Discovering the Zika virus

HONG KONG — Yap Island, a tiny island in the Western Pacific best known for using huge stone discs as currency, was facing a medical mystery.

In 2007, doctors saw an alarming increase in the number of patients with rashes, inflamed eyes and joint pain. Initial tests provided no answers to what was making them sick.

“We didn’t have any idea what it might be,” said Lt. Col. Mark Duffy, a U.S. Air Force public health officer assigned to work on the unknown ailment for the Centers for Disease Control and Prevention’s epidemic intelligence service. “There was some thought it might be a dengue outbreak.”

Dengue is a potentially deadly mosquito-borne disease that affects as many as 100 million people around the world each year. Chikungunya, another virus spread by mosquitoes, was also considered.

But patients’ blood samples tested by a CDC lab in Fort Collins, Colorado, confirmed that the doctors were seeing something novel: It was the world’s first significant Zika outbreak.

For most of its known existence, Zika was little more than a scientific curiosity. After its discovery in 1947, in the forest in Uganda that gave the virus its name, it spread slowly across Africa and Asia. Blood tests have found Zika antibodies in people in India, Pakistan, Malaysia, Vietnam, the Philippines, Thailand and Indonesia — evidence that they had been exposed to the virus. Even so, few cases of the illness had been reported.

For more than half a century there were no confirmed outbreaks of Zika, and only 14 confirmed human cases.

Then, in 2007, Zika appeared on Yap and nearby islands in Micronesia, 800 miles east of the Philippines, where nearly 50 people had been infected. Six years later, it showed up in French Polynesia, 5,000 miles to the southeast of Yap, where thousands contracted the virus.

Zika has now infected an estimated 1.5 million people in Brazil and is rapidly spreading through many parts of the Americas. The newest outbreak has researchers examining its trail across Asia and the Pacific, trying to learn more about the first outbreaks of the disease and why it appears to have gotten so much worse.

“Something very, very different is going on there,” said Duncan Smith, an infectious diseases researcher at Mahidol University in Thailand. “We don’t know what it is at the moment.”

For much of its history, Zika was subject to little research. Just 1 in 5 people who were infected developed symptoms, and they were usually mild and often mistaken for other illnesses.

“There were these odd cases popping up from time to time,” Smith said. “There is so much dengue in this area, and the symptoms of dengue and Zika are quite similar — rash, fever, muscle aches and pains. I wonder if cases of Zika have been occurring but misclassified in the region.”

Why the disease appears to have been milder in Asia is unclear. Smith said that aggressive campaigns to vaccinate for Japanese encephalitis, a virus found in Asia and the Western Pacific, may have had an effect on Zika, but that premise had yet to be investigated.

“Maybe it has become much more aggressive, with a more severe presentation and transmission as a result of it going across the Pacific,” he said. “We won’t know until a lot more work has been done.”

Doctors in Yap soon knew they were facing something different. No deaths or hospitalizations had been reported but 49 confirmed cases and 59 probable cases were identified, far more than ever before.

Exactly how the virus got to the remote archipelago is still unclear, though an infected mosquito or person is the most likely culprit. Duffy noted in a paper for The New England Journal of Medicine in 2009 that a medical volunteer on Yap returned to the United States in July 2007 and tested positive for Zika antibodies, indicating a likely infection.

Air travel and the abundance of mosquitoes in the Pacific region “raise concern for the spread of Zika virus to other islands in Oceania and even to the Americas,” the paper said.

“As an epidemiologist, when you start making predictions about how some of these things are going to behave, they’re going to make you look silly every time,” Duffy said. “But simply raising concern that there is a potential for it to occur eventually, we felt that was a solid statement that we could stand behind.”

When Zika appeared in French Polynesia in 2013, the outbreak on Yap had helped health officials prepare. Labs in the far-flung area had developed methods to test for Zika to help out other Pacific nations, said Van-Mai Cao-Lormeau, an infectious diseases researcher at Institut Louis Malardé on Tahiti, the largest island in French Polynesia.

“This is a small country,” Cao-Lormeau said. “Everyone who worked in the lab had relatives or friends who had seen something that looked like dengue. We had more and more cases.”

The outbreak in French Polynesia was explosive: An estimated 28,000 people, more than 10 percent of the territory’s population, sought treatment. And the potential side effects were more severe than any that had been seen before.

The incidence of Guillain-Barré syndrome, a disease that causes the immune system to attack the nervous system, sometimes causing paralysis, was 20 times higher than what would be normally expected, Cao-Lormeau and colleagues wrote in a 2014 edition of the journal Clinical Microbiology and Infection.

After cases of microcephaly, infants born with abnormally small heads, appeared in Brazil, researchers in French Polynesia did a retrospective investigation of women who were pregnant during the outbreak. They found 17 cases of children with neurological conditions, including microcephaly, Cao-Lormeau said.

Links between the Zika virus and microcephaly and Guillain-Barré have not been confirmed and are still being studied.

Small outbreaks in New Caledonia, the Cook Islands and Easter Island were reported after the French Polynesia outbreak, and Zika has probably spread even more widely in the Pacific without being detected, Cao-Lormeau and colleagues wrote.

Researchers are not certain why the virus seems to be more aggressive in the Americas than in Yap or French Polynesia. One potential factor is the islands’ comparatively small populations, Cao-Lormeau said.

“We are just 270,000 people,” she said. “Because we are small, maybe we won’t see as much adverse effects.”

The other possibility researchers are considering: The virus has mutated and gotten worse.

© 2016 New York Times News Service