The Pandemic Century

by The Pandemic Century- One Hundred Years of Panic, Hysteria

  In addition, there is the ongoing question whether prior exposure to another arbovirus infection or vaccination against yellow fever confers cross-immunity to Zika or, conversely, makes an individual more susceptible. Turchi points out that prior to the 2015 Zika outbreak, Pernambuco had not suffered a major dengue epidemic for several years, whereas in central Brazil and the southeast, dengue had been a more recent visitor. Moreover, the highest rates of CZS were seen in younger women—precisely the group who had less time to be exposed to dengue or to get the yellow fever vaccine. On the other hand, in vitro studies by Marques and his colleagues using serum from pregnant women suggest that the presence of dengue antibodies can make Zika infections more severe. The technical term is antibody-dependent enhancement (ADE). In layman’s language the Zika virus latches onto the dengue antibodies and uses them as camouflage to evade the immune system and ease its entry to a human cell. “Think of it as the viral equivalent of a Trojan horse,” said Marques. When the epidemic broke, such was the demand for testing that his laboratory became a public reference laboratory. Later, Marques and his colleagues developed a rapid diagnostic test for dengue, making it easier to diagnose and differentiate it from Zika. His principal focus now is whether or not ADE might explain the high microcephaly prevalence rates in the northeast and whether high antidengue titers confer protection against Zika. However, he does not discount the possibility that the high rates might be due to an unknown environmental cofactor. “There is still so much we do not know about Zika,” Marques acknowledged. “We have decades of work ahead of us.”

  Like Turchi, Marques was full of praise for Brito, and I was looking forward to meeting him face-to-face. Although we had previously spoken by Skype, his English was halting and as my Portuguese was nonexistent I feared much may have been lost in translation. Fortunately, when we did eventually meet at a restaurant near my hotel, he brought his daughter, Celina, a second year medical student, to translate. The restaurant specialized in tapioca, the traditional accompaniment to any meal in Pernambuco, and after ordering some tapioca flour pancakes we got down to business. Why, during previous Zika outbreaks, had the association with microcephaly and neurological disorders been missed? Why did he think that no one had made the connection before?

  “My father says that when the first microcephaly cases appeared it was easy for him to make the connection because he had been following the Zika epidemic from the beginning,” said Celina. “So naturally one of the first questions he asked the women was whether they remembered having a rash during pregnancy.”

  Yes, but what was it about Pernambuco that made the microcephaly cases so obvious? In other words, why did it become visible here and not somewhere else?

  Brito furrowed his brow as Celina translated my question. Then, nodding intensely, he explained that it was all a matter of numbers. French Polynesia has a population of just under 300,000, whereas the population of Pernambuco is nine million, of which four million live in Recife and the greater urban area. Pernambuco also has a very high birthrate, with some 170,000 babies being delivered at maternity wards across the state every year. In addition, in French Polynesia the microcephaly cases were scattered across the archipelago, whereas in Pernambuco they were concentrated in a handful of hospitals in and around Recife. The result was that it did not require much of an increase in the prevalence rate of microcephaly for these cases to come to pediatricians’ attention. “If you have twenty cases in one room in one week you can’t miss it. That’s why it was easier to recognize here.”

  It was a good answer, the answer you would expect an epidemiologist to give, and as I mulled it over afterwards I was reminded of Turchi’s comment that “her grandmother” could have spotted the microcephaly cases. However, it did not address the deeper questions of causation, of why the risk of microcephaly seemed to be so much higher for women from poor neighborhoods, what the role of social conditions was, and how the provision of adequate water services and sanitation systems affected the transmission dynamics of Zika in Recife and other cities in Brazil. Nor did it address the issue of what measures were needed to interrupt the transmission of the virus by mosquitoes and reduce the risk of Zika infections in the future. Those were questions that were best answered by an entomologist and perhaps by a sociologist.

  Ever since Haddow and Dick isolated Zika from an A. africanus mosquito in Uganda in 1948, it has been assumed that Aedes is the principal vector of the virus in the wild. In Brazil and other parts of South America, most studies have focused on A. aegypti. In addition, Zika can be transmitted by the “Asian tiger mosquito,” Aedes albopictus, which ranges as far north as Chicago and New York during the northern summer.¶ However, Zika has also been isolated from several species of Culex, including C. quinquefasciatus, which is abundant in Brazil, as well as in Asia. Moreover, unlike Aedes, which prefers clean water, C. quinquefasciatus favors dirty water and is happy to breed in sewer runoffs and canals clogged with refuse and other debris.

  In an office a few doors from Turchi’s, another Fiocruz researcher, Constância Ayres, had been taking a closer look at the Culex mosquito and the evidence that it might play a role in transmission. A slim energetic woman with the posture of a ballet dancer, Ayres began by collecting Culex and Aedes mosquitoes from different neighborhoods around Recife and raising them in an insectary. Next, she allowed both sets of mosquitoes to feed on infected blood in her laboratory. Then, a week later she collected saliva from the mosquitoes and assayed them for Zika. Positive results were obtained for both sets of mosquito. In addition, Ayres was able to recover Zika virus from the salivary glands of the Culex, a necessary condition for a “competent” vector. However, despite these results, many experts refused to accept that Culex might be responsible for spreading Zika in the wild, so in 2016 Ayres returned to the field and, using an aspirator, collected more mosquitoes, this time vacuuming them up from residences occupied by individuals with symptoms of Zika. When she returned to the lab and examined her catch, she found she had nearly four times as many Culex as Aedes. Next, she separated out the female mosquitoes of each species, divided them into pools, and assayed them for Zika. Three of the C. quinquefasciatus and two of the A. aegypti pools were positive for Zika.

  Unlike Aedes, Culex is not a sip feeder—the mosquito typically takes just one blood meal per night. However, they are about twenty times as abundant as Aedes in urban areas of Recife with the highest concentrations of microcephaly. The mosquito is similarly ubiquitous in Micronesia and French Polynesia. Interestingly, in these areas researchers were unable to detect Zika in wild-caught Aedes. Unfortunately, no one thought to test C. quinquefasciatus in these places, so it is not known if it could have been a vector for the Zika epidemics there, but the possibility cannot be ruled out.

  If Ayres is right, her findings have important implications for ongoing vector control strategies aimed at reducing the threat of Zika and other arboviruses. At present, mosquito fumigation measures are directed at the Aedes. This is not surprising given its role in transmitting dengue, but Ayres is furious at suggestions by local health chiefs that this is why Recife has not witnessed another outbreak. “The reason we have not seen another Zika epidemic is because the majority of the population now has antibodies. It is not because the mosquitoes that transmit the virus have been eliminated. Unless something is done about Culex, I predict that once immunity wanes, Zika will return.”

  Unfortunately, that is a message no one appeared interested in hearing. Instead, the week I visited Recife, a German biotech company was gearing up to release male A. aegypti mosquitoes artificially infected with Wolbachia bacteria in Corrego do Jenipapo, a sprawling favela in the northeast of the city. The bacteria, which is harbored by 60 percent of the world’s insect species but not Aedes, renders the offspring of the mosquitoes infertile, thereby reducing the size of Aedes populations and their ability to transmit Zika and other arboviruses. Similar trial releases of Wolbachia-modified mosquitoes have taken place in Rio and Medelli
n, in Colombia, and similar genetic modification techniques are being used on the Anopheles mosquitoes that transmit malaria. The trials have the backing of major charitable funders, including the Bill and Melinda Gates Foundation in Seattle, Washington, and the London-based Wellcome Trust, not least because they can be conducted in distinct geographic areas and the effects are relatively easy to quantify using scientific measures—one of the key requisites for global health interventions “from above.” Meanwhile, low-tech ground-up control measures, such as providing bednets and screens for windows, are neglected, as are urban renewal programs that might improve waste management and the provision of water services to the poorest, mosquito-blighted communities.

  One day I accompanied Ayres’s mosquito collectors on one of their regular sweeps through Jaboatão dos Guararapes. The aim was to visit ten addresses in the favela and vacuum up mosquitoes from people’s bedrooms and living rooms, but in the event one of the portable aspirators failed, so it was only possible to visit five addresses. The residents were for the most part elderly and crammed into narrow two- or three-room cinderblock dwellings, one on top of the other. Only two had indoor toilets, and all the cooking and washing took place in the same room, or, if they were lucky, a backyard. Ayres’s top mosquito collector, Miguel Longman, led the way, running his battery-powered Horst Armandilhas aspirator along the walls and countertops, before concentrating on the ceilings and hard-to-reach corners. A typical haul, he told me, was fifty to sixty mosquitoes. While he unhooked the net on his aspirator to inspect his catch, I asked the couple whose home we were in how often they got piped water. Twice a week, came the reply. And the other days? They pointed to two plastic tubs filled with dirty dishwater in their kitchen and a series of water containers lined up on their windowsill. As with the other homes we visited, the windows had no screens, although in this case I noticed their bedroom had a mosquito net. Had she or her husband had Zika? No, came the reply, but several of their neighbors had.

  Later that day, back at IAM, Ayres introduced me to Andre Monteiro, a Fiocruz public health engineer. Monteiro is an expert on the hydrology of the greater Recife area and has made a close study of the city’s sanitation system. Only 6 percent of households in Jaboatão dos Guararapes have access to sewage services, he told me. By contrast, for Recife as a whole the figure is 30 percent. Most of the waste is sluiced into rivulets that flow through people’s backyards and empty into the canals and storm sewers designed to prevent flooding. Up until the 1800s most of the city comprised mangrove swamp, so excess rain water was easily absorbed or was able to flow out to sea with the falling tide. But in the nineteenth century, as Recife expanded, the mangrove swamp was gradually covered to make way for new buildings and roads. To compensate for the loss of natural drainage, Recife’s engineers, inspired by the example of the Dutch, built 200 kilometers of canals, threading them through Recife’s backstreets and alongside the city’s rivers. However, by the 1970s many of the canals had fallen into disrepair and were not being properly maintained, leading to frequent floods (the largest, in 1975, saw 80 percent of the city under water). At the same time, favelas in hills to the north of Recife begun suffering catastrophic mudslides, culminating in one in 2002 in which fifty people lost their lives. But perhaps the city’s most embarrassing moment came in 2013 when a Reuters photographer captured the image of a nine-year-old boy bobbing about in a refuse-filled canal near his home in Canal do Arruda, a favela in northeast Recife. It later transpired that Paulinho da Silveiro was combing the canal for bottles and other recyclable material he could sell and, together with his brothers, was a regular visitor to the polluted waterway. The shocking images prompted the municipal authorities to launch a clean-up campaign, and, although Recife’s canals and rivers are flowing freely again, at low tide it is common to see the river banks choked with plastic bottles and other litter. “The rubbish is a big problem,” says Monteiro, “not only because it affects drainage but because of the mosquitoes that breed in the trapped water.”

  At the end of our interview, Monteiro showed me a heat map of Recife with the areas with the highest numbers of microcephaly cases marked in oranges and reds. Although there were orange dots sprinkled throughout the city, including in middle-class districts such as Boa Vista, the deepest reds coincided with the favelas to the north and south.

  The following day, in search of the mothers of some of these microcephalic babies, I visited a specialist rehabilitation center for sight-impaired children in Ipitunga. Nearly half of children with CZS have severe vision problems due to lesions in their retinas or optic nerves, as well as, in some cases, neurological and cortical-based impairments. To address their vision deficits, Altino Ventura, a medical charity specializing in the treatment of ophthalmic conditions, had already provided several children with corrective magnifying goggles and intensive rehabilitation. Now it had also designed a multisensory kit to help mothers train their children to focus on objects and interact with them better, and had invited several women to test the devices at its Menina dos Olhos rehabilitation center.

  I arrived to find mats with cushions for the children already spread out on the floor and volunteers removing items from the kit—ping pong paddles with bright, painted faces, shakers with long glittery tassels. The session began with a prayer from Altino Ventura’s president, Liana Ventura. “Today is the Sabbath so let us take a moment to recognize all our hard work and the challenges we face in our lives. Lord, show us the light and make us instruments of inspiration and, above all, hope.” Ventura, a professor of ophthalmology, and her husband Marcelo Ventura have won numerous awards for their work. Their foundation, which is open around the clock seven days a week, processes up to five hundred patients a day at its emergency ophthalmic clinic in downtown Recife. Patients come from all over Pernambuco, drawn by the promise of free eye care and corrections for cataracts and other common vision problems. Altino Ventura conducts research into ophthalmological conditions associated with diseases like toxoplasmosis, syphilis, rubella, and cytomegalovirus, which are common in Brazil, and also runs an outreach program on Recife maternity wards. So when babies began presenting with microcephaly and unusual optical lesions in the fall of 2015, it was not long before Liana Ventura was showing an interest. Many of the babies had eyes that were crossed or swiveled aimlessly from side to side. In some cases, the vision loss was profound. “We realized the babies could see only thirty percent of the normal visual field and in a few cases they couldn’t see anything,” she told me. “It was heartbreaking. They could not see their mothers’ faces, they had no interest in anything around them. They cried the whole time.”

  Ninety percent of vision develops in the first year of a child’s life. Without the ability to see, a child’s ability to interact with their primary caregiver and to develop normally is greatly impaired. With corrective goggles, however, the transformation was dramatic. “Their faces lit up immediately and for the first time they smiled,” said Ventura.

  Ventura removed a ping pong paddle from one of the bags and handed it to Joane and Marcilio da Silva, a young couple form Olinda. Their son, Hector, was born with a severe astigmatism but with goggles can now see 60 percent of his visual field. Nevertheless, at twenty months he still could not sit up on his own unaided and had to be propped up with pillows in order to interact with the trainers. Sitting beside them, observing their progress was another young woman, Mylene Helena dos Santos. Aged twenty-three, dos Santos is the mother of three sons, including her youngest, David Henrique. Born in August 2015, David was one of the first cohort of Zika babies and is profoundly disabled. Strapped to a baby seat, with braces supporting his legs, he is unable to swallow properly and has a severe astigmatism. He developed a lung infection when some food got caught in his trachea and had to be rushed to the hospital. The doctors inserted a tube in his stomach so that he could be fed antibiotics, but, according to dos Santos, the tube caused him considerable discomfort. “It is too big so he wriggles the whole time,” she expl
ained. “The doctors have warned me to keep it clean, otherwise it could become infected. I would like to get him goggles but as long as he has stomach problems it is impossible. Hopefully, when he is better.”

  Dos Santos was five months into her pregnancy when an ultrasound revealed David might have a congenital malformation, but no one mentioned microcephaly and she had never heard of Zika. “I only knew about dengue,” she said. She does not recall a rash, but as her pregnancy progressed there were a series of complications, including a leak of amniotic fluid, and she very nearly miscarried. In the event, David was born seven weeks premature. A year later, both mother and son tested positive for Zika.

  Dos Santos is currently living with her parents in Jaboatão dos Guararapes, having separated from David’s father shortly after his birth, and relies on her extended family to care for her other children while she and David travel to medical appointments. “In the beginning everybody wanted to help,” said dos Santos. “But after a year it slowed down and I was removed from a government program. That’s when I turned to Altino Ventura for help.”