RECIFE, Brazil — A procession of mothers pushed children in bulky wheelchairs down a long corridor at a health center in this northeastern Brazilian city, passing patients who glanced at the children, looked away, then looked back, quickly and uneasily.
The children were smartly turned out in Disney T-shirts, striped socks, plastic sandals. Girls had ponytails tied with big bows; many wore brightly colored glasses. And all were profoundly disabled, their limbs rigid, their mouths slack, many with foreheads that sloped sharply back above their dark eyes.
Most Brazilians know as soon as they see them: These are Zika babies, whose mothers were infected with the virus while pregnant during a virulent outbreak of the mosquito-borne illness in 2015 and 2016. The chief signifier at birth was microcephaly, unusually small heads that hinted at the devastating brain damage the virus caused while they were still in utero.
Seven years later, they are now children, many of them nearly as big as their mothers. The sight of them visibly startles people who have not thought about them for years. After the Zika epidemic did not turn into a pandemic that swept the globe, Brazil and the rest of the world moved on.
That has left families in this scrappy corner of Brazil, where the epidemic originated, struggling, mostly alone, to get help for their children, whose mysterious condition presents new challenges constantly. Many rely on charity, such as free physical therapy at the private foundation where they come each week in the procession of wheelchairs. Many of the women pushing the chairs wear T-shirts that say “Fight like a Mother” in Portuguese.
It has also left scientists unable to answer basic questions about the virus and the danger it could pose.
The virus is still circulating at a low level in Brazil and elsewhere in Latin America, as well as in South and Southeast Asia. But attention and funding dried up after the global concerns faded, said Dr. Diana Rojas Alvarez, who leads the Zika work by the World Health Organization.
“This is what happens when you have a public health emergency that affects tropical countries and that doesn’t have the global impact Covid had,” she said. “Initially, there was a lot of interest in developing good treatments and diagnostic tests — I remember being in a meeting where there were 40 vaccine candidates in development. But since 2017, everything went quiet.”
When Zika failed to cause much damage in the United States, both the Centers for Disease Control and Prevention, and the National Institute of Allergies and Infectious Diseases, scaled back their funding for work related to the disease. In Brazil, President Jair Bolsonaro, who took office in early 2019, made deep cuts to scientific research.
The few virologists and infectious disease specialists who continued to work on Zika after the epidemic subsided were forced to set it aside when the coronavirus pandemic hit, Dr. Rojas Alvarez said.
This phenomenon is not uncommon when a public health threat recedes. “All the mysteries of 2016, we still have them,” said Dr. Maria Elisabeth Lopes Moreira, a neonatologist who leads a project following children born with congenital Zika syndrome at a research institute for maternal and child health in Rio de Janeiro.
Seven years after the first mysterious cases of microcephaly were identified in Brazil, scientists are not much closer to understanding how a virus that was first identified 75 years ago in a forest in Uganda and never known to be harmful, turned up in the northeast of Brazil in 2015.
There, it took advantage of a heavy rain season and a booming crop of a mosquito species that made a fine new host to roar through the population, infecting about three-quarters of the residents of Recife and other cities. Scientists have established that a mutation in Zika allowed it to cross the barrier of the placenta in the womb — a first for a mosquito-borne virus — but they don’t know why the babies of some pregnant women who caught Zika escaped unscathed.
Between 7 percent and 14 percent of babies born to mothers who caught Zika while pregnant have congenital Zika syndrome, the spectrum of symptoms observed in infants exposed to the Zika virus in utero. In about 3 percent, the effects include microcephaly.
“What’s the difference between them? I don’t know,” Dr. Moreira said. One factor appears to be when in the course of her pregnancy a mother was infected: the earlier she caught the virus, the more severe impact on the baby. “But we don’t have the budget any more to do research.”
The researchers suspect they have yet to identify all of the affected children. Some babies born to mothers with Zika infections had normal head sizes and did not cause concern until they started to miss basic developmental milestones, and scans revealed they did not have key structures in their brains or had severe calcification of brain tissue.
Now, as the children born at the peak of the Zika outbreak begin to attend school, neurodevelopmental screening may identify more of them, said Dr. Ricardo Ximenes, an epidemiologist and professor of tropical medicine at the Federal University of Pernambuco, who co-directs a large longitudinal study following 700 children with congenital Zika syndrome in Recife. “There may be mild damage of the nervous system that may affect their learning ability, or not; we don’t know.”
For the children who have struggled since birth, there is a “spectrum of symptoms,” Dr. Ximenes said. Many have significant hearing and visual problems. The majority have needed feeding tubes implanted because they cannot swallow. They are hypertonic, with arms and legs held stiffened by overly contracted muscles. Many are now having hip surgeries because their joints malformed as they grew. They have a range of cognitive defects.
“Mostly, they froze in motor and intellectual development at six months,” said Dr. Demócrito de Barros Miranda-Filho, an epidemiologist and associate professor of infectious disease at the State University of Pernambuco, who is following the children with Dr. Ximenes.
Some of the Zika children have died. Dr. Moreira said about one-fifth of the children in the group she has followed since birth have died, many from respiratory infections they contracted after choking on food.
As research funds have dwindled, Dr. Moreira said, so has the once-robust support for the Zika families.
“We are basically forgotten,” said Verônica Santos, who spends her days and nights never more than a few feet away from her son João Guilherme, 7.
João Guilherme now weighs almost as much as his mother does, but he needs her to lift and move him, to attach and clean his feeding tube several times a day, to change his diapers, to suction his throat and to leap up from the floor where she sleeps by his bed and jostle him if an alarm tells her he has stopped breathing in the night.
João Guilherme twitches and groans in recognition when his father lifts him in the air, when his mother smothers him with kisses and when his sisters walk by and drop a smooch on his head. But that is the extent of his communication.
“Sometimes I wonder: What will happen to him when I’m gone?” Ms. Santos said.
Because Ms. Santos is a fierce advocate for her son, he gets physiotherapy and audio and visual stimulation every day. In Recife, about 80 of the Zika children receive free physical therapy and audiological and ophthalmological care at the Altino Ventura Foundation, a private charity. A few hundred more receive therapies and support through a large public hospital.
Many others, however, are being raised by families in the rural interior of the country and have no access to services.
The research group has also identified a cohort of children who were born with microcephaly but do not have brain damage. They have caught up developmentally as they have grown and now are “basically fine,” said Dr. Miranda-Filho.
“This was surprising,” he said.
Researchers say there are also new cases of congenital Zika syndrome occurring, since the virus continues to circulate in Brazil and beyond, said Dr. Albert Ko, an epidemiologist and professor of public health at Yale University. He plunged into research on Zika back in 2015 in low-income neighborhoods in the northeastern Brazilian city of Salvador, where he had been studying infectious disease for years.
Now, he said, transmission of the virus is not being detected there or in other communities that bore the brunt of the epidemic seven years ago because so many people were infected that immunity will likely last for many years. But there are other areas of Brazil and Latin America where the Aedes aegypti mosquito, the primary transmitter of the Zika virus, lives and where most of the population has never been exposed to Zika.
“My suspicion is there is transmission, but it’s not hitting the books, it’s not being detected,” he said. It was only the phenomenally high rate of infection seven years ago that caused enough babies to be born with microcephaly at the same time that it triggered alarm in pediatric neurologists and a rush to unravel the mystery.
Brazil registered 19,719 probable cases of Zika in 2022 by the end of July, likely a fraction of those that have occurred. Some 70 percent of Zika infections are asymptomatic, and if people seek medical help for symptoms, they may be diagnosed with or tested for dengue virus, which can look similar and is much more common. The only existing test for Zika is cross-reactive with dengue antibodies, so a person can easily be misdiagnosed.
“It’s still as urgent as it was back in 2015: We still need better ways to diagnose Zika infection,” Dr. Ko said.
A PCR test for Zika is only effective for about five days at the height of person’s infection. Very few of the women who were infected took that test, which left researchers retrospectively trying to establish that they had Zika during their pregnancies. Dr. Moreira said her priority is development of a test that could be administered at the birth of a child to every woman living in an area that has Aedes aegypti mosquitoes to show if she was recently infected so the newborn could be followed closely.
A strikingly large number of the women who had babies with congenital Zika syndrome, at the height of the epidemic, were Black or mixed race, at least in part because both fall disproportionately into the lowest income groups.
A number of studies have found that Zika infection was worse in low-income areas of cities than in high-income ones. One survey by Dr. Ernesto Marques, an associate professor of infectious diseases and microbiology at the University of Pittsburgh, found that about one-third of high-income women in Recife showed evidence of Zika infection in 2015, while almost two-thirds of low income women did. Low-income women are less likely to have air conditioning, more likely to live at the ground level, more likely to live in areas with poor sanitation, which provide more breeding territory for mosquitoes — and thus are more likely to have been bitten.
“How cruel that you have these gradients in risk that are just created by living in poor communities,” said Dr. Ko.
But Dr. Marques, who is from Recife and who dived into study of the pandemic when it began in 2015, wondered if there were other factors at work. “You see 97 percent of the cases are in lower socioeconomic classes, and only 3 percent in medium and high. Why is that?” he said. “It could be a variety of things: It could be immunological background, it could be other infections you’ve already had making you susceptible, it could be stress during the pregnancy. All these are the things that are associated with poverty in some way that facilitate the virus to cross the placenta.”
He hopes for funding specifically to research genetic factors that may increase susceptibility; while African ancestry has been shown to be protective against dengue, the related virus, he wonders if Indigenous ancestry, which mixed-raced Brazilians often have, will prove to increase vulnerability to Zika.
For now, Dr. Marques and his colleagues can do only the most minimal work on the virus. “Everyone was basically obliged to work on Covid since 2020,” he said. “My lab closed completely, and I could only do work if it was related to Covid.”
At the height of the Zika crisis, the United States government led investment in the search for a vaccine. Dr. Marques called it a model for the Operation Warp Speed effort to find a Covid-19 vaccine.
But this was “turtle speed, not warp speed,” he said, and the vaccine candidates never got past Phase 1 before most interest passed.
It is difficult to test a vaccine without an active outbreak of the virus, but Dr. Marques said there should be a stockpile of candidate vaccines manufactured and ready to deploy if and when there is another surge of cases. There is no antiviral Zika treatment, another research project largely abandoned when the disease waned.
After the outbreak in Brazil, Zika turned up in South and then Southeast Asia, and then once again in Africa, where babies with microcephaly were born in Angola in 2016, although on a much smaller scale than in Brazil. The range of the main vector mosquito is expanding steadily because of climate change and urbanization — two billion people live around the insects now, almost all of them in areas without reliable access to testing or standard maternal screening for fetal development.
But if the virus arrives in a new place when it is not peak mosquito season, then it may not trigger a detectable outbreak. “Are Indians and Thais less susceptible, or are we just not detecting it?” Dr. Ko asked. “Is congenital Zika syndrome being misdiagnosed as something like toxoplasmosis?”
It’s puzzling that the global trajectory of the disease has looked so different from that in Brazil, he said, and it is urgent to answer the question of why. “It is going to come back and hit us, whether it’s in the Americas or other places in the world,” he said. “We haven’t done what’s really needed and set up good surveillance in these low-income countries.”
The research institute where Dr. Ximenes and his colleagues work is cramped and decrepit. The rainy season sent muddy water cresting over the pathways between buildings, and the researchers spoke with a visiting reporter in a meeting-room-turned-supply-closet because their office was flooded. They seem weighed down by the quantity of questions they lack the resources to investigate.
“Is Zika gone, will it come back? We don’t know,” said Dr. Ximenes. “We have to learn as much as we can about what happened to mount a better response to another wave, if it comes.”
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