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early a year after the Zika virus grabbed global attention, it is still confounding the scientific community.

It may not have wowed Congress, or the countries and foundations that normally fund the World Health Organization’s outbreak response efforts, but it has left scientists scrambling for answers to critical questions.

It’s been 13 months since obstetricians in northeastern Brazil started noticing babies being born with grossly underdeveloped heads. In the months since, it has become apparent that the condition — microcephaly — is just the most visible form of the devastation that the virus can wreak when it infects the fetus.

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Let’s explore some of what we’ve learned about Zika over the past year, and some of the most pressing questions that remain to be answered about this unique outbreak.

Lesson: Don’t underestimate a foe you don’t know

Our knowledge base on Zika is so meager because scientists didn’t study it much in the decades after it first appeared in 1947. Don’t blame the scientists: Research funding is scarce and grant applications to study pathogens deemed inconsequential never make it to the top of the pile.

But once Zika forced the world to pay attention, its reputation went from meh to mega.

This virus has so many tricks up its sleeve. It causes birth defects in babies and neurological conditions such as Guillain-Barré syndrome, a type of temporary paralysis, and encephalitis (inflammation of the brain) in some adults. We still don’t know, though, how often infection leads to one of these serious problems.

There have been other surprises. Zika finds its way into semen and tears and saliva and vaginal fluids — and in some cases stays there for months.

Dr. Michael Diamond, a viral immunologist at Washington University School of Medicine in St. Louis, marvels at Zika’s many targets and tactics, and the fact it behaves so differently from a number of closely related viruses — dengue, West Nile virus, Japanese encephalitis — that have been far better studied.

No one was expecting a flavivirus (the family to which Zika belongs) to cause birth defects, but maybe they should have. A cousin, the Wesselbron virus, causes birth defects in sheep and other ungulates (animals with hooves), noted Nikos Vasilakis, an associate professor of pathology at the University of Texas Medical Branch in Galveston.

Lesson: Zika can do damage at any point in a pregnancy

One thing that has become clear is that while there are potential risks to the fetus at all stages in pregnancy, when it comes to Zika and trimesters, first is worst.

But as babies born to women who were infected in pregnancy are assessed and their early development followed, researchers have discovered that a range of birth defects can occur after infection in the womb, and no point in pregnancy appears to be 100 percent safe.

Researchers have warned that babies who appear unscathed at birth may have problems that only become evident later, including hearing and vision loss. There are even questions about whether damage to brain tissues continues after birth.

Lesson: Zika is an STD, part 2

We’ve talked about this before — the astonishing discovery that a virus spread by mosquitoes is also transmitted by sex.

But since then, we’ve learned that it’s not simply that men can infect women through unprotected sex. Men can infect men. Women can infect men — and presumably women. Men who are infected but have no symptoms can infect their sexual partners.

Oral sex, vaginal sex, anal sex — check, check and check.

And while Zika the illness is short-lived, Zika the STD risk hangs around for a while. A puzzling case in France appears to show a man infected his wife somewhere between 34 and 41 days after he got sick.  And doctors in Italy have reported finding traces of Zika in two men’s semen six month after they were infected. It’s not known if their semen contained whole — and infectious — viruses.

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Pressing question: How often does sexual transmission happen? And how big a role does it play in spreading this virus?

If sexual transmission of Zika is rare, this will turn out to be a fascinoma — something for the medical history books. But it’s certainly not clear at this point that sexual transmission of Zika can be dismissed so easily.

A very big concern is that women generally don’t know they are pregnant for some time after conception. During that time, unprotected sex with a partner who has Zika could infect the fetus.

It’s also true that most people who contract Zika show only mild symptoms, and in some cases none at all. In those cases, the only way to prevent sexual transmission is to use condoms or practice abstinence. The WHO recommends six months of that for travelers returning from a place where Zika is spreading. For people living in a Zika transmission area, the risks make for hard choices.

In places where Zika isn’t likely to spread widely, sexual transmission may pose the greatest risk to developing fetuses.

“We really do not know very much about the incidence of and the efficiency of sexual transmission,” said Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases.

“This is critical given that in the USA there are more than 2,700 documented travel-related cases and probably a fewfold more that are unrecognized. If sexual transmission is highly efficient, then we really need to know this.”

Pressing question: Is Zika alone responsible for what the world is seeing?

The huge number of microcephaly cases in northeastern Brazil — far more than any other area has seen to date — has put a much-debated question back into play.

Could something else be aggravating Zika infection, increasing the rate of birth defects in certain areas?

In June, the WHO said it didn’t think so-called cofactors were responsible for the glaring discrepancies in case numbers. But last week, a committee of outside experts advising the WHO on Zika called for research into whether something else contributed to the huge swell of cases in Pernambuco and Recife, Brazil.

Dr. David Heymann, chairman of the committee and a professor of infectious diseases epidemiology at the London School of Hygiene and Tropical Medicine, said a diverse range of factors could have worsened Zika’s wallop in northeastern Brazil. Diet. Concurrent infection with other diseases. Genetic susceptibility. An unidentified environmental contaminant.

Answering this question won’t be easy. “It’s … a broad and complicated research matter,” Heymann warned.

Pressing question: Does prior infection with or vaccination against one of Zika’s cousins help or hurt? Or is that irrelevant?

From a testing point of view, Zika’s genetic resemblance to other flaviviruses is making life really difficult. Antibodies generated by those other viruses — and by vaccines to protect against them if they exist — are pretty much indistinguishable from the antibodies created by Zika infection.

To complicate matters further, places having Zika outbreaks are also places where some of these other viruses spread.

So no one can tell with any certainty whether there are a lot of people in Africa and Asia who are vulnerable to this virus, or whether there are pockets of protected people.

We also don’t know if having had encounters with related viruses makes Zika infection worse. It’s a theory. But a countervailing one is that antibodies to those other diseases may actually blunt Zika’s blow.

Getting an answer to this will be crucial if a Zika vaccine is developed and attempts are made to bring it to market, Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy told STAT.

Pressing question: What made a virus that was formerly a lamb turn into a tiger?

If you’ve been following the Zika outbreak, you’ll have heard that there are two strains of Zika: the African and the Asian. The outbreak in the Americas is caused by a virus from the Asian side of the family tree.

But describing the virus this way is a bit too simplistic, unfortunately, because there is variation within those lineages as well.

Small genetic changes may make a big difference in how Zika viruses behave, said Duane Gubler, a leading expert on mosquito-transmitted diseases who advises the WHO on Zika.

That may be why a virus that has been around for eons is only now being seen as a serious threat. The working hypothesis is that the virus spreading in the Americas, though it came from Asia, has changed somewhat. Work to identify how and whether those changes are responsible for what we’re now seeing is still underway.

Interestingly, analysis of the viruses now spreading in Singapore — which has recorded close to 300 infections in less than two weeks — suggests they are like the classic Asian viruses, not the one from the Americas, the ministry of health reported last weekend.

Osterholm said that may mean people infected in the Singapore outbreak won’t risk the same bad outcomes associated with the strain spreading in the Americas.

But what of the African strain? Guinea Bissau, on the west coast of the continent, has reported some recent Zika case, caused by African lineage viruses. They’ve also found a few babies who were recently born with microcephaly.

Cause or coincidence? People trying to figure out what’s going to happen with Zika would love an answer to that question. And many, many more.

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  • Do you know if microencephalitis, guillan-barre syndrome and hearing loss are actually caused by the zika virus or are the researchers still researching? Since all three of those things are sometimes caused by pesticides and most of these cases are occuring in farming areas… are they considering that possibility that it’s pesticides?

    • The evidence is strongly mounting in favor of Zika. Zika virus has been found in fetal brains that have died in the womb or shortly after birth. Zika virus was also found in brains of fetal mice in experiments. The defects associated with Zika are more severe than are typically seen. Zika infection during pregnancy is the strongest predictor of these defects showing up. And more. While the evidence has not yet reached certainty (as far as that gets in science), the evidence appears to only be moving in one direction.

    • Hi. The belief (and hope) is that infection will lead to immunity. That’s the way with other flaviviruses. But it’s still an educated guess at this point.
      Thanks for the kind words.

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