Zika

by Donald G. McNeil

  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.”

  Dr. William Schaffner, the head of preventive medicine at Vanderbilt University Medical School said he thought just two cases were “not really enough to warrant a big public health recommendation from the CDC.”

  The world was still reeling from the CDC’s travel warning on the basis of thousands of cases, and every week saw two or three more countries added to the list.

  “But it’s provocative,” Dr. Schaffner added. “So someone else could recommend it. And it certainly should be studied.”

  Six days later, on February 2, 2016, there appeared another case of sexual transmission in Texas. Someone living in Dallas had gone to a country where Zika was circulating, had come back, had sex with a partner who had not left the country, and both had come down with Zika symptoms. There was only one explanation.

  I called the Dallas County Health and Human Services Department, asking for more details. The spokeswoman was unhelpful, offering nothing. She finally said that the other country was Venezuela. That was it—nothing about how the county learned of the cases, how it had investigated: nothing.

  Frustrated, I emailed Tom Skinner.

  “Got anyone who can talk about this case of sexual transmission in Dallas? I guess someone’s going to have to hand out condoms along with flyswatters.”

  He replied, “Call Dallas. We confirmed the test results but Dallas did the investigation.”

  I blew up. “Don’t fob me off on Dallas,” I wrote. “They don’t issue national guidelines. My desk wants to make it page one. I’d like to talk to someone ASAP, please. This confirms what scientists have suspected—sexual transmission possible. CDC pages have always mentioned this possibility down at the bottom, but no guidance given out (i.e., condoms, abstinence . . . ). Brits have counseled men to use condoms after traveling to Zika areas. Does CDC plan to issue similar advice?”

  Three minutes later he wrote back, “We’ll have a statement to you ASAP.”

  I should point out that I like Tom. I enjoy his good ol’ boy joking, hearing about his family and his invitations to join him in what he does for fun—attend NASCAR races with a big radio scanner so he can listen in as the drivers debate tactics with their pit crews. He’s very patient and good at his job. It’s not his fault that he’s stuck between his bosses and me.

  An hour and 20 minutes later, the CDC issued an oddly garbled statement. It described the bare details of the case, and then reiterated that the best way to avoid Zika virus was still to prevent mosquito bites, and that travelers should avoid getting bitten on their return to prevent local outbreaks. It repeated its recent advice that women should postpone travel to Zika-hit areas.

  But the statement did contain two sente
nces referring to sex. One read, “Sexual partners can protect themselves by using condoms to prevent spreading sexually transmitted infections.” That sounded as if it been lifted from standard CDC advice about syphilis and HIV. The other was quite odd for CDC-speak: “Pregnant women should also avoid exposure to semen from someone who has been exposed to Zika virus.”

  It concluded, “CDC will issue guidance in the coming days on prevention of sexual transmission of Zika virus, with a focus on the male sexual partners of women who are or who may be pregnant.”

  Three days later, on February 5, the agency did release more detailed guidelines. They suggested that men with pregnant partners wear condoms or abstain from sex for the duration of the pregnancy. For nonpregnant partners they did not specify for how long. (A couple of months later the CDC would refine those suggestions to eight weeks for men with no symptoms and six months for men with symptoms.)

  In retrospect, part of the coyness surrounding the whole Texas episode may have stemmed from something not revealed at the time. When the case was described in the literature two months later, it turned out that both partners were male. The Dallas spokeswoman had studiously avoided using pronouns like “he” and “she.” The CDC had taken pains to say that “in this instance there was no risk to a developing fetus,” when it might have been phrased more simply as “the female partner was not pregnant.” I don’t know why health agencies were reluctant to admit that gay sex could transmit the virus—it’s useful and pertinent public health information—but they went to absurd lengths to conceal it. As of May 31, 2016, the WHO reported 12 cases of probable sexual transmission in countries where mosquitoes were clearly not to blame, and three cases in which Zika virus was detected in men’s semen. All the transmissions were from men to others. In one case, oral sex was suspected but not proven. One man still had it in his semen 62 days after recovering from his fever.

  Sexual politics and CDC timing aside, the idea that a mosquito-borne virus could also be transmitted by sex was, for scientists, mind-boggling.

  “This is a paradigm shift,” Tyler M. Sharp, a CDC epidemiologist, said to me later. “I do arboviruses. I never thought I’d be working on an STD.”

  Viruses mutate constantly, which often shifts their virulence. Some influenza strains become lethal by producing proteins that jam a host’s immune response, for example.

  But one aspect usually remains fixed: how they are transmitted. Many viruses have spherical shells, but the shell surfaces are as different as those on tennis balls, BBs, and popcorn: they match receptors on the cells they infect, and a cell in the throat is very different from one in the gut or one in the vagina. Until recently, scientists believed that a skin virus never evolved into a sneeze virus and a bug-bite virus would never be transmitted by a subway pole.

  Everyone understands mutation. A Great Dane can be mutated into a Chihuahua. But this was like a dog mutating the ability to fly.

  Ebola had defied the stereotype, and that had been realized only two years before, though Ebola had been studied for more than thirty years. Ebola is transmitted by blood, vomit, feces, and contact with dead bodies. It is extremely lethal, but patients who recovered from infection had been considered safe. Then, toward the end of the West Africa outbreak, a woman came down with it, and the only logical explanation was that she had gotten it from sex. The outbreak was almost beaten, cases in the community were rare, and she had had no family contacts, funeral contacts, or anything else. Her one risk was that she had had sex with a former Ebola victim who had long before walked out of an Ebola treatment unit, apparently cured.

  Stunned scientists finally figured out that he must still have had live virus in his testicles. They realized that Ebola could, in rare cases, break into the body’s “immunologically privileged” zones—parts that are normally walled off from circulating blood and have their own sustaining fluids. They are not easily invaded by a virus, but once inside, the virus can replicate in peace, because it’s equally hard for antibodies and white blood cells to get in and kill it.

  The eyes are privileged, and the bizarre effect of Ebola breaking into one American victim’s eye was that it turned his blue eye green for months. The testicles are also privileged, presumably to protect the sperm from damage that might be passed to future generations.

  Zika, like Ebola, seems to be able to breach that defense. Sex is now considered the second-most-common mode of transmission of the epidemic.

  But as of now, no scientific estimate of how often it occurs has been published. And many important questions remain unanswered: Can a man transmit it without ever having symptoms? Does blood have to be in the semen? Can a woman transmit it?

  Scientists just don’t know.

  8

  New York’s First Case

  THE FIRST KNOWN case of Zika in New York City was not connected to Brazil. It occurred in 2013, but little was made of it at the time.

  And as with Brian Foy, it arrived in the blood of a young to middle-aged, highly educated white American male.

  I make that point only because I get regular emails from readers saying things like, “I read your story today about Disease X. This just proves how illegal immigrants are putting us in danger. With our weak border policies, any one of them could be carrying it into the United States and threatening the health of Americans. Why don’t you write about that?”

  In truth, yes, immigrants do bring some diseases to this country. But so do Americans. When the emails aren’t too rude (and ruder than me is a high bar), I answer them, pointing out that the 2009 swine flu spread through the eastern United States thanks to a group of students from a Catholic high school in Queens, New York, who went to Mexico on their spring break. The 1999 West Nile virus epidemic was almost undoubtedly sparked by a tourist returning from the Holy Land; the first cases were also in Queens (it’s where JFK International Airport is), and the strain was identical to one circulating in Israel. And the last polio outbreak in America, in 1979, took place in Amish communities in Iowa, Missouri, Pennsylvania, and Wisconsin. One member of the sect had picked it up at a Mennonite convocation in Canada. The Amish have been Americans since 1760.

  I heard about the case through an email from a public relations person representing the Jonas Nurse Leader Scholarship program. One of its scholars, a nurse-practioner named Dyan J. Summers, had written about it in an article for the Journal of Travel Medicine and at a conference for travel medicine specialists.

  When I called, Dyan described how the patient had walked into her office at Traveler’s Medical Service of New York, on Madison Avenue. He was a regular—a thin, fit 48-year-old who had just come back from a long trek with his wife that took them through Ecuador, Peru, Bolivia, Chile, Easter Island, and Hawaii, with a stopover in French Polynesia.

  He pulled his shirt out of his blue jeans and peeled it off, revealing a pinkish rash he’d had for eleven days.

  “I took one look and said ‘dengue fever,’” Dyan recalled. “He said, ‘I’m not so sure. I think it’s Zika.’”

  “I thought, ‘What?’ she said. “I’d heard of Zika. But nobody was thinking Zika. Nobody thought about Zika until this guy walked into the office.”

  “But you have to understand,” she continued. “This is a very, very bright guy. He’s very savvy, very well traveled. He knows about safe water, he takes his malaria pills and knows what altitudes are safe, he comes here for his pretravel vaccines. He was right on the money, that guy.”

  How had he known?

  “In Polynesia, he read articles about Zika in the local paper.”

  She had snapped a picture of his back, and took blood samples then, and again twenty days later. The CDC testing protocols for Zika at the time said it could do a PCR test for the virus itself only if the blood was taken in the first 10 days of symptoms, and the patient was past that. Otherwise, it required two samples of “convalescent” blood taken at least two
weeks apart so that it could do neutralization assays to compare antibody levels. The blood serum would be diluted again and again and then drops put on flat surfaces covered with cultured cells that had been infected with Zika. They would be checked every few days to see how many cells the antibodies had “saved” from death. If a barely diluted drop of blood from the first sample saved half the cells, and a very diluted drop from the second sample also saved half, then the antibody level in the blood must have increased.

  In his case, because he often put himself in the path of mosquitoes, the traveler had antibodies to dengue, West Nile, and Zika. But his Zika antibody levels had multiplied five times in the 20 days between the two samples, while the other two had remained stable. That was powerful evidence that what he was recovering from was Zika.

  As they talked about the virus’s ramifications, the conversation proved strangely prescient.

  First, the traveler said he had found an article about a scientist in Colorado who had infected his wife—Martin Enserink’s article about Brian Foy. Dyan called it up on her computer, read it, and advised him not to have unprotected sex with his wife. It was almost three years before the CDC issued the same advice.

  “What’s weirder,” she said: “He knew there were cases of Guillain-Barré connected to it.”

  When he was there, in the last week of November 2013, Dr. Mons and her colleagues had probably seen fewer than a dozen cases. It would be a couple of weeks before local newspaper articles mentioned it, and months before doctors collected their data and sent it to medical journals.

  I later met the couple, who live near Central Park. They asked that I use only his first name, Stephen, because they run an adventure travel agency under their married names. Even though he had completely recovered years ago, “people can get a bit freaky about exotic destinations,” he said. “Googling me up with ‘Zika’ can make folks skittish.”