Of the many mysteries that remain about the Zika virus and its attack on the Americas, perhaps the most puzzling one relates to the bizarre distribution of babies born with Zika-induced microcephaly.
After so many such births were recorded in Northeastern Brazil in the last quarter of 2015, the country — and other places where the virus fanned out to from Brazil — braced themselves for a similar tsunami in 2016. But it didn’t materialize — at least not to the same degree.
A new and intriguing letter to the New England Journal of Medicine offers a theory for how to explain the missing microcephaly cases, the babies that were predicted to be born in Northeastern Brazil after Zika’s second wave of infection in the early part of 2016.
The authors suggest the region’s first wave of Zika may have been its only wave of Zika to date. Something that caused similar illness, likely the chikungunya virus, was probably responsible for the high level of fever and rash illnesses Brazil recorded in 2016, they theorized.
The authors — from the Brazilian ministry of health, the Oswaldo Cruz Foundation, the Pan American Health Organization, and the World Health Organization — used information from two databases that capture cases of microcephaly and Guillain-Barré syndrome.
When the data were slotted into a graph, the discrepancy was plain as day. In 2015, a large spike in GBS cases was followed about 23 weeks later by a wave of microcephaly births. But a corresponding spike in GBS cases in early 2016 was not.
Zika infection can trigger GBS, a progressive paralysis from which most people recover. And Zika infection in pregnancy can attack the fetus, leading to microcephaly and other neurological birth defects.
Chikungunya infection can cause GBS. But chikungunya infection in pregnancy is not known to cause microcephaly.
“This is not a statement of fact and proof. This is the best hypothesis,” said Christopher Dye, senior author and an epidemiologist with the WHO.
“The cases in the first year, back in 2015, were really Zika cases. And that’s why we saw the microcephaly in 2015. But in 2016, it was predominantly chikungunya, not Zika, and that’s why we saw Guillain-Barré, but not microcephaly.”
Dye said based on reports of rash and fever in Northeastern Brazil in early 2016, it was expected that about 1,000 babies would be born with Zika-induced microcephaly from late summer onward. Instead, about 80 were recorded in the region.
For many diseases, this type of data mining and hypothesizing would not be needed. During a wave of illness, testing of the sick would show what was infecting them. And studies looking at the blood of people who had previously been ill would indicate how broadly a pathogen had spread.
But one of the vexing dilemmas of the Zika virus is that it so closely resembles related viruses that testing cannot always tell whether a person is infected with Zika or something similar, like dengue. Widespread testing hasn’t been done, Dye said.
He and his co-authors acknowledged there could be other explanations.
For instance, from the earliest stages of the Zika outbreak in the Americas, questions were raised about the high number of microcephaly cases in Northeastern Brazil. No other place experienced so many, leading people to ask whether there was something else there — a co-factor — that exacerbated the impact the virus had on the population of the region.
Dr. David Heymann, who was the chairman of the WHO’s Zika emergency committee — which has been disbanded — told STAT the committee looked at issues like population crowding in the cities of Northeastern Brazil and the nutritional status of people there, among other things.
But no clearly obvious co-factor came to light. And some — questions about local use of insecticides — were ruled out, Dye said.
The letter’s authors cannot exclude the possibility that there was a co-factor there, Dye said. But the fact that there were few microcephaly cases the following year means that the co-factor would have been missing in 2016 — and that makes it less likely.
The authors also noted a third possibility — that women in the region who had seen the possible outcome of a Zika infection in pregnancy might have either avoided pregnancies in large numbers or terminated pregnancies. But if the maternity wards of hospitals in the region had emptied out in 2016, the world would have heard about it by now.
“If there was a huge effect like that, it would have been big news very quickly. It would have been very visible,” Dye said.
If the theory — that Zika blew through Northeastern Brazil in one wave — is correct, it likely means so many people there were infected in 2015 that there were few still vulnerable to the virus in 2016. In some ways, that may be a good sign; it might suggest Zika outbreaks are swift.
But it doesn’t mean the virus is done. More likely, said Dye, is that Zika will return after births create pools of people who have no immunity to the virus, hitting perhaps when people aren’t expecting it.
“But we really can’t rule anything out. And we’re ready for further surprises on Zika virus,” he said.