Rabies

            Rabies is an acute, fatal, encephalomyelitis, caused by a neurotropic rhabdovirus, genus Lyssavirus (1-7 serotypes).

Transmission - is via the saliva of mammals (e.g., dogs, cats, bats, coyotes, foxes, wolves, raccoons, skunks), mainly by bites, but occasionally through inhalation (bat caves) or through corneal grafts.

Epidemiology - Rabies causes 60,000 deaths per year. 50 % of deaths are from the Indian subcontinent. Present on all continents except Antarctica, but especially in India, Southeast Asia, Africa, China, Oceania (Philippines high risk), South and Central America (Peru, Brazil and Mexico).

India - dogs are the main cause. Thailand - 3-6 % of dogs carry rabies in Bangkok and Chiang Mai. North and South America - bats are the main cause. Tourists - significant risk is from monkeys. Children are at risk for significant bites on face and upper body.

Incubation - Average is from 6 - 12 weeks, but can be as short as 6 days and as long as 7 years +.

Clinical Course -

(1) Incubation: Virus spreads along nerve endings, leading to spinal cord and brain. Virus can become inactive, flaring up months or years after the initial bite.

(2) Prodromal: Initial symptoms are itching, tingling, fever, malaise, headache.

(3) Acute disease: 2 forms occur.  Most commonly there is rapid progression with spreading paralysis, confusion, spasms of the muscles involved in swallowing and breathing. Patients appear terrified, have hydrophobia and produce copious saliva. Delirium, convulsions and hallucinations can occur.

Occasionally (20%), course is more protracted with progressive flaccid paralysis

(4) Coma and agonizing death occur within a week.

Diagnosis - Initially can be difficult. Fluorescent antibody test from skin biopsy at nape of neck is best (sensitivity of 86 %). Less reliable tests include antigen tests from saliva, tears and corneal biopsy. Post mortem testing is done for rabies antigen in brain tissue. PCR testing is also becoming available and reliable.

Initial Care - Thorough washing of wound with a 20 % soap solution, followed by irrigation with virucidal agent (e.g., povidone iodine 1%, alcohol 70 % or benzalkonium chloride 0.1 %).

Post Exposure Treatment - Those with no prior/adequate pre-exposure vaccination must undergo the following:

(1) HRIG (Human rabies immune globulin) 20 IU/ kg infiltrated into depths of and around wound (can be diluted 2-3X with normal saline if large area). Purpose is to neutralize rabies antigen in wound site. Remaining HRIG then given as IM at distant site.

ERIG (Equine rabies immune globulin) available in some developing countries. It can cause serum sickness (1%) +/- anaphylaxis (1/ 80,000 doses). Purified ERIG is safer.

NB. Some countries do not have RIG.  RIG can be delayed if animal available for observation up to 7 days after vaccination started.

(2) Post exposure Vaccination -  Gold standard is the Essen schedule as follows: 0, 3, 7, 14, 28 days with inactivated purified cell culture or purified duck embryo vaccines. Vaccine given IM in deltoid or anterolateral thigh (kids). Never given in gluteal. Drawback is cost ($600.00 US).

Alternate schedules are used in some countries (e.g., Thailand Red Cross Schedule using intradermal vaccine on days 0, 3, 7, 28, and 29).

Older nervous tissue vaccines (Semple, Fermi, and suckling mouse brain) are used in some countries. These carry risk of increased allergic reaction and decreased immunogenicity.

Types of vaccines - *HDCV - human diploid cell vaccine (Imovax).

                                 - *PCEC - purified chick embryo rabies vaccine (Rabavert).

                                 - *PDEV - purified duck embryo vaccine.

                                 - *PVRV - purified vero cell rabies vaccine.

                                 -   RVA   - rabies vaccine adsorbed.                                                   

                                                      *interchangeable vaccines.

USA-FDAapproved - HDCV

                                   - PCEC

                                   - RVA

Canada                    - HDCV (Imovax)

Guide  for Post Exposure Treatment -

Bat contact is high risk as teeth marks may be innocuous.

Significant bites, scratches, salivary contamination with suspect or confirmed rabid domestic or wild animal/ or animal unavailable for observation.

Initiate treatment and discontinue only if observed animal is normal, or if animal is euthanized, tested and found to be normal.

No treatment required for touching or feeding animal if skin remains intact.

Post Exposure Treatment - for  patients known to have had previous rabies vaccination with cell culture or duck embryo vaccine +/or  those who have rabies neutralizing antibodies (NAB) > 0.5 IU/ml.

(1) No RIG required.

(2) Vacccination at 0 and 3 days with IM rabies vaccine. Various ID regimes are also available.

Contraindications to Post Exposure Vaccination  - none as rabies is fatal. Those who are HIV+ with low CD4 counts (<300IU) or immunocompromised may need to double the vaccine amount to develop antibody response. Do not use ID vaccination in these groups.

Pre Exposure  Rabies Vaccination - Indicated for rabies lab staff, field researchers, veterinarians, animal handlers, missionaries, military, Peace Corps, CUSO,  cyclists, spelunkers, those in remote sites, and kids.

Vaccination done as follows: 3 doses of cell culture or purified duck embryo vaccine, IM, on days 0, 7, and 21-28.

Intradermal technique is done in many centres, and is cheaper, but should be used with the following precautions:

(1) Cannot be used concurrently with chloroquine or mefloquine (theoretical for latter). Complete ID vaccine 1 month prior to starting chloroquine or mefloquine.

(2) Proper ID technique must be used, with 25-27 gauge, short needle, and staff well trained in technique.

(3) Must test antibody at 4-6 weeks (one week after 3^rd. dose).

(4) USA uses HDCV for intradermal vaccination.

(5) 2 site ID technique may be preferable for some clinics.

Boosters - For infrequent exposure to rabies, no serological testing or booster vaccinations required. For frequent exposure, serological testing is done every 2-3 years. In high-risk lab workers, test every 6 months. Boost if antibody levels are low (should be > 0.5 IU/ml).

Prevention -

Never approach animals.

Defend yourself if animal aggressive.

Be aware of what to do first, and where to look for appropriate vaccine.

Be prepared to travel to well-equipped centre/ avoid older nervous tissue vaccines if possible.

Record vaccine type and RIG product you received overseas.

REFERENCES:

Travellers' Health. How to Stay Healthy Abroad.

Dr. Richard Dawood.

1992.

Don't Drink the Water.

J.S.Keystone (Ed.)

2000.