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

From the Guidelines

Rabies diagnosis is primarily clinical, based on symptoms such as fever, anxiety, confusion, hypersalivation, and hydrophobia, and treatment involves immediate post-exposure prophylaxis (PEP) with 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 often made based on clinical presentation, and laboratory confirmation is not always necessary. However, laboratory tests such as the direct fluorescent antibody test (DFA) can be used to confirm the diagnosis.

Key Considerations

• Prompt wound care, including thorough washing with soap and water, is essential in preventing rabies after exposure.
• Post-exposure prophylaxis (PEP) should be initiated as soon as possible after exposure, with RIG administered at the wound site and a series of four rabies vaccine doses given on days 0,3,7, and 14 after exposure.
• For previously vaccinated individuals, only two vaccine doses (days 0 and 3) are needed without RIG, as they have already developed immunity to the virus.
• Vaccination is highly effective when administered promptly before symptoms develop, and it is crucial to seek medical attention immediately after potential exposure. Some key points to consider in the management of rabies exposure include:
• The importance of prompt medical attention after potential exposure, such as animal bites.
• The need for thorough wound care, including washing with soap and water.
• The administration of RIG and vaccine as part of PEP.
• The importance of completing the full course of vaccination to ensure adequate immunity.

Prevention

Prevention of rabies also includes:

• Vaccinating pets against rabies to reduce the risk of transmission.
• Avoiding contact with wild animals, especially those that may be infected with rabies.
• Pre-exposure vaccination for high-risk individuals, such as veterinarians or travelers to endemic areas. As noted in the study by 1, pre-exposure vaccination should include three 1.0-mL injections of human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV) administered intramuscularly, one injection per day on days 0,7, and 21 or 28.

Treatment

The treatment of rabies exposure involves immediate post-exposure prophylaxis (PEP) with RIG and a series of four rabies vaccine doses given on days 0,3,7, and 14 after exposure, as recommended by the ACIP 1. In the study by 1, the authors note that the utility of the fifth vaccine dose, administered on day 28, is nil, and that the nervous system occurs before the due date of the fifth vaccine dose. The ACIP recommends that PEP should include prompt and thorough wound cleansing, followed by passive rabies immunization with human rabies immune globulin (HRIG) and vaccination with a cell culture rabies vaccine, as noted in the study by 1. For persons who have never been vaccinated against rabies, postexposure antirabies vaccination should always include administration of both passive antibody (HRIG) and vaccine, as recommended by the ACIP 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