How many Zika-infected infants will develop microcephaly and other FAQs

A woman walks past a giant fake mosquito placed on top of a bus shelter as part of an awareness campaign about the Zika virus in Chicago, Illinois, United States, May 16, 2016. Photo by Jim Young REUTERS

When an outbreak strikes, the Epidemic Intelligence Service is the cavalry. The Centers for Disease Control and Prevention ships this branch to the front lines, where they investigate the causes and set up defenses.

A fortnight ago, these disease detectives assembled for their annual conference, and it felt like the first day at Harry Potter's Hogwarts. Some senior leaders donned their versions of wizard cloaks — military-style uniforms — and met with recruits around coffee tables and in hotel conference rooms. A special group of EIS officers met with journalists behind closed doors. The topic: Zika virus.

Microcephaly is an extreme scenario — it's a bullhorn screaming out "something's gone very wrong with brain development.""So, I'm Peggy," said Margaret Honein, epidemiologist and chief of the CDC's birth defects branch, as well as one of the leaders of the agency's Zika response.

Remember last month when the CDC officially confirmed that Zika causes head-shrinking microcephaly and other birth defects? Honein co-authored the report.

Honein was accompanied by three second-year EIS officers who had "made outstanding contributions to the CDC's Zika response," she said. All three, like most of their class, had the rare experience of responding to two global epidemics — first Ebola and now Zika — within their brief, two-year EIS tenure.

Titilope Oduyebo is an obstetrician and gynaecologist (OB/GYN) who joined the response a week before the CDC activated its Zika Emergency Operations Center in late January. She is charged with updating the agency's advice on Zika for pregnant women and providing guidance to state health departments. Romeo Galang is an OB/GYN who specializes in how infectious diseases alter the course of pregnancy. These skills landed him in Puerto Rico early this year, as disease cases climbed precipitously. Morgan Hennessey is a disease data tracker who started looking into Zika in 2014, before the epidemic began, as part of his research with the arbovirus (mosquito-borne virus) disease division. He joined the EOC in February 2016.

These four experts had untold insights into this outbreak, and we had questions.

Getting worse or getting better: What happens next for this outbreak?

Weekly reported cases of Zika virus (green), dengue virus (blue), chikungunya virus (yellow) and microcephaly pick) in Pernambuco State, Brazil from 2015-2016. Chart by the Pan American Health Organization; data by data by Pernambuco State Secretary of Health

The Zika virus outbreak is waning or rising depending on location.

Brazil's outbreak is heading toward halftime. In 2015, cases of the mosquito-borne disease peaked in late March, right as the South American summer ended. This pattern has repeated this year. Pernambuco State, the epicenter of Brazil's outbreak, recorded a peak number of newly reported cases (~1,000 suspected and confirmed) during the last weeks of February. The numbers have waned as temperatures cooled, sliding toward 200 new cases per week in late April. But overall, the Brazilian Ministry of Health has reported 91,000 local cases of Zika as of late March.

Other South American nations have witnessed similar swings, according to Honein, who said Colombia's surge started in back in October and November. The World Health Organization stated that Colombia's outbreak appeared to peak in late February, and "is now in decline."

Further north, the opposite trend has painted the Caribbean, where Zika infections continue to swell.

Colombia's reported cases of Zika virus disease (green line; suspected and confirmed) and neurological syndromes (blue columns) between week 32 of 2015 (early August) to week 17 of 2016 (late April). Chart by Chart by the Pan American Health Organization; data by Colombia Ministry of Health

As of last week, Puerto Rico's Health Department is reporting about 100 confirmed cases per week. The U.S. territory is heading toward its warmer rainy season, when mosquitoes tend to flourish, so more cases are expected. The U.S. territory has recorded 945 confirmed infections since their outbreak began late last year. Models predict Florida and Texas to be most at risk for Zika outbreaks this summer, but neither state has experienced a locally transmitted case yet.

Galang said one of the major challenges in Puerto Rico is keeping local doctors up-to-date on the latest guidance. A thousand cases is a solid groundswell, but many island residents still haven't encountered Zika in their communities.

WATCH: Its economy in shambles, Puerto Rico also stares down the Zika virus

"These doctors are concerned about what should they do should those numbers increase…and all of a sudden patients start beating down the doors," Galang said. "Or like with any physician ordering tests, they wonder how do I interpret it, how fast will I get it back and what should I tell my patient."

One solution is clinician outreach sessions, where members of the CDC or Puerto Rico Department of Health travel around the island and educate 30 to 40 doctors at a time. "Most think about surveillance as data extraction, pouring through medical records. What I wasn't expecting, though, was how interactive it was going to be with the clinicians there," Galang said

What about sexual transmission? Sex could spread Zika to all four corners of the Earth, right?

Nope, Hennessey said. Based on the data, he doesn't think sexual transmission of Zika can sustain itself without mosquito transmission.

Every now and then you'll see a few cases sexually transmitted, but not a majority of cases."By and large, it's going to be mosquitoes. Every now and then you'll see a few cases sexually transmitted, but not a majority of cases," Hennessey said.

Of the 503 Zika cases confirmed in continental U.S., only 10 have been linked to sexual transmission. All involved males transmitting to female or male partners. Oral sex (mouth to penis) occurred in some cases, but it remains unclear if the virus can pass via this route or via open-mouth kissing.

The CDC recommends that men practice safe sex or abstain for at least six months if they've been diagnosed with Zika; or at least eight weeks if they've recently traveled to a Zika-hit area but have shown no symptoms.

One case points to Zika infection lasting up to two months in semen, but the actual time window remains unresolved, Hennessey said. A study in April found the Zika virus's structure remains intact at high temperatures — up to 104 degrees Fahrenheit — which is a sharp contrast to its cousin, dengue.

This resilience may explain why Zika virus can survive in the relatively harsh conditions of semen, saliva and urine.

How many Zika-infected infants will develop birth defects?

Five-month-old twins, Laura (L) and Lucas lie in their bed at their house in Santos, Sao Paulo state, Brazil April 20, 2016. Among the mysteries facing doctors in Brazil battling an epidemic of the little-known Zika virus are cases of women giving birth to twins with only one suffering from microcephaly, a birth defect associated with the disease. Photo by Nacho Doce/REUTERS

It's easy to see the numbers and pictures of underdeveloped infants and wonder, "Is this going to happen to me?"

"Right now, we don't know the absolute risk for a woman if she gets infected during pregnancy," Oduyebo said. "However, we have seen babies being born that have had good outcomes. There are ways to protect yourself, and I think that part of the public story is missing."

The question is, how many infants will have good or bad outcomes?

So far, Honein said only two studies have addressed this question with confidence, but their results vary dramatically. A preliminary report from Rio de Janeiro found 29 percent of pregnancies hit by Zika showed abnormalities. In contrast, a retrospective examination of French Polynesia's 2013-2015 outbreak puts the microcephaly rate closer to 1 percent.

Let's unpack these numbers because they've been quoted frequently, and such a massive difference in outcomes — 1 versus 29 percent — can brew anxiety.

"Zika is unprecedented. It's unprecedented to have a mosquito-borne cause of fetal malformation," CDC director Tom Frieden said at the 65th annual EIS conference. Frieden spent two years in the EIS program in the early 1990s. Photo courtesy of the Centers for Disease Control and Prevention

The French Polynesia study tries to assess the island chain's levels of microcephaly before and after the Zika arrived. They surveyed blood samples and surveillance records to estimate how many people caught the virus for every week of the outbreak. The researchers estimate 31,000 people sought medical attention virus during the outbreak, but only eight cases of microcephaly were recorded. Math models pointed to the first trimester as the most vulnerable period for catching Zika, and the team estimated 1 per 100 Zika-stricken of these pregnancies might yield microcephaly.

The Brazilian study examined a smaller number of cases — 88 pregnant women with Zika infections — but directly examined developing fetuses using ultrasound. The "29 percent" represents 12 fetuses with any signs of abnormalities, but the defects weren't limited to microcephaly. Only 5 percent — 4 pregnancies — showed distinguishable signs of microcephaly.

The CDC is trying to nail down Zika's birth defect risk levels, Honein said. But this discrepancy between microcephaly and other Zika-related birth defects raises another question:

Is the general public focusing too heavily on microcephaly?

Jackeline, 26, holds her son who is 4-months old and born with microcephaly, in front of their house in Olinda, near Recife, Brazil, February 11, 2016. Photo by Nacho Doce/REUTERS

Honein said microcephaly is an extreme scenario — it's a bullhorn screaming out "something's gone very wrong with brain development." It's so rare, especially in the context of infectious disease, that she said many folks on her team had reservations when Brazilian officials began tying Zika to a microcephaly spike last autumn.

Microcephaly "is so difficult to monitor. I think we were all very skeptical," Honein said. Plus, before the outbreak, Brazil's rate of microcephaly — 0.5 cases per 10,000 births — was low compared to other regions, suggesting the condition had been underreported. "Experts say that they would have expected to see around ten times that number on the basis of typical frequencies seen elsewhere," Declan Butler wrote for Nature Magazine in March.

All kinds of cells in the brain seem to be infectedMicrocephaly may signal a more insidious problem, according to Honein. She spotlights a subset of Brazil's microcephaly cases that exhibited a fetal disruption sequence.

Here's what happens. The brain develops fairly normally for a period of time, but the viral infection seems to interrupts things, and the skull collapses. Extra folds of skin builds up as the head shape warps. The excess scalp skin is joined by fluid, which tends to fill in the areas where brain tissue has been destroyed.

"This is a pretty unusual clinical presentation to see, and a very severe outcome," Honein said. "We're seeing, in some babies at least, a very high level of brain destruction."

The latest mouse models, where the disease can be tracked cell by cell, back this idea. Three reports published last week show Zika virus can harm early embryonic neurons in mice. As Columbia University microbiologist Vincent Racaniello wrote about one study from Brazil: "The infected mice also had ocular abnormalities similar to those that have been observed in babies with congenital Zika virus syndrome."

"These papers are really convincing because of the parallels in human fetal brains," University of Michigan virologist Katherine Spindler told PBS NewsHour. She listed enlarged ventricles and smaller brains as examples.

Plus, the virus doesn't stop after attacking the earliest neurons, as another of the three studies found Zika can hit post-mitotic — a.k.a. adult — neurons too.

"All kinds of cells in the brain seem to be infected," Spindler said.

Mice aren't humans, so these studies should be accepted with caution, but the trends may factor into Guillain–Barré syndrome, which primarily afflicts adults.

Oh right, what's happening with Guillain–Barré syndrome?

Of the 58 countries and territories with ongoing Zika outbreaks, 13 have noticed an increase in Guillain-Barré syndrome. Most experts, including Spindler, blame an autoimmune reaction, wherein the body's microbial defenses mistake human tissue as the virus.

NPR recently documented 2 people struggling to recover from Guillain-Barré

But alternative theories are emerging.

"What I'm hearing is that in Brazil, the majority of people with Guillain-Barré are not showing the usual immunological pattern," said Scott Weaver, director of the Institute for Human Infections and Immunity at the University of Texas Medical Branch. This pattern involves human antibodies being formed to target the myelin sheath of neurons.

These results aren't published yet, but they may indicate "more direct damage by the viral infection than is typical in most Guillain-Barré triggered by other viral infections," Weaver said.

Weaver's team is working with several other teams, including pharmaceutical companies and researchers at the National Institutes of Health to develop a Zika vaccine. The NIH expects a small vaccine trial — 80 subjects — to start in September, with a broader rollout in the early part of 2017.

If Zika behaves like its cousin Chikungunya and other flaviviruses, then the main onslaught of the America's Zika epidemic might be over. But a vaccine would still be valuable because viruses like Zika, Chikungunya and dengue never disappear for good, especially in the tropics. Even if herd immunity sets in, the outbreak may persist for half a decade, according to some experts.

A Zika vaccine may offer protection for those living in these areas, as well as anyone who may wish to travel there…like, say…for the upcoming Olympics.

Should people be worried about the Rio Olympics?

A competitor takes part in the Men's Decathlon Pole Vault at the 2016 Rio Olympics Test Event, May 16, 2016. Photo by Ricardo Moraes/REUTERS

Depends on who you ask. Some experts say the games must not proceed, given the risk of spreading the virus to new locations. Last week, the head of the World Health Organization advised that pregnant women avoid traveling to Brazil, but stopped short of saying the games should be canceled.

"You don't want to bring a standstill to the world's movement of people," WHO director Dr. Margaret Chan said, according to the Associated Press. "This is all about risk assessment and risk management."

Daniel Lucey, an infectious disease specialist at Georgetown University, agrees with the WHO for a few reasons. First, the Olympics are being held in the wintertime, when mosquitoes are decreased in number. The specific location is also an advantage. The games are confined to Rio de Janeiro, which lies outside the tropics, so it'll be even cooler. Plus he feels confident that public health officials are making every effort to eradicate mosquitoes in Rio.

"I'm personally going to go there myself, so I'm as confident as I can be that they're going to do everything that they can with national, international health."

Lucey said when it comes to Zika and international travel, people should have more concerns with an overlooked outbreak off the northwest coast of Africa.

Starting in October 2015, Cabo Verde (Cape Verde) experienced a surge of Zika virus. More than 7,000 suspected cases struck the island between then and early March — 165 involved pregnant women. The nation's health minister announced its first case of microcephaly on March 15, and two more followed soon after.

"These are the first and only cases of Zika-linked microcephaly ever reported anywhere in the continent of Africa," Lucey said. Zika originated in Uganda in 1947, but no one reported birth defects during early outbreaks of the African strain or with the subsequent Asian strain that hopped over to the Americas. It's unclear which strain caused Cape Verde's flare up, Lucey said.

Cape Verde also has strong travel ties with Guinea-Bissau and other West African nations where the tropical mosquito carriers of Zika live in heavy abundance.

The situation bothers Lucey because it echoes the early stages of West Africa's Ebola epidemic, wherein the international community was slow to react.

"It's not a verbal exercise. It's people's lives. Babies' lives and welfare are at stake."

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