neuromuscular junction and replicates in muscle cells near the wound. Then it invades the peripheral nervous system through sensory or motor nerve endings. It travels up the nerve axis to the central nervous system and replicates in large quantities in the limbic system of the brain, causing damage to brain tissue and symptoms of uncontrolled behavior.

Susceptible Animals

Almost all mammals are susceptible to rabies virus, but the degree of susceptibility varies.

• Extremely contagious: wolves, foxes, coyotes, jumping rats, cotton rats, jackals.
• Highly infectious: hamsters, skunks, raccoons, domestic cats, rabbits, bats.
• Moderately infectious: dogs, primates.
• Low infectivity: possum.

Transmission

Any mammal can transmit the rabies virus. However, wild animals like bats, raccoons, skunks, and foxes are the most common carriers of the virus. In some regions, particularly in developing countries, domestic dogs are the main source of transmission to humans.

Fig. 2 The role of domestic dogs in the transmission of rabies.²

Rabies in the U.S

Rabies remains a rare but important public health problem in the US. Although canine rabies has been successfully controlled through widespread pet vaccination programs, the wild animal reservoir of the virus still poses a risk.

Signs and Symptoms

Humans and animals infected with rabies typically experience incubation, prodromal, acute excitative, and paralytic/end-stage.

• Incubation: The period before symptoms appear is called incubation and may last from weeks to months. At this time, receiving treatment and injecting rabies vaccine can prevent the onset.
• Prodromal: Prodromal begins when the virus begins to invade the nervous system and usually lasts 2-10 days. Infected animals or humans have tingling wounds and symptoms such as fever, nausea, diarrhea, vomiting, and muscle pain.
• Acute Excitative: A state of hyperexcitability in an infected animal or human. The prominent performance is extreme terror, salivation, fear of water, fear of wind, and severe spasms of throat muscles will occur when encountering sound, light, wind, etc.
• Paralytic/end-stage: Paralysis eventually leads to complete paralysis and subsequent coma. Death usually results from respiratory failure.

Diagnosis of Rabies

BioVenic has made significant advances in diagnostic methods for animal diseases. We provide efficient rabies diagnostics development services to our clients. We use techniques such as immunodiagnostics and molecular diagnostics to help enable early detection of rabies virus in a variety of sample types, including saliva, spinal fluid, brain tissue, etc.

• Direct fluorescent antibody (DFA)
• ELISA
• RT-PCR

Treatment

Once symptoms appear, infected humans and animals die. However, immediate medical attention after exposure can prevent symptoms from developing. Symptoms can be effectively prevented by following several measures.

• Gently but thoroughly clean the wound with soap and water.
• Series of vaccinations.
• Injection of rabies immune globulin into the wound.

Control and Prevention

• Interventions to Prevent Rabies in Humans
  
  • Veterinarians, animal management personnel, hunters, field workers, and personnel who may be exposed to rabies virus should be vaccinated pre-exposure and their antibody titers should be checked regularly.
  • After being bitten by a dog or other animal, promptly vaccinate with rabies immune globulin (RIG).
  • Domestic dogs need vaccinations every year.
  • Control the stray dog population.
• Interventions to Prevent Rabies in Animals
  
  • Unvaccinated dogs/cats bitten by rabid animals should be killed immediately.
  • Regularly vaccinate dogs, cats, and other pets against rabies.
  • Limit your pet's activities and avoid contact with wild animals and bats.

Although rabies is almost under control in developed countries, it nevertheless remains a major global health problem that requires comprehensive prevention, diagnostics, and treatment strategies. BioVenic's expertise and understanding of rabies help provide customers with effective diagnostics development and vaccine development services. If you need our help, please feel free to contact us.

References

1. Schnell, Matthias J, et al. "The cell biology of rabies virus: using stealth to reach the brain." Nature reviews. Microbiology vol. 8,1 (2010): 51-61.
2. Cleaveland, Sarah, et al. "Rabies elimination research: juxtaposing optimism, pragmatism and realism." Proceedings. Biological sciences vol. 284,1869 (2017): 20171880.