By Susan Blumenthal, MD, Ladan Fakory, and Alec Kingston
The spread and impact of the Zika virus is yet another wake-up call for the global community, following the Ebola crisis, that infectious diseases pose significant threats to human health and international security. Since 2007, the disease has been reported in more than 64 countries and territories worldwide. On February 1, 2016, the World Health Organization (WHO) declared that the Zika outbreak was a Public Health Emergency of International Concern. A few days later, the Centers for Disease Control and Prevention (CDC) issued a "level 1" activation for its emergency command center (recently raised to "level 2"), and a week later, the Obama Administration requested $1.86 billion from Congress to fight this public health emergency. On April 7, 2016, the WHO reported that there is scientific consensus that the Zika virus is a cause of microcephaly and Guillain Barre Syndrome (GBS). Then on April 13, 2016, the CDC confirmed that there is no longer any doubt that Zika is a cause of microcephaly and other neurological damage in infants.
Experts estimated that 2.17 billion people are living in tropical and sub-tropical regions, where Zika-carrying mosquitoes can thrive. According to the WHO, as many as 4 million Zika cases are predicted in the Western hemisphere alone by the end of 2016. Since it was first reported in Brazil in 2015, Zika has spread rapidly with most countries in Latin America and the Caribbean reporting local transmission of the virus. There is increasing concern that the disease could affect people living in the United States. As of May 4, 2016, there have been 472 Zika cases reported in 44 U.S. states, and 661 cases reported in 3 U.S. territories, with 631 cases in Puerto Rico alone. The virus is a particular threat to Puerto Rico, where it is estimated that as many as 25% of people living there may become infected with Zika. On April 29, 2016, experts confirmed that the first Zika-related death in the United States occurred in February for a 70-year old Puerto Rican man due to a bleeding disorder, immune thrombocytopenic purpura (ITP). In ITP, the body's immune system attacks the blood cells called platelets that allow clotting. This is the 9th know case of this type of bleeding associated with Zika.
The Zika pandemic underscores the importance of prevention and public health preparedness in mitigating the spread of disease and promoting global health. Since 1976, as many as three new infectious diseases have emerged each year: HIV/AIDS, SARS, H1N1, Ebola, MERS, and West Nile encephalitis are just some of the most serious and headline grabbing ones. As of 2014, more than 346 infectious diseases were linked to 16% of all human deaths worldwide annually.
The devastating impact of infectious disease outbreaks on societies is not a new phenomenon. Communities and countries have experienced the burden of infectious illnesses for millennia. While these diseases can cause debilitating health complications including death, emerging illnesses can also create public panic leading to significant socio-economic impacts affecting education, business, and travel. For example, the World Bank estimates that in 2016, the Zika virus will pose an economic burden of $3.5 billion on Latin America and the Caribbean alone. With more than 2 million people crossing international borders every day and the world more interconnected than ever before, the disruptive potential of infectious disease epidemics has reached unprecedented levels. Now is the time to commit the necessary funding to ensure pandemic preparedness and response. If the necessary investments are made, advances from research hold the promise of effective treatments and vaccines for infectious diseases like Zika and Ebola in the future. However, until that time, coordination, collaboration, and communication across communities and countries are the cornerstones of effective preparedness to prevent disease spread.
History of the Zika Virus
Zika, a flavivirus, was first discovered in 1947 in rhesus monkeys in Uganda. The virus quickly jumped to humans, with the first cases in people recorded in 1952 in Uganda and Tanzania. Outbreaks were reported in Yap in 2007; French Polynesia in 2013; and Brazil, Colombia, and Cabo Verde in 2015. Genetic sequencing reveals that the Zika virus in South America is similar to that found in French Polynesia, suggesting it was introduced to Brazil from an infected traveler from French Polynesia. However, the sequences are not identical which can have important effects on human disease. As of April 14, 2016, the World Health Organization (WHO) reports that 64 countries have shown active transmission of the Zika virus since 2007, with more than 1 million cases in Brazil alone. As the virus rapidly spreads around the world, as many as 4 million Zika cases are predicted in the Western hemisphere by the end of 2016. With the epidemic moving northward and the anticipated hotter summer weather, U.S. officials are concerned about Zika-infected mosquitoes infecting people in Florida, other Gulf coast states, Hawaii, as well as the possible spread northward to Washington DC, New York, and Chicago during the warmer summer months. As of May 4, 2016, there have been 472 Zika cases reported in 44 U.S. states.
Zika, a single-stranded RNA arbovirus, is primarily spread by the Aedes aegypti mosquito, the same species that transmits other infectious diseases, including chikungunya and dengue. Zika can also be spread by the Aedes albopictus mosquito, known as the Asian tiger mosquito. If spread of the virus occurs in America, Aedes aegypti would most likely be the primary vector in urban areas and southern U.S. states along the Gulf Coast, whereas Aedes albopictus could play a larger role in transmission in the U.S. due to its wide distribution as far as New England and the lower Great Lakes. With international trade and travel, humans are contributing to the spread of these mosquitoes to new habitats. The global transportation of cargo and travel by people are partially responsible for introducing these mosquitoes to new continents. In addition, environmental changes including urbanization, dam construction, deforestation, and rising temperatures linked to climate change have increased the number of locations around the world in which these mosquitoes can thrive.
Recent case reports suggest that the Zika virus is being spread through sexual intercourse and blood transfusions. There have been several cases of heterosexual transmission but two weeks ago, the first case of sexual transmission in a gay couple was documented. The CDC continues to investigate these cases and issues updated recommendations for prevention. Efforts to stop the spread of the Zika epidemic will need to effectively address every method of viral transmission.
Zika Symptoms and Disease Course
Most people who are infected with Zika do not experience any symptoms and are unaware that they are infected. However, an estimated 20% of people will have symptoms, including fever, skin rashes, conjunctivitis, headaches, and muscle/joint pain, lasting from 2-7 days. It is not yet known how long the virus remains in a human's blood or semen. One case reported in the United States revealed that the virus was present in the patient's blood 10 weeks after infection. Until the most recent outbreak, Zika was believed to be a relatively benign disease. However, its recent emergence in Brazil, with reports of severe clinical neurological complications in infants and adults, has made this disease a global emergency. Concerns about Zika have been amplified as hundreds of thousands of people plan to travel to Brazil for the upcoming Summer Olympic Games.
Over the past year, health officials have reported a strong link between Zika-infected pregnant mothers and higher than average rates of microcephaly in their babies, a rare birth defect where babies are born with underdeveloped heads. Recently, the CDC confirmed there is now scientific consensus that Zika causes microcephaly. In most cases, the infant's brain has not developed properly, leading to complications, including seizures, developmental delays, and difficulty with coordination, balance, hearing, vision, and possibly death. One study has associated Zika with even more severe birth defects than previously reported as a stillborn baby was found to have almost complete loss of brain tissue. In Brazil alone, more than 4,949 babies were born with microcephaly since 2015, which represents a 20-fold increase from 2010-14. Studies have shown that Zika can spread through a pregnant woman's amniotic fluid and into the brain of her fetus, attacking the neural cells and stunting the infant's brain development. In January 2016, a case of microcephaly in an infant whose mother had lived in Brazil was reported in Hawaii, marking the first U.S. case of brain damage in an infant linked to the Zika virus. Alarmingly, a case in the U.S. revealed that early ultrasounds may miss the fetal damage caused by the Zika virus and that fetal MRIs may be necessary to detect this complication.
Researchers are reporting varying rates of the incidence of microcephaly in infants of babies born to Zika infected mothers. An examination of the pregnancies of 88 women in Rio de Janeiro, published in the New England Journal of Medicine, revealed "serious and frequent problems in fetal and central nervous system development" in 29 percent of women who had experienced Zika symptoms during their pregnancy and had received prenatal imaging. In a retrospective study of the association between Zika virus and microcephaly in French Polynesia during the period of 2013-15, the risk of microcephaly associated with Zika virus infection was 95 cases (34-191) per 10,000 women infected in the first trimester. The differences in rates are large across these studies. Prospective controlled studies are now underway to better determine the incidence of microcephaly in the babies of Zika-infected women. The nine month length of a term pregnancy means that it will take time to get the data needed on the actual risk from exposure to the virus, and also because the risk may vary significantly with each successive week of pregnancy. These devastating cases of microcephaly and other congenital abnormalities in infants underscore the urgency to fight the Zika outbreak with sufficient resources now!
Zika infection has also been linked to Guillain-Barré Syndrome (GBS), a rare condition in which a person's own immune system attacks and damages their peripheral nervous system, sometimes causing life-threatening or permanent muscle weakness or paralysis. Scientists reported the first GBS case linked to the Zika virus in 2014 in French Polynesia. French scientists have been investigating this particular outbreak and confirmed the link between GBS and Zika with additional cases of this neurological complication recently reported in in Brazil. On April 7, 2016, WHO confirmed that there was a link between Zika and GBS but CDC has not yet done so. Another brain disorder has been associated with Zika infections in adults called acute disseminated encephalomyelitis (ADEM), an autoimmune syndrome that affects the brain and spinal cord. ADEM generally occurs in the aftermath of an infection lasting about 6 months, causing significant swelling in the brain and spinal cord that results in weakness, numbness and loss of balance and vision, symptoms similar to multiple sclerosis. This illness adds to the growing evidence of serious neurological damage caused by the Zika virus.
Pandemic Preparedness: A Roadmap of Recommendations
Coordinated pandemic preparedness and response efforts across communities and countries are critical to addressing and controlling Zika and other emerging infectious illness threats in the future. This work should build on decades of research on other flaviviruses including dengue and yellow fever. Fortunately, WHO acted swiftly to declare Zika a public health emergency -- something the organization has done just three times since 2007. The U.S. government responded rapidly as well but additional resources and actions will be needed to contain the spread of this disease.
Listed below are a series of recommendations for pandemic preparedness to help prevent and mitigate the impact of the Zika virus as well as other emerging infectious diseases now and in the years ahead:
1. Coordinate Global Health Systems Infrastructure, Personnel, and Resources
Increased pandemic preparedness to help prevent and contain infectious disease outbreaks, if they should occur, is essential to protecting global health security. A Global Health Security Agenda, endorsed by the G-7, was launched in February 2014 to prevent, detect, and respond to infectious disease outbreaks before they become epidemics. The delayed, but ultimately successful response to the Ebola outbreak in Western Africa to date was in part due to the appointment of an Ebola Coordinator at the White House, who worked across U.S. government agencies and with other nations. Whether Ebola, Zika, or another emerging disease threat, countries must commit the funds, appoint coordinators, and develop a permanent emergency preparedness infrastructure to effectively respond to the Zika epidemic as well as to address the next outbreak of an infectious disease that will invariably occur. The establishment of a permanent "Pandemic Preparedness Coordinator" at the White House who is an experienced manager would be an important step forward to ensuring rapid and successful response to emerging diseases in the future. This person would work across the U.S. government agencies and with the private sector, other governments, and international organizations.
The role of the civil society, local experts, and affected populations must be reinforced at all levels. Their involvement in planning and implementation is essential during the management of crises as well as in developing response plans.
On February 8, 2016, the Obama Administration requested $1.86 billion to fight the Zika epidemic. The Congress is currently debating this funding request. Given the urgency of Zika as a public health threat, on April 6, 2016, the Administration redirected $589 million in unspent funding to combat the Ebola virus to fight the Zika epidemic. Of this amount, $47 million goes to NIAID for Zika research. As of February 16, 2016, WHO committed $56 million, and two days later, the World Bank committed $150 million. This level of support is not sufficient to fight this pandemic! It is critical to mobilize the resources needed to fight this disease. Failure to do so would be a major public health and political mistake with potentially devastating health and economic consequences. By investing in research towards the discovery of a vaccine and antiviral treatments, human suffering and the long-term costs of caring for cases of people with microcephaly, GBS, and ADEM can be averted. Additionally, the results should pay dual dividends to help fight other infectious diseases as well.
Toward this goal, the establishment of a "Global Health Security Fund" is needed with contributions from governments and the private sector worldwide. Such an entity would be helpful in securing funds for building the necessary international infrastructure, including emergency response teams of medical providers, lab technicians, and community health workers. This infrastructure support would help the international community get ahead of the curve in responding collectively to emerging infectious diseases now and in the future. On May 6, 2016, UN Secretary-General Ban Ki-moon announced the establishment of the UN Zika Response Multi-Partner Trust Fund, which will provide a rapid, flexible, and accountable platform to support a coordinated a response to support the global Zika Strategic Response Framework and Joint Operations Plan in consultation with UN agencies, partners, and international public health experts. Donors will contribute to a central "fund" and an Advisory Committee will direct funds to priority activities and programs. This is an important step forward but this Fund should be established as a permanent entity for supporting the global response to all emerging infectious disease threats.
The response to infectious diseases must be fought as if the battle against epidemics were wars against international enemies. This was the framework for America's response to Ebola overseas and in the U.S, and now Brazil's strategy for addressing Zika includes military personnel and public officials who coordinate and mobilize supplies, conduct surveillance activities, build hospitals, oversee community efforts and establish emergency response operations centers.
On April 1, 2016, the CDC convened, a Zika Action Plan Summit, which brought together local, state, and federal health officials as well as maternal health and mosquito eradication experts. The Summit was a forum for sharing best practices which attendees could take home and implement in their communities. Additionally, on April 19-22, 2016, the National Association of County & City Health Officials (NACCHO) convened public health experts to address pandemic preparedness, including how to respond to the Zika threat at the community level.
2. Increased Surveillance and Early Detection
In order to effectively combat the Zika virus, more effective methods for surveillance of bothinfected people and mosquitoes are urgently needed. The Aedes aegypti mosquitoes are aggressive daytime biters that have adapted to breed in both urban and rural areas wherever rain collects and water is stored. Their laid eggs can survive for more than a year even in dry conditions, and the eggs' stickiness allows them to adhere to an array of surfaces, such as tires. These features make Aedes aegypti very difficult to control and track.
Training community members and health workers to observe and report on Zika, and developing integrated systems for collecting and analyzing surveillance data are important. Mechanisms, such as syndromic surveillance, the meaningful use of electronic health records to achieve epidemiological insights, increased communication between hospitals and local and state health departments in the U.S. and around the world, accurate reporting of cases to public health departments, and a global hub of information provided by WHO tracking cases, are needed. Countries must be transparent in reporting Zika cases. Mobile phone technologies can help to improve surveillance by tracking disease outbreaks and sending information to a central global repository of tracking information.
Early detection--the development of a rapid, accurate diagnostic test -- is an urgent priority in preventing further transmission of the virus and providing timely clinical care. Unfortunately, the fact that dengue and chikungunya result in similar clinical pictures and epidemic in the Americas confounds the clinical diagnosis of Zika. Because Zika is closely related to these diseases, serologic samples may often cross-react in tests for these other viruses. The presence of immunoglobulin G antibodies that bind to the Zika virus could be the result of past infections with any of the other flaviviruses or from prior immunization with a flavivirus vaccine. In many Latin American cities, dengue seroprevalence in adults may exceed 90%, thus confounding the diagnosis of Zika. Gene-detection tests, such as the polymerase-chain-reaction (PCR) assay, can reliably distinguish the three viruses, but Zika-specific tests are not yet widely available. Research teams from Texas have recently succeeded in producing a rapid detection test for the Zika virus that can determine its presence within several hours as well as differentiate it from other infectious diseases carried by the Aedes aegypti mosquito, including chikungunya and dengue. On March 18, 2016, the Food and Drug Administration (FDA) issued an emergency use authorization for a 3-in-1 real time PCR laboratory assay for Zika, chikungunya, and dengue. On March 30, 2016, the FDA also said that it would allow the use of an experimental test to check for the presence of the Zika virus in blood donations. This action means that Puerto Rico, which had ceased local blood donations and imported nearly 6,000 units of red blood from the continental United States, will be able to resume collecting donations from residents. And this new tool will also help blood banks in other parts of the country as well. On Friday, April 29, 2016, FDA provided emergency authorization to sell the first commercially developed Zika blood test in the U.S., which should expand testing capacity by doctors and accelerate the diagnosis of the virus.
Last week, a paper-based rapid test for detecting the Zika virus was introduced by a consortium of research groups including MIT, Harvard, and Boston University. The test consists of a paper covered with yellow dots that turns purple in the presence of the RNA of the virus. The test is relatively fast and simple and can be performed in most laboratories with results in about 2-3 hours. It is estimated that the test will cost less than $1 and that results will be delivered faster than PCR assays available today. Scientists freeze dried on paper the cell's normal "machinery including proteins, nucleic acids and ribosomes. The color change on the paper can be read by the eye or by using an extra-sensitive scanner that may eventually be able to measure viral loads in the blood sample. The test has worked on Zika-infected monkey blood, which was used because human samples were difficult to obtain when the research was being conducted. The scientists now want to evaluate the test's effectiveness on humans living in areas of the Zika outbreak in South America. More work is needed to develop and evaluate these kinds of rapid diagnostics that can be used in the field to accurately determine whether people have been infected with flaviviruses including Zika, chikungunya and dengue.
On May 10, 2016, the CDC issued new urine-based testing guidance for detecting the Zika virus. This test may prove to be more effective than a blood-based test since virus particles can be detected for longer time periods and at higher levels in urine than in blood. In testing 66 people in Florida for Zika using blood and urine samples, twice as many urine samples resulted in correctly testing positive compared to blood samples. In addition, the urine tests detect the virus for two weeks after the onset of symptoms, compared to one week for blood tests. For now, the CDC guidelines recommend that patients with Zika symptoms be provided both blood and urine tests, since the blood test also detects the body's immune response to the virus.
On April 19, 2016, a new global "Zika zone" map was launched by a consortium of researchers at major universities worldwide, including the University of Washington and Oxford University. The map calculates when and where the Zika virus is likely to spread based on detailed geographic and environmental conditions data. On April 27, 2016, NASA and the National Center for Atmospheric Research (NCAR) released a map that explores the potential spread of Zika in the U.S., applying factors, such as temperature, poverty levels, amount of rainfall, and travel to America from regions of the world affected by the virus. The goal of this project is to help target a "search and destroy mission" against the deadly Aedes mosquito.
3. Clinical Response
As many as 80% of Zika viral infections are believed to be asymptomatic. Furthermore, there are no antiviral treatments or vaccines currently available to treat or prevent acquisition of the disease. Until there are effective treatments for Zika, physicians and other health care providers should focus on symptomatic management, such as getting adequate rest, preventing dehydration by drinking fluids, taking acetaminophen to relieve fever and pain, and avoiding nonsteroidal anti-inflammatory drugs (NSAIDs). People infected with Zika, chikungunya, or dengue virus should be protected from further mosquito exposure during the first few days of illness to prevent other mosquitoes from becoming infected and reduce the risk of local transmission. Issues related to fetal infection are complex, and strategies are urgently needed to prevent transmission of the virus to infants.
4. Effective Vector Control, Eradication, and Gene Drive Technology
21 century effective vector control strategies must be developed and utilized to prevent the spread of mosquito borne diseases, including Zika, chikungunya, dengue fever, and malaria. There are 3,500 known species of mosquitoes with a few hundred types that bite humans; but, only three species are linked so far to the transmission of human diseases. The Aedes aegypti species transmit Zika, chikungunya, and dengue. Only female mosquitoes bite as they need the amino acids from blood to develop and lay eggs. Male mosquitoes, on the other hand, use nectar as a source of energy. Transmission occurs when female mosquitoes bite an infected human and then transfer the virus to the next person they bite through the mosquitoes' saliva.
Some victories against mosquitoes have occurred, thanks to insecticide-treated bed nets and vaccines against viruses including yellow fever and Japanese encephalitis. In December 2015, the first vaccine for dengue was approved in Mexico. Nevertheless, mosquito borne diseases kill more than 725,000 people a year, mostly due to malaria. Climate change adds a further compounding factor. A 3.6 to 5.4 degree Fahrenheit rise in temperature can increase the number of people at risk of malaria by more than 100 million, according to the WHO. Warmer weather also speeds up the mosquito breeding cycle from about two weeks at 77degrees Fahrenheit to 7-8 days at 82.4 degrees Fahrenheit. The effects of warming temperatures means that mosquitoes carrying Zika can impact people in more regions around the world.
Mosquito control efforts in the U.S. is handled by a patchwork of districts that are coordinated and funded locally. Some of these programs may not be connected to community or state health departments. Most of these programs are aimed at controlling "nuisance" mosquitos rather than disease spreading ones.
Strategies being explored to eradicate human disease spreading mosquitoes include genetic modification, radiation, insecticides, and targeted bacteria. However, these approaches raise several issues: ethical concerns about killing off a species, and the effects on the rest of the ecosystem, including on human health. For example, DDT is no longer recommended for malaria control since it is harmful to the environment as well as humans, with a suspected link to an increased risk for breast and other cancers. While DDT is a banned substance, some experts are advising that restrictions on its use be lifted given the Zika public health emergency. While insecticides have been used with success in many areas of the world, mosquitoes are emerging with resistance to these substances. A new generation of agents is urgently needed in the 21 century for vector control with minimal side effects for humans.
In recent years, scientists are focusing on integrated vector management as well as genetic modification to eradicate mosquitoes. The CDC has instructed health departments to target killing the larvae and adult mosquitoes, indoors and outdoors - a "four corners approach." Since the Aedes aegypti mosquito has a flight range of only 150 yards, typical mosquito control efforts such as community insecticide spraying may be as effective as other vector control tactics, such as targeted spraying around individual homes and disposing of mosquito-breeding habitats like water containers.
Genetic modification is being used by companies to create sterile male mosquitoes that seek out and mate with females. The offspring, in turn, do not survive to adulthood, thus decreasing the mosquito population and spread of mosquito-transmitted diseases. An Aedes Genome Working Group of leading U.S. mosquito scientists is working to create a state-of-the-art DNA map of the Aedes aegypti mosquito to aid in the fight against Zika using the insect's own genetic code. The goal of the group is to develop a new genetic combat strategy against the increasing threat posed by insect transmitted diseases.
A new molecular based technology, CRISPR, a gene snipping tool, creates genetic changes which are then transmitted to a mosquito's offspring. Two approaches are being applied to reduce the threat of mosquitos: 1) modifying a gene so that mosquitos become unsuitable hosts for a pathogen that infects people; and 2) rendering insects extinct by giving their genes male only reproductive instructions. A concern about these approaches expressed by some scientists is the unpredictable ecological impact of a genetically modified species. Gene drive technology is new and promising, but safety concerns have yet to be adequately addressed.
Another approach involves scientists transferring the natural bacteria called Wolbachia, found in 60% of all insect species, to the Aedes aegypti mosquito. Wolbachia was first discovered in a mosquito in 1924 in Boston. Instead of floating in the blood, the bacteria reside inside cells. Female mosquitos carry the Wolbachia bacteria in their eggs, thus infecting offspring. Research has shown that when Wolbachia is present, the mosquito's ability to transmit dengue is significantly reduced. The Eliminate Dengue Program, an international collaboration, uses this approach to block transmission of the virus to humans. In 2011, several hundreds of thousands of Wolbachia infected mosquitos were released in northern Australia. More than 5 years later, most of the mosquitos were found to still have the bacteria present. When these Wolbachia infected mosquitos are widely present, dengue cases have disappeared in that area. A large scale trial will begin in June in Indonesia to scientifically confirm the impact of Wolbachia infected mosquitos on the incidence and prevalence of dengue infection. Researchers are now testing whether this approach can reduce cases of Zika infection. Preliminary findings suggest that Wolbachia suppresses Zika in mosquitos, like it does dengue. More research is needed to evaluate whether this approach can stop human transmission of the Zika virus as well as other diseases carried by mosquitos including malaria, chikungunya, and yellow fever.
Some scientists have expressed concerns that eliminating all mosquitoes would make little sense, since there are more than 3,500 species, fewer than 200 species bite humans, and only 3 species bear the primary responsibility for transmitting disease to people. Mosquitoes that do not bite humans serve as food for frogs, fish, birds, and bats and some may play a role in pollination of plants.
Concerns about modifying mosquitos to prevent Zika transmission to humans have mobilized organizations to take action. The WHO is evaluating guidance concerning transgenic mosquitoes and transgenic bacteria. The FDA has indicated that it believes that genetically modified mosquitoes are "not expected to have any direct impacts on human or animal health." The agency is now soliciting public comment before releasing genetically modified mosquitoes in a field trial in Key West, Florida to evaluate whether using this approach can decrease the population of mosquitoes that carry Zika, chikungunya, and dengue in that state. The Environmental Protection Agency (EPA) has issued several experimental permits to introduce Wolbachia bacteria to prevent mosquito reproduction. Clearly, new, innovative vector control methods are needed in the 21 century but more research will be required on the various types of proposed mosquito eradication methods and their effects on humans and on the ecosystem before implementation to prevent unintended health damaging consequences.
5. Invest in Research
There is a dearth of knowledge about Zika and its clinical course with just 250 scientific journal articles published on the disease to date, compared to more than 19,000 scientific papers published on dengue. More research is needed on the basic pathogenesis of the virus and the immune response to it as well as increasing knowledge about the disease's effects on the brain in fetal development, children and adults. A key priority is a better understanding of the rate of perinatal transmission and the effects of the Zika virus during the first, second and third trimesters of pregnancy on fetal development. The National Institute of Allergy and Infectious Diseases (NIAID) posted a notice regarding its high-priority interest in Zika-related research. In addition, 30 leading scientific research institutions, journals, and funders have agreed to freely share all data and research on the Zika virus to accelerate the fight against its further spread. Governmental and non-governmental research institutions worldwide should share data in the spirit of transparency and collaboration that is needed to eradicate the epidemic. Additionally, recommendations are needed regarding perinatal testing with ultrasound, amniocentesis as well as other methods to assess whether congenital abnormalities are present.
Some organizations have pledged funding to help fight Zika, but much of it is directed at addressing the need to contain the spread of the virus and provide care for the infected. For example, WHO has called for $56 million to help fund the Global Strategic Response Framework and Joint Operations Plan that will guide the international response to the Zika virus. However, only $6.4 million of that $56 million is allocated for research and the total amount of funding is certainly not sufficient to mount an effective eradication and control response. Similarly, the World Bank has pledged $150 million toward the international response to the Zika virus, which includes identifying at-risk individuals, improved public awareness programs, better medical care for pregnant women, but does not include research as a component of its funding plan. More resources are urgently needed to address unanswered questions about Zika, its clinical course, effects of its co-occurrence with other viruses, and to develop better detection methods as well as a vaccine and anti-viral medications.
Scientists have begun a wide range of projects to investigate Zika. At the University of Wisconsin, researchers have injected the Zika virus into the fetus of a rhesus monkey to evaluate how the virus affects the development of the fetus' brain. Scientists are recording and publishing the raw data in real time on the laboratory's website so that all researchers interested in the microcephaly complication can have immediate access to the findings. This type of data sharing and transparency is essential to increase our understanding of Zika and facilitate the discovery of effective treatments as well as a vaccine.
6. Fast Track Vaccine and Anti-Viral Development
Prior to this most recent Zika outbreak, there was little known about the Zika virus; thus, greater knowledge about the natural history of the illness will take time. As a result of emerging evidence linking Zika infection with serious medical complications, including GBS and ADEM, and microcephaly in infants, there is critical need to accelerate the scientific study of Zika including developing new biomedical countermeasures including vaccines and antiviral medications. Increased knowledge about why some people seem to be at greater risk for these complications is an important scientific priority. Since many parts of the world have not reported Zika outbreaks, people have no immunity, and therefore may be more susceptible to the health complications of the virus. Scientists have recently published a detailed picture of the Zika virus' physical structure, which will hopefully help them determine what properties of the virus cause the serious complications and can be targeted with anti-virals and vaccines in the future.
Researchers estimate that a vaccine for the Zika virus is 3-10 years away. The NIH is currently pursuing several Zika vaccine approaches although this timeline may be accelerated if breakthroughs occur. Fortunately, vaccine platforms exist for other flaviviruses that can be used as a starting point for a Zika vaccine. A DNA-based vaccine, a strategy that was successfully used in developing a West Nile virus immunization, works by injecting a DNA fragment instead of a protein fragment to stimulate immunity. Trials of this vaccine type for Zika could begin in early 2017. The second vaccine approach uses a "live attenuated" weakened form of the virus that cannot cause disease but boost immunity building on a similar vaccine strategy used for the closely related dengue virus. Additionally, an investigational vaccine trial is underway using a genetically engineering version of vesicular stomatitis virus (VSV), the same animal virus that successfully led to an investigational Ebola vaccine candidate. This vaccine strategy is in an early stage with plans to test its effectiveness in tissue culture and animal models. According to NIAID, it is feasible that an investigational vaccine would enter early stage clinical trials in 2016 to evaluate whether it is safe and stimulates an immune response in immunized volunteers.
Given the frequency of emerging infectious diseases, a new model for vaccine development is required involving a partnership between the public and private sectors to accelerate the process and create strategies to boost immunity against various virus types. Vaccine platforms for flaviviruses, alphaviruses, and other arbovirus groups that can be quickly modified to express immunogenic antigens of newly emerging viruses should be further developed. The establishment of 21 century vaccine development infrastructure is critical as Zika and Ebola are the most recent of what may be many other emerging infectious disease threats in the years ahead.
Another priority for research efforts must be the discovery of antivirals to help treat Zika, chikungunya and dengue as well as methods to prevent transmission of the virus from a mother to her fetus. These recent viral pandemics underscore that the "one-bug-one-drug" approach is inadequate; broad-spectrum antiviral drugs against whole classes of viruses are urgently needed.
The development of biomedical countermeasures requires the coordination of a broad spectrum of government, NGO, and industry partners to be successful. There needs to be an international approach--a Global Pandemic Preparedness Treatment and Prevention Fund --that has three key components: 1) a focus on basic drug discovery and preclinical development; 2) clinical and advanced product development; and 3) procurement mechanisms and market commitments. No one agency or country can combat Zika or other emerging disease threats alone. An effective response will require a resilient governance structure to coordinate research and product development on a global scale.
7. Build Stronger, Resilient Health Systems
Strong, resilient health systems made all the difference in containing Ebola and preventing its spread. In the United States, the Ebola outbreak has underscored the importance of public health preparedness revitalization. Essential to the prevention and containment of future infectious disease outbreaks globally is a robust investment in building health systems infrastructure in the developing world where these illnesses often first emerge. But such pandemic preparedness is critical in the United States and other developed nations as well. Coordination of efforts and communication are cornerstones of public health preparedness. A ready reserve of well-trained health professionals around the world - an International Health Corps - with health expertise and medical supplies that can be mobilized to respond to a disease outbreak anywhere in the world -- are essential components of an effective response to illnesses like Zika and Ebola. In the United States, the USPHS Commissioned Corps serves a key role in such a response and its role should be further expanded in combating infectious disease outbreaks in the U.S. and globally. Community members and health workers have important roles to play and their contributions at the local level must be expanded.
8. Risk Communication
Governments and international organizations should conduct health education campaigns to raise public awareness about the Zika virus. These campaigns should emphasize helpful strategies for mitigating risks of contracting Zika (e.g., avoid mosquito bites, wear long-sleeved clothing, use insect repellents and insecticides, install window screens and bed-nets, keep windows closed, reduce standing bodies of water, and use air conditioning if available). It is important to have a trusted figure provide periodic updates to the public about the outbreak and steps they can take to prevent infection.
More detailed and easy to access reporting of Zika cases should be included on the CDC Zika information page, including number of states with cases and incidence of microcephaly and GBS. Disaggregation of Zika cases by sex, race, and age should also be reported on the website. The World Health Organization (WHO) is encouraged to place their country Zika statistics in a prominent place on the homepage of their information resources about the virus.
Additionally, travel advisories should be widely disseminated and updated regularly. The CDC has already issued a "level 2" travel health alert to practice enhanced precautions, suggesting that pregnant women postpone travel to any country with active Zika outbreaks, including the 2016 Summer Olympic Games in Rio de Janeiro, Brazil on August 5-21, 2016 and the Paralympic Games on September 7-18, 2016. On March 11, 2016, the CDC updated the travel advisory stating that it was safe for pregnant women to travel to high-elevation cities above 6,500 feet in Zika-infected countries since the Aedes mosquitoes cannot live at those altitudes. CDC recommends that travelers returning from Zika-infected areas use condoms or practice abstinence to avoid infecting a partner through sexual transmission. The CDC recommends that females diagnosed with Zika wait at least eight weeks after the onset of symptoms before trying to get pregnant, and males diagnosed with Zika are advised to wait at least six months before having unprotected sex to prevent transmission of the virus to their partners.
Public health experts should do outreach with the media to ensure accurate reporting about infectious disease outbreaks.
9. Apply Social Media and IT Innovations in Pandemic Preparedness
Technologies including mobile phones and social media should be harnessed to track the spread of Zika and other infectious diseases as well as to disseminate education, clinical and prevention information to the public and health providers. A website and a mobile app that can be translated into various languages should be established to serve as an information hub for emergency global health preparedness. Mobile devices present an enormous untapped platform for instantaneously sharing information and aiding in disease surveillance, treatment and prevention approaches. These devices can also be used to facilitate research collaboration and training in real-time across communities and countries. Crowdsourcing can add to these benefits by creating space for citizens and community representatives to offer strategies and solutions. The role of community members and local efforts is critical to an effective response. However, it should also be noted that such platforms can also spread misinformation so monitoring may be necessary.
10. Address Religious, Ethical, and Legal Concerns
Given the scope of the current Zika outbreak with reported cases of sexual transmission of the Zika virus and the serious complications to infants including microcephaly, issues have been raised about broadening the use and availability of contraceptives in affected countries. Health officials in some nations, including Brazil and El Salvador, have recommended that women avoid pregnancy due to the link between Zika and microcephaly. Many of the affected countries currently have relatively low contraceptive prevalence rates as well as restrictive abortion laws. The United States provides contraception through the Affordable Care Act of 2010 but controversy about this provision of the law persists among some religious groups. Women's reproductive health rights in nations must be ensured and this will also help to prevent tragic cases of microcephaly in fetuses of females who have been infected with the Zika virus.
The International Health Regulations should be implemented with a strong and transparent global governance structure. In the U.S., there are conflicting laws and regulations about authorities for components of pandemic response across states and communities. The federal government has minimal direct legal authority or jurisdiction to direct individual states to implement specific pandemic response measures. These issues must be addressed and resolved as an element of pandemic preparedness planning.
Next Steps: The Way Forward
Many questions regarding the Zika virus remain unanswered. More research is needed on the course of the disease and modes of transmission. Studies are needed about the effects of being infected with more than one virus, such as dengue and chikungunya, on the clinical course of Zika and its health complications in humans. Questions have arisen about cross-immunity and whether previous infection with other flaviviruses affects the clinical course of Zika virus infections in humans. Experts do not yet know whether the Zika virus has become more aggressive over the past decade. How long does the virus remain in the body? Is there sex, racial, or age differences? What are the rates of GBS, ADEM, and microcephaly? What are the effects of the virus at different stages of pregnancy on fetal development? Are there particular risk and protective factors associated with Zika's complications? What are the ecological and evolutionary effects of totally eradicating mosquitoes through genetic engineering and other approaches?
Combating the Zika virus and other emerging disease threats in America and abroad will require funding commitments requested by the Obama Administration and that all governments contribute resources and work collaboratively to coordinate their responses. The development of rapid diagnostics, a vaccine and antivirals are cornerstones in combating the disease. America's efforts would benefit from the appointment of a permanent White House Coordinator who can manage a rapid, comprehensive response domestically, as well as work with partner organizations and governments internationally. WHO convened two International Health Regulations (IHR) Emergency Committees on February 1, 2016 and March 8, 2016, and this committee should continue to advise countries on health systems preparedness, vector control, travel advisories and other measures. Additionally, the G-7 Ise-Shima Summit in Japan on May 26-27, 2016 will be an opportune time for the heads of state of seven major advanced economies - Canada, France, Germany, Italy, Japan, U.S., and the UK - to prioritize strengthening global health security to fight Zika and other diseases today and in the years ahead. With the Olympic Games commencing in Rio de Janeiro on August 5, 2016, more than 10,500 athletes and 600,000 spectators will visit Brazil. There is urgency to contain the outbreak for the safety of the athletes, audiences, citizens and businesses. Of concern is the potential for visitors who contract Zika in Brazil to carry the virus back to their home countries, resulting in additional outbreaks globally.
Throughout history, whether it is the Zika virus, Ebola, AIDS, smallpox, or influenza, infectious diseases have killed more people than wars, making them decisive shapers of history. They remain clear and present dangers to human health, economic development, and national security in an interconnected 21 century world, and we must remain vigilant against them. Making significant investments now to strengthen the scientific knowledge base, develop new global health technologies that can be deployed in combination with proven public health practices, as well as strengthen health systems with a coordinated national and international response, will ensure our ability to fight Zika and other emerging infectious disease threats more swiftly and effectively, moving from peril to progress in the years ahead. Microbes like Zika are ticking time bombs against the health of humanity and failure to fight them is not an option
Rear Admiral Susan Blumenthal, M.D., M.P.A. (ret.) is the Public Health Editor of The Huffington Post. She is a Senior Fellow in Health Policy at New America, Senior Policy and Medical Advisor at amfAR (The Foundation for AIDS Research), and a Clinical Professor at Tufts and Georgetown University Schools of Medicine. Dr. Blumenthal served for more than 20 years in senior health leadership positions in the federal government in the Administrations of four U.S. presidents including as Assistant Surgeon General of the United States, the first Deputy Assistant Secretary of Women's Health, and as Senior Global Health Advisor in the U.S. Department of Health and Human Services, where she focused on global health diplomacy. She also served as a White House advisor on health. Dr. Blumenthal was involved in the U.S. response to bioterrorism with the anthrax attacks in 2001. She has provided pioneering leadership in applying information technology to health, establishing one of the first health websites in the government (womenshealth.gov) and the "Missiles to Mammogram" Initiative that transferred CIA, DOD and NASA imaging technology to improve the early detection of breast and other cancers. Prior to these positions, Dr. Blumenthal was Chief of the Behavioral Medicine and Basic Prevention Research Branch, Head of the Suicide Research Unit, Coordinator of Project Depression, and Chair of the Health and Behavior Coordinating Committee at the National Institutes of Health (NIH). She has chaired many national and global commissions and conferences and is the author of numerous scientific publications. Admiral Blumenthal has received many awards including honorary doctorates and has been decorated with the highest medals of the U.S. Public Health Service for her pioneering leadership and significant contributions to advancing health in the United States and worldwide. Named by the New York Times, the National Library of Medicine and the Medical Herald as one of the most influential women in medicine, Dr. Blumenthal was named the Health Leader of the Year by the Commissioned Officers Association and as a Rock Star of Science by the Geoffrey Beene Foundation.
Ladan Fakory, M.P.A. is a Health Policy Fellow at New America in Washington, D.C. She received her Master's in Public Administration from Harvard University, John F. Kennedy School of Government. She has 11 years of health experience across the U.S. Department of State, U.S. Agency for International Development (USAID), and Walter Reed Army Institute of Research (WRAIR), where she focused on sleep study research, HIV/AIDS prevention, maternal and child health policy, global health diplomacy, and the Millennium Development Goals (MDGs).
Alec Kingston is a Health Policy Intern at New America in Washington, D.C. She is a sophomore in the Edmund A. Walsh School of Foreign Service at Georgetown University, where she is majoring in Science, Technology & International Affairs with a concentration in Global Health as well as a certificate in International Development.