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The mosquito-borne Zika virus has reproductive-age women, families and governments across the Americas nervous, and for good reason. Some 4,000 babies have been born with microcephaly, a condition marked by an abnormally small head and potentially devastating brain damage, very possibly caused by the virus. Zika has been found in more than 20 countries and could infect as many as 4 million people. The U.S. Centers for Disease Control and Prevention has warned pregnant women in the United States against traveling to affected countries. The threat is so severe that the government of El Salvador told women to postpone pregnancy until 2018.

Besides the obvious paradox (how exactly are women supposed to prevent pregnancy in a heavily Catholic country when the Church opposes condoms and birth control pills?), the response to the Zika epidemic from Latin American governments is striking: It distills the disregard so many of them have for women, for maternity, and for the complex and deeply personal calculations all women make when becoming mothers or choosing not to - often at the expense of public health.

According to Gallup polling, people living in Latin American are less likely to say that women are treated with respect and dignity than people living anywhere else in the world. Violence against women is endemic - in Peru, for example, half of women say their first sexual experience was forced. Poverty remains feminized. Contraception access is improving, but remains low for adolescents and low-income women in particular. Half of pregnancies are unplanned. Despite the region's severely restrictive anti-abortion laws, there are an estimated 4.4 million abortions every year in Latin America and the Caribbean, 95 percent of them unsafe. Every year, a million Latin American women end up hospitalized and an estimated 2,000 die from unsafe abortions. Those are epidemics, too, and they've been met largely with a shrug.

Take El Salvador. For every 100,000 women who give birth, 54 die from pregnancy-related causes. (By contrast, in Denmark the number is seven, France is eight and the United States is 14.) And unlike most of the world, maternal deaths in El Salvador have been increasing since 2003.

Rising maternal deaths have yielded little self-inquiry from the country's leaders. El Salvador is one of seven countries in the region that outlaws abortion in all cases, not even permitting procedures to save a pregnant woman's life. Women there go to jail not just for having abortions, but for having stillbirths or premature births officials suspect are abortion-related. When one woman, known internationally as Beatriz, was carrying a pregnancy that not only threatened her life but was anencephalic (that is, the fetus lacked a brain), she petitioned the El Salvador Supreme Court to allow her a life-saving abortion. They denied her, reasoning that the threat to her life "is not actual or imminent, but rather eventual."

Under the law in El Salvador, Zika exposure during pregnancy or a fetus with microcephaly would not be grounds for an abortion.

Microcephaly has a variety of causes, of which Zika is suspected to be only one, but providers say that microcephalic children whose disorders appear to be caused by Zika have particular abnormalities, and those whose mothers were infected during the first trimester suffer the most severe brain damage. Many children being born in Latin America will have profound disabilities and will require care for the rest of their lives. The Salvadoran government expresses concern for those children but little practical assistance to their mothers, and it certainly doesn't defer to women to make critical decisions about their own pregnancies.

Latin American women outside of El Salvador are unlikely to fare better. Ground zero of the Zika outbreak is Recife, a Brazilian city with widespread poverty. A few years back, in Recife, a 9-year-old showed up at the hospital with her mother. She was pregnant with twins after being raped by her stepfather. Under Brazilian law, her case was a trifecta of abortion exceptions: She was a minor, she was a rape victim and, as a tiny girl carrying two fetuses, the pregnancy endangered her life. The Brazilian courts granted her a legal abortion. Nevertheless, the influential Catholic Church stepped in - the local archbishop eventually generated an international spectacle when he excommunicated the girl's mother and the doctor who performed the procedure, but not the rapist stepfather.

The doctor who performed that procedure and was excommunicated for it, Olimpio Moraes, still lives in Brazil. (It was his second excommunication and the Church never sent over the proper paperwork, he said, so maybe it didn't count.) I interviewed him a year and a half ago, at his home in Recife. The girl and her mother, who were from a rural area outside the city, were forced to take on new identities and move after the attention generated by the Church's anti-abortion protests.

The "pro-life" current of Brazilian politics and religion's influences compromise women's health beyond just abortion - according to Moraes, staunch opposition to abortion rights also means that many pregnant and birthing women get substandard care. The clearest example of that, he says, is misoprostol, a drug sold by the brand name Cytotec in Latin America, which induces both labor and abortion and is used to combat hemorrhaging after childbirth.

The drug has lowered rates of maternal death around the globe significantly; it's also decreased illegal abortion deaths, since using misoprostol off-label is a much safer way to end a pregnancy than having a clandestine surgery. But the Brazilian government is so concerned about women terminating pregnancies illicitly that they've heavily restricted access to misoprostol, making it unavailable at pharmacies and, Moraes says, making it more difficult for even hospital maternity wards to stock it: Prohibiting women from terminating pregnancies was more important than giving birthing women easy access to a drug that could save their lives.

Enter Zika. Again, prohibiting women from making their own decisions about pregnancy takes precedence over public health concerns, even while governments scramble to prevent thousands of births of profoundly impaired children. Again, the burden is on women to avoid pregnancy, and again, those same women have few tools to do it. Again, women are being treated like little more than vessels for someone else's interests - now it's avoiding pregnancy, before it was keeping pregnancies they didn't want. At no point have women been given the necessary medical, social and financial support to carry out the task assigned to them.

Zika means women who already carry enormous weight with little assistance are being assigned even more reproductive burdens, in countries where their labor is demeaned and their own decisions denigrated and unsupported. The socioeconomic status of millions of women is unlikely to change in a few weeks. Their access to health care, including contraception and abortion, could - if there's the political willpower. Perhaps the virus will finally make Latin American governments realize the load with which they've saddled women is too heavy. Maybe a mosquito will finally tip the scales.
Correction: An earlier version of this post incorrectly spelled the name of Olimpio Moraes.

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Zika is the latest example of how hard it is to be a woman in Latin America

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The mosquito-borne Zika virus has reproductive-age women, families and governments across the Americas nervous, and for good reason. Some 4,000 babies have been born with microcephaly, a condition marked by an abnormally small head and potentially devastating brain damage, very possibly caused by the virus.

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Recent disease outbreaks of mosquito transmitted pathogens (West Nile, eastern equine encephalitis, dengue, and chikungunya) demonstrate the need to educate children and adults about the public health risks posed by mosquitoes. By participating in this project, individuals will learn how to protect themselves, their family and pets from mosquito transmitted pathogens.

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PowerPoint Presentation Collection Notes Chikungunya Handout Note to Teachers Keys to the worksheets and quizzes are available by emailing us at invasive.mosquito.project@gmail.com.Walter Reed Biosystematics American Mosquito Control Assn. United States CDC CDC Zika Information ECDC Mosquito Infographic Mosquito Byte!

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When people think of genetically modified organisms, food crops like GM corn and soybeans usually come to mind. But engineering more complex living things is now possible, and the controversy surrounding genetic modification has now spread to the lowly mosquito, which is being genetically engineered to control mosquito-borne illnesses.

A U.K.-based company, Oxitec, has altered two genes in the Aedes aegypti mosquito so that when modified males breed with wild females, the offspring inherit a lethal gene and die in the larval stage. The state agency that controls mosquitos in the Florida Keys is awaiting approval from the federal government of a trial release of Oxitec's genetically modified mosquitos to prevent a recurrence of a dengue fever outbreak. But some people in the Keys and elsewhere are up in arms, with more than 155,000 signing a petition opposing the trial of genetically engineered mosquitoes in a small area of 400 households next to Key West.

Many scientists say, however, that genetically modifying the Aedes mosquito - and possibly other types of mosquitoes carrying diseases such as malaria - is a more effective and environmentally benign way of controlling mosquito-borne illnesses than spraying pesticides and other measures. Oxitec's genetically engineered Aedes aegypti has proven itself in other countries, successfully reducing populations of the insect by up to 90 percent in field trials in the Cayman Islands, Brazil, Malaysia, and Panama. Overall, the trials were so successful that Brazil approved the use of the GM mosquitoes last year.

A genetically engineered mosquito has proven itself in other countries, successfully reducing populations of the insect.

"Some people don't want to see GE (genetically engineered) anything," says entomologist Raymond St. Leger, distinguished university professor at the University of Maryland. "It's an emotional response. It's hard to reason people out of a decision they didn't reason themselves into."

St. Leger is now conducting field trials in Burkina Faso to test a method in which a mosquito is exposed to a fungus that prevents it from transmitting malaria. He says that Oxitec's technology to suppress the Aedes aegypti has relatively little environmental risk and that knocking back the mosquito in the Keys, which experienced a dengue outbreak five years ago, "is a matter of urgency.

"You don't want to wait until it's endemic," he says. "The gun is there and cocked and waiting to spread through their mosquitos. The extensive program and spraying with insecticides isn't working. You need to do something now and not wait until dengue is there. It's a very dangerous mosquito doing pretty well for itself in Florida."

Tom Miller, a retired professor of entomology at the University of California, Riverside, says that the genetically modified mosquitoes Oxitec uses to control dengue should not be regulated at all. "The method only releases males that do not [bite and] take blood meals," says Miller. "They seek out wild females of the same species and produce offspring with lethal genes, leaving no survivors. In terms of side effects, it is equivalent to dumping dead insects onto the sidewalk."

The Florida Keys Mosquito Control District first consulted with Oxitec when 28 people in Key West were infected with dengue in 2009 and 2010 - the first outbreak of the disease in Florida in 75 years. Dengue is also known as "breakbone fever" because it causes debilitating bone pain and flu-like symptoms. A severe form of the illness, dengue hemorrhagic fever, can lead to death, although rarely in areas with good medical care.

No dengue cases have been reported in the Keys since 2010. Since the outbreak, local officials have fought the Aedes aegypti - the primary vector for dengue - using every means possible. They spend $1 million of their $10 million annual budget specifically trying to control this one species. It is one of 46 species of mosquitos that live in the Florida Keys, and accounts for 1 percent of the total mosquito population there.

While other mosquitos are nuisances, the problem of the Aedes aegypti is not the itch. The bug contracts diseases like dengue, chikungunya, and yellow fever from humans and then transmits it to people through bites. Only female mosquitos bite, and while other mosquitoes can take their blood meals from animals like dogs and birds, this species relies on humans to survive. It can fly just 100 to 200 yards, so it lays eggs in water that collects near homes, such as in garbage cans, barrels, or in plants. It's an invasive species in Florida and likely came to the U.S. from Africa on European ships carrying early explorers. The Aedes aegypti was once eliminated through the use of chemicals like DDT, but the species has re-emerged in Florida over time.

"From a health standpoint, we don't want to wait until we are fighting the disease," says spokesperson Beth Ranson, of the Florida Keys Mosquito Control District. "We want to prevent it."

Technicians now go door-to-door looking for standing water and remove it. They also use bacteria like Bacillus thuringiensis israelensis to kill larvae, spray chemicals into the air to kill adult bugs, and add larvae-hungry fish to eat mosquitoes in abandoned cisterns or fountains. Despite all this effort, they have only reduced the insects by 50 percent over the past several years.

Opponents of the GM mosquito 'have no argument that makes any sense,' says one scientist.

"We can't go everywhere," says Ranson. "We can't get onto rooftops. We don't have access to some properties. But we hope the Oxitec mosquitoes could get to those hard-to-find females and do the work for us."

Key West resident Mila de Mier started the petition against Oxitec. She lives two miles from the proposed test site and has been outraged by the possibility of trials. She says the local mosquito control has been more than effective. "We have no local dengue now," she says. "Why do a clinical trial in an area with no dengue? If it doesn't work, how do you recall it? I don't want my kids to be laboratory rats."

Mier says she wonders what might happen to her three kids and two dogs if a lab-grown mosquito bit them - a concern that scientists say is unfounded. She is also worried that other mosquitoes, such as the Asian Tiger mosquito, would move in and fill the void in the ecosystem. Other opponents worry that the modified insect might have some unknown harmful effects on the environment.

But Oxitec and numerous scientists say fears about genetically modifying the Aedes aegypti mosquito are largely unfounded. Since only male GM mosquitoes would be released and only female mosquitos bite, it is virtually impossible that humans would be bitten by a modified female. Even if they were, the health impacts would be no different than being bitten by a non-modified mosquito, scientists say. And the self-limiting gene in the lab-grown mosquito is only passed on to another organism through sexual reproduction; a bird, for instance, cannot acquire the gene by eating the bug.

"The anti-GM mosquito, sterile-insect people have become a lunatic fringe," says Miller of UC Riverside. "They have no argument that makes any sense."

The fears expressed by opponents of the GM mosquito initiative in Florida are set against a backdrop of increasing experimentation with genetically modified organisms, says Todd Kuiken, a science and technology expert at the Science, Innovation and Technology Program at the Wilson Center in Washington, D.C. Today 115 different synthetic biology products and applications exist, and they are rapidly advancing.

Some - like a genetically modified, fast-growing salmon - have been languishing in federal regulatory offices for 16 years. Roughly 50 other modified organisms are on the market or close to commercial use. This list includes things like a genetically engineered variety of mustard that is injected with DNA from fireflies; the mustard can then be grown to produce "natural" lighting.

"As more products and platforms move onto the market, there will be increased demand for risk research to underpin regulatory decisions," says Kuiken. "And as more novel species are developed, eco-evolutionary dynamics will need to be evaluated, too."

An expert says the main objection to the technology boils down to its newness, rather than scientific merit.

Miller says that the main objection to Oxitec's technology boils down to its newness, rather than scientific merit. He says that the U.S government has approved similar applications for agriculture, noting that the sterile insect technique that Oxitec adapted to dengue control using modern molecular methods was invented by the U.S. Department of Agriculture more than 70 years ago. It has been used successfully to eradicate screwworm flies from North America and most of Central America and now is used to control a large number of crop insects globally, such as the destructive Med fly.

Miller says that using insecticides is only 2 to 5 percent efficient and has far more serious environmental consequences than genetically modifying mosquitoes.

"Insecticides coat the countryside and always leave a subpopulation of mosquitoes to survive, " says Miller. He says, research suggests that eliminating mosquitos from urban areas has no negative environmental effects.

"We are introducing a new tool to reduce mosquito populations to trace levels that you can do in conjunction with other prevention and control methods," says Hadyn Parry, chief executive officer of Oxitec. "With insecticide, you are spraying away and you may have insecticide resistance because populations are not going down. You are killing a number of insect species in a targeted area. There's collateral damage - while reducing the aegypti species, you are also reducing innocent bystanders and beneficial insects. ... Ours is controlled and precise. It doesn't hang around in the environment."

Two genetic engineering technologies are currently being used to modify mosquitoes, and both are in the trial stage. One is a self-limiting technology, which Oxitec uses, where the modified mosquitoes contain a lethal gene that is passed on to offspring to prevent the larvae from developing into adults. The other is the gene-drive technology, a much more complex modification in which offspring inherit genes that are then passed on to entire populations. This can essentially immunize the pests from getting disease in the first place. The modified mosquito's lifecycle is about a month, and the company has raised more than 150 generations with no mutations to the mosquitoes.
ALSO FROM YALE e360 Frankenfish or Healthy Food? A Lively Debate on GM Salmon
In an online debate for Yale Environment 360, Elliot Entis, whose company has created a genetically modified salmon, discusses the environmental and health impacts of this controversial technology with author Paul Greenberg, a critic of GM fish.READ MORE

While the Keys do not currently have locally transmitted dengue or chikungunya, pre-conditions exist for these diseases to become endemic, public health experts say. The mosquito contracts the disease virus from humans, and with travel increasing from the Caribbean - especially Cuba - into Florida, scientists are concerned. Both diseases are severely debilitating. Chikungunya is similar to dengue but causes such severe joint pain that patients are often bent over from it. Chikungunya was not found in the Americas until December 2013; within 12 months, one million cases of chikungunya had spread throughout the Caribbean.

The Wilson Center's Kuiken, who studies the governance strategies of synthetic biology, says the environmental risks of genetically modifying mosquitoes - which could include the impact of eliminating a mosquito species from an ecosystem - have not been well studied. The regulatory process, he says, for GM products lags far behind technological advancement. The U.S. Food and Drug Administration's Center for Veterinary Medicine has been reviewing the issue of Oxitec's GM Aedes aegypti mosquito since 2011. But this is the first time they have reviewed GM pest control, and Kuiken says it's a decision with far-reaching implications.

"Man has been engineering nature and ecosystems ever since we came out of a cave," says Kuiken. "What is different now is that we are beginning to engineer species. It is a progression on the scale, and it is a big progression."

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Genetically Modified Mosquito Sparks a Controversy in Florida

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Officials in the Florida Keys are seeking to use a GM mosquito that could help prevent a recurrence of dengue fever there. But fears among some residents - which scientists say are unfounded - are slowing the release of mosquitoes whose offspring are genetically programmed to die.

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The World Health Organization's Zika virus website. Here you can find the latest situation reports, news, facts, questions and answers, timelines and infographics on Zika.

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CDC - Home - Division of Vector-Borne Diseases - NCEZID

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Division of Vector-Borne Diseases (DVBD) home page. DVBD is part of the National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).

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Not all mosquitoes transmit diseases, but they can all be a nuisance. There are many different species of mosquitoes with different preferences for climate and breeding territory. Typically, mosquitoes lay their eggs in standing water. Mosquito larvae hatch from the eggs and remain in the water, feeding on tiny organisms. Once they mature, adult mosquitoes leave the water to breed.

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Summit Agenda

Friday, April 1, 2016: Summit Agenda [441 KB, 3 pages]

Pre-Summit Webinar

CDC hosted a webinar to provide guidance for all states on CDC's recommendations for preparing and responding to the emergence of the Zika virus.

Thursday, March 10, 2016, 3:00 pm EST

Zika Action Plan Summit Webinar: Presentation [867 KB, 40 pages]

Transcript

Coordinator: Welcome and thank you for standing by. At this time, all participants are in a listen only mode until the question and answer session of today's conference. At that time, you may press star followed by the number 1 to ask a question.

I would like to inform all parties that today's conference is being recorded. If you have any objections, you may disconnect at this time. Please continue to stand by. The conference will begin momentarily.

Coordinator: You are live in the conference at this time.

Dr. Anne Schuchat: Operator, could you begin the call for us?

Coordinator: Yes, you are live in the conference and you may begin when ready.

Dr. Anne Schuchat: Thank you so much. Good afternoon. This is Anne Schuchat and I really want to welcome everybody to the Zika Action Plan Summit planning call. We're really glad that you could join us today as we talk about CDC's recommendations for preparing and responding to the emergence of the Zika virus.

I'm pleased to be here with you today to update you on CDC's response so far. During the Webinar, we plan to provide you with information on guidelines for a phased response to Zika and considerations as you continue working on your Zika action plans.

We'll also share details about the Zika action plan Summit itself. Recently the White House invited governors and other leaderships from states to attend the first April 1st Zika action plan summit being hosted at the CDC in Atlanta.

The summit will provide state and senior health officials with information and tools to improve Zika preparedness and response in jurisdictions. The summit will also provide participants with the latest Zika science including modes of transmission and implications for pregnant women.

One housekeeping note - there's going to be an opportunity to ask questions through the operator at the end of our presentation during a question and answer session.

If you prefer, please feel free to send a question throughout the session using the Q&A tab on your Live Meeting toolbar. We'll do our best to answer as many questions as we can get to.

What is CDC doing? This winter, CDC began to focus intensively on the Zika virus which had been spreading in the Americas. We dispatched teams to Brazil and elsewhere to work with counterparts on understanding the virus and issued our first travel guidance on January 15th.

On January 22nd, CDC activated its emergency operations center and because emerging data was pointing to clusters of microcephaly and other problems associated with Zika virus, on February 1st the World Health Organization declared a public health emergency of international concern.

On the 8th of February, we elevated our EOC activation to level one, the highest level of response reserved for very critical emergencies. And as you know, on February 8th, the President announced the request for over $1.8 billion in emergency funds.

Zika virus was first discovered in 1947 in a monkey but it has been - probably we have learned more about this virus in the last two or three months than we have in its first 70 years.

Zika is spread primarily through the bite of an Aedes mosquito infected with the virus and most people probably don't know they have the virus. Symptoms are typically quite mild and last for several days to a week.

The greatest risk is to pregnant women and their infants and we have emerging data about that risk and that is really why the focus of state and local preparedness is so urgent.

Once a pregnant woman is infected with the virus through a mosquito bite or potentially through sexual contact with a male who's been infected or who has persistent virus, she can pass the virus on to the fetus and there can be a variety of potential complications to the fetus or potentially to the child.

So far, Zika virus and pregnancy has been linked to fetal loss, to congenital infections including microcephaly, eye problems and impaired growth. We don't have evidence right now that women who deliver a baby who has complications from Zika virus or who loses a pregnancy to Zika virus has any risk for future pregnancies related to her Zika infection.

But we do think that infection during pregnancy can be a real problem. There are many questions right now and we're working very hard to get answers, but we don't know for sure if a pregnant woman is exposed to Zika virus, how likely it is that she'll be infected.

If she's infected, we don't know how likely it is that her pregnancy will have problems or that her fetus will have problems. We don't know if the fetus is infected, how likely it is that there'll be birth defects or even longer-term developmental problems.

This is a critical set of questions that CDC and our counterparts around the world are actively trying to understand. Identifying a new viral cause of a major birth defect is extremely rare.

We know that certain maternal viruses like rubella and CMV can cause birth defects. The association between microcephaly and Zika is the first association between maternal infection and birth, in fact, to be detected in more than 50 years and we are literally learning more every week.

But the evidence for a causal relationship between Zika virus and microcephaly or other adverse pregnancy outcomes gets stronger by the day. CDC and other scientists are working to collect information about women infected with Zika during pregnancy and their infants to learn more about the impact of Zika during pregnancy.

The information collected will direct public health efforts intended to mitigate the impact of Zika and guide recommendations for the evaluation, testing and management of women infected with Zika during pregnancy.

We're also very busy in developing and disseminating clinical guidelines that address the issues for pregnant women, infants and children who have possible Zika virus infections.

We'll be continuing to issue guidance and update guidance as new information becomes available. Before 2015, Zika outbreaks had occurred in Africa, Southeast Asia and the Pacific Islands.

Currently, there are outbreaks occurring in many countries and territories in the Americas. And, as you know, it was last May that Brazil reported the detection of Zika virus and since then, more than 30 countries or territories are reporting it.

I want to caution you before you pay too much attention to the numbers on this next slide, the numbers shown come from (ArboNET). We have made Zika virus reportable and the state and local authorities are doing a great job of reporting cases but these numbers will be reflecting individuals who have been tested, results that our lab confirmed, that get reported and get updated once a week.

And see individuals from the territories are reporting frequently but these numbers will lag behind the actual trajectory of disease and they will only be laboratory confirmed cases.

That said, as of March 9th, 367 cases of Zika virus have been reported to (ArboNET) which is the national arboviral surveillance system managed by CDC and state health departments.

To date, there has been no local mosquito-borne transmission of Zika virus in the US mainland. One-hundred-ninety-three travel associated cases have been reported so far in 31 states and the District of Columbia.

Seventeen of those were pregnant travelers, three were sexually transmitted and one was a congenital transmission. So far, 174 cases of Zika virus have been reported to (ArboNET) from three US territories including 159 cases from Puerto Rico.

The numbers increase every week and we believe this trajectory will continue to increase substantially, particularly in the territories. So what is CDC doing? We're focused on supporting state, local, tribal and territorial response efforts.

We're just at the beginning of the response and its rapidly evolving. The priorities shift as we learn more every day but right now we're working intensively with public health partners and state health departments to monitor the spread of Zika and report cases for public health surveillance, to increase lab capacity for testing and identification of Zika infections, to assist with the development of new or improved tests for the detection of the virus or past infections and working with partners to improve mosquito control efforts.

As you know, we've been providing recommendations for prevention and promoting effective health communication strategies. We are very keen to focus on support to state, local, tribal and territorial response efforts.

That is what the Zika action plan summit is all about and I'm pleased now to introduce our next speaker, Dr. Jennifer McQuiston, who is the deputy incident manager for the Zika response. She's going to discuss guidelines for jurisdictions developing Zika risk-based action plans.

Dr. Jennifer McQuiston: Good afternoon. It's a pleasure to be here to speak with everybody today. As Dr. Schuchat mentioned, I'm going to be talking about some new guidelines that we have recently shared with states for the development of their own state and local risk-based Zika action plans.

And these are recommendations that states might take into account in consider as they begin to work on their own plans. These guidelines are posted on the CDC Web site and the link is here and they've also been shared with state preparedness directors, partners and state health officials yesterday.

When states are beginning to work on their plans, probably a very common question that comes up is what should we do at what time? And the guidelines that we have been working on developing really look at Zika in a phased response.

A lot of states already have (vector) response plans and we know that some states have experienced, not only with the West Nile virus response, but also with chikungunya and dengue outbreaks.

But the Zika response requires some new considerations that are likely not covered in those other response plans including the need to really focus on pregnant women, protecting them from mosquito exposures and also how to incorporate sexual transmission messaging and risk reduction measures in the response plan.

The plan that was shared with states yesterday provides guidance for a phased jurisdictional response based on escalating risk for Zika. This means that states and counties and local jurisdictions might wish to base their response in a very defined geographic area if there's not widespread transmission of Zika within the state.

And the phased response plan gives states and localities ways to do this. This is intended to serve as the support tool for states as they develop their plans. It is just meant to be guidance and it's not meant to be policy.

In order for states and local jurisdictions to think about implementing a phased response, though, there are a few key actions that would really be important. The first is that plans that are already in place are reviewed and you prepare them in the context of a Zika response.

And it's important to do this in advance of Zika transition actually being reported in your state. The vector control piece of the phased plan requires a comprehensive multistep approach and this means that states and jurisdictions should be thinking about how to monitor for Aedes species mosquitoes in their areas, both at the larval and adult stages and think about how to control them and then also how to implement a more urgent response in the event that Zika transmission begins to occur.

A phased response plan also requires that states have a very strong surveillance and diagnostic testing program in order to very quickly diagnose, report and respond to suspected Zika cases.

The phased response plan breaks down a response into four different categories of risk. There's a preparation phase and this is the time period that's really now.

It's pre-mosquito season and that's meant for states where an Aedes aegypti or an Aedes albopictus mosquito is present or possible in a jurisdiction. The second category is during mosquito season and this means that you're actually expecting mosquito biting activity and breeding activity from those mosquito species.

The third phase is confirmed local transmission. This would be the first single case or few cases clustered in a single household or community block in a county or jurisdiction.

And then the fourth category of risk is widespread local transmission within a county or jurisdiction. This means that there are multiple locations with Zika virus cases and that there does not appear to be a clear chain of connection between them.

There is actually a fifth category of risk that we're not going to talk about here and that would be widespread transmission in multiple counties in a region of the states, and that is just because the same recommendations are in effect but they're scaled in a much greater level.

In each risk category, there are response activities that follow these different targeted areas and we're going to talk about each of them. In the preparation phase, as states are beginning to think about what they might do in the event of Zika transmission locally, it's important to think about who's going to provide the leadership at the state and local levels.

And that would include appointing a senior representative to coordinate response efforts in deciding who will be an incident manager during an emergency.

It's important that a lot of state and localities coordinate between state public health officials and vector control officials because, in many cases, those are organized differently and they're not always working in tandem.

But in a situation like this, it's very, very important for the infectious disease officials in a state to be talking with the maternal child health officials in the state and also to be coordinating with their vector control officials.

This is a good time to review any plans the state already has, what the situation looks like for your state and local mosquito control programs, what capacity they have, what their staffing needs are.

This is also a good time to review the processes that you may need for rapid hiring more contracting of services. For example, if your state or local area does not have a vector control program, what contracts would need to be put in place in order to make sure that that capacity is arranged?

Also in the preparation phase, and he state that has Aedes aegypti and Aedes albopictus will likely need to be thinking about how to communicate messages to the residents of their states and jurisdictions.

And this is a good time to begin to prepare a communication campaign. Pregnant women are one of the most important groups for us to focus on for communications.

The truly are the most vulnerable population and why we're treating Zika and the possibility of it in the United States with such urgency. But also travelers returning from countries that have active Zika virus transmission and healthcare providers to know what to look for and how to test patients, all of those have communication needs that can be prepared in advance.

It's important to note here that unlike other vector-borne diseases like chikungunya or West Nile virus, it's really important to include messaging on sexual transmission and steps for prevention for Zika.

In the preparation phase, enhancing surveillance for travel associated Zika cases is also important. Not only does this give providers a chance to be recognizing what Zika could look like and how to report it, identifying travel associated cases early and making sure that they're following recommendations to protect themselves from mosquito bites, may actually help prevent local spread of the virus.

This is also a good time to review your laboratory capacity and to determine if your state is able and ready to test specimens for Zika. For vector control, reviewing and conducting mosquito surveillance activities to assess historic distribution maps is important, but it's also important to note that many of those maps are outdated.

And so as you're preparing for the beginning of mosquito season, you might be thinking about how to do surveillance as mosquitoes start to come out so that those maps can be updated.

This is also a good time to begin planning activities that, from the start of a mosquito season, might help bring population numbers down and then hopefully reduce the likelihood of transmission in the future.

For pregnant women, this is a good time to plan how you might enhance surveillance for Zika in this very vulnerable population. It's also a good time to identify resources that pregnant women might need in the event of local transmission.

And at CDC, working with many of our partners, we have been distributing something called Zika prevention kits in Puerto Rico and some of the other territories that gives pregnant women tools they can use to protect themselves, such as repellents, larvacides that they can use around the homes, condoms to prevent sexual transmission.

So these are the sorts of things that identifying resources in advance and planning for their distribution could be very helpful. We do know that blood safety is a concern with Zika and in Puerto Rico, local blood collections have stopped and they are outsourcing blood according to FDA recommendations.

So within the mainland United States, it's important to think that if local Zika virus transmission is happening, there were also be blood safety issues to think about.

So consulting with your local blood collection centers now on their blood safety plans is important so that everyone understands what that response pattern will look like.

Once mosquito season starts, and here in Georgia, I think we're almost there - it's about 80 degrees here today - it's important for the partners that are going to be working on the Zika response to begin organizing regular meetings and providing updates.

In addition to this, giving everybody information that can be helpful for - to guide their efforts, this is also a great chance to connect with CDC and other partners and find out what they're doing.

From a communications perspective, you don't need to wait for a Zika outbreak to have a communications campaign preparing people, and so messaging for awareness, how they can protect themselves against mosquitoes and really getting people engaged and thinking about how they can reduce residential sources of water they could contribute to Aedes breeding sites is important.

From the surveillance perspective, it's important during mosquito season to rapidly follow up on suspected cases through laboratory testing and to encourage healthcare providers to immediately report those results.

While this needs to be happening even during pre-mosquito season and during mosquito season, it's especially critical because those people need to be contacted and counseled about what they should be doing to protect themselves against mosquito bites.

During this time, as well, vector control mainly focuses on reducing residential sources of water where the mosquitoes can breed and organizing community interventions to disrupt those breeding grounds, so community cleanups, removal of any discarded tires. These are all things that are great to do during mosquito season.

In the event of the first confirmed local transmission case, that would activate the state incident management structure and would result in a connection to CDC and partners to see if additional resources might be needed.

If a state wanted to call an Epi- Aid), this is the time that would happen. Surveillance would include intensifying the - looking for human cases around this first confirmed case.

Ideally you're finding human cases very, very quickly before they become widespread within a county. The only way to know that is to really be intensifying surveillance around that first case.

Vector controls, and a situation like this, if you really only have a localized case were a few cases in a household, vector control might include conducting intensified larval and adult mosquito control it that house or building and in a protective radius around it.

And that would include both residential habitat reduction, reducing water sources. It would include both larvacide and (adulticide) mosquito chemicals, outdoor space spraying.

There are a lot of things that can be done in an intensive way around a case patient's home. In addition, a county may consider additional interventions, whether they wanted to do more widespread spraying through truck-mounted sprayers or even aerial sprays.

The decision about when to move to more widespread spraying is a very local decision and it depends on a lot of factors. But thinking about them in advance and building them into a plan is a great idea.

The first confirmed case of local transmission, it is very likely that pregnant women in that county are going to be very worried. So communicating clearly and early, specifically targeting your messages to pregnant women about what they can do to protect themselves, about where they should go for help is important.

Letting your local blood collection agencies know that you've had a single confirmed case is important and that way they're ready and prepared in the event that transmission becomes more widespread.

Widespread local transmission is the fourth risk category and this is really when you have multiple cases in a county and multiple different areas that don't seem to be all linked in time and space.

States and jurisdictions should really know in advance how they might respond, what their geographic counties might be for aggressive response efforts.

It's envisioned it could be at the county level, it might be at the ZIP Code level. It might be at a level that's contained within the health department's access area, however states decide to do it.

It just needs to be communicated so that the response efforts are understood and that the blood safety centers know or blood collection centers know. This is the time you're going to intensify your communication and outreach to the citizens, letting them know what they need to know to the communication plans you developed in the preparation phase.

And intensifying surveillance for human cases beyond those first cases, really working with your hospitals and clinics. In this phase, vector control needs to become intense and it needs to be expanded to include much wider areas.

And this is where your truck-mounted spraying or your aerial spraying might need to be implemented, depending on your state and county decisions and needs.

Once you have widespread local transmission and you're doing much more urgent sector control, it also becomes very important to monitor the effectiveness of your control efforts, and so mosquito trapping surveillance is one way to do this.

I've gone through - oh, wait, we have a little bit more. Widespread local transmission - pregnant women outreach. We talked about this a little bit. Again, this isn't necessarily guidance that every state or local jurisdiction would follow, but in the event that there's widespread local transmission at a county or jurisdiction level, messaging about whether pregnant women might want to consider changing travel plans could be considered.

Again, that is a very local (need) and decision. Implementing your intervention plans is important. Pregnant women might need special intervention plans.

If they live in homes without air-conditioning or screening, they might need help actually mosquito proofing their homes so that they have a safe environment for the duration of their pregnancy.

You might also consider looking retrospectively for pregnant women who may have had Zika virus to see if any cases were missed so that they can be followed appropriately.

At the point of widespread local transmission, blood safety centers must begin following FDA guidance, and this means that local collection of blood will stop and that they will either need to outsource blood or they could to local collections if and when blood tests become available. Those are still in the research phase and they are not widely available at this time.

And with that, I'm going to turn it over to Christine Kosmos, who heads our state coordination task force. Stop review.

Christine Kosmos: CDC has been activated for a Zika response. We've been working very closely with our state and local partners to assist you with your planning and readiness for Zika.

Now at this point, I want to take a little break and do a quick poll to get a snapshot of where state and locals are in their planning process. This will help us finalize our reparations for the Zika action planning summit here at CDC on April 1st.

So (Demetrius), can we go to the poll? So hopefully you can see this on your screen and it asks you to just describe your jurisdiction's Zika planning efforts to date.

So the responses are , hasn't started yet, you've met but you don't have - or you haven't met but you have plans to do so, your jurisdiction has been meeting and developing your response plan, your jurisdiction already has a draft Zika plan or you're not sure what your jurisdiction's activity has been so far.

So we'll give you a couple of seconds to answer that. Okay, just a couple more seconds. All right, I think we'll close the poll. So essentially what this shows is that states and locals are already meeting and many of you already have a draft action plan in the works which is excellent news.

And since the EOC has been activated here at CDC, we provided a lot of technical assistance to our state and local partners. Specifically, we've had a lot of outreach to state and local lab directors, epidemiologists, NCH directors, preparedness directors, professional partner organizations, just to name a few.

In addition to that, CDC has provided a lot of guidance through MMWRs. We've published eleven MMWRs related to Zika. We've issued eight travel advisories. We've issued more than 20 plans for state and local use.

Some of them for state and planning. Some of them are lab related guidance. Many of them are for clinicians and healthcare providers. You have a lot of communication and risk communication tools on our Web site.

We have Zika posters and fact sheets. And we've also convened more than 40 calls including two national calls into call specifically for clinicians to provide state and locals with the technical assistance that you need.

So in the next few minutes, I want to bring all of this together because we've been dealing with a lot of areas subject matter experts, but this is really our opportunity to pull it all together and provide states and tribes and locals with a coordinated, one-stop shop approach to Zika planning and preparedness and provide your planning teams with CDC's best available advice on how to approach Zika preparedness within state, local and tribal regions.

So in the next few minutes, I'm going to familiarize you with a few of the CDC resources that can really assist you with your planning. So first am going to walk you through the actual Zika action planning template that Jenny just walked through, just to familiarize you with it and show you how it works, so can you click on the link, (Kate) and the planning template form?

So on your screen, you'll see the actual planning template that Jenny walked through. So it's by phase, so you'll see there are the specific actions that Jenny talked about broken out into the preparedness with all the specific guidance documents.

Then it goes into mosquito season, confirm local transmission, widespread local transmission, et cetera. And you'll see in the left column, that's the CDC advice and recommendation and it gives you, on the left - or the right-hand side, opportunity to write some of your jurisdictional action steps.

Now we're hoping that you use this planning template and other resources that we're providing today to really drill down into your specific plans and bring those particular gaps or areas that you want further assistance to the summit on April 1st.

Now, (Kate), can we go to the Zika Web site? So in addition to that, and sort of continuing in the vein of the one-stop shop, I want to just walk through the CDC Zika Web site which is a lot of information specifically for Zika.

It includes the latest guidance documents, MMWRs. You'll see the MMWRs on the right-hand side, also the tools and the templates and the resources for state and local, as well as some public facing documents.

There're Zika FAQs, scientific publications. And please consider this to be one of the best sources of information to assist in your planning and response. And then finally, just - I want to mention that the last thing that we're offering to you or the last thing in this seminar, that we're offering to you, is that our CDC entomologists are finalizing a vector control and surveillance strategy for the US.

We're going to be sending it out to you very soon to assist in your planning, so more to come on that. So to summarize, we are asking you today, and this is kind of your checklist, to assign a lead Zika preparedness coordinator in your team, for those of you that have not yet started, to assess your jurisdictional risk, and there's information included in the planning template that assists you in determining your jurisdictional risk.

Review the existing CDC guidance and resources that we have here and that I just walked through today, including the (ZAP) planning template which we just walked through, as a way to document some of your activities as well is to document some of the areas where you might need some additional technical assistance.

And want to have that draft plan, where you identify some of the gaps in preparedness and response, we're going to ask you to bring that back to the summit on April 1st.

And speaking of the summit, I'm going to turn it back over to Sara Zigler who is going to give you some information about the summit.

Sara Zigler: Thank you, Chris. I'm excited to be able to share information with you all about the Zika Action Plan Summit that will take place on April 1st at CDC. I'm going to provide you a brief overview of the summit and how we think you might be able to best make the summit work for you and your jurisdiction.

The summit will include three tracks - a Zika science plenary, leadership planning for state and local government leaders and readiness action planning for state and local scientific and technical staff.

The first two parts will be streamed via live Webcast and archived on the (ZAP) Web site, which is www.CDC.gov/zap. The science plenary will include who is at risk, how to identify and diagnose cases and preventing and responding to mosquito-borne illnesses.

The leadership planning track will include information on crisis and emergency risk communication and the Zika response and how to manage policy to increase public understanding of Zika.

In addition, in the readiness action planning track, state and local scientific and technical participants will have an opportunity for action planning which will include specialized technical assistance.

So how might you engage in the summit? There are two ways for our state and local partners to engage in the summit - in person, as part of a jurisdiction team or virtually, through the live Webcast of the summit on April 1st.

The live Webcast will be archived for viewing after the summit as well. Please go to our will Web site, www.CDC.gov/zap, to find out more information. CDC encourages participation in person from states and jurisdictions that are most likely to have Aedes aegypti mosquitoes circulating and/or high regional travel volume with returning travelers from countries with local Zika transmission.

There is a listing of those state jurisdictions on the Web site. CDC will be providing financial support for state and local participants that attend the summit. I just want to clarify - CDC will be providing financial support for state and local participants that attend the Zika Action Plan Summit.

Everyone must register for the meeting so that we can make the necessary arrangements. Registration for this summit closes on Tuesday, March 15th. For those of you are contemplating in-person participation, we recommend that you consider a team composition that includes individuals from a variety of disciplines that contribute to your jurisdiction's planning for Zika virus response.

You may consider state and local leaders such as governors, public information officers, a mayor, county commissioners or some scientific and technical staff such as your state health officer, your state epidemiologist, state veterinarian or vector control lead, your state preparedness director, a maternal and child health director, local health and environmental health officials.

We strongly urge state jurisdictions to include local health representation in their team composition. We're planning for a Zika Action Plan Summit that is focused on providing content that will meet the needs of our state, local and tribal partners.

We would appreciate some of your feedback now through two quick rapid polls. We have two questions for you about what might be your priorities for receiving technical assistance from CDC and the other US government partners that will be involved in the summit.

Please select the best option from the two lists that you'll see in this poll. We'll do poll number one and leave this open for a few seconds I let everyone respond. And then we will go to a second question with different options for you to select from.

Please identify your jurisdiction's priority technical assistance (TA) need from this first list. We appreciate that all of you are giving us your feedback so we can consider that as we make the final planning arrangements for the Zika Action Plan Summit.

Thank you all very much. We're going to begin closing out this poll. And now for the second question - please identify your jurisdiction's priority technical assistance needs from this list.

Again, we appreciate this feedback as we will consider it as we make final arrangements for the Zika Action Plan Summit's curriculum. We'll give it just a couple more seconds and then we'll begin to close out this poll.

Thank you all very much for giving us your feedback. We have concluded the presentation section of this Webinar. We're now going to wor- go to questions and answers.

While the operator is opening up the line to receive questions from the phone, we did receive one question in written form that we well answer. The question was too how to define widespread transmission for the purposes of blood safety. I'm going to turn this answer over to Jenny McQuiston.

Jennifer McQuiston: Hi, thanks for this question. So we - CDC, in concert with our state health officials who we consulted on the development of these guidelines, we kind of played with the idea of whether a certain number would be something that we would want to put out there as the designation for widespread transmission. And we talked about five or more cases possibly meeting that definition. But we decided not to actually put it in the guidance because in some cases...

Coordinator: To ask a question on the phone, please press Star 1 and record your name when prompted. Again, to ask a question on the phones, please press Star 1 now.

Jennifer McQuiston: That your county might be having a widespread transmission concern. So this is really something that we're hoping that states and local jurisdictions think about and know what they're trigger point is for widespread transmission. And I think that five or more cases would certainly qualify.

Woman: And operator, we'll go to the phone if there are any questions.

Coordinator: Yes, and again, as a reminder, to ask a question my phone, please press Star 1 and record your name when prompted. One moment, please, for the first question. The first question comes from (Phil Wong). Your line is open.

(Phil Wong): Yes, hi. This is (Phil Wong). I'm with the City of Austin Health and Human Services Department and (this) follows up on the first written question, I think. And you talked about widespread transmission definitions for blood transmission concerns.

Also, I mean, in terms of how the geographic, what, area, you're talk- going to be talking about, and I actually missed the end of the question with some of the question's query procedures that - you know, our blood bank - I just got off the phone with our blood bank and they are very concerned regarding, you know, if our city gets designated or county gets designated as having the widespread transmission, what the implications would be for collecting blood.

Woman: Thanks for that question. We know that these are questions and issues that states and local jurisdictions are definitely going to be thinking about and making decisions about.

And we wanted to roll out the idea of a phased in jurisdictional response because every county and jurisdiction might have a different comfort level and what they feel they want to define as their geographic boundaries for that response.

Some counties may want to do it within the boundaries of their county lines. Some may want to combine counties if they feel like there's a risk for transmission on a border, for example.

Some counties may be very large and feel like they can contain this jurisdiction only within a ZIP Code designation, so it really is left up to the state and local health departments, the boundaries that they want to set for what an active response would be, what your area of active transmission would be defined as, and correspondingly then, what your area of blood safety concerns would be contained within.

(Phil Wong): Okay, thank you.

Coordinator: The next question comes from (Tom Daly). Your line is open.

(Tom Daly): Hi. I was just looking for some clarification on the financial support that you mentioned it to the affected states. Is that - with that the 100% of the travel costs or a certain share?

Woman: It is CDC's intention to support the travel expenses for the state and local representatives with consideration for space capacity that we have within our facilities and other factors.

We have a lot of interest for the Zika Action Plan Summit and so when you contact us through the Web site, you will receive a call back and we will communicate with you and find out more about your interest in attending the summit and work with you to identify the number of people that can be supported from CDC.

(Tom Daly): Okay, great. Thank you.

Coordinator: The next question comes from (Scott Lindquist). Your line is open.

(Scott Lindquist): Hi, this is (Scott Lindquist) calling from Washington state. I guess we're looking for some advice on what our priority is in the state that we clearly do not have this mosquito. Our biggest issues have been around travelers.

So in our action plan, which we've drafted, we do have mosquito control districts. We do have (radication) plans, but quite frankly, it's very unusual for us to see this mosquito at all and probably is not going to be seen in Washington. Any advice for us?

Dr. Anne Schuchat: Yes, hi. This is Anne Schuchat. Thanks for that question. You know, I think the first thing to stress is that this is - this virus is new to the Americas and the mosquito vector, Aedes aegypti, if not, you know, we're not thinking it's going to be a problem in Washington state.

So, you know, the prediction is that you're going to have to deal with transmission from - they you're going to have a lot of travelers and that you may have sexual transmission and that you're going to have communication, laboratory, healthcare of affected babies and communication kinds of concerns and likely, not mosquito types of concerns.

But because this is a new condition, we think it's important to think about things and not wait until you have a problem or wait until we see mosquitoes everywhere.

Certainly we are most concerned about the southern states where we know the vector is common and we also know that the Aedes albopictus can be a vector for this virus and the geographic that might be broader.

I think that the idea that 40 million people travel to Zika affected areas each year and beyond pregnancy, we now have sexual transmission to think about. We feel like every state is going to have some people with Zika infections that are complex and will need to be able to message and manage those.

But I think this - the whole focus on the summit and the planning is to know who the right counterparts are into think ahead to be ready for what's likely and then to have at least thought about what's unlikely.

Jennifer McQuiston: And this is Jennifer McQuiston. I will just add that if you visit the Web site and look at the phased risk-based plan, it outlines some state risk assessments that can be helpful for states in determining what level of plan you want to create and what you want to focus on.

And so the first risk assessment is that all states will likely need to provide public information, particularly to pregnant women because even if you're in a state without Aedes aegypti, you're pregnant women are going to be concerned and want messaging.

And then to assess returning travelers who may have contracted Zika virus infection and manage any risk for sexual transmission. The second state risk assessment would be for states with Aedes albapictus mosquitoes and those dates should presume that transmission as possible and be ready to prevent, detect and respond to cases of Zika.

And then the third state risk assessment would be states with known Aedes aegypti mosquitoes, and those states we think need to develop plans that more intensively monitor for cases, both in returning travelers and also possible local transmission, and then to prepare and respond vigorously to stop clusters of Zika before they become widespread.

So those are the sort of three risk-based assessments that we've put out there. I have an additional question that's command - how will guidance change regarding travel when local transmission is occurring in a locality within the continental United States? I don't think that the risk - the phased risk-based plan necessarily gets into the details of whether travel restrictions would be required or recommended.

I do think that pregnant women should now when there is a local area of transmission where active transmission is happening so that they can make their own decisions about travel. And so I think a lot of that is going to depend on messaging properly so that people are informed and can make their own decisions.

Woman: Maybe I could just supplement that a little bit. I think that we have - you know, you all in the state and local health departments know how many possible scenarios there are, you know, in terms of a back - a home or a block that has the mosquitoes in cases versus large numbers of infected mosquitoes with the virus and then possibly some human cases that have been detected.

You know, we also know that the way people live and travel in the community in the continental US is quite different than in Puerto Rico or much of South America in terms of screens and air-conditioning and, you know, air-conditioned malls and air-conditioned doctor's offices and so forth.

So I think the issue of exactly what might be local - even widespread transmission in the continental US might not look the same as in Puerto Rico or Brazil.

And so the local and state planning really needs to customize (for) what we might see. Obviously, there are some neighborhoods that might be at great risk in the continental US and I think that's the type of scenario that we should be thinking of.

One of the factors that we want people to plan on is mosquito (unintelligible) and that can help you understand hotspots and where we'll need to be making sure we have control.

Woman: This is a great time to add that during the summit, on April 1st, there is actually going to be a track where we're inviting states and localities to share their personal experiences in managing vector-borne outbreaks associated with Aedes aegypti. So we will hopefully have state and local representatives they can talk about what they've done in similar situations that can help inform the local decision.

Woman: Operator, we'll go back for a couple more phone questions.

Coordinator: Thank you. The next question comes from Zach Thompson. Your line is open.

Zach Thompson: Zach Thompson, director of Dallas County Health and Human Services. I'm joined here with our health authority, Dr. Christopher Perkins. I want to commend you for the summit call today and I participated on a similar call earlier this week on Tuesday, March 8th.

I guess my question I want to reiterate how important it is and how critical local health departments will be to participate in person at the summit. We're on the front lines.

As you know, Dallas County had the second sexually-transmitted case of Zika. Also, we've been involved in day-to-day planning, so I'm hoping that you could pass on to Dr. Frieden, the importance of local health departments being a part of the state team since we're actually on the front line, have to deal with the municipalities, have to deal with the elected officials. And so any summit that does not include local health departments will definitely have a big gap. So thanks a lot.

Woman: Thanks very much for that comment and I just want to reassure you that we are addressing local health department engagement in the summit in two ways. First, by encouraging our state jurisdictions to include (local) representation, and also, by working proactively with the states from the local health departments that we have heard from to ensure that the representa- composition of any team is reflective of the needs of that jurisdiction. We understand your concerns and we're trying to be very responsive to that.

Coordinator: The next question comes from (Laquanda Nesbitt). Your line is open.

(Laquanda Nesbitt): Hi. My question has been asked and answered. Thank you.

Coordinator: And so the next question is from (Mary McIntyre). Your line is open.

(Mary McIntyre): Yes, this is Mary McIntyre, Alabama Department of Public Health. I have several people here in the room with me. But we wanted to know is, we're focusing on the composition of the team and what you're looking at as far as the maximum number of people that would be allowed to come from any state. If we are trying to actually address state, local and partners in this effort, what is the number that we should be aiming for?

Woman: Thanks so much for the question. What we would, one, want to remind you, that for any team members that are not able to travel in person to CDC, that we will have live Webcasts of the large majority of the summit.

In addition to that, when you contact us through the Web site, you will get a call back from a member of our ZAP registration planning team who will work with you to identify the number of individuals we can support on the team.

Because of the large interest for this meeting, it is not a one-size-fits-all answer for this situation for the ZAP planning Summit and so we'll work with you individually to address that question and we encourage you to contact us as soon as possible so we can get those plans underway.

(Mary McIntyre): Thank you. We have. We've contacted you.

Woman: So we had one additional question that came in on email and we're going to ask Dr. Matt Kuehnert who works with lead safety here at CDC to answer it.

Dr. Matt Kuehnert: The question was, is there specific guidance on planning for blood supply interruption in the case of widespread local transmission? And we would - that's a great question.

We would encourage state and local health departments to reach out to blood centers that locally collect in their area. We've already heard from Texas that blood centers are reaching out to you.

And we can certainly help in that regard and discuss that in the summit. What I will say now is that there is a plan to have blood donor screening tests available in April and by FDA guidance, the - what blood centers have to follow is that if there isn't a screening test available, then in an area of local transmission, they essentially need to outsource until the screening test is available.

In addition, but centers may not, depending on the situation, choose to screen and want to outsource. So it's going to be a blood center by blood center decision. Not all blood centers are the American Red Cross. There're smaller blood centers as many of you know.

So I think it's important to reach out to them and speak to them about what their plans are to best understand what their scenarios are and what can be done to assist them.

Woman: Operator, we have time for one more question before will complete the meeting.

Coordinator: Very good, and the next question comes from (Kim Stein). Your line is open.

(Kim Stein): Hi. I'm calling from the Michigan Department of Health and my question has to do with human case surveillance. We're curious to know if - or if and when some of the Southern tier states, where, you know, (HSI) is, you know, present, when the states may begin screening people want travelers for Zika virus in order to detect local transmission. The current guidelines don't permit us (screening) the people have not traveled out of the United States yet.

Jennifer McQuiston: I'm sorry, this is Jennifer. I think we're trying to understand the question. The call came through and it broke up a little bit for us. Is the question when states and the southern part of the United States will begin to test symptomatic people who have not traveled?

(Kim Stein): Yes. I mean, you mentioned in Georgia, for instance, you know, mosquito season is upon you. So in other words, how will we know when that virus has reached the continental United States?

Marc Fisher: This is Marc Fisher with the epidemiology team here and that's a very good question. It's very difficult to identify the, you know, first local transmission in a given area. So right now, as you mentioned, the testing recommendations are for symptomatic persons who have a specific exposure that is through travel or a sexual contact of somebody who has traveled. And the only testing for asymptomatic people would be for pregnant women who have travelled.

The identification of the first local transmission in an area is really going to come from a combination of information that's going to come from recognition of an unusual cluster of illness, of people with fever and rash or from mosquito surveillance or issues regarding possibly blood transmission. There's not going to be a way to, during mosquito season, to test every person who has a symptomatic illness and has not traveled to identify the first case.

(Kim Stein): To know if there's any test available for mosquitoes at this time for Zika.

Woman: So there are tests that can be applied to testing mosquito pools but at this time we're not recommending it necessarily as a strategy for all states. But these are great questions that I think we can begin to talk about at the summit and be able to make sure that we've got technical expertise available for states that would wish to test mosquito pools that they have the guidance that they need.

Woman: We are reaching the end of our Webinar time. We would appreciate, for those of you that have participated in the Webinar, to give us some feedback. We have two more questions that are coming up they were welcome to answer for us, and on those questions, as you give us your feedback, we also have an email address where you're welcome to send any comments or questions to us about any of the contents that we covered today.

It will help inform our preparations for the Zika Action Plan Summit in the coming weeks. We're looking forward to you all participating with us in that summit virtually or in person depending on what's most appropriate for your jurisdiction.

Woman: So the first question is that you understand the purpose of the Zika Action Plan Summit and then we have one more question after that. You can provide feedback to us at ZAPSummit@cdc.gov.

Again, that email address is ZAPSummit@cdc.gov. For additional information about registering for the Zika Action Plan Summit, please go to our Web site, www.CDC.gov/zap.

There's a link there where you can click on it to submit a registration request to us and then we will get in touch with you to have a conversation at a designated time to find out more information about your jurisdiction's interest and then be able to follow up with you to make arrangements for you to engage either virtually or in person at the Zika Action Plan Summit.

Next question, close out the poll. This last question is, how valuable was this Webinar to you? Thank you all very much for participating in this Webinar and we look forward to continuing to work with you in the coming weeks as we prepare for our Zika action plans.

Coordinator: And that does conclude today's conference. Thank you for your participation. You may disconnect at this time.

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Friday, April 1, 2016: Summit Agenda [441 KB, 3 pages] CDC hosted a webinar to provide guidance for all states on CDC's recommendations for preparing and responding to the emergence of the Zika virus. Thursday, March 10, 2016, 3:00 pm EST Zika Action Plan Summit Webinar: Presentation [867 KB, 40 pages] Coordinator: Welcome and thank you for standing by.

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A full list of Cayman Islands Government Television news stories about Zika and the Friendly Aedes Aegypti Project can be found here

Wild Mosquito Problem

Aedes aegypti is a non-native mosquito species found in the Cayman Islands. These mosquitoes are more than just a nuisance as they can spread serious diseases such as Zika, dengue and chikungunya. Aedes aegypti is particularly difficult to control as it lives around humans, and the Cayman Islands Mosquito Research and Control Unit (MRCU) is looking for new technologies to suppress the population of these disease carriers.

Oxitec's Technique

Oxitec has developed an innovative technique for controlling Aedes aegypti mosquitoes. Oxitec mosquitoes have been engineered to contain a self-liming gene. Male mosquitoes are released to mate with wild females, passing on this gene to their offspring. Their offspring die before reaching adulthood, so the mosquito population declines.

Oxitec's mosquitoes do not stay in the environment, as both the released mosquitoes and their offspring will die. The approach is very targeted: it only affects the Aedes aegypti mosquitoes - the carriers of diseases - because the Oxitec males only produce offspring with their own species. It may also reduce the need for insecticides, allowing more beneficial predators and insects to flourish.

Previous trials in the Cayman Islands, Brazil and Panama, have all shown that the release of Oxitec's Friendly mosquitoes reduces the wild population by more than 90%.
Project Plan
Following the projects conducted in Cayman Islands in 2009 and 2010, Oxitec is again working with MRCU on a pilot project in West Bay, an area of Grand Cayman that is a hotspot for the Aedes aegypti mosquito. The treatment area encompasses about 1,800 residents, and standard mosquito control measures are continuing during the project. This programme started at the end of July 2016, after a period of ongoing community engagement, and includes nine months of mosquito releases to bring down the population of Aedes aegypti. The project has been approved by local regulatory authorities. It is anticipated that the mosquito releases will be rolled out across Grand Cayman, subject to the relevant approvals, to protect people throughout the island from mosquito-borne viruses. The Sister Islands are unaffected by Aedes aegypti to the extent that they pose a disease-threat.
Publications www.oxitec.com/publications Questions? cayman@oxitec.com
FAQ
What is dengue?
Dengue fever is a severe, flu-like illness that affects infants, young children and adults. Dengue fever is transmitted principally by the bite of an Aedes aegypti mosquito infected with any one of the four versions of the dengue virus (and a fifth serotype of dengue has now been discovered in Malaysia). Symptoms appear in 3-4 days (average 4-7 days) after the infective bite. Dengue haemorrhagic fever (DHF) and Dengue Shock Syndrome (DSS) are potentially lethal complications, particularly in children, and early clinical diagnosis and careful clinical management by experienced physicians and nurses is necessary to reduce the number of fatalities.

Dengue can only be transmitted by the bite of an infected mosquito and only female mosquitoes bite. The main vector is the mosquito Aedes aegypti, which originated from Africa and has spread around the world, largely in the last 50 years and, as it has done so, dengue fever has followed and increased dramatically.

The global numbers of dengue cases have grown 30-fold in only 50 years because current control methods, relying mostly on insecticides are not adequate to control this mosquito.

Each year there are an estimated 400 million dengue infections, with 500,000 cases so severe they require hospitalisation and 22,000 deaths, many of them children. New approaches are needed.
Further reading WHO dengue fever factsheet CDC dengue fever What is Zika?
Zika is a flavivirus, transmitted primarily by Aedes mosquitoes. The virus was originally identified in Uganda in 1947, and the first major outbreaks occurred in the Pacific, on Yap Island in 2007 and French Polynesia in 2013. In 2015 an outbreak was reported in Brazil, which subsequently spread to a large number of countries in the Americas, as well as elsewhere.

Some areas with Zika outbreaks have reported an increase in babies born with microcephaly as well as an increase in Guillain-Barré syndrome, a disorder in which the body's immune system attacks its nerve cells. According to the WHO, there is evidence that Zika virus can cause these disorders. Because of the increased incidence of these disorders in areas of a Zika outbreak, the WHO declared a Public Health Emergency of International Concern on February 1 2016, which was lifted in November 2016. "We are not downgrading the importance of Zika," said Dr. Peter Salama, executive director of the WHO's health emergencies programme. "Zika is here to stay, and the WHO's response is here to stay."

According to the Centers for Disease Control (CDC) in the United States, many people infected with Zika do not show symptoms so they may not know that they have the virus. When symptoms do occur, they are usually mild and last for a few days to a week. Symptoms include fever, skin rashes, conjunctivitis, muscle and joint pain, and headache.

In addition to transmission via the Aedes mosquito vector, sexual transmission of the Zika virus has been described in certain cases, and the presence of the Zika virus in semen has also been found.

There is currently no vaccine for Zika, so control of the mosquito and avoidance of bites are the best ways to combat the disease.
Further reading WHO Zika factsheet What is chikungunya?
Chikungunya (CHIKV) is a viral disease transmitted to humans by infected mosquitoes. The disease shares some clinical signs with dengue such as fever, severe joint pain, muscle pain, headache, nausea, fatigue as well as rash, and can be misdiagnosed in areas where dengue is common.

Chikungunya, like Zika and dengue, has resulted in a number of neurologic diseases such as Guillain-Barré Syndrome, meningoencephalitis, and cranial nerve palsies. Additionally CHIKV has been associated with rheumatic disorders including rheumatoid arthritis, spondyloarthritis, and undifferentiated polyarthritis. Other serious complications of CHIKV that are rare include myocarditis, ocular disease (uveitis, retinitis), acute renal disease, and severe bulbous lesions. Additionally intrapartum transmission of CHIKV can result in complications for the baby, including neurologic disease, hemorrhagic symptoms, and myocardial disease. Furthermore after maternal CHIKV infection, there have been rare reports of spontaneous abortions.

There is no available vaccine or specific medication for the virus.

Until recently the disease occurred mainly in Africa, Asia and the Indian subcontinent. In recent decades, mosquito vectors of chikungunya have spread to Europe and the Americas. In 2007, disease transmission was reported for the first time in a localised outbreak in northeastern Italy. In December 2013 the first case was reported in the Caribbean and within 12 months there were an estimated 1 million cases in the region according to the CDC.
Further reading: WHO chikungunya factsheet CDC chikungunya Do all mosquitoes spread dengue, Zika and chikungunya?
No. Aedes aegypti is the species of mosquito which is primarily responsible for spreading these diseases. Only female mosquitoes can bite and spread disease - males do not bite. Other Aedes species, such as Aedes albopictus, can also spread disease, but are not very efficient: Aedes aegypti is overwhelmingly the main vector, and it is this species that is responsible for almost all of the Zika, dengue and chikungunya epidemics around the world. Other mosquito species bite humans but do not spread these diseases.
How does the Oxitec mosquito work?
The Oxitec mosquito (also known as OX513A or the Friendly Aedes aegypti) has been engineered to express two genes, a colour marker and the 'self-limiting' pest control gene which causes offspring to die. The modified male insects are released to mate with wild pest females, they pass on these two genes, and over 95% of the offspring die before reaching adulthood. The pest population is brought under control with successive releases.
The colour marker
All Oxitec mosquitoesand their offspring express a fluorescent protein that can be seen using a special light. In the Oxitec mosquito this can be seen at the larval and pupal stage. The colour marker is an important part of our approach. We can collect larvae from the area of release and use the colour marker to see how many are Oxitec mosquitoes and how many are wild pest mosquitoes. Using this colour marker we can adjust the number of Oxitec mosquitoes we need to release and we can monitor their mating success. We can then increase or decrease the number of mosquitoes released to optimise release efficiency and control of pest Aedes aegypti. The ability to monitor the insects we release and the effect on the target population in real-time is a key feature of this approach.

With the colour marker we can detect our product in the field and monitor its effect closely to offer mosquito-control agencies the most targeted release programme to control mosquitoes.
The 'self-limiting' gene
At Oxitec, we have introduced a gene into the mosquitoes so that their cells do not function as they should (also known as a 'self-limiting' gene because it makes mosquito reproduction a dead-end - the offspring do not survive to adulthood). As a result, more than 95% of the Oxitec mosquitoes die before they become adults and do not live to breed further and the population is reduced. Aedes aegypti do not produce live offspring with other species so the control is species-specific and the genes don't spread. The released mosquitoes and their offspring die and so the genes also do not persist in the environment. The colour marker and self-limiting genes are non-toxic and non-allergenic, so if animals were bitten by Oxitec mosquitoes, or predators eat Oxitec mosquitoes, it would be the same as getting bitten by or eating wild ones.

For releases, we need to rear mosquitoes effectively and therefore need to turn off the self-limiting system. If the mosquito larvae in the production unit are given small quantities of tetracycline, this acts as an antidote inactivating the self-limiting gene. The antidote is not present in sufficient quantities in the environment to allow inactivation of the self-limiting gene, so offspring of the Oxitec mosquito will not reach adulthood.
Have Oxitec mosquitoes been tested outdoors?
Yes. From 2009, Oxitec and independent collaborators (below) have performed open release tests of Oxitec's Aedes aegypti (under permit from the appropriate regulators) in several countries, including the Cayman Islands, Malaysia, Panama and Brazil. In each trial Oxitec mosquitoes reduced the local Aedes aegypti population by more than 90%. There have been no noted adverse events or effects.

This is a level of control significantly greater than can be achieved with insecticides (typically 30%; Ballenger-Browning & Elder 2009) and one where we consider the environmental impact to be much lighter. Use of Oxitec's Friendly Aedes aegypti could significantly reduce the volume and incidence of insecticide spraying.

In every case to date, these mosquito trials have been carried out by external institutes or agencies. Oxitec has provided the OX513A strain and technical support. These external evaluators are:

The Mosquito Research Control Unit (MRCU) in Cayman

The Institute of Medical Research (IMR) in Malaysia

Moscamed and University of Sao Paulo in Brazil

The Gorgas Memorial Institute in Panama

In each case the institutes above are able to publish or publicise their results, which they have done through a combination of publications, conference presentations, or other media.

The WHO Vector Control Advisory Group (VCAG) has specifically recommended planned pilot deployment of Oxitec's self-limiting mosquitoes under operational conditions.
Why not just use insecticides?
Insecticides are designed to kill insects and they can be very effective, although the development of insecticide resistance can affect their level of control. In the Cayman Islands, Aedes aegypti are resistant to many of the available insecticides, and so new tools are needed to control the mosquitoes.

Another challenge of insecticide control comes from the fact that Aedes aegypti generally only fly short distances (about 200 yards in their lifetime), so they tend to stay in and around human dwellings. Breeding sites around homes can be difficult to find, and even if a public health authority has access to everyone's homes to spray and treat standing water and containers on a very regular basis, it is still difficult to find and spray every area, and current methods of control are only 30-50% effective at best. This is why there is a pressing need to develop new tools to control this mosquito species. Oxitec's technology can be used alongside other methods such as insecticide as part of an integrated pest management strategy.
Are Oxitec's mosquitoes compatible with mosquitoes found in the Cayman Islands?
Yes. Aedes aegypti is a species that originated in North Africa and has been spread around the world by human activities over time. The spread has occurred mainly passively though the movement of freight and goods from one country to another. Consequently it is thought that there are only two groups of Aedes aegypti - one in North Africa and one in the rest of the world. In the Cayman Islands, Aedes aegypti is a non-native species, just as it is in all the Americas. Oxitec mosquitoes are a strain of this same species so they mate successfully. Mating studies of Oxitec's OX513A strain have been carried out with local Aedes aegypti in many countries, showing they're able to compete and mate as effectively as local males.
If Aedes aegypti is controlled, could another species like Aedes albopictus move in?
Aedes aegypti is overwhelmingly the major threat in terms of its ability to efficiently spread Zika, dengue and chikungunya, and is the main target of mosquito control programmes aiming to reduce disease risk. Aedes albopictus has the capacity to spread diseases but is relatively inefficient at disease transmission. Aedes aegypti feeds almost exclusively on humans.

It lives in and around the home and can take multiple bites to get a blood meal. These features make it highly effective at spreading disease once a person has entered an area carrying the virus. Aedes albopictus, by contrast, is an aggressive biter and will tend to secure its blood meal more easily from a variety of sources. It is less selective about what it bites - so it will bite dogs, birds, etc. which are unaffected and do not act as a source for onward transmission to people. The two species can occupy the same habitat but Aedes aegypti is predominately restricted to areas of human habitation whereas Aedes albopictus is not, and tends to live more in forested areas and underbrush, etc.

In areas of overlap, it is likely there will be an element of competition for breeding sites, but there is no 'general rule' as to whether reduction in the number of one species will have an effect on the other. A year-long trial of Oxitec's Friendly Aedes aegypti in Panama found no evidence that suppressing Aedes aegypti increased numbers of Aedes albopictus. However, as Aedes aegypti is the major threat in terms of disease, even if the numbers of Aedes aegypti fell and Aedes albopictus were seen to rise, the disease threat would still be significantly reduced. Oxitec monitors both species in our field trials and projects, and will do so in this project in West Bay.
Could Aedes aegypti be eradicated?
A goal of this programme is to demonstrate the ability to control the local non-native Aedes aegypti population. Worldwide eradication of a species using this technique, we believe, is not possible or practical, because the mosquito lives around people and has managed to spread around the world by travelling with people as they move around. However, it may be possible to completely eradicate Aedes aegypti from certain limited localities such as islands. This will require strict monitoring at points of entry, to ensure it is not reintroduced.
Is the Oxitec mosquito harmful to humans or animals?
No.The proteins of the introduced genes (colour marker and self-limiting gene) are non-toxic and non-allergenic. The gene that prevents the offspring from surviving to adulthood affects only those mosquitoes that inherit it, and works by causing subtle adjustments to the insect cells, rather than being toxic.

Animals that eat the Friendly Aedes aegypti mosquito will ingest nutritional elements - protein, fat, carbohydrate and others - just as they would from eating any mosquito, but they cannot take up and incorporate new genes into the genome through this route. .

Independent studies as part of the regulatory approval process showed that OX513A had no effect on arthropods/fish in feeding studies compared to non-GM Aedes aegypti, even when they were fed artificially high levels of the GM mosquitoes in their diet - much higher than they would ever eat in the wild.

To date, more than 150 million Oxitec mosquitoes have been released worldwide in different countries and there have been no reports of adverse impacts.

Aedes aegypti mosquitoes only mate successfully with their own species. They cannot produce viable offspring with other insects in the wild, not even with another species of mosquito, so they cannot pass the genes on to other species through reproduction.

It is important to note that the Oxitec mosquitoes can only fly about 200 yards and their offspring die, so the effect is extremely localised. Potential effects of Oxitec Friendly mosquitoes only affect the area in which they are released.

We have been asked whether the food chain could be affected if this approach was adopted widely. There are no predators that are reliant on a single mosquito species as their food source, as they will eat a range of insects. Aedes aegypti is a non-native species in the Cayman Islands and there is nothing that depends on it as a food source.

By contrast, the use of insecticides is less discriminating. Insecticide sprays can kill many species and will impact the diversity of insect life and dependent species. By targeting only the key insect species capable of disease transmission Oxitec believes that insecticide spraying can be reduced, to help protect biodiversity in the area.
Do you release male and female mosquitoes?
Oxitec releases virtually all males. We sort the males from the females as pupae and have a greater than 99.9% sorting efficiency. Inevitably we will release a very small number of females but this is negligible compared to the number of wild females that are already in the environment. Any Oxitec females released are disease-free as they have been reared in the lab, and it is extremely unlikey that they would live long enough in the wild to be capable of transmitting disease (see next paragraph). During the trial in Panama, the number of female Oxitec mosquitoes released was equivalent to less than one per person per year.
What would happen if a person or animal got bitten by an Oxitec mosquito?
The bite of an Oxitec female mosquito is the same as a wild one because the proteins of the two introduced genes (self-limiting gene and colour marker) are not produced in the mosquito saliva, so a person bitten by a female mosquito would not be exposed to the introduced proteins. In addition, these proteins are non-toxic and non-allergenic. This information is based on studies by the National Institute of Health, USA, and by Oxitec.
How many mosquitoes will be released?
The number is determined during the programme. There are about 1000 mosquitoes released per pot, and the number of pots and release sites is adjusted during the programme There are usually three releases per week, and the males disperse quickly.

In a previous 6-month long trial in Cayman in 2010, 3.3 million mosquitoes were released, which resulted in more than 90% suppression of the target Aedes aegypti population. In Panama, a similar-sized trial worked out to a release of less than 5,000 mosquitoes per person across the entire 6-month trial to achieve suppression of the local Aedes aegypti population by more than 90%.
What is the lifespan of Oxitec mosquitoes?
Oxitec mosquitoes tend to live less than one week. Females that have mated an Oxitec male lay eggs which hatch into larvae, but do not develop into adults.
How do you rear mosquitoes if the offspring die?
In a production facility, the larvae are given an antidote in their rearing water from the tetracycline family which inactivates the self-limiting gene. This enables us to rear large numbers of mosquitoes. Those that are released cannot access this antidote in the right quantities and/or at the right time and so the self-limiting gene works effectively, as demonstrated by field trials in different countries.
Has the Oxitec mosquito been independently evaluated?
Yes. Independent collaborators around the world have conducted extensive testing on Oxitec's OX513A mosquitoes since the strain was first developed in 2002. The WHO Vector Control Advisory Group (VCAG) also recommended planned pilot deployment of Oxitec's self-limiting mosquitoes under operational conditions.

Oxitec insects (mosquitoes and other species) have been tested by independent laboratories including the Institute Pasteur in Paris, the Gorgas Memorial Institute in Panama, the Institute for Medical Research in Malaysia, the University of Colorado (USA) and the United States University of Health Sciences (USUHS). The Centre for Medical and Veterinary Entomology (CMAVE) at Gainesville, FL has also tested our mosquitoes in contained outdoor cage trials.

Outdoor trials, have been carried out by the Mosquito Research and Control Unit Cayman (in 2009 and 2010), the Gorgas Memorial Institute in Panama, the Institute for Medical Research in Malaysia, and Moscamed and the University of São Paulo in Brazil. In each of the outdoor suppression trials, the wild population of Aedes aegypti in the areas has been reduced by more than 90%.
Who is regulating the current GM programme in West Bay, Grand Cayman?
Two parties are regulating the programme: the National Conservation Council for the releases of the mosquitoes, and the Department of Agriculture for the importation of Oxitec's Friendly Aedes aegypti,.
Where can I get more information?
Oxitec scientists publish data in peer reviewed journals. Information pertaining to our products, and regulatory reviews of their safety is available on public websites. Here's a link to our publications: http://www.oxitec.com/category/publications/.

Further information from MRCU can be obtained from Information Officer Catherine MacGillivray at catherine.macgillivray@gov.ky or tel: (345) 949-2557.

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The Friendly Aedes Aegypti Project - MRCU

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Oxitec and the Mosquito Research and Control Unit (MRCU) The Cayman Islands Mosquito research & Control Unit (MRCU) and the Uk based biotechnology firm Oxitec are collaborating on a project with the Friendly Aedes aegypti mosquito.For more information you can view our Oxitec & MRCU questions & answers......

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The world's biggest collection of Zika virus is housed in a tan concrete building, rising up from the flat campus of the University of Texas Medical Branch here in Galveston. Inside, armed guards watch the lobby, and access to certain floors requires special clearance. These safeguards are in place because other viruses, including those that cause Ebola and severe acute respiratory syndrome (SARS), are also on the premises.

Zika is not as easily spread as deadly Ebola, so the laboratories that work with the mosquito-carried virus do not require spacesuit-like protection gear. On a recent visit I held a clear plastic bag containing the complete virus collection in my bare hands. Inside the bag the 17 vials of pure, freeze-dried virus resembled old glue. They did not look like the material of a global health crisis that has panicked entire nations. (The scientist who handed me the bag did keep one hand hovering nearby, presumably ready to catch if I dropped it.) Despite the modest appearance, experiments with the collection may be researchers' best hope of understanding how the virus got so out of control-and what to do about it.

The virus was first detected in Uganda, and for more than 60 years it stayed small and scientists took little notice, believing all it did was cause symptoms on par with a mild flu. But since 2015 Zika has ricocheted to more than 40 countries, transmitted by mosquito bite or human sexual contact. Researchers now blame it for terrible birth defects, including microcephaly, when babies are born with abnormally tiny heads, and Guillain-Barré syndrome, an autoimmune disease that can affect patients of any age. "The more we learn the worse it gets," says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Virologists now need to figure out which of two potential causes is responsible for the Zika explosion. One possibility is that genetic changes within the virus supercharged its ability to infect people and cause disease. The second scenario is that the change happened outside the virus: After decades of relative isolation it reached dense population areas, providing more fertile ground for its spread. If researchers identify new mutations within the virus that also allow it to breach the placenta and cause microcephaly in fetuses, then they could be on the lookout for ways to combat that transmission, too.

If the outbreaks are just the result of environmental changes, perhaps Zika was always capable of causing serious effects, but they were rare in small populations and only became obvious when the virus hit a lot of people. "It could just be a numbers game," says Erin Staples, a U.S. Centers for Disease Control and Prevention medical epidemiologist. (There is a third, less-accepted theory suggesting that previous exposure to another virus called dengue could somehow make people more susceptible to Zika. But there is little support for this compared with the other two ideas.)

Galveston is an ideal place to tackle this inside versus outside debate because the Medical Branch research center is home to the massive World Reference Center for Emerging Viruses and Arboviruses. (The latter are viruses carried by ticks, mosquitoes or other arthropods.) The collection includes more than 7,000 pathogens. Investigators also have a variety of specialized resources for testing virus infectivity in various bugs and animals, sequencing viral genes and imaging pathogen structures.

Spitting Image

For choosing among competing theories about what went wrong with Zika, it also helps that arbovirus expert Scott Weaver, the university's director of the Institute for Human Infections and Immunity, and his colleagues have become good at a rather arcane skill: making mosquitoes spit.

For the past fewmonths Weaver's team has fed lab-grown mosquitoes, related to the insects spreading disease in Brazil and the Dominican Republic, blood meals spiked with either a 2015 Zika strain from Mexico, a 2010 strain from Cambodia or a 1984 strain from Senegal. The scientists wait a bit, then coax the mosquitoes to spit, and examine that saliva for the amount of Zika virus particles it contains. Comparing mosquitoes that carry different Zika strains lets the researchers test whether newer strains travel more quickly from insects' guts to their saliva than do older strains. Such increased speed in a virus is often caused by a genetic change. If the virus now found in the Americas and Caribbean moves into the bugs' spit faster than other strains do, it could fuel a larger, faster-moving outbreak in humans-and favor the inside version in the inside/outside hypotheses duel.

Doctoral student Christopher Roundy has become the main drool wrangler. "Basically I spend my days collecting mosquito spit," Roundy says. "It doesn't sound that glamorous." Roundy begins the tests in Weaver's lab by mixing a specific strain of Zika with human blood donated by a local hospital. (The blood was getting too old for use in human transfusions.) Then he pours the spiked blood into a metal canister that he covers with skin from a mouse-mosquitoes are more likely to bite through skin. The other side of the canister is hooked to a heater, because mosquitoes also prefer warm meals. The whole setup is then placed, skin-side down, over the opening of a small Styrofoam container holding dozens of female mosquitoes (males do not bite). Frenzied by the smell of blood, the females stab their proboscises through the skin, sometimes two or three times. Once they are full their stomachs become red and engorged-making it clear that they have eaten.

For some, this is their last meal. Every day afterward a small number of those bugs are killed and taken apart. Their bodies, sans legs, are blended into a slurry; the legs are similarly pureed and studied separately. Both batches of bug bits are then scrutinized for signs of the virus-indicators of how far the pathogen traveled in the body.

After eight days Roundy turns his attention to the bugs' spit. He stuns a handful of the remaining live mosquitoes by placing them in the freezer for about a minute. Then, Roundy uses tweezers and a magnifying glass to gently guide each of their proboscises into a small tube containing a salt solution. That exposure to the salty mix forces them to drool. He adds that spit to dishes of cells and mixes in chemicals that cause Zika-infected cells to turn a purplish color. The purple cells are visible to the naked eye. Under a microscope, Roundy also examines the spit for tiny purple blotches-viral particles-that he might have missed.

If there are genetic changes in newer Zika strains, Roundy, Weaver and UTMB pathologist Nikos Vasilakis are particularly interested in any that might help the virus infiltrate human cells or aid its journey via mosquito bite. They also want to know if mutations may explain its connections to microcephaly. More virus in any single drop of blood, for example- thanks to boosted replication rates of the organism-could perhaps help the virus to more readily cross the placental barrier and reach a developing fetus. If there are no such changes, that is telling, too. It shifts the balance toward the "outside" environmental idea.

Searching for inside/outside evidence using this method has worked before. The same Galveston team used a similar approach to determine that another mosquito-borne disease, chikungunya, had mutated in the past. By studying spit they found that specific genetic adaptations allowed that virus, normally spread by the Aedes aegypti mosquito, to expand its range by jumping to a different carrier, the Aedes albopictus mosquito. A single amino acid change in one of the virus's glycoproteins, for example, allowed the virus to replicate about 40 times easier in the bug than it once did. The information prompted health workers to expand warnings about the disease to more areas of the Pacific rather than limit them to those locations at risk from one of the species. (It is unlikely that Zika made a similar species jump because the virus is already thriving in areas with A. aegypti, Weaver says.)

Moving Target

The Zika test results were finalized in late April. After tracking different strains of the virus via thousands of bugs the Galveston team came to a quiet conclusion: The latest Zika strain does not appear to be more active or more easily transmissible than are prior strains. In fact, older Zika from Africa in the 1980s is a bit quicker traveling through the mosquito body. The discovery does not completely eliminate the idea of harmful genetic changes yet this evidence tips the scales of blame toward the environment.

For scientists such as Weaver who are concerned about public health, the environmental tilt is disquieting. "It's bad news in a way because that tells us that the strain that is circulating today in Asia and Africa probably has at least the same capacity to initiate urban epidemics," he says. (Immunity in some of those populations from past outbreaks, however, may be protecting them from large epidemics.) The serious symptoms became more apparent as more people grew ill and public health officials saw enough of an uptick in microcephaly, other birth defects and Guillain-Barré to fuel concern and further investigation.

Kathryn Hanley, a biology professor at New Mexico State University who investigates viruses such as dengue and Zika, notes the environment and internal mutations actually could be working together. "These are not mutually exclusive hypotheses," she says. "It could be that the virus previously had little access to urban populations, but on the way to getting that access it also acquired mutations that increased its transmission." Researchers at Galveston and elsewhere plan further tests on insects and animals to explore this and other ideas.

There are still many unknowns about the virus. For instance, the way Zika infects human cells and hijacks their machinery to copy itself many times has proved elusive. And because this virus looks so much like dengue, testing for Zika has remained a serious challenge, complicating efforts to accurately track the spread. The first large outbreak-in 2007 on Yap Island in Micronesia-infected 70 percent of the island's population but was only identified because scientists had been deployed there on the assumption the isle was under siege by dengue. Other Zika cases have undoubtedly been missed altogether, scientists say.

That suggests researchers have underestimated this virus all along. Perhaps other benign-seeming threats could be more dangerous than previously thought as well, they worry. "You should not necessarily be scared, but you have to be open-minded and quick to respond," says the CDC's Staples. If Zika as well as other emerging viruses have unexpected effects as they reach different populations, it is a serious problem. Without better global surveillance of diseases in remote locations, health agencies will find it hard to foresee or prepare for an organism that could be quickly transported to an urban area and spiral out of control.

Such surveillance is currently not done: Many developing nations have little health infrastructure and few available resources to strengthen it. Moreover, most of the World Health Organization's annual budget comes from donor countries that earmark it for specific projects such as HIV prevention or polio eradication, not surveillance of amorphous threats.

Humanity is not without defenses, however. Some insecticides and larvicides work on the A. aegypti mosquito, Zika's preferred host, so disease control experts know which mosquitoes to study and target. Still, says Ann Powers, acting chief of the CDC's Arboviral Diseases Branch, "we need to be more vigilant." All it takes to change the profile of a disease, she knows, is a few extra mosquito bites.

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The world's biggest collection of Zika virus is housed in a tan concrete building, rising up from the flat campus of the University of Texas Medical Branch here in Galveston. Inside, armed guards watch the lobby, and access to certain floors requires special clearance.

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Malaria continues to plague the world's population, particularly inhabitants of sub-Saharan Africa, where it kills at least one person every 30 seconds. Efforts to eradicate the disease in the 1950s and 1960s met with failure, and current control measures such as antimalarial drugs are swiftly losing their potency. Now researchers have sequenced the genetic codes of the most deadly malarial parasite and a mosquito that carries it. Scientists hope the findings, published this week in the journals Science and Nature, will aid in the development of novel approaches to combating the disease.

Writing in Nature, a team of more than 150 scientists describes the genome of Plasmodium falciparum, a parasite that causes malaria. The analysis, which took six years to complete, identified 14 chromosomes containing almost 5,300 genes, including nearly 200 that produce proteins to help P. falciparum evade the body's defense mechanisms. A better understanding of their functions may point to potential new targets for antimalarial drugs.

Because transmission of malaria requires a mosquito vector, controlling or killing the insects is another route to disease control. To that end, the work published in Science could help. A consortium of researchers led by Celera Genomics has sequenced the DNA of Anopheles gambiae, the primary species of mosquito that transmits malaria to humans. According to the report, the genome is 278 million bases long and contains almost 14,000 genes. The scientists have started the daunting task of identifying their functions. In particular, they investigated which genes were turned on or off when female mosquitoes feed on blood. "Those are the pathways that are likely to be useful in finding points of intervention for developing new insecticides or transmission-blocking vaccines," says lead study author Robert A. Holt of Celera. "I think the most important thing the genome will facilitate in the immediate future is understanding the molecular basis of resistance to insecticides, and finding new insecticide targets."

Additional research published in both journals has shed further light on both P. falciparum and mosquito genetics. Laurence J. Zwiebel of Vanderbilt University and his colleagues pinpointed 276 genes that are critical to A. gambiae's sensory systems, which it uses to identify its human prey. If they can identify those that the mosquito uses to smell humans, Zwiebel says, it could be possible to create new repellants against the pests. Kenneth Vernick of New York University School of Medicine and his colleagues have discovered genes in natural populations of A. gambiae that confer resistance to the malarial parasite, allowing the insect to act as a vector while not succumbing to the disease.

Researchers with the World Health Organization's Special Program for Research and Training in Tropical Diseases in Switzerland describe the new findings, particularly the genome sequences, as a breakthrough for public health and "a major contribution to efforts to combat malaria and other mosquito-borne diseases." Despite these encouraging words, however, actually using the information to save lives will most likely require more money than the $200 million currently available each year for malaria research, scientists say. The required funds will near several billion dollars a year for a generation or so, writes Jeffery D. Sachs of the Earth Institute of Columbia University in a commentary in Science. Although that amount may seem daunting, he concludes, it "will be a very small price to pay for millions of lives saved per year and for hundreds of millions of people to be given the change to escape from the vicious cycle of poverty and disease."

ABOUT THE AUTHOR(S)

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Scientists Sequence Genomes of Malarial Parasite and Mosquito

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Malaria continues to plague the world's population, particularly inhabitants of sub-Saharan Africa, where it kills at least one person every 30 seconds. Efforts to eradicate the disease in the 1950s and 1960s met with failure, and current control measures such as antimalarial drugs are swiftly losing their potency.

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It's been a year since the untreatable Zika virus was first identified in the Americas.

Since then, it's grown into a global health emergency, with public health officials, governments, and researchers alike scrambling for solutions.

One solution? Getting rid of Zika's main method of spreading from person to person, the Aedes aegypti mosquito. To do this, one company is genetically engineering the bugs so they pass a lethal gene to their offspring.

A small region just south of Cuba just announced plans to deploy the critters to fend off Zika, making it the second location to do so. The US is still considering using the mosquitoes in certain areas, but hasn't done so yet.

The region is the Cayman Islands, a British territory of about 58,000 people composed of three islands (of which only one has the potential for locally transmitted Zika - no cases have been reported just yet*).

Oxitec, the biotech company that makes these mosquitoes, launched another GM-mosquito disease-prevention program in Brazil in 2015 which targeted dengue and yellow fever, two diseases that are also transmitted by the A. aegypti mosquito. Oxitec has since expanded that program in response to the Zika outbreak.

To fend off the disease-carrying bugs, Oxitec genetically modifies male mosquitoes to carry a lethal gene. Those bugs mate with female mosquitoes, pass on the gene that kills that offspring before it becomes an adult mosquito - and eventually, a sizeably smaller mosquito population.

The Cayman Island project is focused on the Grand Cayman island. For the first two months, Oxitec and the Cayman Islands' Mosquito Research and Control Unit (MRCU) will educate people about the mosquitoes and make sure they're aware these bugs are not the ones spreading disease. Then, Oxitec will deploy enough mosquitoes to try and protect an area of 1,800 residents on the Grand Cayman island from Zika. From there, the project can expand as necessary.

"It is one of those times where you are very grateful to see a mosquito, because you know it's going to do its job, and there will be fewer mosquitoes around to bite and transmit disease once it's done," Dr. Alan Wheeler, an assistant director with the MRCU said in a news release.

As with anything that includes the words "genetically modified," some are leery about the prospect of this potential solution, instead suggesting that they're part of the reason the Zika outbreak has been so extreme. But so far, there's no evidence that the genetically modified mosquitoes play a role, Dr. Andrew Pavia, Chief of the Division of Pediatric Infectious Diseases at the University of Utah Health Care told Business Insider in January.
*This post has been updated to reflect that no cases of locally transmitted Zika have been reported on the Cayman Islands yet.

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Another region is joining in the fight to use genetically modified mosquitoes to fight Zika

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It's been a year since the untreatable Zika virus was first identified in the Americas. Since then, it's grown into a global health emergency, with public health officials, governments, and researchers alike scrambling for solutions. One solution? Getting rid of Zika's main method of spreading from person to person, the Aedes aegypti mosquito.

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This article was originally published with the title "The Zika Virus"

ABOUT THE AUTHOR(S)

Dwayne Godwin

Dwayne Godwin is a neuroscientist at the Wake Forest University School of Medicine.

Jorge Cham

Jorge Cham draws the comic strip Piled Higher and Deeper at www.phdcomics.com. He is also co-author of the new book We Have No Idea: A Guide to the Unknown Universe, published by Riverhead Books.

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This article was originally published with the title "The Zika Virus" Dwayne Godwin Dwayne Godwin is a neuroscientist at the Wake Forest University School of Medicine. Jorge Cham Jorge Cham draws the comic strip Piled Higher and Deeper at www.phdcomics.com.

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The history of Zika virus is a digital timeline with videos, infographics, documents, studies, and maps, that depict the story of the disease from when it was first identified in 1947 to 2016, when WHO announced a public health emergency.

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June 17, 2016 - Biology professor Peter Armbruster is studying the Asian tiger mosquito ( Aedes albopictus) to, among other research avenues, discover how it manages a process called diapause.

In diapause, the adult female Asian tiger mosquito (and some other insects) measures day length and uses that information to cause its offspring to go into a state of dormancy and survive over the winter.

"What's so cool about it is they're using the day length before winter arrives, in September, to in a physiological sense, anticipate the environment their offspring will experience and modify the development of the offspring so they can cope with their future conditions," Armbruster notes.

Bigger 'lunchbox'

He says the diapause eggs are larger and have a thicker wax layer on them, which helps them to retain water more effectively.

Diapause eggs also contain more lipids that non-diapause eggs.

"The mom packs a bigger lunchbox, so to speak, to help her offspring survive through the winter," the biologist explains.

Interfering with Diapause

The worst offender involving the Zika virus is the Aedes aegypti mosquito, which cannot go into diapause, but the Asian tiger mosquito is also capable of infecting people with the virus, most likely in Brazil.

Armbruster's National Institutes of Health-funded research is relevant to the Zika virus epidemic because diapause involves the manipulation of a broad range of basic physiological processes, such as lipid metabolism, energy storage and other aspects of energy metabolism.

"Even if we didn't interfere with diapause per se, we're identifying the molecular pathways controlling a lot of basic physiological processes that could provide targets for vector control," he says.

In other words, understanding the molecular mechanism that allows the Asian tiger female to produce diapause eggs could result in the development of an intervention to prevent the females from using the technique

"That would presumably knock the populations down quite substantially over the winter," the professor says.

Elephants to Mosquitoes

The professor has traveled to Japan in the past as well as numerous places in the United States to literally chase after Asian tiger mosquitoes.

At Georgetown, he takes care of tens of thousands of mosquitoes in white breeding buckets, sometimes putting them literally on ice so he can monitor their diapause behavior. He wasn't always interested in mosquitoes.

"In grad school I thought about studying elephants, but I decided on mosquitoes instead because of the ability recreate their habitat in a lab," he says, "and my interest in the disease transmission aspect."

Junkyards and Tire Piles

He jokes about the non-glamorous nature of his work, haunting junk yards and used auto salvage lots compared to researchers such as Janet Mann, who studies dolphins in pristine Shark Bay, Australia.

Armbruster and his research team scour junkyards, auto salvage yards and tire piles for breeding mosquitoes and bring them back to the lab.

"I'll never forget the first time I took my younger son collecting, and we went to this junkyard and I got a tire and siphoned some water out of the tire, and I said, 'Look Alex, look at all these mosquitoes - isn't that great?' "

"I could just see the horror in the eyes of an 8-year-old boy who just realized that what his father does for a living is to suck water out of old used tires."

Alex Armbruster is now a rising junior in the College.

Insect Invasion

The Asian tiger mosquito invaded Houston, Texas, in 1985.

"The most likely scenario is that a shipment of infested used tires from Japan was transported into Houston, and they spread from there," the biology professor notes.

He says that within a year the mosquitoes had traveled over 500 kilometers and now are observed as far north on the East Coast about half a mile from the Newark Airport.

"That was not the result of adult mosquitoes flying," he explains, "that was because these containers where they live as larvae tend to get moved around, and we still don't know if there may have been multiple invasions in the U.S. - that's also something we're working on."

Armbruster said the Asian tigers were appealing as a research topic because they represent a natural experiment to study how they adapt as they spread across North America.

Cautionary Tale

The majority of the 174 native North American species of mosquitoes do not carry diseases.

Most of them are just annoying. But he thinks Americans should err on the side of caution, especially since climate change will increase both numbers and range of the Adedes albopictus.

"The higher temperatures will likely increase their ability to transmit disease," he notes.

He believes that companies that claim to rid your yard of mosquitoes are a bad idea. Mosquito control, often organized at the county level, is somewhat haphazard, he says, with some counties being very effective and others very ineffective.

And the companies, which never coordinate with county mosquito control functions, can actually make the problem worse.

"If the county comes in, they're trying to do a systematic control effort over a whole neighborhood," Armbruster says. "If you hire one of these companies to come to your house, they're going to treat your yard and that's it. So if there are mosquitoes next door, that's not going to help matters, and as soon as the insecticides wear off the mosquitoes are going to be right back."

The more effective way to battle the bugs is to have local mosquito control officials identify the larval habitats and get rid of them.

A Difficult Problem

On the personal level, people should make sure there aren't any containers on their property that will fill up with water and become a mosquito-breeding haven, the professor says.

Getting rid of mosquitoes capable of transmitting serious diseases is a difficult problem.

"There are proposals to create genetically modified mosquitoes that aren't capable of transmitting the virus, but how you would get these genetically modified mosquitoes to spread in natural populations is not a trivial problem," he says, "because often they don't survive or reproduce as well as the natural mosquitoes."

"Unless there's some genetically engineered kind of mechanism that actually actively spreads the change that affects disease transmission then you're not going to get it to spread through a natural population," the biologist explains.

"On the one hand, these are pretty exciting times," he adds. "There are all these new genetic technologies that have been developed that make these kinds of interventions a possibility, but we don't know enough about the natural ecology of the mosquitoes to know exactly what's going to happen when we introduce these things into the wild."

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Mosquito Research May Help Fight Zika Virus Transmission

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June 17, 2016 - Biology professor Peter Armbruster is studying the Asian tiger mosquito ( Aedes albopictus) to, among other research avenues, discover how it manages a process called diapause. In diapause, the adult female Asian tiger mosquito (and some other insects) measures day length and uses that information to cause its offspring to go into a state of dormancy and survive over the winter.

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Editor's Note: This story was originally published in the December 2004 issue of Scientific American.

In an episode of the classic 1950s television comedy The Honeymooners, Brooklyn bus driver Ralph Kramden loudly explains to his wife, Alice, "You know that I know how easy you get the virus." Half a century ago even regular folks like the Kramdens had some knowledge of viruses-as microscopic bringers of disease. Yet it is almost certain that they did not know exactly what a virus was. They were, and are, not alone.

For about 100 years, the scientifi c community has repeatedly changed its collective mind over what viruses are. First seen as poisons, then as life-forms, then biological chemicals, viruses today are thought of as being in a gray area between living and nonliving: they cannot replicate on their own but can do so in truly living cells and can also affect the behavior of their hosts profoundly. The categorization of viruses as nonliving during much of the modern era of biological science has had an unintended consequence: it has led most researchers to ignore viruses in the study of evolution. Finally, however, scientists are beginning to appreciate viruses as fundamental players in the history of life.

Coming to Terms
It is easy to see why viruses have been diffi cult to pigeonhole. They seem to vary with each lens applied to examine them. The initial interest in viruses stemmed from their association with diseases-the word "virus" has its roots in the Latin term for "poison." In the late 19th century researchers realized that certain diseases, including rabies and foot-and-mouth, were caused by particles that seemed to behave like bacteria but were much smaller. Because they were clearly biological themselves and could be spread from one victim to another with obvious biological effects, viruses were then thought to be the simplest of all living, gene-bearing life-forms.

Their demotion to inert chemicals came after 1935, when Wendell M. Stanley and his colleagues, at what is now the Rockefeller University in New York City, crystallized a virus- tobacco mosaic virus-for the fi rst time. They saw that it consisted of a package of complex biochemicals. But it lacked essential systems necessary for metabolic functions, the biochemical activity of life. Stanley shared the 1946 Nobel Prize- in chemistry, not in physiology or medicine-for this work.

Further research by Stanley and others established that a virus consists of nucleic acids (DNA or RNA) enclosed in a protein coat that may also shelter viral proteins involved in infection. By that description, a virus seems more like a chemistry set than an organism. But when a virus enters a cell (called a host after infection), it is far from inactive. It sheds its coat, bares its genes and induces the cell's own replication machinery to reproduce the intruder's DNA or RNA and manufacture more viral protein based on the instructions in the viral nucleic acid. The newly created viral bits assemble and, voilà, more virus arises, which also may infect other cells.

These behaviors are what led many to think of viruses as existing at the border between chemistry and life. More poetically, virologists Marc H. V. van Regenmortel of the University of Strasbourg in France and Brian W. J. Mahy of the Centers for Disease Control and Prevention have recently said that with their dependence on host cells, viruses lead "a kind of borrowed life." Interestingly, even though biologists long favored the view that viruses were mere boxes of chemicals, they took advantage of viral activity in host cells to determine how nucleic acids code for proteins: indeed, modern molecular biology rests on a foundation of information gained through viruses.

Molecular biologists went on to crystallize most of the essential components of cells and are today accustomed to thinking about cellular constituents-for example, ribosomes, mitochondria, membranes, DNA and proteins-as either chemical machinery or the stuff that the machinery uses or produces. This exposure to multiple complex chemical structures that carry out the processes of life is probably a reason that most molecular biologists do not spend a lot of time puzzling over whether viruses are alive. For them, that exercise might seem equivalent to pondering whether those individual subcellular constituents are alive on their own. This myopic view allows them to see only how viruses co-opt cells or cause disease. The more sweeping question of viral contributions to the history of life on earth, which I will address shortly, remains for the most part unanswered and even unasked.

To Be or Not to Be
The seemingly simple question of whether or not viruses are alive, which my students often ask, has probably defi ed a simple answer all these years because it raises a fundamental issue: What exactly defi nes "life?" A precise scientifi c defi nition of life is an elusive thing, but most observers would agree that life includes certain qualities in addition to an ability to replicate. For example, a living entity is in a state bounded by birth and death. Living organisms also are thought to require a degree of biochemical autonomy, carrying on the metabolic activities that produce the molecules and energy needed to sustain the organism. This level of autonomy is essential to most definitions.

Viruses, however, parasitize essentially all biomolecular aspects of life. That is, they depend on the host cell for the raw materials and energy necessary for nucleic acid synthesis, protein synthesis, processing and transport, and all other biochemical activities that allow the virus to multiply and spread. One might then conclude that even though these processes come under viral direction, viruses are simply nonliving parasites of living metabolic systems. But a spectrum may exist between what is certainly alive and what is not.

A rock is not alive. A metabolically active sack, devoid of genetic material and the potential for propagation, is also not alive. A bacterium, though, is alive. Although it is a single cell, it can generate energy and the molecules needed to sustain itself, and it can reproduce. But what about a seed? A seed might not be considered alive. Yet it has a potential for life, and it may be destroyed. In this regard, viruses resemble seeds more than they do live cells. They have a certain potential, which can be snuffed out, but they do not attain the more autonomous state of life.

Another way to think about life is as an emergent property of a collection of certain nonliving things. Both life and consciousness are examples of emergent complex systems. They each require a critical level of complexity or interaction to achieve their respective states. A neuron by itself, or even in a network of nerves, is not conscious-whole brain complexity is needed. Yet even an intact human brain can be biologically alive but incapable of consciousness, or "brain-dead." Similarly, neither cellular nor viral individual genes or proteins are by themselves alive. The enucleated cell is akin to the state of being braindead, in that it lacks a full critical complexity. A virus, too, fails to reach a critical complexity. So life itself is an emergent, complex state, but it is made from the same fundamental, physical building blocks that constitute a virus. Approached from this perspective, viruses, though not fully alive, may be thought of as being more than inert matter: they verge on life.

In fact, in October, French researchers announced fi ndings that illustrate afresh just how close some viruses might come. Didier Raoult and his colleagues at the University of the Mediterranean in Marseille announced that they had sequenced the genome of the largest known virus, Mimivirus, which was discovered in 1992. The virus, about the same size as a small bacterium, infects amoebae. Sequence analysis of the virus revealed numerous genes previously thought to exist only in cellular organisms. Some of these genes are involved in making the proteins encoded by the viral DNA and may make it easier for Mimivirus to co-opt host cell replication systems. As the research team noted in its report in the journal Science, the enormous complexity of the Mimivirus's genetic complement "challenges the established frontier between viruses and parasitic cellular organisms."

Impact on Evolution
Debates over whether to label viruses as living lead naturally to another question: Is pondering the status of viruses as living or nonliving more than a philosophical exercise, the basis of a lively and heated rhetorical debate but with little real consequence? I think the issue is important, because how scientists regard this question infl uences their thinking about the mechanisms of evolution.

Viruses have their own, ancient evolutionary history, dating to the very origin of cellular life. For example, some viral- repair enzymes-which excise and resynthesize damaged DNA, mend oxygen radical damage, and so on- are unique to certain viruses and have existed almost unchanged probably for billions of years.

Nevertheless, most evolutionary biologists hold that because viruses are not alive, they are unworthy of serious consideration when trying to understand evolution. They also look on viruses as coming from host genes that somehow escaped the host and acquired a protein coat. In this view, viruses are fugitive host genes that have degenerated into parasites. And with viruses thus dismissed from the web of life, important contributions they may have made to the origin of species and the maintenance of life may go unrecognized. (Indeed, only four of the 1,205 pages of the 2002 volume The Encyclopedia of Evolution are devoted to viruses.)

Of course, evolutionary biologists do not deny that viruses have had some role in evolution. But by viewing viruses as inanimate, these investigators place them in the same category of infl uences as, say, climate change. Such external infl uences select among individuals having varied, genetically controlled traits; those individuals most able to survive and thrive when faced with these challenges go on to reproduce most successfully and hence spread their genes to future generations.

But viruses directly exchange genetic information with living organisms-that is, within the web of life itself. A possible surprise to most physicians, and perhaps to most evolutionary biologists as well, is that most known viruses are persistent and innocuous, not pathogenic. They take up residence in cells, where they may remain dormant for long periods or take advantage of the cells' replication apparatus to reproduce at a slow and steady rate. These viruses have developed many clever ways to avoid detection by the host immune system- essentially every step in the immune process can be altered or controlled by various genes found in one virus or another.

Furthermore, a virus genome (the entire complement of DNA or RNA) can permanently colonize its host, adding viral genes to host lineages and ultimately becoming a critical part of the host species' genome. Viruses therefore surely have effects that are faster and more direct than those of external forces that simply select among more slowly generated, internal genetic variations. The huge population of viruses, combined with their rapid rates of replication and mutation, makes them the world's leading source of genetic innovation: they constantly "invent" new genes. And unique genes of viral origin may travel, finding their way into other organisms and contributing to evolutionary change.

Data published by the International Human Genome Sequencing Consortium indicate that somewhere between 113 and 223 genes present in bacteria and in the human genome are absent in well-studied organisms-such as the yeast Saccharomyces cerevisiae, the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans -that lie in between those two evolutionary extremes. Some researchers thought that these organisms, which arose after bacteria but before vertebrates, simply lost the genes in question at some point in their evolutionary history. Others suggested that these genes had been transferred directly to the human lineage by invading bacteria.

My colleague Victor DeFilippis of the Vaccine and Gene Therapy Institute of the Oregon Health and Science University and I suggested a third alternative: viruses may originate genes, then colonize two different lineages-for example, bacteria and vertebrates. A gene apparently bestowed on humanity by bacteria may have been given to both by a virus.

In fact, along with other researchers, Philip Bell of Macquarie University in Sydney, Australia, and I contend that the cell nucleus itself is of viral origin. The advent of the nucleus- which differentiates eukaryotes (organisms whose cells contain a true nucleus), including humans, from prokaryotes, such as bacteria-cannot be satisfactorily explained solely by the gradual adaptation of prokaryotic cells until they became eukaryotic. Rather the nucleus may have evolved from a persisting large DNA virus that made a permanent home within prokaryotes. Some support for this idea comes from sequence data showing that the gene for a DNA polymerase (a DNAcopying enzyme) in the virus called T4, which infects bacteria, is closely related to other DNA polymerase genes in both eukaryotes and the viruses that infect them. Patrick Forterre of the University of Paris-Sud has also analyzed enzymes responsible for DNA replication and has concluded that the genes for such enzymes in eukaryotes probably have a viral origin.

From single-celled organisms to human populations, viruses affect all life on earth, often determining what will survive. But viruses themselves also evolve. New viruses, such as the AIDS-causing HIV-1, may be the only biological entities that researchers can actually witness come into being, providing a real-time example of evolution in action.

Viruses matter to life. They are the constantly changing boundary between the worlds of biology and biochemistry. As we continue to unravel the genomes of more and more organisms, the contributions from this dynamic and ancient gene pool should become apparent. Nobel laureate Salvador Luria mused about the viral infl uence on evolution in 1959. "May we not feel," he wrote, "that in the virus, in their merging with the cellular genome and reemerging from them, we observe the units and process which, in the course of evolution, have created the successful genetic patterns that underlie all living cells?" Regardless of whether or not we consider viruses to be alive, it is time to acknowledge and study them in their natural context-within the web of life.

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Editor's Note: This story was originally published in the December 2004 issue of Scientific American. In an episode of the classic 1950s television comedy The Honeymooners, Brooklyn bus driver Ralph Kramden loudly explains to his wife, Alice, "You know that I know how easy you get the virus."