Zika (9 page)

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“If you infected them halfway through gestation, the offspring got the mouse equivalent of depression—they were withdrawn; they sat in a corner of their cage and didn't interact at all,” he said.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 impairment.” 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

B
EFORE
B
RAZIL, 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.)

Shortly after Brian returned to Colorado, he and his wife, Joy L. Chilson Foy, a nurse and the mother of their four children, had sex. Six days after he got back, he fell sick, with a rash, fatigue, a headache, and swollen joints. He was sure it was something mosquito-borne he'd picked up in Senegal; he was even surer when Kevin fell ill with the same symptoms. But four days after that, Joy also fell ill. Her symptoms were similar, but worse; she had bloodshot eyes that hurt in bright light, a bad headache, chills, and an intense red rash.

Brian also developed other curious symptoms: pain between his legs and difficulty urinating, suggesting an inflamed prostate, and then a reddish-brown tinge in his semen that looked like blood. Joy “was not happy about any of it,” he recalled.

But it was a puzzle: They were in northern Colorado. Joy had not left the United States in a year. There were no disease-transmitting
Aedes
mosquitoes in the Rockies, and even if there had been, it would have taken at least 15 days for a virus picked up by a mosquito to reproduce and make its way from the abdomen to the salivary glands.

Mosquito transmission seemed impossible. Perhaps, they thought, by a total coincidence, Joy had caught something communicable that was different but with similar symptoms. But there were no likely candidates, and whatever it was, their children didn't catch it.

Because Brian was a scientist, he had his own blood drawn, along with Kevin's and Joy's. Some went to the CDC for testing, and some he stored in his lab freezers.

The CDC tested for diseases known to circulate in West Africa. Brian and Kevin came up positive for antibodies to dengue. Joy did not.

But Brian and Kevin also might have had dengue from earlier trips. The CDC's answer was: “We think you two had dengue. We don't know what your wife had.”

For more than a year, that's where the mystery stood, until Kevin went back to Senegal. While there, he had a beer with an entomologist from the University of Texas Medical Branch named Andrew Haddow. As luck would have it, he was the grandson of Alexander Haddow, one of the discoverers of Zika. After hearing the symptoms, he suggested testing the stored blood for 16 different local viruses, including Zika, and once he got home, he helped them do so through a UTMB laboratory that had the right reagents.

Brian and Kevin came up positive for dengue again and for yellow fever—which made sense because they had had shots. But all three, including Joy, came out positive for antibodies to Zika.

The only obvious explanation was sexual transmission. In 2011, Brian wrote a paper for the CDC journal
Emerging Infectious Diseases
.

“If sexual transmission could be verified in subsequent studies,” he concluded, “this would have major implications toward the epidemiology of Zika virus and possibly other arthropod-borne viruses.”

The paper described only the curious case of Patients 1, 2, and 3, but Martin Enserink, a reporter for
Science
magazine, realized that they were the first three coauthors and called to ask about their identity, and Brian confirmed it.

Once Zika became a household word, Brian gave a few TV interviews about the case. Joy did not join him on camera. The initial
EID
article had been illustrated with a photo of her bare rash-covered back. But she wanted her 15 minutes of fame as the poster girl for sexual transmission of arboviruses to end right there.

“This stuff gets sensationalized,” Brian told me. “I'm fine with it, as long as it doesn't get too silly and crazy. I'm all about the science. But she's annoyed with the whole thing.”

Since their case, only one other had raised even the possibility of sexual transmission.

It was in a relatively minor paper by a French Polynesian scientific team. Its members and colleagues in New Caledonia had been the first to discover that the virus was present at high levels in urine as well as blood (and that urine tests were more accurate than blood tests). The case described a 44-year-old Tahitian man who had recently recovered from a bout of fever that sounded like Zika but that he had not been tested for. He finally saw a doctor because, although the fever was gone, he had genital pain and blood in his ejaculate. Tests showed that he no longer had Zika virus in his blood, although he did have antibodies. He did have virus in his urine and even higher levels in his semen. It was not clear exactly what the source was; the pain and blood suggested an infection of the testicles or perhaps the prostate gland. The authors surmised that theoretically it was possible that he could pass the infection on through sex, though there was no suggestion that he had done so.

On January 25, 2016, I wrote an article about the two cases. The CDC had issued its travel advisory for pregnant women only 10 days before. The Zika pages on its website at the time had a brief note saying there had been two cases in which the possibility of sexual transmission had been raised, by the Foys and the Tahitian man.

I called some infectious disease experts to learn what they thought. Given how fast the disease was spreading, did this possibility warrant more alarm?

Dr. Weaver at UTMB said he thought the risk was high enough to worry about. If he were a man with Zika symptoms, he said, “I'd wait a couple of months before having unprotected sex. And if my wife was of child-bearing age, I'd want to use protection, certainly for a few weeks.”