RABIES: Trading Fear for Facts

posted April 15th, 2010 by
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Rabies remains a fatal disease long after the laws of Eshnunna, an archaeological find near Baghdad, decreed that the owner of a rabid dog owed compensation to the victim’s family. Then, 4,000 years ago, as today rabies is in a category of its own.

We regard the probability of contracting cancer in our lifetimes with cooler detachment than the improbability-in the United States-of being ever nipped by a rabid animal (Table 1). While it is true that rabies has the highest case mortality rate of any infectious disease and that there is no cure after onset of clinical symptoms, the overall facts are not so gloomy. Rabies (1) is easily preventable, (2) the time between exposure and onset of the disease allows time to stop the advancing virus, and (3) the vaccines used, when timely and correctly administered, are uniformly effective.

The same cannot be said about other dread diseases. According to the Centers for Disease Control and Prevention (CDC) an average of two or three people die of rabies in the US each year, usually for not seeking help soon enough. US patients are often infected abroad. US and Canada, which have rabies surveillance and prevention programs, as well as proven and safe vaccines, are low risk for rabies, as are Australia, New Zealand, Japan, Chile and Uruguay, and much of Europe. In contrast, the annual tally of human rabies deaths worldwide is around 55,000 – 50-60% in India. In Asia, Africa, Central and most of South America, and Eastern Europe rabies is enzootic and a public health concern, worse because vaccines may be hard to obtain or of dubious efficacy.

What exactly is rabies?
Rabies is a viral disease that affects mammals. It is zoonotic, spreading from animals to people – and vice versa, if an infected human were to bite a dog. The virus is generally transmitted through the saliva as a result of a bite. Nonbite exposures are those in which contaminated saliva or neuronal tissue make contact with an open wound, scratch, mucous membrane, or the eye. Not all contact with an infected animal constitutes a rabies “exposure.” Petting or handling, and contact with blood, urine, or feces do not pose risk of infection. Nor does contact with saliva, provided the skin is intact! It is also important to note that the rabies virus is present in the saliva only during the final stages of infection, about the time symptoms appear.

Once introduced into the bloodstream of the new host, the virus is replicated in the muscle cells (not in the bloodstream), passing via the peripheral nervous system toward the central nervous system. At this stage it is disseminated to the allimportant salivary glands that make transmission possible. The virus finally invades the spinal cord and the brain causing acute inflammation and with it the characteristic clinical symptoms.

After exposure, the incubation period in humans is usually several weeks to months, but ranges from days (in severe bites to head or neck) to, in rare cases, a year or more if the wound was superficial.
The advance of the rabies virus can be arrested while it remains in skin and muscle cells, but once it spreads to a neuron it becomes insulated from the immune system and vaccines can’t reach it.

The final stages of infection are:

1. Prodromal stage, 1-3 days characterized by departure from normal habits (e.g., a friendly pet avoiding his people, a wild animal behaving as if tame, a nocturnal animal active in daytime, etc.); also confusion and misbehavior.

2. “Furious” or excitative, 3-4 days of hyperactivity to external stimuli like noise, wind, running water; aggression. This is when dogs tend to rove and bite. As the victim enters the final stage, facial and throat muscles undergo painful spasms, making it impossible to swallow either water (thus the term “hydrophobia,” fear of water) or saliva, causing drooling or frothing of the mouth (the signature symptom, which per se is not symptomatic).

3. Paralytic stage, with loss of coordination (Table 2). The victim finds an isolated place to suffer convulsions, lapse into a coma, and die, generally from respiratory arrest. “Dumb” or paralytic rabies differs in that there is no furious stage. Paralysis, usually of the lower jaw, is the first indication, spreading quickly to the limbs and vital organs resulting in death. The signs of dumb rabies may look like choking. An emphatic word of caution: Rabies symptoms vary from one individual to another and also from one species to another, resembling in all cases those of other diseases or conditions. Impossible though it is to diagnose rabies at a glance, millions of healthy animals have been executed for no more than drooling or biting in self-defense.

Conversely, in situations where rabies is a not-so-remote possibility, say, a choking dog in the streets of Calcutta, it is sad but prudent to leave the animal to his suffering and alert the authorities.

Dogs, cats, or ferrets rarely live beyond 10 days after the onset of signs, which is why they must be quarantined and observed after a bite incident. If the quarantined animal survives for 10 days, rabies is unlikely and almost certainly the virus was not in the saliva at the time of the bite. Everyone can breathe easy and resume normal lives. However, if signs of illness develop during observation, the animal must be euthanized and the head sent for fluorescent antibody testing of brain tissue.

There is less certainty about incubation periods in wild animals. Because an accurate diag nosis of rabies in these cases is only possible in the lab, the procedure in the US requires that (1) exotic pets, (2) wild/domestic hybrids, and (3) wild animals (if caught) who have bitten or scratched a person be euthanized by a veterinarian and the head removed and shipped under refrigeration (not frozen) to a public health laboratory for testing. Bats, if caught, must be sent whole for analysis.

Research has failed so far to produce a reliable live-animal rabies test. The waste of life in these cases is even more tragic in view of the disparity between the large number of animals killed for testing and the miniscule percentage that test positive. Therefore, the development of a reliable live test should be a priority of veterinary and epidemiology researchers.

Organ, tissue, vascular, and corneal transplants have caused human-to-human rabies transmission. In 2004 four US patients contracted clinical rabies and died as a result of a single donor whose death was not recognized as rabies. There have been cases reported in four other countries.

“A dandy excuse” Most warm-blooded animals are susceptible to rabies, but not uniformly so. Rodents (squirrels, mice, gerbils, guinea pigs, hamsters, chipmunks, muskrats, beavers, etc.), lagomorphs (rabbits and hare), marsupials (including the American opossum), and primates (other than humans) are more resistant to rabies than other mammals. Birds are immune.

Terrestrial carnivores most often infected with rabies (known as vector species) in the US are skunks, raccoons, and foxes. Human rabies in the US, however, is mostly bat-related, in some cases without the victim being aware of a bite. There is no reason to panic because 94% of the bats submitted for testing are not rabid, but it is wise to avoid situations where a bat may sneak up on you (Table 3).

Dogs and cats have not been the main reservoir of rabies in the US since the early 1950s. The number of infected farm animals also dropped drastically at that time. And in 1958, for the first time, there were more reports of wildlife rabies than dog rabies. Why? Because as systematic vaccination of pets reduced the incidence of rabies in domestic animals, and as wildlife monitoring became a science, the occurrence of rabies in wild species began to receive attention. It follows that with improved surveillance and diagnosis techniques the rabies reservoir in wildlife was recognized.

Wrongly assuming that sylvan rabies was spreading – instead of finally being noticed – wildlife management resorted to trapping-poisoning shooting. This reckless MO was predictably welcomed by hunters, trappers, ranchers, and their political minions, who found rabies “a dandy excuse” as a journalist wrote, for the elimination of animals who interfered with their interests, or to be able to up the intake of furbearers, or just to target-shoot live “trash” animals for clean family fun.

A rational approach to check the spread of rabies in wildlife is the release of oral vaccination food baits in strategic wilderness areas. As animals eat the baits and become immunized they come to reinforce the population of healthy individuals which are nature’s buffer force between a minority of infected wild animals and humans or domestic animals.

Not curable, preventable

Louis Pasteur and Emile Roux made history in 1885 by using serum made from the dried spinal cord of rabbits injected with the rabies virus to inoculate a boy severely bitten by a rabid dog. Following a regime of 12 shots, the boy survived and the experiment opened the possibility of escaping certain death.

Rabies vaccines induce an active immune response that includes the production of virus neutralizing antibodies. Whether to start a vaccination series or not after a suspected rabies exposure depends on several factors to be discussed between the victim and the attending physician in consultation with local health authorities. Postexposure prophylaxis, as rabies vaccines are often called, is an urgency (not an emergency) and should start as soon as possible.
If observation or testing turn out negative, then prophylaxis is not required. But if the animal is not available and there is the slightest possibility of infection, then prophylaxis is the right choice. Between 20,000 and 40,000 people receive a full series of rabies vaccines every year in the US; 10 to 12 million worldwide.

Postexposure prophylaxis consists of (1) thorough cleansing of the wound with soap and abundant running water, (2) local infiltration of rabies immune globulin, RIG, to bridge the gap until the first vaccine starts producing active immunity, and (3) a 5-dose prophylaxis of intramuscular shots in the shoulder area over a 28-day period. This treatment is uniformly effective when promptly and correctly administered.

Prophylaxis received outside the US can be substandard. The patient should remember the name of the vaccine, its manufacturer, and dates of inoculation, to be able to inform his Stateside physician upon return. Also insist that the vaccine be administered on the shoulder and not the gluteal area, where it may be less effective.
Traveling to enzootic regions of the world presents risks that justify “pre-exposure” prophylaxis.

Even though it doesn’t eliminate the need for further injections after a bite, pre-exposure prophylaxis (1) simplifies prophylaxis after exposure, (2) primes the immune response in case of unrecognized exposure (as in a bat bite) bridging the gap of an unintended delay in medical attention, and (3) provides immunity between exposure and prophylaxis in remote areas where it may not be available.
Pre-exposure prophylaxis is a necessity for individuals who work with rabies virus and rabies diagnostic testing; veterinary personnel, animal control, and wildlife officers where rabies is enzootic; and anyone who handles bats or goes near them, like spelunkers.

Neither pre- nor postexposure rabies vaccines have serious reactions; the most common being headache and local tenderness in the area of injection. Rabies vaccines are so benign that pregnancy is not a contraindication and neither rabies exposure nor prophylaxis are reasons to terminate pregnancy.

Rabies kills, but the number of casualties would be lower if ignorance and apathy were as easy to neutralize as the virus.

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