by The Pandemic Century- One Hundred Years of Panic, Hysteria
If Heymann had been hesitating about recommending a pheic before, as soon as the committee began reviewing the evidence his doubts evaporated. The first shock was the presentation of new evidence from French Polynesia indicating that there had been an increase in neurological disorders, including Guillain-Barré, coincident with the 2014 Zika epidemic, something that had not been reported at the time. In addition, it was discovered that the authorities had overlooked several cases of neurological damage in fetuses. None of the affected mothers had recalled being ill during pregnancy, but four had subsequently tested positive for flavivirus antibodies, suggesting they could have been carrying silent Zika infections. These discoveries were game changers. As Chan was to put it: “Now it wasn’t ‘only Brazil’ any more.”
Another critical determinant was Heymann’s realization that the clusters of microcephaly and neurological disorders required “intensified research.” Without this research, and the deployment of rapid diagnostic tests to enhance the surveillance and diagnosis of Zika infections, it would be very difficult to establish a causative link or, conversely, to rule one out. Declaring a pheic would have a galvanizing effect, Heymann calculated, making a coordinated international response and the development of a vaccine that much easier. On precautionary grounds, then, and to avert a potentially bigger crisis, the committee was justified in ruling that the clusters represented an “extraordinary event” and a public health threat to other parts of the world. “That is the pheic,” Heymann explained, sitting alongside Chan as she announced the decision to the world’s press on February 1, 2016. “The pheic has to do with proving whether the clusters are or are not linked to the Zika virus.”
EVEN BEFORE THE WHO’s announcement, speculation about Zika and its effects on women’s gestation cycles was sparking hysterical headlines around the world. Now that hysteria had ramped up several notches, the Rio Olympics committee decided it had no choice but to issue its own travel advisory. Standing in front of a poster showing a mosquito with a red line through it and the caption “Mensagem sobre Zika” (“Message about Zika”), João Granjeiro, the director of medical services for Rio 2016, advised athletes and visitors attending the games to smother themselves in mosquito repellant, shut their windows, and use air conditioners to minimize the risks of being bitten. He could offer little reassurance to pregnant women, however. Instead, he echoed previous government advice that expectant mothers should think twice about travel to Brazil. By now, imported Zika cases in travelers who had recently visited South America were being reported from Ireland to Australia, and the United States had confirmed a rare case of sexual transmission of the virus in Texas, further ratcheting up the hysteria. “No one is safe from Zika” screamed the Daily Mail in an article revealing that more than 21,000 Colombian women had contracted the virus. “Living with Zika,” declared another story illustrated with pictures of women cradling microcephalic babies at a rehabilitation center in Recife—victims of what the Daily Mail referred to as the “head-shrinking bug.”
By June, with reports that the virus had spread to Mexico and the Caribbean and that the CDC was monitoring 279 pregnant women with confirmed or suspected Zika infections in the United States, the outbreak took on panic proportions. Newlyweds who had been looking forward to honeymoons in Puerto Rico and Costa Rica canceled their trips, while retirees, whose childrearing days were long behind them, reconsidered plans for leisurely Caribbean cruises. Soon athletes were also exhibiting signs of Zika hysteria. One of the first to fall victim was the world’s number one golfer, Jason Day, whose wife had recently given birth to their second child. When Day announced he would not be competing at the Olympics because of his concerns about Zika, several other famous golfers followed suit. Meanwhile, Greg Rutherford, the British Olympic long jump champion who was a hot favorite to repeat his gold medal–winning performance at Rio, revealed he had taken the precaution of freezing his sperm (even so, his partner, Susie, and their son Milo would not be attending). Even normally level-headed commentators such as Amir Attaran, professor of law and medicine at the University of Ottawa, got publicly involved, signing an open letter with one hundred other public health experts calling on the International Olympic Committee to move or postpone the games. “The fire is already burning but that is not a rationale not to do anything about the Olympics,” Attaran explained. “It is not time now to throw more gasoline on the fire.”
By now fumigation brigades, their numbers swelled by 55,000 Brazilian military personnel, were going door-to-door in Rio and other Brazilian cities, spraying insecticides and handing out educational leaflets aimed at persuading people to remove sources of standing water. The Aedes had not seen an assault of this magnitude since the 1930s when the Brazilian dictator Getúlio Vargas, with financial support from the Rockefeller Foundation, authorized a military-style program of larval reduction in an effort to eradicate yellow fever. Then, city and town dwellers had been compelled to destroy mosquito breeding sites or risk fines for noncompliance, but by 2016 Brazil was no longer a dictatorship and the authorities could not force disadvantaged communities living in the shadow of the Olympic village to cooperate. Instead, the last-minute blitz fueled conspiracy theories that insecticides and larvicides were to blame and that medical technology, not the mosquito, was the culprit. However, it was in Miami, another subtropical city 4,000 miles to the north, that the buzz and clamor around Zika reached fever pitch when in August the CDC issued a travel warning advising pregnant woman to avoid a one-square-mile area of the city. Fourteen people had been diagnosed with Zika after being bitten by mosquitoes in and around the trendy Wynwood arts district, and although Florida’s governor, Rick Scott, insisted that Miami was still open for business, the CDC begged to differ. As planes loaded with an insecticide called Naled stepped up their aerial bombing missions, Wynwood became a ghost town, prompting protests about “chemical warfare.” The protestors’ voices were soon joined by those of hotel and casino operators in and around South Beach, nervous about the impact the Zika scare was having on summer tourist bookings. The only silver lining was that the panic persuaded politicians in Washington to pass a $1.1 billion funding package for Zika that had been deadlocked in Congress for months. Though by the time Congress approved the bill in late September the summer mosquito season was drawing to a close, those funds were desperately needed for future Zika control measures and, just as important, research into vaccines.
Today, the panic over Zika is a fading memory. The Olympic Games went ahead as scheduled, and while a few athletes tested positive for the virus none developed serious illnesses or neurological complications. Nor did their wives return home to be confronted, nine months later, with the news that their children had microcephaly. And while the epidemic eventually spread to eighty-four countries, and the virus is now firmly entrenched throughout the Americas, at the time of writing Zika is no longer considered an international health emergency. The WHO lifted the pheic in November 2016 after a systematic review of the scientific evidence left experts in no doubt that Zika was a cause of congenital brain abnormalities, including microcephaly seen in newborns (six months later, in May 2017, Brazil’s Ministry of Health followed suit). There are even several candidate vaccines in the pipeline, but given the ethical problems of conducting trials with pregnant women—the main target for such vaccines—and the fact that vaccines themselves can sometimes trigger Guillain-Barré, making it difficult to distinguish the effects of vaccination from those associated with infection, such vaccines are unlikely to be available for several years. Meanwhile, the social and environmental conditions that turn Brazil’s favelas into fertile breeding grounds for Aedes and other Zika-bearing mosquitoes that transmit the virus have not gone away, nor have mosquitoes stopped taking blood meals.
IN JULY 2017 I traveled to Recife to speak to the Brazilian doctors, epidemiologists, and virologists who had been at the forefront of the outbreak. At that point Zika was no longer front-page news; in the first six months of 2017 the CDC had
registered just one case of local transmission in the United States. Moreover, with a huge cholera outbreak raging in Yemen, the WHO’s attention was firmly back on Africa. Arriving at my hotel in Boa Viagem within sight of Recife’s famous reefs, I found that the news shows were preoccupied with a yellow fever outbreak that had begun in Minas Gerais state and was now encroaching on the environs of São Paolo and Rio. But though Zika was no longer a pressing public health issue, there were still many unanswered questions.
For instance, though it had been established that the virus that triggered the outbreak in Brazil in 2015 was the same as the one that had caused the outbreak in French Polynesia two years earlier, and that both were descended from an Asian strain of Zika, it was still not known how the virus had reached Brazil. It used to be thought that Zika arrived during the FIFA World Cup that had kicked off in Rio in June 2014. This seemed plausible, particularly as one of the host cities had been Natal, until it was pointed out that no Pacific countries had sent teams to the competition. The next suggestion was that the virus may have been introduced during the Va’a World Sprint Championship held in Rio de Janeiro in August of the same year. This was more likely, as four Pacific countries (French Polynesia, New Caledonia, Cook Islands, and Easter Island) had sent canoe squads to the competition. However, this theory was undermined by a letter published in Nature in May 2017 in which an international team of scientists announced they had collected fifty-eight Zika virus isolates from Brazil and other countries in the Americas and sequenced their genomes. Using phylogenetic analysis to run the molecular clocks of the isolates backwards in time, the scientists showed that all the strains descended from an ancestral virus that had arrived in northeast Brazil around February 2014. If the analysis was accurate, that suggested Zika had been in Brazil six months before the sprint championship and fifteen months before the confirmation of the first Zika cases by Brazil’s Ministry of Health. Zika’s precise relationship to microcephaly presented a similar puzzle because it was still not known how and why the Zika virus triggered birth defects in some women but not others, or whether apparently normal newborns might present with developmental problems in later childhood. Nor could anyone say what the long-term prognosis was for Brazil’s Zika babies and what the risks were of sexual transmission of the virus.
I was keen to find out what Brito and Marques made of these questions and to hear their thoughts as to why the outbreak had proved so explosive in Pernambuco (by now, a paper in The Lancet had shown that the northeast had accounted for 70 percent of microcephaly cases during the first wave of the epidemic). I also wanted to visit Jaboatão dos Guararapes and other impoverished communities in the greater Recife metropolitan area and speak to entomologists investigating mosquito breeding patterns and Zika’s transmission dynamics. But most of all I wanted to meet the women who had given birth to the first cohort of microcephalic babies, and find out what provisions had been made for them and how they were coping now that the world’s interest had moved on. In short, I wanted to see what the epidemic looked like since Zika had once again become an object of neglect.
I was hoping to find some of the answers at the IAM, the research center where Marques has his laboratory. Located on a sprawling campus in northeastern Recife, it was here that Brito first presented his theory of a link between Zika and Guillain-Barré, and that Marques’s colleague, the Fiocruz epidemiologist Celina Turchi, coordinated the initial investigation into microcephaly. Realizing the scale of the threat, Turchi was instrumental in reaching out to other researchers around the world and lobbying the authorities to issue a public health alert. Such were the consequent offers of support, the director of IAM offered to lend her his office. It was here that, two years later, I caught up with Turchi sitting at a large glass desk surrounded by her assistants still busily sorting papers and responding to queries from the public. “Even today there are people who still believe the rumors that the epidemic was due to insecticides or the rubella vaccine,” she said. “The latest conspiracy theory is that the virus is being spread by transgenic [genetically modified] mosquitoes,” she added, rolling her eyes. “We have no choice but to respond to each and every one.”
A soft-spoken woman, Turchi’s voice becomes louder, her speech more urgent, as she recalled the shock of the first wave of microcephaly cases and the challenges facing Brazilian mothers of Zika babies as they struggle to raise severely disabled children in a climate of mounting austerity and cuts to public health programs. Visiting the maternity wards in the early days of the epidemic was “frightening,” she said. “I remember seeing four or five babies with no forehead and a very strange skull structure. They looked very different from babies with congenital microcephaly. My grandmother could have diagnosed it.”
One of Turchi’s first moves, once she had been briefed by Brito (“he had the whole thing worked out”), was to call other epidemiologists both in Recife and abroad and ask whether they had noticed similar increases in microcephaly, including during the epidemic in French Polynesia. A retrospective investigation of birth records there subsequently turned up seventeen cases of neurological malformations and showed that the peak had been missed because most women had terminated their pregnancies rather than give birth to microcephalic children. By contrast, in Brazil where abortion is illegal, it is very difficult to get a termination unless you are wealthy and can afford to travel abroad for the procedure.
At this point, Turchi began to worry that the cases in maternity wards in Recife might be the tip of an iceberg. “We didn’t know how it was going to turn out, but we could see that it was going to be something really big.” It was around this time that some pediatricians began urging the Pernambuco health authorities to revise the reporting criteria for microcephaly. Contrary to the suggestion that it was Brazil’s live birth system that had led to the increase in reported microcephaly cases, prior to December 2015 the Ministry of Health had lowered the head circumference limit from 33 cm to 32 cm, reducing the number of newborns likely to be categorized as microcephalic.
Now the figures are in, and it is clear that the upsurge was not a reporting artifact. In all, Brazil recorded 4,783 suspected cases of microcephaly and 476 deaths in 2015, as opposed to 147 cases in 2014. The highest rates were in the northeast, with 56.7 cases per 10,000 live births at the peak of the epidemic in November 2015. That rate was twenty-four times higher than the historical mean in Brazil. By contrast, in the southeast, where Zika appeared later and was generally less severe, the rates were far lower—5.5 cases per 10,000 live births, which is similar to the rates observed in the United States (the overall rate for Brazil was 18 per 10,000). The question is, how much of this increase was due to Zika, as opposed to another cofactor, and why was the peak observed in the northeast so much higher than in other areas of Brazil?
In an attempt to answer that question, in 2016 Turchi initiated a case control study with colleagues from the London School of Hygiene and Tropical Medicine in which women attending antenatal clinics in Recife were screened for Zika. The laboratory-confirmed cases were then followed to term, together with those of two controls who had tested negative for the virus. The babies were examined for microcephaly and other manifestations of congenital Zika syndrome with clearly defined denominators.
At the time of the epidemic, rumors abounded that the higher prevalence of microcephaly in the northeast might be due to exposure to insecticides used to control mosquitoes. Another widespread conspiracy theory was that the fault lay with vaccines administered during pregnancy. Now that the results of the study are in, both theories can be ruled out. Researchers found no statistically significant correlation between the incidence of microcephaly and exposure to insecticides or vaccines. By contrast the odds of association with prior Zika infection was 95 percent.
Unfortunately the study was unable to investigate the association—long suspected by researchers—between the incidence of microcephaly and a mother’s socioeconomic background. That would require better Zika seroprevalenc
e data in order to ascertain whether women included in the study are representative of the wider population. More importantly, because Zika was not a reportable condition at the time of the epidemic, researchers have no way of gauging the total number of babies born to pregnant women infected with Zika in 2015–2016 and thus whether the high rates of microcephaly observed in the northeast were really as high as they seem. Laura Rodrigues, a professor of infectious disease epidemiology at the London School of Hygiene and Tropical Medicine who works closely with Turchi, suspects that northeastern Brazil may have had a fast-moving outbreak of a particularly severe strain of Zika. However, Rodrigues also acknowledges that this is “a gut feeling” and without better data she cannot be sure.
Another open question is the extent to which the higher microcephaly prevalence rates may have been due to higher mosquito densities and women’s greater risk of exposure to Zika because of social behaviors and environmental conditions. Climate scientists point out that 2015 was an El Niño year in South America, with higher than normal amounts of rainfall in northeast Brazil, increasing the risk of flooding. Coupled with rising temperatures due to climate change, this could have accelerated the reproductive cycle and density of Aedes and the mosquito’s transmission of the virus. “I do feel it’s got to do with the environment and social conditions,” said Turchi. “Recife is a highly urbanized area, and it’s a city crossed by rivers with a lot of swamp areas, so there are lot of mosquitoes. And because it’s hot, people do not cover up: they are very exposed.” Indeed, in Jaboatão dos Guararapes and other poor communities it is not unusual to find upwards of a thousand people crammed into an area measuring one hundred square meters, and since many accommodations lack screened windows and even fewer have air conditioning, occupants are frequently bitten many times in the same night by the same mosquitoes. Then there is the fact that piped water supplies are erratic, meaning that many residents have no choice but to store water in bottles and buckets in their backyards, or that when it rains channels behind people’s homes fill with sewage and garbage, providing perfect breeding sites for mosquitoes.