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Zika fever, or Zika virus is a mosquito transmitted virus that can cause asymptomatic or mild infection in humans. This virus is also known to cause birth defects in babies when mothers have been affected.  The mosquitos associated with Zika virus are the daytime-active Aedes mosquitos, A. aegypti and A. albopictus. This virus classifies in the Flavivirdae family with the genus Falvivirus.

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Zika is spread mostly by the bite of an infected Aedes species mosquito. The best way to prevent Zika is to protect yourself from mosquito bites.

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In 1947, scientists were doing routine samples of rhesus monkeys for research in Yellow fever in the Zika Forest of Uganda. In 1948, scientists discovered that the Andes mosquitos were the cause of Zika. In 1952, the first human cases were reported in Uganda and Tanzania.

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The rise in the spread of Zika virus has been accompanied by a rise in cases of microcephaly and Guillain-Barré syndrome. First identified in Uganda in 1947 in monkeys, Zika was later identified in humans in 1952. The first large outbreak of disease caused by Zika infection was reported from the Island of Yap in 2007. There are currently several countries experiencing Zika virus outbreaks.

Zika: The origin and spread of a mosquito-borne virus
The following article summarizes the spread of Zika infection from the earliest discovery in 1947 to 7 February 2016.

1947: Scientists conducting routine surveillance for yellow fever in the Zika forest of Uganda isolate the Zika virus in samples taken from a captive, sentinel rhesus monkey.
1948: The virus is recovered from the mosquito Aedes africanus, caught on a tree platform in the Zika forest.
1952: The first human cases are detected in Uganda and the United Republic of Tanzania in a study demonstrating the presence of neutralizing antibodies to Zika virus in sera.

1969-1983: The known geographical distribution of Zika expands to equatorial Asia, including India, Indonesia, Malaysia and Pakistan, where the virus is detected in mosquitos. As in Africa, sporadic human cases occur but no outbreaks are detected and the disease in humans continues to be regarded as rare, with mild symptoms.
2007: Zika spreads from Africa and Asia to cause the first large outbreak in humans on the Pacific island of Yap, in the Federated States of Micronesia. Prior to this event, no outbreaks and only 14 cases of human Zika virus disease had been documented worldwide.
2013-2014: The virus causes outbreaks in four other groups of Pacific islands: French Polynesia, Easter Island, the Cook Islands, and New Caledonia.26,27 The outbreak in French Polynesia, generating thousands of suspected infections, is intensively investigated. The results of retrospective investigations are reported to WHO on 24 November 2015 and 27 January 2016.

2 March 2015: Brazil notifies WHO of reports of an illness characterized by skin rash in northeastern states. From February 2015 to 29 April 2015, nearly 7000 cases of illness with skin rash are reported in these states. All cases are mild, with no reported deaths. Zika was not suspected at this stage, and no tests for Zika were carried out.
1 February 2016: WHO declares that the recent association of Zika infection with clusters of microcephaly and other neurological disorders constitutes a Public Health Emergency of International Concern.

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The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement.

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The rise in the spread of Zika virus has been accompanied by a rise in cases of microcephaly and Guillain-Barré syndrome. First identified in Uganda in 1947 in monkeys, Zika was later identified in humans in 1952. The first large outbreak of disease caused by Zika infection was reported from the Island of Yap in 2007.

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Zika virus is is a mosquito-born virus from the Flavivirus genus. This is also considered a zoonotic disease. A zoonotic disease is an infection spread between human and animal.

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The first cases of Zika in 1967 were reported in Uganda, Africa. The first cases in America were first seen in 2007.

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In 1947, researchers isolated a new virus from a rhesus monkey in a tropical forest near Entebbe, Uganda. The virus, of the Flavivirus genus, was named Zika after the forest in which it was discovered. The Zika virus (ZIKV) is closely related to other mosquito-borne flaviviruses, including the well-known West Nile, dengue and Japanese encephalitis viruses.

Shortly after its discovery, ZIKV was isolated from Zika forest Aedes africanus mosquitoes. Further research determined that Aedes aegypti as well as Aedes africanus was a vector for ZIKV, passing the virus between monkeys and mice and suggesting that the mosquito could also transmit the virus to humans.

For decades, the virus remained off the global radar, but was believed to be pervasive in parts of Africa-specifically tropical regions in the middle of the continent (south of the Sahara Desert and north of Namibia, Zambia, and Mozambique). But in 2007 the Yap Islands of Micronesia, a small group of islands in the western Pacific Ocean, experienced the first major outbreak of ZIKV outside of Africa. According to a NEJM study, about 73% of the residents of the Yap Islands were infected with ZIKV.

Prior to 2007 reports of ZIKV infection described the virus causing nonspecific symptoms reminiscent of the common cold or dengue fever. This allowed the virus to hide in plain sight, causing no fatal infections or any symptoms that would distinguish it from another viral infection. There exist large numbers of viruses that infect humans but don't cause disease, such as human hepegivirus 1, a seemingly nonpathogenic relative of Hepatitis C Virus. Thus, Zika was deemed generally benign, until questions began to arise during the Yap Islands outbreak of 2007. This specific outbreak was interesting because while the congenital symptoms of ZIKV infection were not yet observed, reports from physicians on the islands indicated that the virus was similar to dengue, but was not behaving like other clinically determined dengue infections. For the first time, ZIKV had developed novel symptoms that separated it from other general viral infections.

Pacific countries in which ZIKV circulation has been reported up to January 2016. Abbreviations: WP, West Papua; PNG, Papua New Guinea.

In 2013, the virus leapt to Cambodia, Thailand and then French Polynesia, where it produced several large outbreaks (Figure 1). It was in French Polynesia where health care workers first observed the unique congenital and neurological symptoms of ZIKV that drew media attention. ZIKV then moved to northeastern Brazil early in 2014, and spread through the Americas, peaking in 2016.

Zika, the "Benign" Virus, Turns Bad

In 2014-2015, patients had been streaming into Brazilian hospitals with rashes, fevers and conjunctivitis, seemingly with some sort of mystery infection (Figure 2). Over 6,800 blood samples were tested for parvovirus, dengue and chikungunya, among others, and each was systematically ruled out. Finally, ZIKV was confirmed to be the agent responsible for the multitude of infections. Hearing this news, the Brazilian health minister at the time, Dr. Arthur Chioro, stated to reporters, "Zika virus doesn't worry us, it's a benign disease." But soon after his public statement, concerning evidence to the contrary emerged.

Zika-associated conjunctivitis and rash. "Top left photo courtesy of H. P. Mallet, Department of Health of French Polynesia; top right, bottom left, and bottom right photos by V. M. Cao-Lormeau and E. Grange, Institut Louis Malardé

Babies were being born with tiny heads in alarming numbers. None of the affected infants tested positive for ZIKV, but their mothers had experienced a mysterious rash, consistent with ZIKV infection, early in their pregnancies. Soon after, ZIKV was found in the amniotic fluid of one pregnant monther, as well as in the blood of two stillborn and malformed fetuses. It soon became apparent that ZIKV infection could be transmitted between mother and fetus, and was linked with newborn microcephaly (babies with unusually small heads). On February 2, 2016, ZIKV was deemed a public health emergency of international concern(PHEIC) by the World Health Organization. Its rapid expansion from Brazil throughout the Americas caused great concern as ZIKV made its way across the U.S. border and into Texas, Florida and Hawaii.

ZIKV's quick spread was thought to be due to the Aedes mosquitoes common to South America and Central America countries as well as some southern states of the U.S. As a result, the CDC released a domestic travel advisory warning pregnant and soon-to-be pregnant women to avoid travel to Central and South America, the Caribbean and Miami-Dade county in Florida.

In the meantime, scientists and policy makers were struggling to understand why ZIKV moved into the Americas so rapidly. Dr. Michael Diamond, a microbiologist and pathologist at the Washington University School of Medicine, believes that ZIKV moved into a new niche where humans were completely immunologically naive, allowing the virus to spread like wildfire among people whose immune systems had never encountered the virus before. It is probable that as the virus moved from monkey to human, it evolved to better fill its new niche, and that the virus became more virulent as it adapted to the human immune system. This in part explains why the ZIKV infection symptoms appeared to change as the virus spread from Africa to Asia to South America.

Zika Falls Off the Radar - But Why?

In 2017, reports of ZIKV outbreaks reduced drastically and infection numbers today are markedly down from the 2016 peak. Thus far in 2018, the CDC has reported only 34 cases of ZIKV in the U.S., all from travelers returning to the U.S. from Zika affected areas. Compare that to the 5,168 symptomatic ZIKV disease cases reported in 2016. In the U.S. territories of Puerto Rico, American Samoa, and the U.S. Virgin Islands, there have only been 74 symptomatic ZIKV cases in 2018, compared to 36,512 cases reported in 2016. Even in South America, ZIKV infections have significantly dropped-from over 30,000 suspected and confirmed cases in early 2016 to an average of 293 in the last half of 2017.

Experts like Diamond say the swift drop in ZIKV cases is likely due to the development of herd immunity. When ZIKV first spread from central Africa, humans were immunologically naive and didn't have natural defenses against the viral infection. Now, two years after the peak, enough people have become immune to the virus, somewhat like the immunity gained after a bout of chickenpox, to halt the ZIKV transmission chain.

"If a large enough proportion of the herd-be it cows or mice or people-are resistant to a disease, it's very difficult for the disease to spread," Dr. Uriel Kitron, an expert in viruses transmitted by mosquitoes at Emory University, told the Chicago Tribune last year, when ZIKV numbers were first beginning to drop.

Many people who become infected with ZIKV don't have symptoms, or have symptoms closely resembling those of the common cold. Thus, areas where the disease was endemic may have large populations of people who were unknowingly infected and are now immune. This prevents the virus from moving from person to person, even in an area teeming with mosquitoes. ZIKV transmission requires mosquitoes to bite people with active disease, so the insect can carry the virus to a new host. If few individuals produce an active infection, the probability of a mosquito biting someone with active disease and transmitting it to one of the few susceptible individuals in the population drops precipitously.

What is the Future of Zika Virus?

"But don't get too comfortable just yet," says Dr. Scott Weaver, Director of the Institute for Human Infections and Immunity at University of Texas Medical Branch in Galveston, Texas. He says there simply isn't enough surveillance of the virus in South America due to lack of resources, so the absence of large outbreaks doesn't necessarily mean a complete absence of ZIKV transmission. Furthermore, because the virus is constantly mutating, herd immunity only lasts for a limited time.

Even if ZIKV were to suddenly cease to exist, concerns for those who had been infected or born to infected mothers would remain. Only 6% of pregnancies where the mother was exposed to ZIKV resulted in obvious birth defects. What that means for the other 94% of ZIKV-exposed pregnancies remains unclear. ZIKV targets neurons, and researchers are trying to uncover how the virus affects the development of babies born from ZIKV-infected mothers. Only time will tell if these children will develop normally.

ZIKV can also affect adults long after the infection subsides. A rare autoimmune nervous system condition called Guillain-Barre syndrome can be triggered if ZIKV infects neurons. The affected person's immune system wrongly attacks its own neurons, causing a wide variety of symptoms ranging from mild weakness to complete body paralysis. In April of this year, the Brazilian Journal of Infectious Diseases published a meta-analysis on the incidence of Guillain-Barre syndrome in association with ZIKV infection. Researchers concluded that there have been about 1,500 cases of ZIKV-associated Guillain-Barre syndrome-roughly translating to a rate of less than 1% of all ZIKV infections, but there may be many more unreported cases of people who didn't know they were infected with ZIKV.

Zika Research Leads Scientists to Mosquitos, Microbes and Vaccines

In the past 2 years, the scientific community has answered important questions regarding ZIKV virulence, viral evolution and immune system evasion. In June, researchers produced the highest-resolution image of the ZIKV virus (or any flavivirus) yet, leading them to better understand the three-dimensional structure and biophysics of the virus. Scientists are beginning to unravel how ZIKV causes congenital disease, but many unanswered questions remain, including what are the dynamics of ZIKV transmission, how ZIKV persists and how it reacts with related viruses.

In 2016, the international ZIKV epidemic and subsequent panic led the United States to quickly divert $1.1 billion into ZIKV research over two years. Now it is 2018, and many of the R21 grants awarded in 2016 to study ZIKV are expiring. Furthermore, reduction in ZIKV outbreaks means that many grants won't be renewed this year. So, where does this leave ZIKV research, particularly vaccine development?

There's some good news. The National Institute of Allergy and Infectious Disease has developed several ZIKV vaccine candidates, one of which is currently in phase 2 clinical trials in Texas, Puerto Rico, South and Central America.

Another approach to fighting current and possible future ZIKV infections is targeting the vector, Aedesmosquitoes. Using insecticides, which seems like an obvious solution, dramatically impacts other organisms occupying ecological niches in which Aedes mosquitoes reside. Rather, scientists and ecologists of the World Mosquito Program favor alternate solutions, such as using Wolbachia bacteria. Certain Wolbachia strains , when introduced into Aedes mosquitoes, block the transmission of ZIKV, dengue and Chikungunya virus. The bacteria are transmitted to the next generation of mosquitoes within the eggs, so the program is self-sustaining. A successful trial has eliminated dengue cases in Townsville, Australia, and similar strategies may work to eliminate the spread of ZIKV by mosquitoes.

Will Zika Virus Come Back?

Unfortunately, based on the behavior of other flaviviruses, we can probably expect ZIKV to resurface. In the case of West Nile Virus, outbreaks stopped appearing for a couple of years, but then returned; with dengue, infections increase every summer, tracking the increase of the mosquito population. Researchers are not yet sure what the trajectory of ZIKV will be but caution people to remain vigilant, particularly pregnant women and those traveling into endemic areas.

Further Reading and Media Links:
American Society for Microbiology - Zika Virus Press Conference 2016
Wolbachia wStri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication

Musso D. and Gubler D.J. Zika Virus. Clinical Microbiology Reviews. 2015

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Where Did Zika Go (And Will It Come Back)? | ASM.org

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In 1947, researchers isolated a new virus from a rhesus monkey in a tropical forest near Entebbe, Uganda. The virus, of the Flavivirus genus, was named Zika after the forest in which it was discovered. The Zika virus (ZIKV) is closely related to other mosquito-borne flaviviruses, including the well-known West Nile, dengue and Japanese encephalitis viruses.

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Currently, there are no reports of Zika virus. In 2018, there was no evidence of Zika transmission by mosquitos in America. In 2019, there were no confirmed reports.

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Areas of countries and territories throughout the world with active Zika virus transmission.

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The virulence of a disease or organism is the ability to cause harm to the host. Typically, the virulence of Zika is mild and deaths and hospitalizations are uncommon.

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Abstract

Zika virus (ZIKV) is now in a post-pandemic period, for which the potential for re-emergence and future spread is unknown. Adding to this uncertainty is the unique capacity of ZIKV to directly transmit between humans via sexual transmission. Recently, we demonstrated that direct transmission of ZIKV between vertebrate hosts leads to rapid adaptation resulting in enhanced virulence in mice and the emergence of three amino acid substitutions (NS2A-A117V, NS2A- A117T, and NS4A-E19G) shared among all vertebrate-passaged lineages. Here, we further characterized these host-adapted viruses and found that vertebrate-passaged viruses also have enhanced transmission potential in mosquitoes. To understand the contribution of genetic changes to the enhanced virulence and transmission phenotype, we engineered these amino acid substitutions, singly and in combination, into a ZIKV infectious clone. We found that NS4A- E19G contributed to the enhanced virulence and mortality phenotype in mice. Further analyses revealed that NS4A-E19G results in increased neurotropism and distinct innate immune signaling patterns in the brain. None of the substitutions contributed to changes in transmission potential in mosquitoes. Together, these findings suggest that direct transmission chains could enable the emergence of more virulent ZIKV strains without compromising mosquito transmission capacity, although the underlying genetics of these adaptations are complex.

Competing Interest Statement

The authors have declared no competing interest.

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Gain without pain: Adaptation and increased virulence of Zika virus in vertebrate host without fitness cost in mosquito vector

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Zika virus (ZIKV) is now in a post-pandemic period, for which the potential for re-emergence and future spread is unknown. Adding to this uncertainty is the unique capacity of ZIKV to directly transmit between humans via sexual transmission.

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This is an article from 2017. This talks about the continuing challenges that US Public Health face forward.

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Testimony of Luciana Borio, M.D.,
FDA Acting Chief Scientist

Before the
United States House of Representatives
Committee on Energy and Commerce Subcommittee on Oversight and Investigations

May 23, 2017

INTRODUCTION

Good morning Chairman Murphy, Ranking Member DeGette, and members of the Subcommittee. I am Dr. Luciana Borio, Acting Chief Scientist at the Food and Drug Administration (FDA). Thank you for the opportunity to appear today to discuss FDA's actions in response to the Zika virus outbreak.

Zika virus was first identified in 1947 in Uganda. Since then, sporadic cases and a few outbreaks have been recognized in a number of locations, including parts of Africa, Asia, and the Pacific. However, the situation has changed dramatically since May 2015, when the first local transmission of Zika virus in the Americas was confirmed in Brazil. According to the World Health Organization, from 2015 through March 10, 2017, 61 countries and territories-including the United States, the Commonwealth of Puerto Rico, the U.S. Virgin Islands, and American Samoa-have had ongoing transmission following a new introduction of Zika virus or with a reintroduction into an area where transmission had been interrupted. Additionally, 13 countries have reported evidence of person-to-person transmission, 31 countries or territories have reported microcephaly and other central nervous system malformations that are potentially associated with Zika virus infection, and 23 countries or territories have reported an increase in the incidence of Guillain-Barre Syndrome (GBS) or laboratory confirmation of Zika virus infection among GBS cases.

In the United States, there have been 5,282 Zika virus disease cases reported in the states [5,010 cases in travelers returning from affected areas, 224 cases acquired through presumed local mosquito-borne transmission in Florida (218 cases) and Texas (6 cases), and 48 cases acquired through other routes, including sexual transmission] and 36,583 Zika virus disease cases reported in the US territories [143 cases in travelers returning from affected areas and 36,440 cases acquired through presumed local mosquito-borne transmission] as of May 17, 2017.As of May 09, 2017, there are 1,845 pregnant women in the states and District of Columbia and 3,795 pregnant women in the US territories with laboratory-reported evidence of possible Zika virus infection.

FDA RESPONSE TO THE ZIKA VIRUS OUTBREAK

FDA has taken several steps to rapidly respond to the Zika virus outbreak and remains actively engaged with other components of the Department of Health and Human Services (HHS)-including the Office of the Assistant Secretary for Preparedness and Response (ASPR) and its Biomedical Advanced Research and Development Authority (BARDA), the National Institutes of Health (NIH), and the Centers for Disease Control and Prevention (CDC)-as well as with partners across the U.S. Government, the private sector, and the international community to minimize the impact of this outbreak. FDA's primary areas of activity include: (1) supporting the development and availability of diagnostic tests that may be useful for identifying the presence of, or prior exposure to, Zika virus; (2) providing advice and consultation to facilitate rapid development of investigational vaccines and therapeutics; (3) advancing the use of innovative strategies under FDA's regulatory authorities to help suppress the population of Zika virus-carrying mosquitoes; (4) protecting the public from fraudulent products that claim to prevent, diagnose, treat, or cure Zika virus disease; and (5) protecting the safety of the nation's blood supply and human cells, tissues, and cellular and tissue-based products (such as corneas, bone, skin, heart valves, and semen) used for medical, surgical, or reproductive procedures.

Diagnostic Tests

At the start of the Zika virus outbreak in the Americas, there were no diagnostic tests for the detection of Zika virus authorized for use in the United States. FDA worked with CDC, which was developing diagnostic tests, to make Zika diagnostic tests rapidly available. FDA was able to authorize the use of two CDC tests under FDA's Emergency Use Authorization (EUA) authority in February and March of 2016. FDA also-in keeping with FDA's normal practice for responding to emerging infectious disease outbreaks-reached out to diagnostic manufacturers to encourage them to develop needed diagnostic tests for Zika virus. FDA immediately began working interactively with manufacturers interested in developing diagnostic tests for Zika virus to help accelerate development programs-including clarifying EUA data requirements for the Zika diagnostic tests-and to ensure that their tests are properly validated before they are used to inform patient care. FDA granted an EUA for the first commercial test in April 2016.

FDA has taken several proactive steps to help advance the development of diagnostic tests for Zika virus. For example, FDA developed and made available EUA review templates delineating data requirements for a Zika virus diagnostic EUA. FDA has fulfilled more than 100 requests for the EUA templates. In addition, to help Zika diagnostic manufacturers develop nucleic acid testing-based diagnostic devices, FDA created Zika virus reference materials that are available to Zika diagnostic manufacturers that have a pre-EUA submission with FDA and have established the analytical performance of their assay. FDA has fulfilled 17 requests for the reference materials.

FDA has continued to work interactively with Zika virus diagnostic manufacturers throughout the product development process to address scientific challenges, review data, and provide feedback based on the latest available scientific information. For example, FDA has had more than 15 face-to-face meetings, 150 teleconferences, and more than 3,500 emails with diagnostic developers or Zika experts to support the development of Zika diagnostics. This collaboration has been extremely successful, and to date, FDA has authorized the use of sixteen diagnostic tests for Zika virus under FDA's EUA authority-13 nucleic acid testing-based tests to diagnose active infection (12 of which are currently available) and 3 serological tests to assess whether individuals who may have recently been exposed to Zika had actually been infected. It is important to note that, as a result of these efforts, diagnostic tests for Zika virus are now available in laboratories throughout the United States including automated, high throughput tests. The serological tests to assess whether individuals who may have been exposed to Zika recently had actually been infected are especially important for women given the link between Zika virus infection and congenital Zika syndrome, including microcephaly and other birth defects, in babies of mothers who were infected with Zika virus during their pregnancy.

FDA continues to work with diagnostic manufacturers once their tests are authorized under EUA to further product development, improve product performance, and make sure that authorized tests continue to meet EUA standards and public health needs. For example, FDA has issued 21 amendments to EUAs for the authorized Zika diagnostic tests-upon request from the product manufacturers-to add additional instruments or specimen types for testing. In addition, FDA is continuing to work to help advance the development of diagnostic tests for Zika virus. For example, FDA is supporting the validation and use of a World Health Organization reference panel to be developed into an international standard for serological assays. FDA also monitors the performance of Zika diagnostic tests authorized under EUA and works with manufacturers and laboratory personnel to quickly resolve any issues that may arise. Toward that end, FDA has established an email account that laboratory personnel using Zika diagnostic assays under EUA are encouraged to use to report performance concerns directly to FDA (CDRH-EUA-Reporting@fda.hhs.gov), in addition to reporting concerns to the manufacturer.

All information about diagnostic tests for Zika virus authorized under EUA, such as letters of authorization, labeling that includes the tests' performance data, and fact sheets for patients and health care providers, are readily available on the FDA website.

Vaccines and Therapies

There are no vaccines or treatments for Zika virus at this time. Development programs are in the relatively early stages, but several vaccine candidates continue to progress at an expedited pace. FDA is actively engaged with NIH and BARDA, the international community, and product developers to help accelerate development programs. FDA is working with medical product developers to provide technical support and clarify regulatory and data requirements necessary to move products forward in development as quickly as possible. One of our highest priorities is to facilitate the development and availability of an effective Zika virus vaccine as quickly as possible and we are working closely with NIH, BARDA, CDC, and the private sector on this. Although therapeutic development proposals are generally at an earlier stage than for vaccines, FDA has also engaged in preliminary discussions of potential approaches to the development of therapeutics and is open to ongoing interactions to provide input on such development proposals.

Vector Control

In the United States, mosquito control is typically achieved by a multi-faceted approach that relies on a range of tools, including surveillance of mosquito activity, reduction in breeding sites, and the use of chemical and biological control methods. FDA's involvement in mosquito control is through the oversight of products that help suppress the population of virus-carrying mosquitoes that fall under FDA's regulatory authorities. With respect to Zika virus, there has been public discussion of a new method to potentially help control mosquito populations through the use of a genetically engineered (GE) line of the mosquito Aedes aegypti (OX513A) developed by Oxitec, Ltd. The release of male Oxitec GE mosquitoes is intended to cause suppression of the mosquito population in a release area over time because the offspring resulting from the mating of male GE mosquitoes with wild-type females do not develop to adulthood.

FDA reviewed information in an Investigational New Animal Drug (INAD) file from Oxitec Ltd. regarding the potential use of the company's GE mosquito with the intent of suppressing the population of Aedes aegypti mosquitoes at the release site in Key Haven, Florida. On August 5, 2016, FDA completed the environmental review for a proposed field trial of Oxitec's GE mosquitoes in Key Haven, Florida, and published a final environmental assessment-or EA- and finding of no significant impact-or FONSI-stating that the proposed field trial will not have significant impacts on the environment. This enabled the field trial to proceed, provided all other local, state, and federal requirements are met. Ultimately, Oxitec, together with its local partner, the Florida Keys Mosquito Control District, decided not move forward with the Key Haven field trial as the result of a November 8, 2016, referendum on the use of GE mosquitoes that found Key Haven residents did not support the trial. Since then, FDA and Oxitec have maintained an open line of communication and FDA stands ready to promptly review any submissions should, for example, Oxitec decide to pursue a field trial in another location.

Meanwhile, in January 2017, FDA issued draft guidance (developed in coordination with the Environmental Protection Agency (EPA)) that clarifies that mosquito-related products intended to function as pesticides by preventing, destroying, repelling, or mitigating mosquitoes for population control purposes are not "drugs" under the Federal Food, Drug, and Cosmetic Act (FD&C Act). If the guidance is finalized, these products will be regulated by EPA as "pesticides" under the Federal Insecticide, Fungicide, and Rodenticide Act. FDA would continue to have jurisdiction over mosquito-related products that otherwise meet the FD&C Act drug definition, such as those intended to prevent, treat, or cure a disease or to reduce the viral or pathogen load in a mosquito. The 30-day public comment period for the draft guidance closed on February 21, 2017. FDA is currently considering the comments.

Fraudulent Product Claims

Unfortunately, during emerging infectious disease outbreaks such as this, fraudulent products that claim to prevent, treat, or cure a disease frequently appear on the market. FDA is actively monitoring for fraudulent products and false product claims related to Zika virus and will implement enforcement actions, as warranted, to protect the public health.

Blood Supply and Tissue Safety

One of FDA's first actions in response to the Zika virus outbreak was to take important steps to help protect the safety of the blood supply. FDA issued guidance in February 2016 that recommended the deferral of individuals from donating blood if they had been to areas with active Zika virus transmission, were potentially exposed to the virus, or had a confirmed infection. The guidance also recommended that areas with active Zika virus transmission, like Puerto Rico, obtain whole blood and blood components from areas of the United States without active virus transmission until a blood donor screening test for Zika virus became available to ensure the safety of their blood supply. Until blood donor screening tests for Zika virus became available, HHS arranged for and funded shipments of blood products from the continental United States to Puerto Rico to ensure an adequate supply of safe blood for its residents during this interim period. Concomitantly, FDA worked closely with the test kit developers in a highly accelerated time frame to make available the first investigational test for blood screening in March 2016. The availability of this investigational test, which has been in use in Puerto Rico since early April 2016, enabled blood establishments to resume safe blood collection in areas with active Zika virus transmission. A second investigational blood screening test was made available in June 2016. Together, these tests enabled blood donor screening to be put in place across the United States where active Zika virus transmission was established as well as in areas where local virus transmission was anticipated, helping to maintain an adequate and safe blood supply.

In August 2016, after careful consideration of the evolving scientific and epidemiologic data (including the significant number of travel-associated cases of Zika across the continental US), consultation with other public health agencies, and taking into consideration the potential serious health consequences of Zika virus infection to pregnant women and children born to women exposed to Zika virus during pregnancy, FDA issued updated guidance recommending that all states and U.S. territories screen blood with an approved investigational blood screening test. The guidance recommended a staggered implementation of blood screening across the nation, with immediate implementation in states and territories with one or more locally-acquired mosquito-borne cases of Zika virus, implementation within four weeks in states with proximity to areas with locally-acquired Zika virus cases or other epidemiological linkages to Zika virus (such as a high number of travel-associated Zika cases), and implementation within 12 weeks in all other states and territories.

FDA worked with blood collection establishments to facilitate implementation of the revised guidance across the U.S. and its territories. As of May 2, 2017, 376 presumptive viremic blood donations have been prevented from entering the blood supply in the United States and its territories.

FDA is continuing to monitor the evolving scientific and epidemiologic data on Zika virus and will update its guidance for blood donor testing as necessary based on additional information that may become available that would support reassessing the blood donor testing situation while adequately protecting the blood supply.

Zika virus also poses a risk for transmission by human cells, tissues, and cellular and tissue-based products (HCT/Ps) such as corneas, bone, skin, heart valves, and semen used for medical, surgical, or reproductive procedures. Because of this risk, FDA issued guidance in February 2016 recommending that donors of HCT/Ps be considered ineligible if they were diagnosed with Zika virus infection, were in an area with active Zika virus transmission, or had sex with a male with either of those risk factors, within the past six months. FDA is continuing to assess the evolving scientific and epidemiologic data on Zika virus as well as supporting research to help better understand the persistence of Zika virus in cells and tissues, and will update its guidance if necessary to better reduce the risk of Zika virus transmission through HCT/Ps used for medical, surgical, or reproductive procedures.

CONCLUSION

FDA is fully committed to remaining highly responsive and adaptive to the complex range of issues the Zika virus outbreak has presented and will continue to present. Developing the medical products necessary to help bring this outbreak under control is highly complex and will require a sustained effort. Close cooperation and collaboration within FDA, within the U.S. Government, with our international partners, and with product developers is essential to help facilitate the development and availability of medical products to respond to Zika virus as quickly as possible. FDA is wholly prepared to leverage its authorities to the fullest extent practicable to help accelerate the development and availability of safe and effective products with the potential to help mitigate the Zika virus outbreak as quickly as the science will allow.

Thank you. I am happy to answer your questions.

Footnotes

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Testimony: Luciana Borio on Response to the Zika Virus, 05.23.2017

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Testimony of Luciana Borio, M.D., FDA Acting Chief Scientist Before the United States House of Representatives Committee on Energy and Commerce Subcommittee on Oversight and Investigations May 23, 2017 Good morning Chairman Murphy, Ranking Member DeGette, and members of the Subcommittee. I am Dr. Luciana Borio, Acting Chief Scientist at the Food and Drug Administration (FDA).

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Article pertaining to possible vaccines for the future!

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Current Advances in Zika Vaccine Development - PubMed

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Zika virus (ZIKV), an emerging arthropod-borne flavivirus, was first isolated in Uganda in 1947 from monkeys and first detected in humans in Nigeria in 1952; it has been associated with a dramatic burden worldwide. Since then, interventions to reduce the burden of ZIKV infection have been mainly res…

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Testing has been made more available and the CDC discuss their future plans for Zika virus and other diseases.

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New Ways to Look Inside the Virus

As Zika virus rapidly spread throughout South and Central America in 2015, scientists noticed an increase in cases of microcephaly, the devastating birth defect where a baby's head is much smaller than expected. They wondered if Zika infection during pregnancy might cause birth defects. Deciphering the relationship between the two wasn't easy. Zika virus had just emerged for the first time in the Western Hemisphere, and many people infected with Zika virus don't have symptoms or will only have mild symptoms.

Testing tissues

During the first months of the outbreak, NCEZID scientists developed special tests that identified the virus in brain tissues from infants who died from microcephaly and in placentas from women who had miscarriages. This discovery cemented the connection between birth defects and Zika virus infectionExternal during pregnancy. They also found that the virus could make copies of itself in the fetuses' brains and in women's placentas and persist in these tissues for months. This may help explain how the virus can cause so much damage.

Laser Microdissection

NCEZID scientists used a technique known as laser microdissection to pinpoint the specific cells where Zika virus might be persisting and replicating. This involves looking under the microscope and guiding a laser to cut away specific cells from areas of the brain and placental tissues, so scientists could measure the amount of Zika virus genetic materials (RNA) in specific cells. This testing method sheds light on where the virus may replicate and how it moves across the placenta from the mother to the fetus and infects the fetuses' brains.

NCEZID scientists developed tests and techniques to show Zika virus causes birth defects and pregnancy losses when a woman is infected during pregnancy.

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New Ways to Look Inside the Virus As Zika virus rapidly spread throughout South and Central America in 2015, scientists noticed an increase in cases of microcephaly, the devastating birth defect where a baby's head is much smaller than expected. They wondered if Zika infection during pregnancy might cause birth defects.

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This is the page for how congress responded to Zika Virus during the Obama presidency. It includes any statements and briefings, speeches, or improvements during the Zika outbreak.

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There is no cure for Zika. What could have been better is more education on preventing Zika and when to be concerned, specifically in pregnant women. What the US plans to do is to continue the funding for research and the knowledge on Zika.

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The Virginia Hospital & Healthcare Association and the Virginia Department of Health held a joint press conference July 13, 2016 to highlight the importance of Zika prevention habits, and the ongoing coordination and cooperation between hospitals and health systems and the public health infrastructure to prepare for a range of public health challenges, including infectious...

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The Economic and Social Impact of Zika on Women in the United States and Brazil

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The Economic and Social Impact of Zika on Women in the United States and Brazil

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Currently, there is research going on to help with with individuals suffering with Zika, specifically babies. There seems to be a lot of ideas in the works to be prepared for a Zika outbreak, but since it has been “quiet” with no new cases, it is hard to put the innovations to the test.

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In 2015, Zika virus swept through Brazil and the Americas. It was the first time a mosquito-borne virus was known to cause severe birth defects, and the World Health Organization declared it a "public health emergency that warranted a global response."

"This was a truly unprecedented phenomenon," says Dr. Albert Ko, an epidemiologist at the Yale School of Public Health who has worked in Brazil for over two decades. "There was a new, emerging pathogen in the world." The pandemic's emergency status was lifted in November 2016. But it left more than 3,700 children born with birth defects - the most severe of which is microcephaly, where babies are born with small heads and brain damage - in its aftermath.

In the three years since it ended, the pandemic has become an object of obsession for scientists, who have published more than 6,000 research papers about it. What did they conclude? To find out, Ko and two colleagues reviewed a selection of those publications. They found that researchers have been able to follow long-term health consequences in children infected with the virus before birth. But progress on beating the pandemic turned out to be an impediment to further research into vaccines and diagnostics that could help prevent other epidemics in the future.

Their new paper, out Wednesday in the New England Journal of Medicine, finds that Zika's origins and effects are complicated, that outbreaks are still happening and worrisome in Asia, and that we are ill-prepared for the next time Zika hits.

Here's what they found:

Good news: The percentage of children being born with microcephaly to mothers who contracted Zika is lower than epidemiologists initially thought.

Bad news: Researchers are finding that children who are born asymptomatic can develop Zika-related problems later on.

Of the pregnant people infected with Zika virus, studies show that just 5%-14% give birth to children with signs of congenital Zika syndrome (which can cause developmental issues with their brains and vision), and a 4%-6% subset have children with microcephaly.

That's a lot lower than researchers initially thought, and it means that some 70%-80% of pregnant women who get Zika don't transmit the infection to the child. And even when they do, some 10%-20% of babies with Zika are born with no initial signs of birth defects.

Unfortunately, researchers are also discovering that babies with Zika who seem fine at birth can exhibit issues with seizures, vision and brain development in their first year and perhaps beyond. "As we're following these babies," says Ko, "maybe what we're seeing is just the tip of the iceberg. There may be other, more subtle defects that affect language and cognition [later on]."

It's not totally clear what causes some babies to be born with birth defects and not others, but researchers have narrowed the causes. They know for sure that it doesn't come from exposure to pesticides or vaccines. Timing seems important: Mothers who are infected in the first trimester are two to three times more likely to have babies with complications. It may also have to do with a parent's genetic makeup, and previous exposure to other viruses like dengue.

Good news: We learned a lot of new things about Zika during and after the pandemic.

Bad news: We don't have a history of good data on Zika, so it's hard to isolate the signal from the noise.

At first, public health researchers thought that a particular strain of the Zika virus - the one circulating in the Americas, with roots in Asia - was the only strain that caused birth defects like microcephaly.

Now, evidence shows that other strains can cause birth defects too. In African and Asian countries where Zika has circulated for decades, birth defects may have flown under the radar simply because the medical community wasn't watching closely for them.

"It takes a lot of surveillance to detect these cases," says Scott Weaver, director of the Institute for Human Infections and Immunity at the University of Texas Medical Branch. "It took literally millions of infections before this was even noticed [in the Americas]." Given that the rate of mothers with Zika giving birth to babies with microcephaly is 4%-6%, it might have taken a concentrated setting - as in northeast Brazil, where millions of childbearing women were first exposed to Zika in a short period of time - for the connection between the virus and birth defects to be visible.

The upshot, the researchers found, is that there's not enough evidence to say that any strain of Zika is low-risk - in contrast to what the Indian government stated during a 2018 outbreak in northwest India.

And while Zika's most severe impact is on developing babies, it may also have disturbing impacts on the general population. We're also learning about Zika's association with a rare and nasty variation of Guillain-Barré syndrome, an autoimmune disorder that leads to weakness and sometimes paralysis.

"The Guillain-Barré disease that occurs is more severe ... and can have more long-lasting, permanent effects," says Dr. Sankar Swaminathan, chief of the Division of Infectious Diseases at the University of Utah. He says the version of Guillain-Barré connected with Zika comes at a relatively high incidence and affects younger people.

Good news: We're in a quiet phase with Zika.

Bad news: Researchers think Zika will strike again; they just don't know where or when. And when it comes, we're not fully prepared.

"I think the most important lesson to learn is that Mother Nature is always in charge," says Dr. Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

Human action didn't end the epidemic. The public health community worked to contain it, through diagnostics, education and travel advisories. But ultimately, the virus ran its course, infected a large portion of the population, and herd immunity developed, thus halting the spread.

"This is what happens with a lot of different epidemics," says epidemiologist Ko. "Once a large proportion of the population is infected, they're immune and they actually protect other people from getting infected."

"Right now, Zika transmission in the Western Hemisphere is very, very low," says Dr. Lyle Petersen, director of the CDC's Division of Vector-Borne Diseases. "That doesn't mean it's gone away completely, or that we won't have to worry about it in the future." Over time, as people who are not immune to Zika are born into, or move into, a community, the population becomes susceptible to another outbreak. "Could it be in five, 10, 20 years? We don't really know," Petersen says.

In the time that the virus was active, the research community made quick strides in developing diagnostic tests and vaccine candidates: Within six months of the pandemic declaration, vaccines were in the first stage of clinical trials. But the pandemic trailed off a few months later, leaving vaccines stuck in the approval pipeline, without enough people at risk of Zika to get through phase 2 and 3 clinical trials.

"We have huge populations that are considered completely naive because there is no vaccine currently and people haven't been exposed to this virus," says Christine Kreuder Johnson, director of the EpiCenter for Disease Dynamics at the University of California, Davis.

Researchers are now considering different pathways to approval, like "human challenge studies," in which people volunteer to get the vaccine and then be purposely exposed to the virus.

The other big problem that has not been cracked is mosquito control. The main culprit in Zika's spread is a mosquito species called Aedes aegypti, which thrives in small water containers. "One little bottlecap in a ditch can serve as a wonderful breeding site for mosquitoes like this," says Osterholm. Besides Zika, the mosquito also carries dengue, chikungunya and yellow fever, and its home range overlaps with the settlements of over 2 billion people in the Americas, Africa and Asia (Zika can also be transmitted sexually and through blood infusions).

Petersen says the U.S. capacity for mosquito control and surveillance is lacking. "Here at the CDC, we have 12,000 employees, and 12 of them are medical entomologists," he says, way down from the 1950s, when half the CDC's workforce was involved in malaria and mosquito control. During the national Zika virus response, Petersen pulled a retired CDC worker "off a sailboat in the Caribbean" to come back and work on the effort. "We really need to build our mosquito surveillance and control in the U.S. ... It can't be done with one year of Zika supplemental funding. It's a long-term effort that's needed."

Researchers are watching areas of South and Southeast Asia, where outbreaks have been reported in populations that haven't been exposed before. They also think it could return in force to the Americas, particularly in areas that were spared in the last wave. "São Paulo had very little Zika activity - that's a city that is ripe for a major epidemic," says Osterholm, because it's a concentration of people who are currently not immune. "It's just a matter of the wrong mosquito infecting the wrong population," he says, "and then you've got an epidemic."

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Zika: Researchers Are Learning More About The Long-Term Consequences For Children

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In 2015, Zika virus swept through Brazil and the Americas. It was the first time a mosquito-borne virus was known to cause severe birth defects, and the World Health Organization declared it a "public health emergency that warranted a global response."