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One tweet that shows how the Zika virus caught scientists flat-footed

Two years ago, hardly anyone had heard of the Zika virus. A handful of specialists knew of it as a mostly benign mosquito-borne disease that jumped from Africa to a few Pacific islands and occasionally caused, at worst, mild fever, aches, or rash. Nothing to fret about.

Then everything changed. The virus arrived in Brazil in 2014, likely brought by a World Cup traveler, and spread rapidly throughout Latin America, carried by the pervasive Aedes aegypti mosquito and infecting millions. Suddenly, Zika appeared to be doing things no one thought it could do — like (possibly) causing microcephaly, a birth defect characterized by shrunken heads, in infants.

Scientists were caught completely flat-footed. Thomas Frieden, the director of the Centers for Disease Control and Prevention, pointed out today that the entire research literature on Zika could, when printed out, basically fit into a shoebox:

That's it. That's everything we know right now. A small stack of papers.

To put this in context, a search on the PubMed database reveals 14,000-plus hits for "dengue fever," another mosquito-borne disease afflicting the region. For "West Nile virus," you get 5,962 hits. For "Zika virus," just 146.

That's a big reason why this outbreak has unnerved so many people. The Zika virus has infected more than 1 million people in Brazil and South America and has been spreading "explosively," as the World Health Organization put it, to Central America, the Caribbean, and even the southern United States. Yet there are all sorts of basic things that scientists are still racing to figure out. Like:

1) What does Zika actually do to people? Scientists have long known that the vast majority of people who contract Zika don't get any symptoms at all. A small fraction (20 percent or so) develop mild fevers, aches, and rashes.

Yet that might not be the end of the story. Since the Brazil outbreak, evidence has surfaced that pregnant women who contract Zika may be able to pass it to their infants, causing microcephaly (shrunken heads and incomplete brain development). Unfortunately, scientists still don't know how that happens, how often it happens, or whether it's a major risk or minor one. Maybe something else is causing the apparent uptick of microcephaly cases in Brazil. It's unclear.

And in the absence of clarity, we're seeing lots of panic and calls for drastic measures — many Latin American countries are simply telling women to postpone pregnancy.

2) Can Zika really cause Guillain-Barré syndrome in adults? This is a neurological condition that can cause muscle weakness and even paralysis, lasting weeks, months, or even years. A link seems possible, but scientists are still trying to figure this one out.

3) How do you actually test for and track the virus? Again, about 80 percent of people who get Zika don't show any symptoms (but they can still spread the disease if they are bitten by a mosquito). That makes monitoring the outbreak much, much harder. The fact that Zika may be mutating and the fact that it's similar to other flaviviruses like dengue and yellow fever make testing even tougher.

4) How does Zika actually spread? Right now, scientists think the disease is mainly spread when Aedes aegypti mosquitoes, a species ubiquitous in Latin America and the southern United States, bites an infected person and then bites an uninfected person.

But that still leaves plenty of questions. It's unclear whether Aedes albopictus, a similar mosquito with a larger range throughout North America, might also help spread the virus. And scientists are investigating whether Culex mosquitoes, another common species, could be a carrier.

(Javier Zarracina/Vox)

On top of that, scientists are learning that Zika can sometimes be spread through sexual contact (though it's unclear how long the virus stays in semen). And it's possible, though not certain, that Zika could be spread through saliva. Figuring this stuff out is crucial for halting the current outbreak. See Julia Belluz's great piece on this for more.

A related question is why Zika has spread with such alarming speed throughout South and Central America. Is it just because the disease is hitting a population with no natural defenses? Or has the virus mutated in some way that makes it easier to spread?

5) How do we make a Zika vaccine? Making a vaccine takes years, as Brian Resnick nicely explained. And it will take even longer because research on Zika is so primitive. "Nobody thought Zika was a high enough priority to warrant making a vaccine for it," Peter Hotez, a tropical disease expert, told Resnick. "It was always the last slide on a PowerPoint presentation about arboviruses."

The good news is that research is ramping up, particularly since the World Health Organization declared an emergency. Experts on viruses, on tropical disease outbreaks, on mosquito control — they're all starting to dig into these questions. Just this week a paper in the New England Journal of Medicine published the strongest evidence yet of a link between Zika and microcephaly. And the Obama administration recently asked Congress for $1.8 billion, with a big chunk of that aimed at bolstering the CDC's research and containment programs.

But there's no question the world has been caught by surprise, which means there is going to be a lot of uncertainty about Zika in the meanwhile.

Further reading:

  • 9 questions about the Zika virus you were too embarrassed to ask
  • The unsexy truth about how to kill mosquitoes and stop the Zika virus
  • The National Institute of Allergy and Infectious Diseases listed a number of "high priority" Zika research questions it would like to fund. So if you have good ideas about "studies to develop animal models to study ZIKV pathogenesis," now's your chance.