Scientists in the UK have started work on developing a vaccine to protect women against the Zika virus.
The £4.7m project, involving the universities of Manchester and Liverpool, and Public Health England, aims to have trials on humans up and running within the next three years.
When cases of babies born with abnormally small heads were first reported in late 2015, Brazilians were frightened and bewildered. Few had heard of the rare birth defect microcephaly, or were aware that it restricts growth of the skull and can cause learning, cognitive and motor difficulties. Nor did scientists know why cases were concentrated in Brazil’s impoverished, dry north-east. Two and a half years later, they still don’t.
The Brazilian government quickly blamed Zika – an obscure, mosquito-borne virus, previously unknown in the Americas. The World Health Organization declared a public health emergency, and panic grew as Zika spread across the region.
Then the outbreak petered out, leaving Brazil with more than 3,000 babies affected by what its government calls “developmental and growth alternations possibly related to Zika virus infection”.
Two-thirds of those children are here in the north-east. As of December, 438 were in the state of Pernambuco. Yet just 700-odd cases of what is now called congenital Zika syndrome have been confirmed across the whole of the rest of the Americas, according to the Pan American Health Organization. And nobody can explain the discrepancy.
“We were braced for a large epidemic of microcephaly. We didn’t see that,” said Albert Ko, professor of epidemiology and medicine at the Yale School of Public Health, who has studied the epidemic. “It’s still a little bit embarrassing that we don’t know these answers.”
Zika was first discovered in Uganda in 1947, and spread quietly through Asia. An outbreak in French Polynesia in 2013-14 caused a noticeable upswing in microcephaly cases. A 2016 study concluded that Zika arrived in the Americas between May-December 2013, when air travel from Zika-infected countries to Brazil was increasing. In June 2013, Tahiti even played a soccer match in Recife as part of the Confederations Cup.
By 2015, the virus was infecting huge numbers in Brazil’s north-east, said Ko, including up to 60% of all pregnant women.
“It’s this proverbial perfect storm-type situation,” Ko said. “There are some transmission chains that create large epidemics and others that just burn out and die.”
Zika reached much more populous states in Brazil’s south-east, like Rio de Janeiro. But Rio has almost half the congenital Zika cases of Pernambuco, and twice the population.
Oliver Brady is an assistant professor in arboviral epidemiology at the London School of Hygiene and Tropical Medicine, who is studying the virus for the Brazilian government. He said Zika’s spread was much patchier in Rio, where mosquitoes are also much less active in the cooler, drier winter. The north-east had more cases.
As one dose of Zika is believed to give immunity, when a second, less intense Zika outbreak followed in 2016, north-eastern cities like Recife and Salvador – capital of Bahia state, which had the most microcephaly cases, at 509 – had reached “critical threshold”.
“That’s the proportion of people that need to be infected for the disease to die out,” Brady said – 63%, in Salvador’s case.
Ernesto Marques, a professor of infectious diseases and vaccines at the University of Pittsburgh, said investigating hypotheses is hampered by a lack of reliable data on how many people caught Zika. It is tricky to diagnose: in most cases, the virus is asymptomatic, retrospective tests are not conclusive, and it is easily confused with viruses like dengue.
“There are a lot of unknowns in this story,” Marques said.
Marques is also a researcher at Brazilian government research institute Fiocruz in Recife, which set up a microcephaly epidemic research group to study the outbreak. Last December, the group published a study confirming the association between microcephaly and congenital Zika virus infection, which also eliminated suspicions that either vaccines or a chemical larvicide called pyriproxyfen, used in some areas around Recife, could have been responsible.
A further study this year found higher levels of microcephaly associated with precarious living conditions, with poor or open sewage and irregular water supplies favouring the proliferation of the Aedes aegypti mosquito that spreads Zika. In Pernambuco, 11% of people don’t have a fresh water supply and only 32% get their sewage treated, according to the state government-controlled sanitation company, Compesa.
One of the study’s researchers, Ricardo Ximenes, is a professor of epidemiology and infectious diseases at Pernambuco’s state and federal universities.
His team believes that microcephaly is just the tip of the iceberg, and that other malformations also caused by Zika will appear as children grow up.
Some scientists have hypothesised that dengue, another mosquito-spread disease present in Brazil, could increase the risk of Zika infection. And a new sibling study from researchers at the University of São Paulo, published in February, provided intriguing evidence that genetics could make some babies more susceptible to congenital Zika syndrome than others. It studied identical twins, where both had microcephaly, and non-identical where, in six of seven cases, only one did.
“There could be genetic variants increasing risk, they could be more present in that population,” said Mayana Zatz, a professor of genetics and the study’s coordinator. “But this is a hypothesis.”
In Recife, the city government reduced the density of mosquitoes by cleaning areas where the insects were intensely concentrated, educating citizens, and even monitoring water containers without lids from traffic control cameras, city health secretary Jailson Correia said. Now they are planning to release sterile mosquitoes.
But as officials from the UN and World Health Organization argued in 2016, improving Brazil’s woeful sanitation is also vital to stopping Zika. According to the WHO, 35 million people in Brazil lack adequate sanitation and 3.8 million are without safe drinking water.
The uncertainty is leaving Brazilian women unsure of the risks. In 2016, according to the state government, births in Pernambuco fell to 131,000, down from 145,000 the previous year. Brazil’s birth rate, which rose in 2014-15, also fell in 2016, by 5.1%.
Fatima Marinho, head of non-communicable diseases at the Ministry of Health, believes some women held off becoming pregnant – or had abortions, illegal in Brazil. Zika cases have almost zeroed out, she said, but another outbreak could happen. “We cannot discount this possibility.”