What is the diagnosis and treatment for Rabies (Rabies virus infection)?

From the Guidelines

Rabies diagnosis is primarily clinical, and treatment involves immediate post-exposure prophylaxis (PEP) with a dose of rabies immune globulin (RIG) and a series of four rabies vaccine doses given on days 0,3,7, and 14 after exposure, as recommended by the Advisory Committee on Immunization Practices (ACIP) 1. The diagnosis of rabies is based on clinical symptoms, and laboratory tests such as direct fluorescent antibody testing, polymerase chain reaction, and serology can confirm the diagnosis. However, treatment should not be delayed pending laboratory confirmation.

Key Considerations

• The most critical factor in preventing rabies is prompt medical intervention after exposure, including wound cleansing and administration of RIG and vaccine.
• The ACIP recommends a 4-dose vaccination regimen for previously unvaccinated individuals, with doses given on days 0,3,7, and 14 after exposure 1.
• For previously vaccinated individuals, only two doses of vaccine (no RIG) are needed on days 0 and 3.
• Early symptoms of rabies include fever, headache, and general weakness, progressing to confusion, anxiety, hallucinations, hydrophobia, and eventually coma and death.

Treatment Regimen

• The treatment regimen for rabies exposure consists of:
  • Immediate wound cleansing
  • Administration of RIG (20 IU/kg body weight) on day 0
  • A series of four rabies vaccine doses given on days 0,3,7, and 14 after exposure
• The vaccine regimen can be adjusted based on the individual's vaccination history and the severity of the exposure.

Prevention

• Prevention is critical in reducing the risk of rabies transmission, and measures include:
  • Avoiding contact with wild animals
  • Vaccinating pets
  • Seeking immediate medical care after potential exposure
• The rabies virus travels through nerve cells to the brain, which explains the neurological symptoms, and the disease's nearly 100% fatality rate once symptoms appear underscores the urgency of preventive treatment after exposure 1.

From the FDA Drug Label

The only documented cases of rabies from human-to-human transmission have occurred in patients who received corneas transplanted from persons who died of rabies undiagnosed at the time of death. Rabies is transmitted only when the virus is introduced into open cuts or wounds in skin or mucous membranes. Two categories of exposure should be considered: Bite: any penetration of the skin by teeth. Bites to the face and hands carry the highest risk, but the site of the bite should not influence the decision to begin treatment. Nonbite: scratches, abrasions, open wounds or mucous membranes contaminated with saliva or any potentially infectious material, such as brain tissue, from a rabid animal constitute nonbite exposures.

Diagnosis of Rabies: The diagnosis of rabies is based on the presence of symptoms such as:

• Bites or nonbite exposures to animals suspected of having rabies
• Unprovoked attacks by animals
• Presence of rabies in the region
• Laboratory diagnostic testing (e.g., direct fluorescent antibody test)

Treatment of Rabies: The treatment of rabies includes:

• Local treatment of wounds: Immediate and thorough washing of all bite wounds and scratches with soap and water
• Active immunization: Administration of rabies vaccine as soon as possible after exposure
• Passive immunization: Administration of Rabies Immune Globulin (Human) in conjunction with rabies vaccine
• Post-exposure prophylaxis: Initiation of treatment as soon as possible after exposure, considering factors such as animal species, circumstances of the bite, and vaccination status of the animal 2, 3, 2

From the Research

Diagnosis of Rabies

• The diagnosis of rabies is primarily based on clinical symptoms and laboratory tests 4
• Clinical symptoms include hydrophobia, agitation, and paralysis, which appear after an incubation period ranging from a few days to several months or even years 4

Treatment of Rabies

• Post-exposure prophylaxis (PEP) is the primary treatment for preventing rabies after a potential exposure, which includes wound cleansing, administration of rabies vaccine, and administration of human rabies immune globulin 5, 6, 4
• Pre-exposure prophylaxis involves the administration of the rabies vaccine to individuals at high risk for exposure to rabies viruses, such as laboratory workers, veterinarians, and animal control workers 4
• The treatment of clinical rabies consists of medical support in an intensive care unit, using a multifaceted approach that includes supportive care, heavy sedation, analgesics, anticonvulsants, and antivirals 4

Post-Exposure Prophylaxis (PEP)

• PEP schedules requiring up to 5 clinic visits over the course of approximately one month have been recommended by the WHO 6
• Abridged schedules with less doses have potential to save costs, increase patient compliance, and thereby improve equitable access to life-saving PEP for at-risk populations 6
• The 1-week, 2-site ID PEP schedule was found to be most advantageous, as it was safe, immunogenic, supported by clinical outcome data and involved the least direct costs compared to other schedules 6

Challenges in Rabies Post-Exposure Prophylaxis

• Deviations from R-PEP guidelines were found in 51% of patients, including incorrect administration of rabies immunoglobulin and incorrect vaccination schemes 7
• There is a high need for education on indication for R-PEP and for implementation of precise R-PEP treatment guidelines in daily clinical practice 7, 8