Like its close relative the West Nile virus, the Japanese encephalitis virus spreads via mosquito. Blood-suckers snacking on sick birds or pigs pick up the pathogen and pass it on to their next meal. Now, Swiss researchers have found for the first time that the virus, the leading cause of childhood encephalitis in Asia, can be transmitted directly between pigs—without a mosquito go-between. The findings might help explain why the virus sometimes persists over the winter, when mosquito populations decline.
Although Japanese encephalitis is rare in the United States, the World Health Organization estimates it causes 68,000 severe illnesses annually in Asia. Most infected people get away with little more than a headache and a fever. But of those who do develop full-on encephalitis, 20% to 30% die; 30% to 50% of the remainder suffer lifelong neurological or psychiatric problems.
The mosquitos that transmit Japanese encephalitis thrive year-round in tropical regions in Southeast Asia, particularly where marshy rice paddies filled with wading birds and standing water are found in close proximity to pig farms. The insects die off over the winter in more temperate climes, and new infections wane as a consequence. But scientists were baffled by historical reports of the virus recurring on the same farms in temperate northern Japan year after year, and of outbreaks in pigs without evidence of mosquitos carrying the virus in the area. Somehow, it seemed, the virus was occasionally surviving the winter even without mosquitos around to spread it.
“If you look in the older literature, you find a lot of speculation,” says Artur Summerfield, a virologist at the Institute of Virology and Immunology in Bern, Switzerland, who led the study. “But nobody was able to demonstrate where [the virus] was sleeping in the winter.”
Summerfield and his colleagues suspected pigs, long recognized as effective “amplifying” hosts of the virus. Culex tritaeniorhynchus, the mosquito species thought to play the largest role in Japanese encephalitis transmission, love to feed on swine. And when the pigs get sick, they carry a high enough viral load in their blood that they can infect new mosquitos. But—until now—pigs hadn’t been shown to pass the virus directly among themselves.
Summerfield and his colleagues infected five pigs with the Japanese encephalitis virus and then housed the animals with healthy pigs in a lab. Several days later, some of the healthy pigs picked up the virus and became sick. Follow-up studies showed that the virus lingered for weeks in the pigs’ lymphatic tissue and tonsils, the team reports this week in Nature Communications. Summerfield says the results could help explain how the virus has, on occasion, overwintered in places where mosquitos can’t breed year-round.
A Japanese encephalitis vaccine is available for both humans and pigs—a strategy that could help prevent the disease from spreading on farms—but the frequency of use varies by region. In some areas, it’s not cost-effective to vaccinate pigs because they breed and turn over so quickly, says David Beasley, a microbiologist at the University of Texas Medical Branch in Galveston. That’s unfortunate, he adds, because pigs are very good reservoirs of the disease for precisely the same reason.
But because the experiments were done in a lab, it’s still unclear whether pig-to-pig transmission actually takes place on farms or in the wild. If it does, "it’s probably not the dominant mode of transmission,” says Juliet Pulliam, a disease ecologist at the University of Florida in Gainesville. So even if pig-to-pig transmission plays a role in local outbreaks, it is unlikely to drive a human epidemic.
Although this is the first time mosquito-free transmission has been reported for Japanese encephalitis, other lab studies have shown bird-to-bird transmission of West Nile virus. And the mosquito-borne virus that causes the disease Zika, another in the same broad class of viruses, may be able to spread human-to-human via sex. The U.S. Centers for Disease Control and Prevention is investigating, but has not yet confirmed, numerous recent reports of Zika possibly spread in this way.
Some scientists suspect that this uptick in reports of mosquito-free transmission might be because we’re paying more attention. “As we’re getting better at looking at things, people are noticing these weird patterns,” Pulliam says. “We’re starting to pick up on things that maybe we wouldn’t have picked up on before."
However, Summerfield cautions against drawing too close a comparison between the viruses that cause Zika and Japanese encephalitis. Although they belong to the same broader class of viruses, they’re transmitted by different species of mosquitos and harbored in different vertebrate hosts. Plus, humans are dead-end hosts for Japanese encephalitis—though we can fall quite ill with the disease, there’s not enough of the virus in our blood to pass the infection along via mosquitoes.
The next step, Summerfield says, is to see whether the lab findings hold up in the field. But this kind of study is long-term and logistically challenging, so he hopes that researchers in Asia will follow up to test farm transmission in affected areas.