Demystifying Zika
Collaboration
The Science
The Olympics
Man vs Mosquito

Introduction

On February 1, 2016, the World Health Organization declared Zika a public health emergency of international concern. Only the fourth such warning of its kind (H1N1, polio, and Ebola represent the others), it has impacted so many people.

Since then, the Zika virus crisis makes headlines nearly every day. The steady barrage of information and breaking news make it challenging to follow. At a time when a global health crisis paints a backdrop in our lives, it may be reassuring to better understand what the Zika virus scare is all about. This story was designed to help you navigate the ever changing landscape of a world health emergency. What does it mean to stop the virus? How are scientists developing strategies to thwart its transmission? Why is this public health challenge different from ones we’ve faced before? What are we learning that we can apply to future situations of this kind?

This article represents a snapshot of the Zika virus story at this moment in time. Yet we hope that the story serves to inspire by highlighting the advances made by the research community, global health policy leaders, the clinicians currently in the trenches, and even those who are suffering directly, as they are the ones providing the information and the data needed to effectively wage and win this battle.

DEMYSTIFYING THE ZIKA CRISIS

How serious is this, really?

In the months since Zika was declared a public health emergency, updates about the epidemic seemed to grow more concerning with each passing day. The number of known Zika infections continued to increase as the virus spread across countries, and then continents. While some reports were encouraging at first—infection seemed to be peaking in certain locations—the incidence continued to jump borders, as expected. Even more troubling were the grim outcomes of babies born to Zika-infected mothers.

Total number of cases, suspected and confirmed, and deaths in select countries

0

94,112

196,976

0

0

0

Source: Pan American Health Organization / World Health Organization. Zika suspected and confirmed cases reported by countries and territories in the Americas Cumulative cases, 2015-2016. Updated as of 15 September 2016.

Timeline of selected Zika-related events

The Zika virus is first isolated in a rhesus monkey in the Zika Forest in Uganda and first recovered from a Aedes africanus mosquito in 1948.

The first confirmed case of Zika fever in a human occurs in Uganda in a field researcher, who experiences a mild, non-itchy rash.

Samples in Brazil first test positive for the Zika virus.

A sharp increase in the number of microcephaly cases in Brazil is reported.

The Ministry of Health in Brazil declares a national public health emergency.

Puerto Rico reports the first locally acquired case of Zika virus infection.

WHO declares the Zika virus outbreak to be a Public Health Emergency of International Concern (PHEIC).

WHO advises pregnant women to avoid travel to areas where the transmission of the Zika virus is active.

The CDC confirms 4 cases of locally transmitted cases of Zika infection in Miami, Florida, the first locally transmitted cases confirmed in the U.S. mainland.

The U.S. government declares a public health emergency in Puerto Rico as a result of a Zika epidemic.

Singapore’s Ministry of Health confirms the first case of locally-transmitted Zika infections in the country.

Health Minister of Malaysia confirms the first locally transmitted case of Zika in Malaysia.

 
 
2015
2016

How debilitating are the symptoms if you are infected?

Just a year after Zika became somewhat of a household name, most of us are familiar with the health threats associated with infection. They include flu-like symptoms such as fever, muscle aches and joint pain, as well as a skin rash, and pink-eye, or conjunctivitis. These symptoms run the gamut in terms of severity, and the level to which they impact a person is also very subjective, so it is hard to quantitate. Many infected with Zika remain asymptomatic and never even realize they’ve been infected. Probably the biggest concern for those infected with Zika, if not pregnant, is the risk of developing Guillain-Barré syndrome.

The most severe, and most talked about, is the potential for a pregnant woman infected with Zika to give birth to a baby with microcephaly and other neurological deficits. This fear is valid and is now the main driver in stopping the spread of the virus.

The exact risk remains unknown, but some studies report it to be between 1% and 13%. The Director of the U.S. Centers for Disease Control and Prevention, Dr. Tom Frieden, issued a statement calling this unprecedented. He said, “never before in history has there been a situation when a bite from a mosquito can result in such a devastating scenario."

Image courtesy of the Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities

When Zika virus infection was first linked to babies born with microcephaly, it was initially believed that babies in utero were most susceptible to the virus when the mother was infected early in pregnancy. More recent research and epidemiological information has demonstrated that may not be true. Pregnant women infected with Zika in later stages of pregnancy may be just as susceptible in passing the virus on to their fetus.

As Zika has spread to more countries, and more time has passed since Zika-infected mothers have given birth, another form of microcephaly, called late-onset microcephaly, has been identified. In these cases, babies appear to have normal sized heads at birth, but due to infection of their brains, their head size does not continue to grow and they develop microcephaly at a later stage—typically by about six months of age. This finding was observed by researchers who followed over 1200 cases of Zika-affected pregnancies in Brazil. Whether microcephaly develops early or late in development, the results are equally devastating and can be life threatening.

What it feels like to learn you’ve been infected with Zika

It’s one thing to read about the potential health issues that stem from Zika infection when you’re not directly affected. It’s another thing, however, to consider them when you have been diagnosed with Zika, and particularly if your infection occurred at a time when family planning was at stake.

This interview with Dr. Carl Schreck III, a research assistant professor at the Cooperative Institute for Climate and Satellites at North Carolina State University, provides a sense of what it’s like to learn you’ve been infected with Zika and the implications it can have. Schreck was bit by a Zika-carrying mosquito while attending the American Meteorological Society’s Conference on Hurricanes and Tropical Meteorology in Puerto Rico in April, 2016.

“I went to my doctor and he laughed off Zika at first. But my wife and I were thinking about having a second baby, so after a couple days he did a blood test and it came back positive.”

1. Were you concerned about Zika prior to traveling to Puerto Rico this past spring?

At first no, but later yes. My initial reaction was that I’m not a pregnant woman, so it doesn’t matter for me. Even when I heard that it could be transmitted sexually, it didn’t initially register that I could get it and pass it to my wife, who could transmit it to a fetus if we tried to have a baby. We have a 3-year-old and really want to try for another kid. My wife’s a teacher, so this summer would’ve worked out perfectly to try.

Before the trip, the guidance I saw was that men shouldn’t try to have kids within 8 weeks of returning. The conference was in April, so even 8 weeks wouldn’t really affect our family planning. It wasn’t until I got back and had symptoms that I learned of the new guidance of 6+ months for men who test positive.

2. Did you do anything “extra” to lower your chance of infection (bug repellent, clothing, etc)?

No, I meant to bring DEET, but I wasn’t sure if it was allowed on planes. I was going to buy it at the hotel instead, but my flight got in late and I forgot. I was great about sunscreen every day, but I don’t know why I never got bug spray.

3. How did you first find out you were infected?

I had a rash on my torso and arms. I first noticed it after mowing the lawn, so I thought it might be poison ivy, but it didn’t itch. I went to my doctor and he laughed off Zika at first. But my wife and I were thinking about having a second baby, so after a couple days he did a blood test and it came back positive.

4. What kind of symptoms did you have, if any, and how long did they last?

Just the rash. Maybe some fatigue. They lasted about 3–7 days.

5. What kind of test did you take that confirmed infection?

Just a blood test. But I've since enrolled in a CDC study to track how long it stays in my system. I send them urine and semen samples every two weeks. I was hoping the CDC would tell me when I'm clean, but they're worried about false-negatives. So they won't tell me my results until the 6 months are up. But at least then I'll know with one hundred percent certainty if I'm clean.

6. What was your reaction when you tested positive?

Frustrated. As I mentioned, we were really hoping to try for another kid this summer. Having to wait until November is a challenge with my wife's teaching schedule. We still haven't decided what we'll do then. I also under-estimated how people would react to hearing that I was positive. Some of my coworkers are pregnant and were worried about being around me, even though I was no longer contagious to mosquitoes by the time I told them. Plus there are no mosquitoes in our office building. Other folks were expecting to hear that it was much worse/dangerous for me.

7. What are your thoughts about the Zika virus health crisis in general having experienced it firsthand?

That it's getting simultaneously too much and too little attention. It's not Ebola, it shouldn't be feared in that same way. It doesn't really affect adults. But at the same time, it's much easier to transmit than Ebola because of the mosquito side. And it's sad that babies with life-threatening defects just aren't as newsworthy as people whose faces are bleeding.

UNHERALDED COLLABORATION

While the Zika crisis shares the same official designation as the three other public health emergencies that preceded it, the global response has been rather different. Especially compared to the Ebola crisis, which left more than 11,000 people dead worldwide, progress in combatting Zika is substantially better. The World Health Organization quickly mobilized its partners, which proved to be beneficial. The general response by the global community of research scientists is also having a powerful effect. In other words, the spirit of collaboration and sharing of resources to accelerate the pace of research seems to be making a difference. A sense of international coordination, forged in part by the necessity to stem the rate of Zika’s spread, is noticeable this time.

What better place to begin describing examples of collaborative science than those working directly to understand Zika in the country considered “ground zero” for the current Zika outbreak: Brazil.

The Oswaldo Cruz Foundation, also known as Fiocruz, is a public foundation directly linked to the Brazilian Ministry of Health and tasked with producing and sharing knowledge and technologies aimed at improving the public health of Brazil. Researchers there are proud of the way in which they were able to quickly detect the disease and conduct a great deal of research in an equally short period of time. This led to a rapid national mobilization and the creation of a network involving a number of different research centers throughout Brazil.

What these participating scientists say is so unique about the success they’re so far seeing is the attitude of their research community. An ordinarily competitive climate has given way to one of collaboration, allowing them to quickly achieve efficient solutions.

"In these dark times, competition is gone—instead, there’s a union between researchers. We present and share information to achieve efficient solutions."

Fast access to data promotes more collaboration

It helps that more researchers are uniting in the face of a global health crisis, and one of the biggest benefits of this union is their willingness to share critical scientific data. One research group in particular has paved the way for sharing data in the most accessible way possible—through posting it on an open portal.

Soon after WHO made the Zika crisis official, virologist Dr. David O’Connor at the University of Wisconsin-Madison (Department of Pathology and Laboratory Medicine) announced the decision to post his lab’s raw data online. Their work entailed infecting macaques with Zika virus and then recording the daily concentration of viral load in the animals’ bodily fluids. The protocol was designed to determine if viral material was present in saliva and urine, in addition to blood, and if so, for how long. This represented the first time that the group made data available in real time. The goal? To speed up research about Zika.

By making this raw data public, and choosing not to first collect, analyze, present, write, submit and potentially publish the data in a peer-reviewed journal, O’Connor is hopefully achieving this goal of moving Zika research forward more quickly. He encourages those who access his results to contact him to suggest changes in the experimental designs or offer their analyses of what the data implies.

Dr. O’Connor shared his thoughts about this style of collaboration with us:

The real origins of this idea to share came a few years ago during the Ebola outbreak. One research group made a lot of their genomic sequencing data public to all, and because of this my colleagues and I here were able to obtain that data, re-analyze the sequence, and see it through a different set of eyes. What followed from this was the opportunity to write and publish an entire paper, in collaboration with their group, without having to collect any data in my own lab. I realized the value in sharing data. So our lab decided to adapt that concept as a goal this year and make our data more accessible.

Once we got going with our Zika-related work we realized there were a lot of people who had contributed to the design of the study and who were keen to learn how the studies were going. We needed to be able to share data so everyone would weigh in. My colleague Dr. Tom Friedrich and I brainstormed about how—and we thought, why not make it publicly available through an online portal?

We initially thought that there would only be a small number of specialized researchers interested in this, but our data portal has attracted a much wider audience. This is still surprising to us!  When I look at some of the scientists who are publishing in the literature and have credited us with helping them, I’m really gratified to see that it might have helped. A few other groups have since expressed enthusiasm for doing the same thing, but there’s still a gap about the best way of actually doing it. One of the arguments I have heard against data sharing is the fear of being scooped. But that involves a lot of hubris and believing that everyone has the time to actually troll other people’s data. In my mind, that is not a realistic concern.

“I’m really gratified to see that how this may have helped.”

The ZEST Team (Zika Experimental Science Team). From left, Rodrigo Brindeiro, Renato Santana Aguiar, David O'Connor, Gabriel Goncalves and Dawn Dudley. O'Connor and Dudley are from UW-Madison. The other three are collaborators from the Federal University of Rio de Janeiro. (Photo credit: David O'Connor)

O’Connor’s team has served as a model as a growing number of research initiatives and organizations are following suit. In February of this year a group of more than 30 leading global health organizations called for all Zika-related research data to be made rapidly available and open to all. A consensus statement was published; it reads in part as this:

“In the context of a public health emergency of international concern, there is an imperative on all parties to make any information available that might have value in combatting the crisis. We are committed to working in partnership to ensure that the global response to public health emergencies is informed by the best available research evidence and data.”

Many prestigious journals including those in the Nature Publishing Group, as well as the Science Publishing Group, agreed to make all content concerning Zika virus free to access; furthermore, the editors promised that any prior release of data or preprint provided ahead of submission would not jeopardize consideration of a regular submission. The World Health Organization also announced a 'Zika Open' initiative, in which all relevant submissions to its Bulletin were guaranteed to be posted online within 24 hours.

The gravity of the Zika health crisis has inspired a spirit of collaboration and global support that has touched the research community in ways never experienced before.

An unlikely research partnership working to develop a vaccine

It’s not common for a European pharmaceutical company to team up with a research branch affiliated with the United States military. Yet that is exactly the pairing that may lead to an effective vaccine against Zika virus infection. The French company Sanofi Pasteur announced in July that it was working with U.S. Army researchers at the Walter Reed Army Institute of Research (WRAIR) on the development of a potential vaccine.

The partnership entailed the transfer of inactivated Zika virus, created at Walter Reed in Silver Spring, Maryland, to Sanofi Pasteur headquartered in Lyon, France. Together these organizations hope to advance pre-clinical studies with the technology successfully used to develop both the dengue fever and Japanese encephalitis vaccines.

These infectious agents all belong to the same family of viruses, flaviviruses, and are transmitted by the same type of mosquito, those of the Aedes genus. Since the three viruses share genetic similarities, it was logical for Sanofi Pasteur, an experienced company who licensed these earlier vaccines, to get involved and offer its expertise.

WRAIR scientist Colonel Nelson Michael, Director of the U.S. Military HIV Research Program, led his team in the development of the vaccine using a strain of Zika isolated in Puerto Rico. The vaccine relies on inactivated virus that must be produced in abundant levels and meet the FDA’s stringent specifications for human vaccine trials—that is where the partnership with Sanofi Pasteur fits in. Preliminary results have been promising as mice infected with Zika were protected from the virus when injected with just one shot of the experimental vaccine. The hope is that clinical trials will progress quickly and eventually result in a vaccine approved for use by all.

The power of social media in uniting scientists

Social media might not be the typical way to rally competing scientists to join in a united effort, but in this case, it worked like magic. As the story goes, Dr. Leslie B. Vosshall, a mosquito researcher at Rockefeller University in New York, sent “a series of frustrated Twitter posts” in January asking for advice on constructing a detailed genomic map of the Aedes aegypti mosquito, the vector that carries Zika.

What followed were interested replies via Twitter, and as word spread, emails too. This eventually led to a fruitful gathering of seemingly disparate scientists who had once known each other better as competitors for precious research funding.

The effort yielded a productive nine-way video conference call and the official launch of the Aedes Genome Working Group. The group is comprised of virologists, molecular biologists, population geneticists and other experts in genomics, working in locations ranging from New York to California to Virginia to England, and supported by research institutes that include the NIH, the Broad Institute of MIT, and biotech company Pacific Biosciences.

The participants in the Aedes Genome Working Group held a nine-way videoconference call in January, led by Leslie B. Vosshall, top center (New York Times).

Some may argue that a detailed state-of-the art DNA map of the Aedes mosquito might not necessarily represent the most straightforward approach to stopping the spread of the Zika virus. But this crafty vehicle is also associated with transmitting dengue, chikungunya, and yellow fever, so teasing apart its genome may provide important clues about the biology of the pest. Three different types of DNA sequencing make up the official game plan now in motion, thanks to the funding that the group succeeded in raising. We must wait to find out what their work reveals.

Solving The Science

To solve the mystery of the Zika virus and the puzzling symptoms it causes, scientists had to first ask the question: what is the responsible agent? The Zika virus is not new—it was first reported in 1947 in Uganda. This finding led to a great deal of important work that proved it is transmitted by a specific strain of mosquito, Aedes aegypti. The spread of Zika to several other countries in Africa, and then into Asia, was also previously known, allowing scientists to track its path and lay a foundation for the critical research that would later become necessary. It wasn’t until an alarming number of babies were born with microcephaly in northeastern Brazil in 2015 that the world took notice, and Zika was on its way to becoming a household name.

Last year’s discovery of the presence of Zika virus in Brazil is credited to several scientists, including Dr. Gubio Soares Campos. A virologist at Brazil’s Federal University of Bahia, he is described by those who know him as a very humble and modest man. When asked to explain how it feels to have impacted a world health crisis in such a meaningful way, he offered only this:

Brazilian virologist Gubio Soares Campos.(Photo by Christophe Simon/AFP/Getty Images)

"The discovery of the Zika virus, for me, is my little contribution to the world so we can all live in a happier place."

How does a mosquito actually transmit a virus?

While the role of the Aedes aegypti mosquito in transmitting Zika, as well as dengue and yellow fever, is well established, not many understand how that actually happens. Much has been shared and publicized about protecting oneself from the bite of a potentially dangerous insect. Not as much has been explained in terms of how a mosquito can transmit a virus.

First, the basics of the Zika virus machinery. The Zika virus contains a single-stranded positive-sense RNA, 10,794 bases in length. The RNA is flanked by two non-coding regions and encodes three key structural proteins (capsid (C), precursor membrane (prM), envelope (E)) along with numerous non-structural proteins (NS1-NS5). The envelope protein comprises the majority of the virus’s surface structure and is also involved in aspects of viral replication including binding to the host cell and membrane fusion.

The way in which mosquitoes serve as vehicles for transmitting and spreading the virus is also known. A female mosquito (male mosquitoes don’t bite people; the blood that females seek is needed to lay eggs) must feed on an individual already infected with the virus. The active virus, present in that individual’s blood, travels through the mosquito from its probiscus (mouth) and up through its head where it travels down to the midgut. Once there it enters the mosquito’s circulatory system and wends its way back up to the salivary glands of the mosquito. Upon biting another person, the mosquito first injects its virus-infected saliva before feeding upon the blood of this next victim. That person then serves as a breeding ground for mosquitoes who transmit it to others.

Zika virus and the neurological system

The biggest black box for the scientific community studying Zika is how it does so much damage to the human neurological system. Seemingly innocuous at first, when early reports and statistics demonstrated that the majority of infected individuals have mild to no symptoms, Zika is now understood to be dangerous. How it infects developing embryos in utero and causes microcephaly and major brain deficits is the most critical question out there.

The microcephaly concern increases as time goes by. It isn’t known yet how the virus causes brain damage; those mechanisms are still under intense scrutiny by labs around the world. What is known and supported by repeated studies is that the virus is found in the amniotic fluid surrounding babies born with microcephaly. The virus has been shown to cross the placenta and attack fetal nerve cells—including some that develop into the brain. One type of cell, radial glial cells, form the initial scaffolding that directs other fetal brain cells into place, and these have been shown to be particularly vulnerable to infection. In another study, researchers exposed fetal stem cells to Zika and found that the virus attacked cortical neural progenitor cells which go on to form the cortex—the region of the brain responsible for many higher functions.

By understanding which fetal nerve cells are Zika targets, researchers can better hone in on how the virus enters those cells and what pathways it disrupts to cause neurological deficits. A major discovery is the role of the AXL protein, a cell surface receptor used by the virus to gain entry into skin cells. A recent study found that the same receptor is present on the surface of three types of fetal brain cells, and the evidence supports the role of this receptor in brain cell infection.

Structure of Zika virus as solved by cryo-electron microscopy. Photo courtesy of Vincent Racaniello.

Current state of Zika diagnostics

Because the Zika virus shares significant similarities with other disease-causing viruses such as dengue, developing a diagnostic test for Zika virus did not require any new breakthroughs. The ability to quickly test individuals believed to be infected with Zika allowed public health organizations to more easily follow its spread and send effective advisories. The most common diagnostic test requires a simple blood draw or urine sample; a patient’s blood or urine is screened for IgM and IgG antibodies against Zika. The most specific results are found when testing for antibodies specially raised to the viral NS1 (non-structural protein 1) antigen. Zika antibody results take only a few days.

A more sophisticated and rapid molecular test designed to identify the Zika virus genome in human serum entails the real-time reverse transcription-polymerase chain reaction. Identification of viral RNA can sometimes be made before the presence of viral protein, so this diagnostic step allows for detection soon after infection. This test is recommended for symptomatic individuals within the first two weeks after symptom onset. It can also be used on urine samples. As this test becomes more widely available, more accurate counts of infected individuals can help in the epidemiological studies necessary to thwart the global health crisis.

THE OLYMPIC GAMES GO ON

Just months before the Games of the XXXI Olympiad were set to begin in Rio de Janeiro, the world was watching, waiting and wondering. As new headlines about the spread of Zika continued to break, those involved in the Rio Games realized they were facing a serious issue. Beyond the organizers, the athletes themselves were forced to question the risks involved in traveling to Rio. How unfortunate that the nation deemed as “ground zero” of a global health emergency was the very nation where a half million susceptible people from all around the world were descending upon in the spirit of sports.

On August 5 the Olympic torch was lit and the opening ceremony went on as planned. In the end a number of qualifiers bowed out. At the same time, the majority of them decided to take their chances. With the support of their countries’ public health officials they were provided information and tools to protect themselves. The role of public health experts in communicating with their athletes was a critical component of the decision making process for many. And the investment of nearly six million dollars by Brazil’s Ministry of Health to help ensure the safety of those attending was a key factor in allowing the Games to go on.

How individual countries prepared their Olympic delegations

Dr. Philippe Levan, the physician for France’s National Olympic Committee, was interviewed about his nation’s plan to protect its athletes. As he explained, each competitor was provided with a bottle of mosquito repellent and mosquito netting before leaving France. The French athletes received several briefings on the topic and were reassured that by using protection, both in the form of repellent and when engaging in sexual activity, they should feel safe competing in Rio.

The German delegation received similar information and resources to take with them on their trip to Brazil. The athletes were each equipped with bug spray and mosquito nets prior to their travels, and most spoke about the importance of staying protected, being aware and focusing on doing the best they could in competition.

Members of the Olympic team from Mexico each received a kit containing mosquito repellent, condoms, and information on how to prevent mosquito bites. The Australian delegation claimed an even more effective tool against the disease—they were provided with “Zika-proof” condoms by pharmaceutical companies. The prophylactics contain an anti-microbial agent believed to offer greater protection.

The South Korean Olympic team sports their uniforms, fabricated from mosquito-repellent material. (Photo by Chung Sung-Jun/Getty Images)

Some individuals traveling to Brazil resorted to more extreme measures as a safety precaution. John Speraw, the coach of the United States men’s indoor volleyball team, chose to freeze his sperm before the trip to use for a planned future pregnancy, if the need arose. British champion long jumper Greg Rutherford also had his sperm frozen.

American soccer player Hope Solo created a stir when she tweeted this photo.

The world health crisis, played out against the backdrop of the 2016 Olympics, proved to be fortuitous to innovative companies with relevant solutions. Greenlid Envirosciences, based in Toronto, Ontario, launched a new patented product, Biotrap—the first ever biodegradable mosquito trap. The trap is designed to target and eliminate female mosquitoes and their larvae, the main vector of Zika, dengue, malaria and other mosquito-borne illnesses. The technology employs both a mosquito attractant and an environmentally safe insecticide that kills mosquitoes. To activate the trap simply add water; once filled the trap is biodegradable and compostable. The company donated Biotraps to the Canadian Olympic Foundation where they were used around the Canada Olympic House in Rio.

To go, or not to go

On the other end of the spectrum were the few athletes who chose to withdraw from the Games when the Zika virus threat was at its height. These athletes, most notably Irish golfer Rory McIlroy, Australian golfer Jason Day, and American golfers Jordan Spieth and Dustin Johnson, cited concerns about Zika virus. American cyclist Tejay van Garderen withdrew two months before the Games began because his wife was pregnant. Canadian tennis champion Milos Raonic, Czech Republic Grand Slam finalist Tomas Berdych, and Romanian tennis star Simona Halep also stated that the uncertainty around Zika factored into their withdrawal from the Games. Their decisions attracted tremendous international attention and no shortage of opinionated testimony.

Athletes who chose to withdraw from the Rio Olympic Games.

Olympic Games 2016: Zika postscript

It is too soon to tell if those who risked the Zika virus threat to compete in Rio, or their family members, will suffer any kind of long term health effects. There’s no doubt that athletes and spectators who traveled to Rio de Janeiro will be carefully monitored, just as there’s great hope that the low rate of infection predicted by epidemiologists will hold true. Some countries such as Australia had a plan in place for greeting its athletes when they arrived home—this included individual disinfection, treatment of high-risk cargo unloaded from the aircraft and ongoing monitoring. All arriving from Brazil were also reminded to practice safe sex over the next eight weeks as “precaution is the best protection.”

Taylor Phinney, a member of the U.S. Olympic cycling team, competed in Rio—his third Olympic games. He was joined there by his mother, former Olympic cyclist and speed skater, Connie Carpenter-Phinney, and they both found that the Zika virus concerns did not impact their experience.

U.S. Olympian Taylor Phinney competing in the Rio 2016 Olympic Games. (Photo by Phil Walter/Getty Images)

“Zika had no effect on the Rio Games. It was their [Brazil’s] winter. No one used bug spray and no one got sick. While it is a problem for pregnant women, the media turned it into something much bigger.”

The U.S. National Institutes of Health announced that it will study athletes who participated in the Olympic Games to gain a better understanding of viral infection. The organization plans to recruit at least one thousand athletes, coaches and staff members to provide samples of bodily fluids for routine testing. The goal is to learn more about factors for infection as well as how long the virus remains in the body.

And, as of late August 2016, the World Health Organization posted on its website that not one single confirmed case of Zika virus associated with the Olympics had yet to be reported. Still, the organization pointed out that the majority of cases go unreported because as many as 80 percent of people who get Zika don’t even realize they've been infected. The next critical phase of monitoring involves the potential for sexual transmission of the virus as it can persist in semen for months. It may take some time for the full picture to emerge.

MAN VERSUS MOSQUITO

Perhaps the most critical component of the Zika global health emergency are the measures being taken to end it. A number of strategies are now underway, from the more immediate and localized points of attack, to the more elegant and long lasting scientific solutions.

Spraying mosquitoes away

The photos continue to circulate, a bit eerie in nature, showing suited, masked and hooded exterminators wielding giant spray guns. Yet this approach of industrialized mosquito repellent spraying is effective. It was used in Brazil when the Zika crisis first developed, and is now following the spread of the virus from Puerto Rico to Peru and on to the United States. Communities in the city of Miami, Florida were the first in the U.S. to engage in spraying when the first cases of Zika were reported there. More recently the strategy has been used in New York City as a preventative measure during the high months of summer when mosquitoes are at their worst.

Spraying against Zika virus in Kuala Lumpur, Malaysia. (Photo by Alexandra Radu/Anadolu Agency/Getty Images)

In Cuba, “mosquito guns” are commonplace. Those armed with the devices, which resemble large hairdryers, walk around and spray a thick white cloud. The mosquitoes quickly disappear. The nation has benefitted from this pro-active and intensive approach; it has been among the last of the Caribbean countries to report local transmission of Zika. But it will be a challenge to keep the numbers down given the growing interest of travelers from all around the world to visit Cuba now that its doors have opened.

Aerial insecticide spraying campaigns have been conducted as well to reduce adult mosquito populations. The state of Florida launched its first in early August, shortly after the U.S. Centers for Disease Control and Prevention issued an unprecedented travel warning in certain Miami neighborhoods. Naled, a member of the class of insecticides called organophosphates, has been used for the aerial spraying campaigns and has been approved by the U.S. Environmental Protection Agency.

A plane sprays pesticide over the Wynwood neighborhood in Miami, Florida. (Photo by Joe Raedle/Getty Images)

The same chemical was recommended for aerial spraying in Puerto Rico but was met with protests because of concern for the environment and native insects and agriculture. Puerto Rico's government ultimately shipped back the pesticide, joining groups such as the European Union which have banned naled.

Naled, also known as Dibrom, is dimethyl 1,2-dibromo-2,2-dichloroethylphosphate. It targets adult mosquitoes, specifically the nervous system of insects. The synthetic chemical interferes with the enzymes acetylcholinesterase and other cholinesterases and disrupts nerve impulses to kill or disable the insect.

Using genomics to mount more effective protection

While insecticide spraying represents a short term solution to diminishing the mosquito population and thereby decreasing Zika transmission, a long term goal for protecting people from the virus is well along its way. So far along, thanks to collaborative efforts and a shared determination to find an answer, that the first ever vaccine against Zika forged its way into a clinical trial in record time.

It was announced in early August, 2016 that the first Zika investigational DNA vaccine approach, similar to that developed and effectively used against the West Nile virus, was approved for use in a phase I clinical trial.

In a departure from traditional strategies for creating vaccines, the Zika vaccine now being tested incorporates viral DNA. Conventional approaches use a live attenuated infectious agent, or inactivated whole virus, which replicates within the host without causing disease. Both effectively serve to stimulate the host’s immune system to mount a response that protects the host against the infectious agent. This approach was taken to develop several other promising Zika vaccines that are expected to enter phase I clinical trials in the near future.

DNA vaccines use a genetically engineered plasmid containing DNA sequence that encodes a viral protein. The Zika DNA vaccine encodes the genes for two Zika structural proteins, the pre-membrane and envelope proteins. These protein antigens are produced using the host’s own DNA translation machinery.

The DNA vaccine offers advantages over live, attenuated or inactivated whole virus vaccines, including the stimulation of a more thorough immune response involving both B-cell and T-cells. It also triggers a cell-mediated immune response which may ultimately yield more durable and lasting protection against the disease. DNA vaccines have been found to work relatively faster and are less costly to manufacture on a large scale compared to the labor and time intensive approaches necessary to grow large batches of attenuated viruses for vaccine production. Lastly, DNA vaccines are believed to be safer as they eliminate the need to inject infectious material into the host.

Steps for creating a DNA vaccine for the Zika virus

The RNA is extracted from the virus and converted to DNA.

Based on the DNA sequence primers specific to the prM and E gene region are produced. These primers are used to generate a cDNA fragment containing both the prM and E genes.

The cDNA fragment is then inserted into a circular piece of DNA called a plasmid.

The plasmid carrying the prM and E genes are grown in large quantities in bacteria and purified by column chromatography.

The purified DNA plasmids carrying the prM and E genes make up the investigational Zika DNA vaccine.

The National Institute of Allergy and Infectious Diseases' Vaccine Research Center spearheaded the development of the first Zika DNA vaccine, and was granted approval to begin a small phase I clinical trial involving eighty patients. The goal is to assess the safety and immune response over time; results are expected by the end of 2016. If this initial study proves that the vaccine is safe and effective in mounting an immune response, a larger study in Zika-affected countries could begin in early 2017.

A second DNA vaccine trial commenced this summer—one developed by the Pennsylvania-based company, Inovio Pharmaceuticals. The U.S. FDA initially approved the study, a multi-center Phase I trial to evaluate Zika DNA vaccine GLS-5700. Since then Health Canada’s Health Products and Food Branch also approved the study extending the clinical sites to Miami, Philadelphia and Quebec City. The company demonstrated that their Zika vaccine established a record as the fastest-ever vaccine development from conceptualization through human applications. This is a testament to the value of collaborations and united support offered in the face of a global health crisis.

Conclusion

Collaboration. Partnership. Open data. Tenacity. Sportsmanship. These are all words that can legitimately be used when writing of the global health crisis called Zika. These very descriptors are what perhaps set this particular health challenge apart from earlier ones our world has faced. Never before have the Olympic Games been touched so directly by a threat of infection. Never before has the open sharing of critical data factored into the rapid progress that research scientists are experiencing as they race to find answers. And never before have vaccines been pushed through from concept to delivery in such a short amount of time. While this crisis continues—for there is much more to this ongoing story—there is a shared sense of optimism that Zika will soon be understood and contained.

Written by: Nicole Sandler Designed by: Michael Stormberg and Tim Rickey Animation and original illustrations by: Aaron Wardell