Zika virus is a member of the flavivirus family related to dengue virus, yellow fever virus, and West Nile virus, and its primary mode of transmission is via mosquito, most notably by the Aedes aegypti mosquito. Aedes albopictus mosquitoes are a potential vector for the Zika virus. The disease was first identified in the Zika Forest in Africa in the 1940s, from which it subsequently moved eastwards over the following decades, though the Pacific Islands until it reached Brazil, where the population had no indigenous immunity against the virus. According to CDC officials with whom we spoke, the United States also has no indigenous immunity to the Zika virus. A major factor contributing to the declaration of Zika virus disease as a Public Health Emergency of International Concern by the World Health Organization (WHO) is a possible link between Zika virus and microcephaly as well as Guillain-Barré syndrome. Microcephaly—an abnormally small head due to failure of brain growth—is a concern because children with microcephaly can experience impaired cognitive development, delayed motor function and speech, seizures, and reduced life expectancy. To better understand the spread of this disease worldwide, epidemiological studies are required. Epidemiology is concerned with the patterns of disease occurrence in human populations and of the factors that influence these patterns. The goals of epidemiologic study, and more specifically outbreak investigations, are to determine the extent and distribution of the disease in the population, the causes and factors associated with the disease and its modes of transmission, the natural history of disease, and the basis for developing preventive strategies or interventions (see figure 1). The United States has played a significant role in improving global disease surveillance and response capacity. In the mid-1990s, recognizing the threat posed by previously unknown infectious diseases, the United States and other countries initiated a broader effort to ensure that countries can detect disease outbreaks that may constitute a Public Health Emergency of International Concern. The United States has participated in the WHO’s efforts to develop and implement the International Health Regulations, currently an agreement among 196 countries, to develop and maintain global capabilities to detect and respond to disease and public health threats. The CDC has helped to define and establish the International Health Regulations and has been designated by the WHO as a key partner in helping to implement the critical capacities for detecting and responding to emerging infectious disease outbreaks. The recent Ebola outbreak in West Africa has highlighted the importance of further improving the U.S. government’s global disease surveillance efforts. To help ensure that such threats are addressed early and at their source, the “National Health Security Strategy and Implementation Plan 2015-2018” released by the U.S. Department of Health and Human Services prioritizes efforts to strengthen national capacities and capabilities globally to detect disease in a timely manner, prevent the global spread of public health threats and diseases, and respond to public health emergencies. For example, CDC’ s Global Disease Detection and Field Epidemiology Training programs aim to strengthen laboratory systems for the rapid detection and control of emerging infectious diseases and train epidemiologists to effectively detect, investigate, and respond to health threats. While several countries have reported outbreaks of Zika virus disease, unanswered questions remain regarding the epidemiology and the transmission of the disease. Many factors, including a large number of asymptomatic patients, mild symptoms, a lack of a consistent international case definition of Zika virus disease, as well as of microcephaly, and a lack of validated diagnostic tests complicate our understanding of the virus and may hinder our response to the current outbreak. Questions also remain regarding the strength of the association between Zika virus infection and microcephaly or Guillain-Barré syndrome. Since the 1960s, the Zika virus has been known to occur within a narrow equatorial belt from Africa to Asia. In 2007, the virus was detected in Yap Island, the first report that the virus spread outside of Africa and Indonesia to Pacific Islands. In 2014, the virus spread east across the Pacific Ocean to French Polynesia, then to Easter Island. According to the WHO, the virus has continued to spread to the Americas, with the outbreak in Brazil that began in May 2015 and is ongoing. Zika has spread to Mexico, Central America, the Caribbean, and South America, where the outbreak has reached epidemic levels (see figure 2). Recent outbreaks have also been reported in Puerto Rico, as well as the Cape Verde Islands. According to CDC documentation, Zika virus disease is now a nationally notifiable disease. As of February 24, 2016, 107 cases of continental U.S. travel-associated Zika virus disease have been reported, according to CDC. Although CDC documentation states that Zika virus has not yet seen local mosquito-borne spread in the continental United States, some states have mosquito species potentially capable of transmitting the virus. Incidences of mosquito-borne transmission have been reported in the Commonwealth of Puerto Rico, the U.S. Virgin Islands, and American Samoa. The first locally-acquired case of Zika virus disease in Puerto Rico was reported in December of 2015. Through late January of 2016, about 30 additional laboratory-confirmed cases were identified in Puerto Rico, including one pregnant woman. In January of 2016, the CDC issued travel guidance for travel to affected countries, including the use of enhanced precautions for all travelers, as well as the recommendation that pregnant women postpone travel to affected areas. According to CDC documentation, there are a few known routes of transmission of the Zika virus to and among people. These include mosquitoes, mother to child, sexual contact and blood transfusions. The Zika virus is transmitted to people primarily through the bite of infected Aedes species mosquitoes (primarily Aedes aegypti and possibly Aedes albopictus). These are the same mosquitoes that spread dengue and chikungunya viruses. These mosquitoes typically lay eggs in and near standing water in containers like buckets, bowls, animal dishes, flower pots, and vases. They prefer to bite people, and live both indoors and outdoors. Mosquitoes that spread dengue, chikungunya, and Zika are aggressive daytime biters, but also bite at night. Mosquitoes can become infected when they feed on a person already infected with the virus. According to the CDC, the Zika virus is rarely transmitted from an infected mother to child, and there have been no reports of infants contracting the Zika virus through breastfeeding. It is possible but rare that an infected mother would pass the virus to a newborn at delivery. However, an infected mother can pass the Zika virus to her fetus during pregnancy. According to the CDC, it is possible for the Zika virus to be spread by a man to his sexual partners. A few recent cases of Zika virus transmission were reported through sexual contact. In December 2013, during a Zika virus outbreak in French Polynesia, Zika was isolated from the semen of a patient. In one known case of likely sexual transmission, the virus was spread before symptoms developed. The virus appears to be present in semen longer than in blood. Sexual transmission of the disease— acquired outside of the United States—has been reported in the United States. As of February 23, 2016, the CDC and state public health departments are investigating 14 additional reports of possible sexual transmission of the virus, including several involving pregnant women. Zika virus can also be transmitted through blood transfusion, according to U.S. Food and Drug Administration (FDA) documents. While there have been no reports to date of Zika virus entering the U.S. blood supply, the risk of blood transmission is considered high based on the most current scientific research of how Zika virus and similar viruses (i.e. flaviviruses) are spread, as well as recent reports of transfusion-associated infection outside of the United States, according to the FDA. CDC reports that there have been reports of possible blood transfusion transmission cases in Brazil. During the French Polynesian outbreak in 2013, 2.8 percent of blood donors tested positive for Zika. The maximum time the virus remains in the bloodstream is unknown, but scientists estimate that it is less than 28 days. On February 16, 2016, as a safety measure against the emerging Zika virus outbreak, the FDA issued new guidance recommending that blood donors be deferred for four weeks if they have been to areas with active Zika virus transmission, potentially have been exposed to the virus, or have had a confirmed Zika virus infection. While scientific studies have identified Zika viral components in saliva and urine, they did not report disease transmission from those bodily fluids. It is not currently known if infection with the Zika virus causes, facilitates, or is otherwise associated with the development of certain neurologic and auto-immune conditions. Although strongly suspected, a report suggests the causal relation between in-utero exposure to Zika and microcephaly is yet to be established. Scientific literature has identified several possible linkages, including the presence of Zika virus in fetal brain tissue, as well as evidence of the virus crossing the placental barrier, suggesting a causal effect is plausible, but not yet proven. For example, a fetal autopsy identified an abnormally small brain, as well physical markers of developmental delays, along with the Zika virus in the brain. The mother in the case reported an illness with a fever and rash at the end of the first trimester of pregnancy while she was living in Brazil. A retrospective analysis was reported to the WHO in 2015-2016 of a previous outbreak of Zika virus disease in 2013-2014 in French Polynesia, also established elevated numbers of neurological disorders for that outbreak. The potential association of Guillain-Barré syndrome and Zika virus disease was suspected prior to the recent Brazilian Zika disease outbreak. According to the European Center for Disease Control, the 2013 to 2014 French Polynesian outbreak of Zika virus disease was reportedly the largest documented outbreak at that time.