Last year a team of researchers from Peru and the U.S. made a discovery that challenged one of the most widely held assumptions about rabies—that the virus is nearly always fatal unless doctors administer a vaccine before it reaches the brain. Based on the results of blood tests, the scientists learned that half a dozen villagers in a remote part of the Peruvian Amazon had previously been infected—probably through bites from vampire bats, which are common in the area. But instead of suffering the agonizing deaths for which rabies is infamous, the villagers had recovered and apparently developed immunity to further infection.

The discovery put the Peruvians on a short list of people who have survived rabies without a vaccine. The best-known member of that select group is Jeanna Giese, a Wisconsin teenager who lived through the disease in 2004, also after contact with a bat. Out of desperation, Giese's physician improvised a risky treatment that included putting the girl into a controlled coma, which apparently allowed her body enough time to destroy the microscopic intruder. Doctors have since refined the treatment, now known as the Milwaukee protocol, and tried it on at least 39 other never vaccinated patients. Five more people have survived.

The mixed success rates, and the 2012 Peruvian study, underscore how little scientists know about rabies, despite its long history as a menace to humanity. Based on accumulating evidence, though, researchers now recognize that not all rabies infections are equal or universally fatal. Many different animals, including dogs, bats, foxes and raccoons, carry various strains of the rabies virus. The varieties hosted by bats and foxes appear to be weaker, and some people's immune systems may be able to defeat them without a vaccine. Dogs, however, carry a more virulent strain that has rarely been vanquished without medical intervention. To this day, canines remain the largest and most dangerous group of rabies carriers worldwide.

Even if doctors one day perfect a treatment for the later stages of rabies, the procedure would likely be complicated and expensive. Most public health experts think that the best way to control rabies is to vaccinate the most dangerous hosts: all domestic and stray dogs, particularly in the developing world. One such veterinary program in the Philippines has dramatically reduced deaths among humans, and others are under way in India and Tanzania.

Dreaded Disease

Rabies kills about 55,000 people every year worldwide—an admittedly smaller toll than, say, AIDS or influenza. The virus's horrific reputation is nonetheless richly deserved. Symptoms emerge slowly in anywhere from a few weeks to—in rare cases—more than a year after contact with a rabid animal. The rabies virus crawls from nerve cell to nerve cell, eventually making its way from the site of the bite or wound to the brain. Fatigue, fever and chills gradually give way to hallucinations, anxiety, violent convulsions and the telltale foaming at the mouth once the virus reaches the salivary glands. Death is painful and terrifying, which is why standard medical practice calls for keeping patients sedated in the last phases of the disease.

Louis Pasteur's development of a rabies vaccine in 1885 prevented such gruesome outcomes if doctors acted quickly. (More than a century later most rabies deaths in the industrial world—including one or two each year in the U.S.—occur because a bite was not recognized or not taken seriously.) But his success had an unintended consequence: as explained in the 2012 book Rabid: A Cultural History of the World's Most Diabolical Virus (Viking Adult), rabies became a low priority for the budding field of biomedical research.

So when 15-year-old Giese entered Children's Hospital of Wisconsin in Milwaukee in 2004 with full-blown rabies, one month after a bite from a bat flitting around her church, there was still no successful treatment. She was feverish, semiconscious and jerking involuntarily.

Her physician, Rodney E. Willoughby, Jr., a pediatric infectious disease specialist, had never seen a case of rabies. He scoured the scant medical literature and found a gleam of hope: an experiment in which keeping rats anesthetized somehow allowed them to recover from a rabies infection. The rabies virus disrupts the usual electrical and chemical communication between neurons in the brain stem, which in turn loses its ability to regulate the heart and lungs. Perhaps, Willoughby reasoned, effectively silencing the brain with general anesthetics—while keeping the patient alive with a heart-bypass machine and mechanical ventilator—would buy the immune system enough time to destroy the virus. He decided to try it.

Against all odds, the therapy succeeded. Giese survived the viral storm, although she suffered some brain damage and spent two years relearning how to speak, stand and walk. She graduated from college in 2011 and now works as an animal caretaker and motivational speaker. Meanwhile Willoughby has continued to tinker with his intervention. But even he admits that the procedure is not a viable option for most clinics, because it demands so many resources.

In fact, some researchers wonder whether the Milwaukee protocol is truly effective at all. These naysayers have proposed that the real secret to at least some patients' survival is the fact that they were bitten by animals other than dogs that transmit either very tiny doses of rabies virus or strains that the human immune system can clear on its own.

Canine Carriers

While doctors debate whether the Milwaukee protocol works, public health experts agree that the most effective way to deal with rabies is to stop the disease at its source. Globally, domesticated and stray dogs are responsible for nearly all the 55,000 rabies deaths every year, according to the World Health Organization. The burden tends to fall most heavily on people (especially children) in rural areas, which have limited access to the rabies vaccine given annually to more than 15 million people to try to prevent the illness after someone has been exposed.

That leaves preventing rabies in dogs as the best option for reducing the number of deaths in humans. On a purely economic basis, mass dog vaccination certainly makes sense. Canine vaccines are not only less expensive than injections for people, they are far less expensive than critical care treatment of a human rabies case. But it can be difficult, politically speaking, to get anyone to pay attention to the health and welfare of dogs when people's needs remain so much more obvious in so many parts of the world, says Charles Rupprecht, formerly rabies chief at the U.S. Centers for Disease Control and Prevention and now director of research at the nonprofit Global Alliance for Rabies Control (GARC). “Medicine addresses human health issues, and agriculture addresses livestock—dogs are neither,” he says. “It takes vision to see that this is a public health problem: you vaccinate dogs, human rabies cases come down, and you can put your public health dollars toward other goals.”

Despite the daunting numbers—by one estimate the world count of stray dogs is 375 million—GARC researchers believe that dog vaccination programs are logistically feasible, and they have established pilot projects in Africa and Asia (some with support from the Bill & Melinda Gates Foundation). On the Philippine island of Bohol (human population: 1.3 million), researchers vaccinated an estimated 70 percent of the dog population. Before 2007 about 10 people died from rabies each year; since 2008 only one person has died of the disease.

Persuading people to vaccinate their pets is not always easy. Dealing with stray dogs is even more challenging. Because of a relentless rise in the number of rabies deaths in rural China, mostly in the south, that country has organized several mass killings of dogs, which disease-control experts and animal-rights activists have harshly criticized. Even if the cullings are effective in the short term, the stray populations inevitably rebound, as will the virus. Meanwhile the popularity of keeping dogs as pets—around half of which may be unvaccinated—continues to increase as Chinese workers become more prosperous.

Perhaps vaccinating dogs will seem like a more workable plan once researchers figure out how to do away with injections, which require rounding up animals, as well as proper refrigeration and storage of the inoculations. A few especially promising projects spread food pellets laced with vaccines, similar to the blocks of treated fishmeal that have been used to control raccoon rabies in the U.S. Some of the food pellets also include sterilizing contraceptives to reduce numbers of unvaccinated newborns and shrink the size of stray populations.

Rupprecht points out that if such vaccines, still in development for dogs, can be commercialized, they would find a ready market in China and India, the countries with the largest populations of strays and the most deaths from rabies. The necessary business know-how and technical acumen are already in place: China and India happen to be the biggest vaccine-manufacturing countries in the developing world.