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.

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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.

It is bats that have become the problem for humans in the U.S., accounting for more than two-thirds of rabies cases.

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.

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Dr. Larry Madoff is director of the Division of Epidemiology and Immunization at the Massachusetts Department of Public Health (MDPH) and professor of medicine at the University of Massachusetts Medical School. More

Dr. Larry Madoff is director of the Division of Epidemiology and Immunization at the Massachusetts Department of Public Health (MDPH) and professor of medicine at the University of Massachusetts Medical School. He is an attending physician in the Division of Infectious Diseases and Immunology at University of Massachusetts Memorial Medical Center and Associate Director of Infection Control.

He is a graduate of Yale College and Tufts University School of Medicine. He trained in Internal Medicine at New York Hospital-Cornell and received his Infectious Disease Fellowship training at the Brigham and Women's Hospital, Beth Israel Hospital, and the Dana-Farber Cancer Center program at Harvard Medical School. From 1989 until 2008, he was on the faculty of Harvard Medical School where he performed research on bacterial pathogenesis and vaccine design at the Channing Laboratory. He was an attending physician on the infectious disease service at Brigham and Women's Hospital and director of the Global Travel Health Clinic there.

Since 2002, Dr. Madoff has served as editor of ProMED (the program for Monitoring Emerging Diseases), an Internet-based emerging disease surveillance system with over 55,000 subscribers. He is a fellow of the American College of Physicians and the Infectious Disease Society of America and a member of the American Society of Microbiology, the Massachusetts Infection Disease Society, and the Massachusetts Medical Society.

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