Emergency Treatment of Rabies

Author: Raffi Kapitanyan, MD; Chief Editor: Robert E O'Connor, MD, MPH; John Bertolini, MD, FACEP

Overview
Rabies, a viral disease of the central nervous system (CNS), is widespread throughout the world. (See
the image below.)

Hematoxylin and eosin stain of Negri body in a rabies-infected neuron. Courtesy of the US Centers for Disease
Control and Prevention.

Treatment of rabies should be based on history and exposure. One should not withhold treatment while
waiting for diagnostic tests.

Emergency Department Care

Treatment discussed here focuses on animal exposures where rabies transmission is a possibility.
This is the primary concern of the emergency physician. Treatment of human rabies is supportive and
often involves therapy for other possible etiologies before specific diagnosis is made, usually
postmortem or well into an intensive care unit (ICU) hospitalization.

Eliciting a history of recent animal or bite exposures is of utmost importance, as many patients
described in the literature were initially sent home by the emergency department.

Postexposure prophylaxis (PEP) consists of wound cleaning, vaccination, and administration of rabies
immunoglobulin.

Wound Cleaning
Immediate therapy, provided prior to the administration of vaccine and immunoglobulin, consists of the
thorough cleaning of all bite and scratch wounds with soap and water, 2% benzalkonium chloride,
and/or a virucidal agent (ie, povidone-iodine solution). Wound cleaning alone has been shown to
reduce the likelihood of rabies transmission in animal studies. Provide wound care as needed; tetanus
prophylaxis is usually indicated, as are measures to prevent bacterial infection. When appropriate,
wound closure should be avoided.[1]

Vaccines
The 2 rabies vaccines currently available in the United States are the human diploid cell
vaccine (HDCV, Imovax) and the purified chick embryo cell vaccine (PCECV, RabAvert). Both are
made for intramuscular administration and are equal in efficacy and safety. The vaccine takes 7-10
days to induce an active immune response, with immunity lasting approximately 2 years.

Once a vaccination series is initiated, it is usually completed with the same vaccine product, although
no trials have been done to study the effects (beneficial or adverse) of beginning with one and ending
with another.[1]

Slight erythema may be expected with both vaccines, but any further skin changes should be reported
to the health department to determine actual necessity of vaccine.

No postexposure vaccine failures in the United States have been reported since HDCV was licensed
in 1980. Of 13 cases of postexposure treatment failure that occurred outside the United States, all
were from not cleaning wounds, not giving rabies vaccine, or giving rabies vaccine into the gluteal
region rather than the deltoid region.

Rabies Immunoglobulins
Passive immunization with human rabies immunoglobulin (HRIG, HyperRab, Imogam) provides
immediate protection.

The immunoglobulin elicits neutralizing antibodies and has a half-life of 21 days.

Products are from hyperimmunized human donor plasma and could potentially contain infectious
agents, although this risk is small secondary to initial screening of donors. Currently, no documented
transmission of adventitious agents exists.[1]

Neural tissue rabies vaccines should no longer be used, although they may still be used in some
developing countries.

In countries that cannot afford the 5-dose regimen, the World Health Organization (WHO) states that
2 regimens are available that fulfill their requirements. These have been used in developing countries
as replacements for the more expensive injections. These injections should be administered in
consultation with the Centers for Disease Control and Prevention (CDC).

Postexposure Prophylaxis in Previously Unvaccinated

Immunocompetent Persons
Human rabies immunoglobulin
Administer one dose (20 IU/kg) to produce virus-neutralizing antibodies. Administer on day 0 at the
same time as the vaccine. If not immediately available, the HRIG should be administered as soon as
it becomes available up until and including day 7 of treatment. Concentrate as much of the dose as
possible in and around the wound (if wound location allows). The remaining HRIG should be
administered intramuscularly at a site distance from the vaccine administration.[2]

Case reports have documented safe administration of HRIG and HDCV during pregnancy.

Vaccine
Four doses (1 mL each) of either HDCV or PCECV vaccine should be administered on days 0, 3, 7,
and 14. The first dose should be administered as soon as possible after exposure. It should be given
intramuscularly into the deltoid muscle of adults. In children, it should be administered into either the
deltoid muscle or the anterolateral aspect of the thigh. Do not use the gluteal region, because this
could result in a decreased immunologic response. It is important to give all 4 doses.[2]
Postexposure Prophylaxis in Immunocompromised Persons
Immunocompromised persons should receive HRIG and the vaccine as described above but should,
in addition, receive a fifth dose, on day 28. Any immunosuppressive agents should be stopped during
rabies PEP unless necessary and essential for management of another condition.

Additionally, serum should be tested to document seroconversion 1-2 weeks after completing PEP.
The rapid fluorescent focus inhibition test (RFFIT) should be used to determine that an appropriate
antibody response has developed. If the patient does not seroconvert, the patient should continue
management with both the physician and public health officials.[2]

Postexposure Prophylaxis in Previously Vaccinated Persons

Previously vaccinated persons include those who have received the 3-dose preexposure series of
HDCV, rabies adsorbed virus (RVA), or PCECV; a full PEP; or a previous vaccination with any rabies
vaccine with a documented history of seroconversion.

HRIG should not be administered.

For the vaccine, administer 2 doses (1 mL each) into the deltoid muscle on day 0 and day 3.

References
1. Manning SE, Rupprecht CE, Fishbein D, Hanlon CA, Lumlertdacha B, Guerra M, et al.
Human rabies prevention--United States, 2008: recommendations of the Advisory
Committee on Immunization Practices.MMWR Recomm Rep. 2008 May 23. 57:1-
28. [Medline].

2. Rupprecht CE, Briggs D, Brown CM, Franka R, Katz SL, Kerr HD, et al. Use of a reduced (4-
dose) vaccine schedule for postexposure prophylaxis to prevent human rabies:
recommendations of the advisory committee on immunization practices. MMWR Recomm
Rep. 2010 Mar 19. 59:1-9. [Medline].