Rabies, the disease that drives infected victims wild, is almost always fatal once it reaches the brain. A new finding from two remote communities in the Peruvian Amazon may reveal a chink in the virus's armor. Scientists have tested six native people there who have never received a vaccination yet appear to have developed natural antibodies to the virus. The researchers think that vampire bats, common in the region, bit the sleeping humans and passed along small amounts of the virus over time. The multiple, low-dose exposures gave each person’s immune system a chance to learn how to fight back.

The scientists, from the Centers for Disease Control and Prevention (CDC) and the Peruvian Ministry of Health, made their finding during a search for emerging infectious diseases harbored by bats. They surveyed two communities, Truenococha and Santa Marta, which are respectively two and six hours away from the closest health post and only reachable by boat. "Generally the communities don't appreciate the risk of rabies from a bite," says Amy Gilbert, a postdoctoral fellow at the CDC's National Center for Emerging and Zoonotic Infectious Diseases, who co-led the work. "They don't know how it is transmitted and are unlikely to seek treatment because of the low perceived risk and because care is very far away."

Gilbert and her fellow researchers interviewed 92 people in the two communities and drew blood samples from 63 of them. They found seven individuals who had antibodies that could trigger a fight to neutralize rabies. All of the people reported exposure to bats, whether through a bite, scratch or just a brush against bare skin. Only one of the seven had received vaccine after being exposed, however. The findings were published in the August 2012 issue of the American Journal of Tropical Medicine and Hygiene.

The researchers do not know exactly how the antibodies arose, Gilbert explains. The most likely explanation is that multiple bites over time gave these individuals a low does of live virus—enough to develop an immune response without a full-blown central nervous system infection. "We don't have any evidence that these people had the clinical presentation of the symptoms associated with rabies," Gilbert says. It is possible that the native population, long subject to vampire bats, may have developed genetic protection against rabies. Or this particular strain of rabies is less virulent. The researchers have no data to back either conclusion, but they also cannot rule them out.

"This study is based on a very small amount of scientific data," says Craig Hooper, an immunologist at Thomas Jefferson University not involved in the work. The interviews are an interesting, rich source of information, he says, but the six people who may have developed natural immunity have very low levels of antibody. Additionally, the levels were observed by only one, fairly conventional, technique. More sensitive tests taken over time could reveal when the individuals were infected and how fiercely the infection raged, he says.

Rabies jumps from host to host through the bite of an infected animal. The virus itself travels from the wound to the brain through an unusual highway. Instead of swirling through the blood, it creeps along nerve fibers. This slow progress explains the variable timing of symptoms following a bite: the farther the bite is from the brain, the longer the virus must crawl. The time lag also gives bite victims the opportunity to seek treatment. A vaccine and treatment with rabies-specific antibodies, even after a bite, arms the immune system to fight off the virus. Contrary to popular belief, the post-exposure treatment for previously unvaccinated people is just four shots to the upper arm over two weeks. People who have been previously vaccinated for protection against the virus only need two shots. The critical moment is when the virus reaches the central nervous system (CNS). Without treatment, weeks or months after an attack the virus triggers a full-blown CNS infection, complete with slavering, snarling, aggression and hydrophobia. At this point, it is usually too late for even the best medical treatment.

The study shows that rabies is not always lethal. This understanding, if backed and deepened by further studies, could lead to new treatments. The work implies that some people escape infection after exposure to a small amount of the virus, but Gilbert says it is not clear from the researcher's work if the Peruvians developed true immunity to the virus. Instead the presence of antibodies indicates possible previous non-fatal infection. For now, prevention is the most effective strategy to combat rabies.

Efforts to stamp out the disease through programs that vaccinate domesticated animals such as dogs are largely successful in developed countries, but the rabies virus still kills 55,000 people each year according to the World Health Organization. About 81 percent of rabies outbreaks in Peru from 1996 to 2010 were linked to vampire bat bites, according to the Peruvian Ministry of Health (pdf in Spanish). Vampire bats regularly prey on livestock, but will feed on humans if given the opportunity.

Despite the typically dire consequences, a few individuals have apparently survived rabies infection of the central immune system. An Alaskan trapper may have developed immunity after years of skinning foxes. In 2011, an eight-year-old Californian girl developed the characteristic throat spasms that prevent eating and drinking, traditionally called hydrophobia. The infection reached her cerebrospinal fluid and brain. After intensive care, she made a full recovery.

Most notably, a Wisconsin teenager survived CNS infection after a creative physician put her in a medically induced coma and then administered the anti-rabies virus treatment. He hoped to slow the creep of the disease and give her body a chance to fight back. Since then, several physicians have tried the Milwaukee protocol, but none have replicated the first success.

The discovery of natural antibodies and possible immunity in the Peruvians should not slow efforts to eradicate the disease, Gilbert emphasizes. "Despite finding antibodies in these persons, we don't consider them protected," she says. An editorial that accompanies the research paper echoes her thoughts. The writer, Rodney Willoughby, a physician at the Medical College of Wisconsin, created the Milwaukee protocol. He writes that this discovery is "an opportunity for novel therapeutics" and should spur researchers to find a rabies cure.