By David Cyranoski

Scientists from Japan's premier primate research center are struggling to reassure the public that a mysterious illness killing their monkeys poses no threat to humans. Almost a decade after it first appeared, scientists from Kyoto University's Primate Research Institute (PRI) described the disease and their unsuccessful search for a cause in an online publication on July 1 and in a press release on July. 7 But their account leaves other researchers hungry for details.

In the first outbreak to hit the PRI in Inuyama, near Nagoya, between July 2001 and July 2002, seven Japanese macaques (Macaca fuscata) fell ill and six of them died from what the institute scientists provisionally call a "hemorrhagic syndrome." Symptoms included anorexia, lethargy, pallor and nasal hemorrhaging. Autopsies revealed bleeding in the lungs and intestines. Genetic, bacterial and toxicological tests failed to pinpoint a cause, and after the outbreak ran its course, operations at the institute returned to normal. But between March 2008 and April 2010, another 39 cases appeared in the same species. Of those, 25 died of the disease and 13 were humanely killed. Only one monkey survived each outbreak.

On July 1, an institute committee set up after the second outbreak published its findings in the online version of the Japanese-language journal Primate Research. The committee tested blood, feces and tissues from the diseased monkeys for six bacteria and 16 viruses. The tests, which included PCR analysis, turned up nothing that could explain the deaths. François Villinger, director of pathology at the Yerkes National Primate Research Center in Atlanta, Ga., says that Japanese laboratories tend to have excellent diagnostic capabilities: "Therefore I have confidence in the fact that the illness is probably not due to any of the known agents inducing hemorrhagic fevers."

PRI director Tetsuro Matsuzawa spoke out against suggestions in the local media that the disease could spread to humans or other animals. At the July 7 press conference, he stressed that none of the other primate species at the institute, which houses more than 1,200 animals from 13 species, including chimpanzees, marmosets and crab-eating macaques, has contracted the syndrome. The humans who handled the monkeys also show no symptoms. "I don't like the headlines in the news media," he says. "We think that the hemorrhagic syndrome is due to a species-specific pathogen of the Japanese monkeys."

Matsuzawa says that the institute did not publish its findings earlier because it feared causing panic in the wider population. Cases are still occurring, but following the use of disinfectants and the isolation of sick monkeys, the pace has slowed to one case in May and one in June. Matsuzawa is holding back some data for a more detailed future publication and would not answer Nature's questions about whether his group is also probing possible environmental causes, which bacteria and viruses have been tested for, and what analysis of the two surviving monkeys has revealed.

By screening the 790 remaining Japanese macaques for other viruses and bacteria and running genetic tests, Matsuzawa hopes to pin down the cause of the syndrome and to create a test for early diagnosis. He says that he is looking for collaborators, and animal-pathogen researchers contacted by Nature are certainly eager to learn more about the illness. Primate disease specialist Sonia Altizer of the University of Georgia in Athens wonders whether any of the animals were recently captured in the wild, where they could have picked up the infection, and whether animals were housed singly or in groups. "Knowing the possible contacts between animals and the chronological pattern of illness or deaths might also help determine whether this was indeed an infectious agent, and the possible routes of transmission," she says.

She also asks what measures the human workers were taking before the outbreaks to minimize transmission of infectious agents between monkeys and humans. "Presumably there would be some pretty careful measures in place that would limit human exposure to any contaminant or pathogen," she says, "so saying that humans are not susceptible to me seems premature."