Introduction
Rabies is a serious viral illness affecting the brain and saliva glands of mammals, particularly meat eating species (carnivores) such as dogs and cats, but also wild animals like bats, skunks, raccoons,foxes and woodchucks.
There are several subtypes of rabies viruses typical for different animal species. Typically man becomes infected because of a bite from a rabid dog, cat or bat and the virus, which is carried in the saliva of the rabid animal enters into the human through the skin wound.
Without therapy it would now follow the skin nerves into the spinal cord and eventually enter into the brain where it multiplies. It then switches from there into other nerve pathways going to the saliva glands, the throat area and muscles used to swallow. The virus also multiplies in the respiratory center with the neurotoxin destroying the nerve cells there, which eventually leads to an inability to breathe and death.
Every year about 100,000 people die from rabies throughout the world, mostly from rabid dog bites. As the rabid virus leaves very characteristic inclusion bodies in the brain cells that are called “Negri bodies“, one of the tests to see whether a dog that has bitten a patient, was rabid is to kill the dog and examine the dog’s brain histologically for the presence of Negri bodies.
As there are blood tests available now that are very sensitive, the procedure has changed: the dog is caught and kept in a kennel for 10 day observation. A veterinarian can then determine whether the dog is rabid or not. Should the dog be diagnosed clinically with rabies, it would still have to be killed and the brain examined. However, many dogs are healthy and do not have to be killed and can be released after the incubation period.
Signs and Symptoms
The incubation time typically is 10 to 50 days. The rabies virus is a Lyssavirus, an RNA virus. It is the only type of Lyssavirus that affects man (Ref. 11, p. 1812). At this stage it is important that the physician does a thorough washout and cleaning of the wound under a local anesthetic as this removes the majority of the virus and the bacteria from the saliva of the animal (see below).
In the first two to three days the wound becomes painful, the patient becomes febrile, may vomit and may develop nausea and a loss of appetite. Due to the neurotoxin that is circulating the patient may now develop hallucinations, confusion, anxiety, bizarre behavior including biting. There often is an excruciating pain around the throat and with drinking fluids so that the patient will avoid doing this, thus the old-fashioned term “hydrophobia” for rabies. The patient is thirsty though and is getting dehydrated quickly, which adds to the mental confusion.
As more levels of the spinal cord get involved with infection with rabies virus,there is a progressive inability to first move the extremities, then the trunk muscles and finally the face and neck muscles (called “paralysis of muscles”). Symptoms of encephalitis with headaches, confusion and agitation are a sign that the brain is now infected. Death occurs from an inability to breathe and swallow or from secondary sepsis or meningitis from other bacteria or fungi that entered the system through the bite injury.
Diagnostic tests
A highly sensitive fluorescent antibody test on the one hand and a virus isolation test on the other hand can replace the killing of the suspected rabid dog as already indicated above. Arising antibody titer in a human is also a very worrisome diagnostic test that would indicate exposure to rabies. However, the clinician should treat the patient right away on suspicion as waiting for results is unsafe and would jeopardize the patient’s prognosis.
Treatment
As death happens in almost all cases of rabies about 3 to 10 days after the onset of symptoms, it is clear that the physician must be very aggressive in any case suspicious for rabies exposure.
After a bite wound the wound is thoroughly scrubbed and washed out under local anesthetic to reduce the potential amount of viral load. A good amount of rabies immunoglobuline (=RIG) is then injected into the wound area and the rest given normally by injection. The wound is then closed. In addition an active rabies immunization is then started on the day of the bite, but injected in another site. The old vaccines that used to be painful are no longer used. There are now two vaccines that are used instead: the human diploid cell rabies vaccine(=HDCV) and the rabies vaccine, absorbed (=RVA). Either of them can be used in combination with RIG. Five doses of HDCV or RVA have to be given on the day of the bite, at 3, 7, 14 and 28 days. The WHO recommends a 6th dose 3 months after the bite. Here is a summary regarding the treatment after an animal bite (modified from Ref. 6, p. 1298).
Treatment after bite from animal with possible rabies
Type of animal: | What to do with animal: | Therapy of patient: |
cats and dogs | observe animal for 10 days; kill animal, if it turns rabid and look for Negri bodies | No vaccination generally unless rabies proven in animal; if rabid, then vaccinate immediately. |
raccoons, foxes, bats, skunks, woodchucks | consider wild animals as rabid unless they can be retained and proven by lab tests to be rabies free | Immediately vaccinate |
rats, mice, rabbits, hares, livestock | these animals seem to have a natural immunity to rabies | contact public health officer regarding the recommendation for the area where bite took place, but rarely is vaccination required |
References:
1. The Merck Manual, 7th edition, by M. H. Beers et al., Whitehouse Station, N.J., 1999. Chapter 161.
2. TC Dixon et al. N Engl J Med 1999 Sep 9;341(11):815-826.
3. F Charatan BMJ 2000 Oct 21;321(7267):980.
4. The Merck Manual, 7th edition, by M. H. Beers et al., Whitehouse Station, N.J., 1999. Chapter 43.
5. JR Zunt and CM Marra Neurol Clinics Vol.17, No.4,1999: 675-689.
6. The Merck Manual, 7th edition, by M. H. Beers et al., Whitehouse Station, N.J., 1999. Chapter 162.
7. LE Chapman : Antivir Ther 1999; 4(4): 211-19.
8. HW Cho: Vaccine 1999 Jun 4; 17(20-21): 2569-2575.
9. DO Freedman et al. Med Clinics N. Amer. Vol.83, No 4 (July 1999): 865-883.
10. SP Fisher-Hoch et al. J Virol 2000 Aug; 74(15): 6777-6783.
11. Mandell: Principles and Practice of Infectious Diseases, 5th ed., © 2000 Churchill Livingstone, Inc.
12. Goldman: Cecil Textbook of Medicine, 21st ed., Copyright © 2000 W. B. Saunders Company
13. PE Sax: Infect DisClinics of N America Vol.15, No 2 (June 2001): 433-455.
14. David Heymann, MD, Editor: Control of Communicable Diseases Manual, 18th Edition, 2004, American Public Health Association.