The disease goes through three stages. The initial, or prodromal, stage involves itching and burning at the portal of entry (bite wound), nausea, vomiting, and possibly a melancholy mood. In the second or excitative stage, cramps and spasms of the pharynx and larynx are the main symptoms, rendering swallowing very painful. The spasms can be induced by the mere sight of water ("hydrophobia"). Other mild acoustic and visual stimuli may elicit exaggerated reactions including attacks of cramps and violent anger, hitting, biting, and screaming. Death occurs within three to four days at the earliest. The third, paralytic, stage may develop instead of early death, with ascending paralysis and asphyxia, leading to exitus. Therapy is exclusively symptomatic. Since the patient experiences the disease in a fully conscious state, most of the medication serves to alleviate the pain and anxiety states. The disease runs essentially the same course in humans and animals, whereby the behavior of animals is often radically altered: wild animals lose their fear of humans and tame pets become aggressive. Rabies with the excitative stage is known as "furious rabies," without it as "dumb rabies."
Diagnosis. An intra-vitam laboratory diagnosis is established by examining an impression preparation from the cornea or skin biopsies with immuno-fluorescence. Postmortem, rabies viruses can be found in the brain tissue of humans and animals by inoculating newborn mice or cell cultures with brain tissue or saliva.
Because antibody production begins so late, serodiagnosis is not practicable. Serological analysis is used to check for vaccine protection. Useful technical tools include an EIA or neutralization test (RFFIT, rapid fluorescent focus inhibition test in cell cultures). Special laboratories are used for the diagnostic testing.
Epidemiology. Lyssavirus type 1 is endemic to North America and Europe in wild animals (sylvatic rabies) and in certain tropical areas in domestic pets as well, in particular dogs (urban rabies). The reservoir for the remaining lyssa-virus types are bloodsucking (hemovorous) as well as fructivorous and insectivorous bats.
The virus is excreted with the saliva of the diseased or terminal incubator animal and enters other animals or humans through scratch or bite wounds. The virus is highly labile, so transmission on contaminated objects is very rare. Human-to-human transmission has not been confirmed with the exception of cases in which rabies in corneal donors had gone unnoticed.
Prevention. The long incubation period of the rabies virus—in humans several weeks to several months, depending on the localization and severity of the bite wound—makes postexposure protective vaccination feasible. Development of the vaccine originated with Pasteur, who used a dead vaccine from the neural tissues of infected animals. Use of this original rabies vaccine often resulted in severe side effects with allergic encephalomyelitis. The vaccine types in use today are produced in diploid human embryonal cells (HDCV = human diploid cell vaccine), hen fibroblasts or duck embryos. No further adverse reactions have been described with these vaccines, so that 8 earlier apprehensions about the rabies vaccine are no longer justified.
The postexposure procedure depends on the type of contact, the species and condition of the biting animal and the epidemiological situation (Table 8.7). Exposure is constituted by a bite, wound contamination with saliva or licking of the mucosa, but not by simple petting. In endemic regions, any animal that bites unprovoked must be suspected of being rabid.
Postexposure prophylaxis begins with a rigorous wound toilet, the most important part of which is thorough washing out of the wound with soap, water, and a disinfectant agent. Passive immunization with 20 lU/kg human rabies immunoglobulin (RIG) is then begun, whereby half of the dose is instilled around the wound and the other half is injected i.m. Concurrently, active immunization is started with six doses of HDVC injected i.m. on days 0,3,7,14,30, and 90. The current therapeutic measures are summarized in Table 8.7.
Important: postexposure vaccination is apparently ineffective against the African viral strains (types 2-4).
Table 8.7 Rabies: Postexposure Prophylaxis (according to WHO recommendations issued in Geneva, 1992)
Animal species, Condition of animals Treatment of exposed epidemiological situation person1
Not from endemic area: Dog, cat
Healthy, can be observed for 10 days
Suspected rabies or rabid, unknown, escaped
HDCV and RIG2
None; if animal develops rabies within 10 days, begin immediately with HDCV/RIG
HDCV and RIG
Depends on epidemiological situation
Wild carnivore, bats Always consider rabid HDCV and RIG
pending negative lab results
Other wild animals:
From endemic area - HDCV and RIG
Not from endemic area - Depends on epidemiological situation
8 HDCV: human diploid cell vaccine (active vaccination); RIG: rabies immunoglobulin from human source (passive vaccination).
1 Treatment comprises administration of RIG and HDCV (see text). WHO recommendations also allow use of HDCV alone in cases of minor exposure (licking of skin).
2 Discontinue treatment if animal under observation remains healthy for 10 days.
Persons exposed to an increased risk of contracting rabies can also be given pre-exposure protection with three doses of HDCV. Postexposure treatment is then limited to the wound toilet and HDCV injections.
Postexposure prophylaxis is impracticable in animals. Dogs and cats in particular must be vaccinated with living vaccine grown in duck embryos. In wild animals (foxes), oral bait vaccination programs have been successful. If the bait contains the attenuated rabies virus, exposure to it must be considered rabies exposure and the postexposure prophylactic procedure must be carried out. This does not apply to use of the recombinant vaccinia virus. However, see p. 428 on the pathogenicity of the vaccinia virus.
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