Zika

by Donald G. McNeil

  Moreover, the WHO declares emergencies awkwardly. So awkwardly that its bureaucrats rarely even use the word. They usually say “pikes,” from PHEIC, a “public health emergency of international concern,” although I have heard it pronounced as “picks” and even “fakes.” The agency had previously declared just three in its history, because it had obtained the power only in 2007, when the Geneva assembly changed the house rules.

  The first was in 2009, over the swine flu pandemic, the third was in 2014 over Ebola in West Africa. The second was an oddity; it was declared in early 2014, over polio. Polio was the opposite of an epidemic. It was on the brink of extinction. It had been held down to a few hundred cases a year globally for decades, but it had suddenly begun spreading again in Africa and the Middle East.

  In the 2014 Ebola outbreak, Dr. Margaret Chan, the director general, had been accused by Médecins Sans Frontières and others of waiting too long to declare an emergency. She was clearly not planning to make that mistake again, but even in top gear, the WHO is ponderous.

  It convened a committee of experts in Geneva on February 1 and invited various scientists fighting Zika to give evidence, all behind closed doors so that they could discuss data that was still unpublished.

  Later that day, on the “pretty unanimous” advice of the committee, according to its chairman, Dr. David L. Heymann, Dr. Chan declared a PHEIC. She worded it very carefully: the emergency was not over the spread of Zika itself, it was over the possibility that Zika caused microcephaly.

  In essence, it was a plea for scientists around the world to cooperate on answering that question instead of hoarding their data until academic journals felt like publishing it. And it was an official wake-up call to the health ministers of countries with their heads in the sand that they had a problem.

  One of the things we Americans don’t realize is how truly indifferent many other governments are to the fates of their people. We’re used to our politicians reacting, even overreacting, to news, because they can remind voters at election time how quick they were. But many countries—whether nominally democratic, socialist, or communist—are run by elites focused on lining their own pockets or consolidating their power, and the possibility that their women—especially their poorest women—may have deformed babies doesn’t really move them. If their wives and daughters get pregnant, they can always move to Paris or London. The WHO’s leaders will never say that aloud about their club members, but they know it. Making those elites realize that a new problem is real, and not just something that Washington has cooked up for its own nefarious purposes, is part of the WHO’s job.

  On the ground, nothing really changed. The WHO does not have its own army of doctors, or an emergency fund. Instead, it requests help from national health agencies like the CDC and provides diplomatic cover when planeloads of them land in fragile but proud countries that might otherwise fear swarms of foreign doctors, many in military uniforms. That’s how, for example, Cuban and American doctors ended up working side by side in Ebola treatment units in Africa.

  The PHEIC did raise the disease’s profile, although it was already pretty high. It also boosted scientific cooperation in a different way: many medical journals, from the famous New England Journal of Medicine to the relatively obscure Cell Stem Cell, began posting Zika-related studies online as fast as they received them. Most scientists cannot fight their instinct to hoard data, because publication makes their careers. But when the journals took the brakes off, rushing research onto the web, the knowledge gained became a de facto form of international scientific collaboration.

  In fact, within a week, something extraordinary happened. All the major science journals signed a pledge called “Statement on Data Sharing in Public Health Emergencies.” It bound them to make all articles they published about Zika available free online for the duration of the emergency, instead of charging their normal subscription rates, which could run into hundreds of dollars. Research funders—both public ones like the National Institutes of Health and private ones like the Gates Foundation—also signed it, promising to require anyone to whom they gave money to share data as fast as it could be written up.

  One scientist set an example by going much further: he began doing his important experiments online, for anyone who wanted to follow them. David O’Connor, a pathologist at the medical school of the University of Wisconsin, had a colony of macaque monkeys. He infected several pregnant ones with the Zika virus and described their progress day by day. He posted their blood tests, amniocentesis results, and ultrasound pictures. One of the first things he revealed was that the high levels of virus in the monkeys’ blood persisted for weeks—a very bad sign, since nonpregnant people usually clear the virus in about ten days.

  The WHO did not declare Zika a pandemic instead of an epidemic. Its definitions of what constitutes a pandemic sometimes shift, but usually refer to a “novel” virus. Zika wasn’t novel, since it was discovered in 1947 (although a new fight could eventually arise over that if genetic sequencing shows disease-altering changes, such as a mutation that made it more lethal). Declaring a pandemic would probably not have changed anything for the United States, but some countries have response mechanisms that are triggered by it.

  Thankfully, no one asked the WHO to referee a fight over the name “Zika.” As with “Sin Nombre virus,” naming conventions had created a nightmare in the 2009 flu pandemic. That novel influenza virus had first been spotted in a pig-farming town named La Gloria in Mexico’s state of Veracruz. (Which was unusual because, historically, new flus were first detected in Hong Kong, and it was assumed that they originated on the pig and poultry farms of southern China.)

  Flus have been around forever, but they become “novel” easily because they have eight loosely connected genes that can be readily swapped between viral strains in a game of mix ’n’ match. The new mix had two pig genes and arose in a piggery, so it was called a “swine flu” even though it was by then a human one, too. At that point the pork industry howled, saying the name was killing bacon sales. The name also sparked a crisis in Egypt, where the government slaughtered 300,000 pigs belonging to the Coptic Christian minority. It was religious prejudice, not public health; Egypt didn’t have a single case of the flu then. It also had unforeseen consequences, since the Copts collected Cairo’s garbage to feed their pigs.

  Bending to pressure, the WHO stopped saying “swine flu.” There was a long history of naming flus after their supposed places of origin—the Hong Kong flu, the Asian flu, the Russian flu, the Spanish flu. But a PAHO official strongly objected to “Mexican flu” or “Veracruz flu,” or even “La Gloria flu,” claiming that any place-name would demonize people from that place. Maddeningly, the WHO kept changing its institutional mind. First, it called the new flu just “H1N1,” but that was confusing, because there is a seasonal H1N1. Then it was “A (H1N1) S-O.I.V.” for type A (H1N1) swine-origin influenza virus. But headline writers and television anchors refused to touch that. Finally, it became “Pandemic (H1N1) 2009.” But just calling it the 2009 swine flu has stuck.

  The WHO emergency merely raised the appetite for stories. My colleague Catherine Saint Louis did one about microcephaly and its consequences for children, explaining that some were profoundly disabled, while some were called “microcephalic” but simply had small heads and were of normal or near-normal intelligence. The BBC did twinned profiles of two British boys close in age to each other. One could run and kick a soccer ball clumsily but could not speak words and had emotional struggles. The other had a smallish head and complained that it ached, as if his skull wasn’t big enough for his brain. But he was articulate and apparently doing well in school.

  French Polynesian scientists and colleagues in France released an important paper in the Lancet, a British medical journal. After reading the headlines about babies with microcephaly in Brazil, they had begun a hunt through the island’s records of births and medical abortions after their Zika
outbreak. They had found 19 cases of congenital abnormalities, including 8 of microcephaly, 7 of them in a tight cluster of pregnancies that had begun during four months when the epidemic was peaking.

  My colleague Sabrina Tavernise interviewed Brazilian doctors about their first recollections, and did a story about mosquito control and how hard it was to kill Aedes aegypti because it bred and lived indoors with its victims, as cockroaches do, not off in the swamps, as some other species did.

  From Brazil, Simon did one describing the tremendous surge the country had had in Guillain-Barré syndrome a year earlier, in early 2015, as soon as Zika had turned intense. It had been noticed by the health authorities, there had been worrying headlines in Brazil, and some scientists had noted French Polynesia’s experience, but it had not alarmed the whole world. He found Patricia Brito, a 20-year-old bakery cashier who was in intensive care for 40 days and said it was “more terrifying than any horror movie,” and Geraldo da Silva, a 43-year-old construction worker who said he had felt he was “drowning in a sea of mud.”

  Another rare Zika complication that was a footnote in the academic articles about Polynesia eventually made headlines because it caused the first American death. It was an unstoppable case of immune thrombocytopenic purpura, a tongue-twister of a name that means “purple skin caused by leaking capillaries caused by low platelets (thrombocytes) caused by an immune system problem.”

  The first American to die of Zika was not a baby but a Puerto Rican man in his 70s. He succumbed in February 2016, but the connection to Zika wasn’t confirmed for two months. First, the health department and its CDC advisers had to find the antibodies in his blood—antibody testing takes much longer in tropical areas because dengue and yellow fever cross-react on the preliminary antibody tests, creating false positives. To distinguish them from each other, scientists must do “neutralization assays,” a version of the same work that Zika’s discoverers did in mice, but carried out in flat flasks of live cultured cells instead. It is faster than using whole mice, but still takes days or weeks. Then they had to dig up his medical records and interview his family and his doctors to be sure he hadn’t had anything else.

  The man was reasonably healthy for his age before developing Zika symptoms in January, quite early in the island’s outbreak. He recovered, and everything looked fine. But a few days later, he demonstrated “bleeding manifestations,” which the initial CDC report did not detail but, given the later diagnosis, presumably included blood leaking from his gums and nostrils as well as petechiae, tiny dot-like bruises all over his skin caused by leaky capillaries. If the bleeding doesn’t stop, the dots grow until they merge, becoming purpura.

  That would have alarmed him and his family. He went to a doctor, who hospitalized him. In less than 24 hours, he was dead.

  Immune thrombocytopenic purpura (ITP) is related to Guillain-Barré, except that the antibodies triggered by the late immune reaction don’t attack the nerve cells. They attack the platelets, which the blood needs in order to clot. Without them, one simply bleeds to death internally. If ITP had occured in Brazil, it had not appeared in headlines or in medical literature. By the time the death in Puerto Rico was confirmed, it had been declared the cause of death in three cases in Colombia.

  But that was a very rare condition. Another frightening possibility surfaced when I was in conversation with Dr. W. Ian Lipkin, the famous virus hunter who runs the Columbia University Center for Infection and Immunity.

  I asked him about the theory that microcephaly might be a consequence of an initial dengue infection that was followed by Zika.

  He argued that microcephaly didn’t need a viral one-two punch. Several years earlier, he said, his lab had given monkeys Bornavirus (a rare virus that attracted little attention until it killed three German squirrel breeders) and their babies had been microcephalic.

  What people didn’t realize, he said, was that microcephaly was just the tip of the iceberg. Regarding Brazilian kids whose mothers had Zika but who appeared healthy at birth, he said, “I wouldn’t be surprised if we saw big upswings in ADHD, in autism, in epilepsy, and in schizophrenia.”

  That was a horrible thought, I replied. I’d assumed most damage would be apparent at birth. Didn’t schizophrenia usually strike young adults?

  Yes, he said, it would appear only later. But infections of the fetal brain could have a whole range of consequences. The gross ones were obvious; the subtler ones might emerge only in twenty years. “We’re looking at a large group of individuals who may not be able to function in the world.”

  And there was no way to know which outcome was most likely, he added. In 2010, his lab had infected pregnant mice with a synthetic RNA virus that replicated in fetal mouse brains. The results were wildly unpredictable.

  “If you infected them halfway through gestation, the offspring got the mouse equivalent of depression—they were withdrawn; they sat in a corner of their cage and didn’t interact at all,” he said. “If you did it two-thirds of the way through, they were hyperactive, the equivalent of manic.”

  I consulted other experts on fetal brain development, and they agreed with Ian. Schizophrenia runs in families, so it is assumed to be linked to genes. It is also brought on or worsened by trauma such as sexual abuse, abandonment, or heavy drug use. But there was a growing body of evidence that infections in utero played a role. For example, adults born in late winter and early spring had schizophrenia more often than those born in summer and fall. The suspicion was that flu viruses their mothers caught shortly before their births did something harmful. The virus itself didn’t have to reach the baby’s brain, the theory went: even the “cytokine storm” that the mother’s immune system generated in response could cross the placenta.

  In 1988, Finnish researchers looked at schizophrenia rates in age cohorts and reported that it was quite high in the slice of the population born right after the 1957 Asian flu.

  And a pioneer of schizophrenia research, Dr. E. Fuller Torrey, said he believed Rosemary Kennedy, President John F. Kennedy’s older sister, had been a victim of the Spanish flu. Born at its height in 1918, she struggled to learn to read anything harder than Winnie the Pooh and in her late teens developed schizophrenia symptoms, including violent outbursts. At 23, she had one of the earliest prefontal lobotomies performed on her, and she was institutionalized until her death. Some historians had blamed it on oxygen deprivation at birth, but Dr. Torrey thought subtle damage from the flu epidemic was a more likely explanation.

  Whether psychiatric problems are in the future of babies with Zika won’t be known for years. As of now, though, doctors in Brazil and elsewhere are describing problems that confirm Ian’s basic premise: fetal death and profound microcephaly are just the most extreme end of a whole spectrum of damage suffered by Zika babies. Some have normal-looking heads, but also both small empty spots and calcifications in the brain, produced when cells die and stop filling the spaces they should. The holes appear in different parts of the brain in different children, so some may have problems with decision-making while others may have trouble running or walking. Damage to the long nerves attaching the eyes and ears to the brain has also been observed.

  Eventually, scientists from French Polynesia and France were to publish a follow-up study on the 19 pregnancies in which brain damage had been detected, usually on ultrasound. Eleven of them had been aborted. (In cases of severe malformation, French law permits termination of even a full-term pregnancy, as long as the scans have been sent to the Prenatal Multidisciplinary Diagnostic Center in East Paris and a committee there has approved.)

  Eight babies were clearly microcephalic. Six were not, but had brain lesions. Five appeared to be normal but, after birth, displayed problems that indicated brainstem damage.

  Two have since died. Six that were still alive had been flown to France or Australia to be assessed and treated at top neurological hospitals. All six had “severe neurological impa
irment.” They were born unable to suck, swallow, or clear their lungs, so they lived in intensive care units needing tube feeding and regular aspiration. They had other problems, as well, including epilepsy or irregular heartbeats, jaws and tongues that hadn’t formed completely and thus partially blocked their airways.

  Some of the mothers of the 19, the report said, had had Zika, but without symptoms. They had had no warning until they saw their ultrasound scans.

  7

  Sexual Transmission

  BEFORE BRAZIL, EVEN before French Polynesia, the United States had a confirmed case of Zika. And it was one that would eventually make medical history, because it provided the first hint that Zika could be transmitted by sex.

  It had happened in 2008. Brian D. Foy, a skinny, boyish-looking 36-year-old vector biologist and malaria researcher at Colorado State University, was on a trip to Senegal, in East Africa. He and one of his grad students, Kevin Kobylinski, 27, were gathering mosquitoes.

  Photographs from their trip show them grinning and looking like ragged extras from the cast of Ghostbusters, wearing headlamps and backpack vacuum cleaners with long suction nozzles for aspirating mosquitoes out of the dark eaves of huts. They are standing on a wide dirt road in the countryside, and it is clearly hot. They are wearing cargo pants and T-shirts. “We were bitten a lot,” Brian said later.

  By coincidence, I had spoken to Brian in 2011, and later met him at a tropical medicine conference. His Senegal research was based on an idea I found fascinating: fighting malaria through xenointoxication, which sounds like intergalactic beer pong but is Greek for “poisoning the guest.” The villagers from whose huts he and Kevin had been collecting mosquitoes were all taking a deworming drug, ivermectin. After it got rid of their worms, it lingered in their blood for weeks, and, like the worms, the mosquitoes that sucked their blood died of it, too. His theory was that, given often enough, deworming pills could wipe out malaria in an area. (Other experts considered the idea clever but impractical because the distribution of deworming pills to remote villages even twice a year was hard, and the pills also caused rare but dangerous side effects that had to be tested for.)