The Zika questions that science needs to answer
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The pictures have grabbed the world by the heart. Tiny heads with wizened faces that look older than they should.

Brazil’s surge in babies born with a condition known as microcephaly has turned global attention to an outbreak of Zika virus, which is suspected to have caused a spike in the cases. On Monday, the World Health Organization declared the severe health complications associated with Zika to be an international public health emergency.

But even as we’re flooded with new information about Zika, the truth is very little is known about the virus, and scientists, public health leaders, and others are scrambling to learn more.

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Here are some of the important known unknowns:

Are we sure that Zika is behind the rise in microcephaly cases?

No. There is some evidence that supports the theory that infection during a woman’s pregnancy results in her child having microcephaly. Traces of the Zika virus were found in the brains of two microcephalic infants who died shortly after birth as well as in the amniotic fluid and placentas of several pregnant women who were carrying fetuses with microcephaly.

Those are strong hints. But scientists still need studies following more women who were infected in pregnancy. They also need studies that analyze, in minute detail, the experiences of women who had babies with microcephaly versus the experiences of women who had Zika but didn’t give birth to a microcephalic baby during the same timeframe.

Researchers are trying to study the virus in animals. If infection of a pregnant mouse, say, resulted in microcephaly in the pup, that would help answer the question. But scientists haven’t yet found an animal model — a species that gets sick in the way humans do — for Zika virus. A number of research teams are hard at work on this task.

How big is the increase in microcephaly cases in Brazil?

The initial reports out of Brazil were alarming. The country’s health ministry said there have been more than 4,000 cases since October. In the five years before the outbreak, there were about 175 cases a year.

But people have questioned the estimates. Brazil’s historic numbers are too low to be realistic, some experts have argued.

Dr. Cynthia Moore, director of the Centers for Disease Control and Prevention’s division of birth defects and developmental disabilities, recently said it is hard to come up with an accurate number of cases of microcephaly in a population. But she said in the United States it is estimated that between two and 12 cases occur in every 10,000 babies born.

Given Brazil’s birth rate — roughly 3 million babies are born there each year — there has likely been some under-reporting of the condition in the past.

That said, public health authorities elsewhere do believe Brazil has seen a real rise in microcephaly cases, and especially among severe cases.

If Zika virus infection in pregnancy can lead to microcephaly, when is the at-risk period?

Is infection at any point in a pregnancy dangerous? Or is it only early in the pregnancy? Knowing the answer could help public health officials fine-tune travel warnings for women who are pregnant or considering getting pregnant.

What percentage of women infected during pregnancy go on to have a baby with microcephaly? Is there any way to figure out why some women don’t while others do?

Again, this is about quantifying the risk. What seems clear is that it’s not 100 percent of the infected pregnant women. It’s some portion, but what portion remains to be seen.

What do we know about the links between Zika infection and Guillain-Barré syndrome?

Guillain-Barré syndrome is a neurological condition that induces progressive paralysis. People who develop it generally recover, and recover fully, though some die. Recovery can take months or longer, however. And some patients need to spend time on a ventilator, a machine that breathes for them, because they cannot.

A number of things can lead to GBS. Infections are among the triggers, as are some vaccines.

Several countries experiencing Zika virus outbreaks have reported a spike in the number of GBS cases. Brazil has reported an increase. So have Colombia and El Salvador, which recorded 46 cases over a recent five-week period. Normally the country sees 14 GBS cases a month.

It’s important to find out whether Zika infection is responsible for this increase and who is most at risk of developing it. Figuring out how often it develops is also crucial; patients with GBS require a lot of intensive health care, and countries will need to plan for these cases.

If the increase in GBS cases is linked to the Zika outbreak, what is the cause? Is the virus provoking the condition? Or is it being caused by an overactive immune response to the infection?

That may sound like, “Which came first? The chicken or the egg?” But it’s not a philosophical exercise. The answer has implications for the development of a Zika vaccine, said Michael Osterholm, who co-chaired an international committee that advised on the work to develop Ebola vaccines.

If it appears that GBS is being caused by the immune system’s reaction to the infection, that will raise questions about whether a vaccine would also induce the condition, said Osterholm, director of the University of Minnesota’s Center for Infectious Disease Research and Policy.

With GBS on the table, regulatory agencies like the Food and Drug Administration and pharmaceutical companies will likely be cautious when it comes to fast-tracking vaccine candidates, he suggested, especially considering the target market for the vaccine would be girls and women of childbearing age.

Why is a virus that has been around for decades acting differently all of a sudden?

The Zika virus was first discovered in 1947, recovered from a rhesus monkey in the Zika Forest of Uganda. In 1954, it was first found to infect a person. In the decades since, it has seemed like an insignificant virus.

But in 2007 it started to show up in new places — Yap, in Micronesia — and in an outbreak in French Polynesia in 2013-14 it was believed to be linked to increases in both microcephaly and GBS.

What happened? Why is the virus suddenly causing more serious health consequences for some people infected? Researchers are looking at the genetic sequences of recent Zika viruses to compare them to past samples to see if the virus has changed.

Alex Hogan/STAT Zika virus, which can be transmitted by mosquitos, has exploded onto the world stage.

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