The State of Rabies: Treating a Disease That Often Leads to Death

The archetypal zoonotic disease, rabies can spread between animals and humans as it has the ability to infect -- and kill -- all mammals.


When my father was a boy, in the 1930s, living in Clinton, Massachusetts, he was attacked and bitten by a dog in the woods near his home. The animal was never found and, rabies being so prevalent among feral dogs at the time, he was forced to undergo preventive treatment for the disease. In the late 19th century, Louis Pasteur devised a strategy to immunize against rabies by progressively attenuating a virus by successive passage through rabbit spinal cords. The "Pasteur Treatment" involved injections of up to 25 doses of this crudely purified vaccine, three on the first day and then one per day over the next three weeks into the abdominal wall. The idea is to develop immunity -- antibodies to the virus -- before the virus has a chance to invade the central nervous system. Throughout his life, my father recalled the horror of the treatment -- even more than that of the dog bite.

Painful as it was, the treatment may well have saved him from the gruesome fate of rabies. We learned last week that a man in Massachusetts had been diagnosed with rabies. Believed to be the first case acquired in the state since 1935, the man is in critical condition, indicating that he is already manifesting the disease. Sadly, at this stage, rabies most often leads inexorably to death.

The disease has become rare in this country, with no more than a handful of cases occurring throughout the U.S. in a given year. (Worldwide, however, rabies is common. Estimates put the number of cases between 55,000 and 70,000, nearly all from the bites of rabid dogs.) Rabies can begin insidiously, anywhere from a week to many months after the bite of a rabid animal. Agitation, fever, restlessness, irritability, and increased sensation at the site of the bite may be the initial symptoms. Delirium often ensues. Classic hydrophobia, when it develops, is startling. Initially manifest as the inability to swallow liquids, it progresses to the point that merely the sight of liquid can cause gagging and laryngeal spasm. This finding is so classically associated with rabies, in animals as well as people, that hydrophobia and rabies were once synonymous.

Wild swings in pulse and blood pressure follow (as the autonomic nervous system becomes affected), waning of consciousness, and finally seizures and respiratory arrest, with most affected dying within a week of contracting the illness. Historically, survival from rabies infection has been extremely rare. A recent approach pioneered in Wisconsin in 2004 appears to have led to a handful of survivors, but the prognosis remains grim.

Rabies is perhaps the archetypal zoonotic disease, one spread between animals and humans. It has an extremely broad host range, with the ability to infect all mammals. The ancients understood that when a mad dog bit another dog, it too became mad. Canine rabies remains a huge problem around the world, but in the U.S., where vaccination of dogs against rabies has become nearly universal, other species have become more important in spreading rabies. Skunks, foxes, and raccoons are all important to the rabies problem in various parts of the U.S.

While rabies is transmissible between any species, most transmission occurs within the species -- bat to bat, raccoon to raccoon -- and the virus adapts slightly to its host. That means each virus carries a signature in its genetic sequence indicating the species and geographic location of the "donor." In one recent case, we were surprised to learn that a patient had died of infection by a rabies virus whose genetic signature indicated that it originated in a South American dog, though he was reported not to have been in that region for many years. It remains mysterious whether we were missing some history of a more-recent visit there, or the incubation period was unusually long.

But it is bats that have become the problem for humans in the U.S., accounting for more than two-thirds of rabies cases. That doesn't mean they should be eradicated, of course: Bats are too important to the ecosystem to think of as disease-spreading pests. Their insectivorous diet makes them vital to reducing the burden of disease-transmitting mosquitoes. Nonetheless, keeping bats out of our homes, particularly our sleeping quarters, is a key public health measure in reducing human rabies. Bats have small, very sharp teeth and a sleeping victim may simply be unaware that a bite has occurred. For that reason, we counsel people to get prophylaxis if they wake up in a room where a bat is found, whether or not they are aware of a bite.

With a disease so horrible, and treatment problematic, prevention is the mainstay of public health. More effective and tolerable post-exposure prophylaxis also began to appear in the past few decades. Now, instead of the 25 abdominal shots my father endured, we offer a single dose of antiserum (infused around the wound or given intramuscularly) and four doses of a much safer rabies vaccine given over a two-week period. This is almost completely successful in preventing the disease when given within a reasonable time after exposure. (With domestic animals, we can even observe the biting animal for signs of rabies; if none manifest within ten days, the animal is deemed free of the disease and prophylaxis can be avoided.) There are problems with this approach, however: it is very expensive, and in many parts of the world, where rabies is prevalent, it is simply not available. The fact of so few cases here, and the easy availability of prophylaxis, means we are lucky. While working on better treatments, we should work on ways of vaccinating dogs and lowering the cost of prevention in the rest of the world.

Image: Jessica Rinaldi/Reuters.