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Authors: Donald G. McNeil

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On the Move

T
HE FIRST TIME
Zika was noticed outside of Africa and Asia was in 2007, when Thane Hancock, a family physician working for the Yap Department of Health Services, sent an email to the CDC in Atlanta asking for help. Yap is one of the Caroline Islands in the western Pacific, and about 500 Yap islanders, Hancock said, had come down with something that resembled mild dengue, but didn't come up positive on the dengue test kits the island had on hand.

Yap had a mere 7,000 inhabitants, so 500 cases constituted a big outbreak.

Yap is part of the Federated States of Micronesia. In World War II, a Japanese bomber group and about 6,000 troops were based on it, and the U.S. Navy bombed it repeatedly. With Japan's surrender, the United States seized the islands. They became independent in 1986, but signed a Compact of Free Association with the United States. They are not a territory like Puerto Rico or Guam, but still loosely attached, so when they needed help, they turned to the CDC.

The email arrived in late May and was forwarded to the Epidemic Intelligence Service. The EIS is the CDC's elite division of disease detectives, and competition to get into each year's class of 75 trainees is stiff. Its symbol is a globe with a shoe sole superimposed on it, and the sole is worn through, like a detective's who will stop at nothing. The service investigates about 100 outbreaks a year—everything from
E. coli
killing fast-food customers in the Midwest to rashes on an island half a world away.

On June 13, Lieutenant Colonel (Dr.) Mark Duffy, an Air Force epidemiologist assigned to the division of vector-borne infectious diseases, and Dr. Tai-Ho Chen, a medical officer in the EIS Field Assignments branch, arrived on Yap. They immediately started seeing patients in the island's five clinics and sent samples to the agency's arbovirus laboratory in Fort Collins, Colorado.

Dengue kept looking like the most likely explanation, Dr. Duffy said later, until the results came back on June 22. It was something new for the Pacific, and something that had never been seen causing a big outbreak before: Zika virus.

That was eye-opening. The scant existing literature described it as an African virus. Yap Island is a
long
way from Africa, by any route.

The team expanded to eight members—seven Americans and one from France's Pasteur Institute. They spent the next six weeks there.

“We worked through hot, humid weather punctuated by daily drenching rains,” Dr. Chen later wrote for the
EIS Bulletin
. “We completed household survey activities despite heavy rain and winds of Tropical Storm Man-Yi (later a Category 4 typhoon when it hit Japan). Memorable events include the team eating a reef fish caught by Mark, drinking home-brewed beer, and listening to our French entomologist playing the ukulele and singing ‘Drunken Sailor.'”

Like the British authorities in Nigeria, the CDC did a serosurvey. Serosurveys are like opinion polls: you pick a representative sample of the population, meet the selected people, and dig deeply into the data they give you. But after asking them lots of questions, you check their answers by looking in their blood.

The team went to 170 households, inquiring about a family's recent symptoms, taking blood, making notes about the household environment (standing water, screens, etc.), and collecting mosquitoes. It also went to all the island's hospitals and clinics, pulling records and interviewing doctors.

The epidemic, they realized, had peaked in May, just as Dr. Hancock was asking for help. In all, it lasted only five months. But by screening the blood for antibodies and looking at who had reported symptoms, they became the first scientists to figure out the dynamics of a Zika epidemic in a “naïve” population—one in which no one was immune.

They calculated that 73 percent of the island got the disease in that five-month window. By August, it was over. Cases disappeared, and there has not been one on Yap since—presumably because herd immunity is so high. Almost everyone is immune, so even if one naïve person brought it back, there wouldn't be enough susceptibles around to let a new outbreak start.

Four out of five who got the disease never knew it. They showed no symptoms.

And it had been universally mild. No one had been seriously ill. No one had died.

“Our health care system is doing fine,” Dr. Hancock told a Reuters reporter who telephoned from Hong Kong. “We haven't been overloaded by heaps of patients coming in.”

The virus's next appearance would be a bit different.

Zika wouldn't be heard from again for another six years, and it would be on another dot in the Pacific 5,000 miles to the east: Tahiti, the main island of French Polynesia.

French Polynesia consists of 118 islands scattered over an area 10 times the size of France. The whole country has a population of only 270,000, with about 75 percent of it living on Tahiti or neighboring Moorea.

Polynesia is much more closely connected to France than Micronesia is to the United States. As an “overseas collectivity,” it has some autonomy, but it sends deputies to the National Assembly in Paris and is patrolled by French troops and gendarmes. It benefits from the connection in various ways. One is that it has had a very impressive medical surveillance network in place since 2009, with 50 sentinel sites on 25 different islands—a mix of public and private clinics. The doctors at those sites saw almost a quarter of the population, and they were expected to file weekly reports to Papeete, the capital. At the top of the chain was the national hospital and the Louis Malardé Institute, which had connections to the Pasteur Institute in Paris, one of the world's top medical research institutions.

On October 7, 2013, the first alert went out: clinics on several islands were reporting an “eruption” of patients with fevers, rashes, bloodshot eyes, and painful and swollen joints.

Blood samples began coming into the Malardé Institute. At first, a new outbreak of dengue was suspected. There are four strains of dengue, and types 1 and 3 had both been seen in the islands since February. But Van-Mai Cao-Lormeau, the head of the institute's laboratory, was doubtful.

“Tahiti is a small island,” she told NPR News later. “So in the lab we had relatives, family, and friends who were getting sick who we knew had already had dengue several times.”

Even a first bout of dengue can be painful, and a new infection with a different type is usually much worse. But these cases were consistently mild. Dr. Cao-Lormeau's lab was unusually well-prepared. Because it did regular dengue testing as a courtesy for Micronesia, it not only knew about the Yap investigation but had the CDC's Zika-testing protocols.

The first household tested for Zika contained a 53-year-old Tahiti resident, her 52-year-old husband, and 42-year-old son-in-law. They were negative for dengue, chikungunya, and West Nile, and “inconclusive” for Zika. But soon afterwards, a 57-year-old man came up positive. After that, more than half of the next 700 samples tested came up positive, so the lab finally stopped bothering.

It was official: the world's second major Zika outbreak was on.

That confirmation, issued on October 30, reported a total of 600 suspected and confirmed cases from multiple islands, suggesting that the virus had spread quietly for weeks before even French Polynesia's impressive surveillance network picked it up. Within two months, it had reached all 76 inhabited islands across the five sweeping archipelagoes that make up the territory.

Dr. Didier Musso, chief of the institute's emerging diseases unit, told the local government about it and asked Paris for help. But the response was initially tepid. After all, the CDC had described Zika as mild.

Then, in early November 2013, something alarming happened.

Patients began arriving at emergency rooms in varying degrees of paralysis. Most reported having had Zika symptoms in the last 15 days.

The first was a woman in her 40s, with partial paralysis of her arms, legs, and face. She was treated with immunoglobulin and, within two weeks, went home. Her blood was sent to a military hospital in France, which found that, besides Zika, she had antibodies to all four types of dengue—some old infections, some new.

Dr. Sandrine Mons, head of the intensive care unit at the national hospital, recognized the paralysis cases as Guillain-Barré syndrome. It was not unheard of—the country had 3 to 5 cases every year, although there had been a bump of 10 cases in 2010, which had been a big year for dengue. But all of a sudden, there were dozens of victims.

“Up till then, everyone thought this was a benign disease,” Dr. Mons later told
Le Figaro
. “But as the Guillain-Barré cases kept going up, people began to be afraid. We ultimately had 42 cases, 16 of them in intensive care. The ones who were completely quadriplegic, with their breathing muscles paralyzed, had to be on a ventilator and artificial feeding for one to two months.” Even some of the less serious patients had brain inflammation, persistent partial paralysis of the face or one side of the body, and vision problems. One developed a heart rhythm problem.

Guillain-Barré is usually temporary but always frightening. Victims have typically recovered from an earlier flu, stomach virus, or bacterial infection and think they are out of the woods. Then they start to sense that something is wrong—often just a tingling in the hands and feet and a sense of malaise. But as it progresses up the limbs, it feels as if they were turning to stone. It can stop—or not. If it reaches the diaphragm and chest walls, a patient who isn't ventilated immediately will die, wide awake and terrified, staring at the ceiling.

It's an autoimmune reaction to the earlier infection, in which the immune system produces antibodies that attack the body's own peripheral nerve cells. There is no cure. There are two types of treatment that can speed recovery. If a hospital has a plasmapheresis machine—or, during an outbreak, enough of them—“plasma exchange” is done. The machine draws blood from one vein, separates out the red and white blood cells and the platelets and returns them to the patient through another vein. The clear plasma, which contains the dangerous antibodies, is discarded. The body is forced to make more plasma, and, if the autoimmune reaction has died down, it won't have the antibodies. The alternative is immunoglobulin treatment: patients get large doses of plasma from healthy blood donors. Their antibodies somehow block or counteract the dangerous ones. Immunoglobulin therapy has its risks, including the transmitting of viruses. But if no plasmapheresis machine is available, there may be no choice.

Guillain-Barré usually fades away, but it can take many months. Some victims never fully recover muscle tone. Some live with constant pain.

Four cases of “immune thrombocytopenic purpura”—a condition related to Guillain-Barré—were noted. Nothing much was made of them at the time, but that condition would come up later when the epidemic reached American soil.

Papeete's rehabilitation center, used to housing only a few patients, suddenly had 18 with serious neurological problems, and it struggled to cope.

The worst-off was Larry Ly, a big, broad-shouldered, 42-year-old soccer-playing maintenance technician. On December 3, he drove his daughter to school, came home feeling bad, and lay down. Within two minutes, starting from his feet, he became totally paralyzed, he told STAT news later. “I was lucky it didn't happen when I was driving,” he said. He struggled to breathe in the ambulance, and a hole had to be cut in his neck to intubate him.

He was in intensive care for eight months and was still in rehabilitation earlier this year to recover from surgery to free up an arm that prolonged paralysis had frozen in place.

As fear of the disease rose, the government stepped up mosquito spraying. Then the rumor spread that the insecticide, deltamethrin, and not some mystery virus, was responsible for the paralysis. Some mayors openly refused to spray their towns. French Polynesia's health minister, Beatrice Chansin, made a show of visiting paralyzed patients in the rehabilitation center and held a press conference at their bedsides to say spraying was crucial and deltamethrin was considered safe by the World Health Organization (WHO).
Finally, the French high commissioner stepped in, reminding the mayors that, under French territorial law, if they failed to take precautions against “fires, floods, dike breaches, landslides, avalanches, or
epidemics of contagious disease
,” they were not protected by their official status and could be held personally liable for the medical costs of their town's victims.

By April 2014, when the epidemic was officially over, the sentinel sites had reported 8,750 patients seeking care. The health department's epidemiologist, Dr. Henri-Pierre Mallet, calculated that 32,000 people, or about 12 percent of the country's population, had Zika symptoms severe enough to warrant a visit to a doctor. He concluded that the virus had reached 66 percent of the population.

The outbreak had been well underway by October 2013, when it was spotted. It peaked in December and had fallen to near zero by April. Not a case has been reported since August 2014.

The Guillain-Barré “attack rate” was judged to be 1 for every 4,200 Zika infections. That is about 25 times the normal background rate for the world, which is 1 for every 100,000 people per year.

The typical Guillain-Barré victim was a male over the age of 40.

None of the early reports mentioned microcephaly, or any particular problems for babies at all.

In an interview with the French news magazine
Le Point
in 2016, Dr. Musso was blunt and bitter. When he had asked for help, he said, the South Pacific Commission and the WHO had sent experts, but the government in Paris had largely ignored him. What help he did get came from the Pasteur Institute and a military hospital in Marseille, he said.

“We toughed it out alone to isolate the virus, develop diagnostic tests, manage the patients, and face the first serious unexpected complications,” he said. “When you live at the far end of the world, you learn to cope.”

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