Good quality diagnostic tests that are  fit for purpose and can provide accurate results can help in reducing the  burden of infectious diseases. Since the Zika virus was a newly emerging  infectious disease threat in the United States, and relatively little was  known about the virus prior to 2016, CDC and the states were not fully  equipped with information and resources needed for a rapid response at  the outset of the recent outbreaks. What Is Known about the Epidemiology of Zika Virus

Knowledge about Zika virus epidemiology has increased in the past year,  including information about Zika virus disease incidence and distribution  of cases and its associated adverse health outcomes. Zika Virus Cases Reported in the U.S. States and Territories

Between January 1, 2015 and April 5, 2017, reported Zika virus disease  cases numbered 5,197 in the United States. What Is Not Known about the Epidemiology of Zika Virus

While much has been learned about the epidemiology of Zika virus, many  unknowns remain, including  the total number of infections;  the biological mechanisms, risks, reasons for geographic differences,  and full spectrum of outcomes associated with maternal-fetal  transmission;  the presence and duration of the virus in different bodily fluids;  the role of prior Zika virus infections or exposure to other related  flaviviruses; and  the full spectrum of outcomes of Zika virus infection. Characteristics of Different Diagnostic Tests Varied, Manufacturers and Users Faced Several Challenges, and FDA and CDC Did Not Consistently Communicate Sufficient Information

Authorized diagnostic tests used for the recent Zika virus outbreak varied  in their performance and operational characteristics. Diagnostic  test users also encountered challenges, including determining the most  accurate test to use, comparing clinical performance characteristics  across tests, and obtaining equipment required to conduct authorized  tests. Moreover, CDC and FDA did not consistently  communicate sufficient information about Zika virus diagnostic tests that  could have enabled users to more easily identify the test that could detect  the smallest amount of virus in a sample. These authorized diagnostic  tests for the Zika virus vary in their performance and operational  characteristics. 6). Manufacturers and Users Faced Several Challenges in Developing and Using Zika Diagnostic Tests

We identified five challenges that manufacturers of diagnostic tests faced  related to Zika virus diagnostic testing, research, and development, and  regulatory approval: (1) biological aspects of the virus and the immune  response, including low levels of virus in the bodily fluids of infected  patients for short periods of time and the cross-reactivity of antibodies to  other flaviviruses, (2) difficulty in accessing well-characterized clinical  samples, (3) getting access to EUA tests for use as a comparator assay,  (4) gaining cooperation with international entities, and (5) challenges  interacting with FDA during review. Mosquito Control Methods Have Strengths and Limitations, and Federal Agencies Face Several Challenges Assisting These Efforts

		Mosquito Control Methods in the United States Are Often Combined Under Integrated Vector Management

Types of mosquito control methods available in the United States include:  (1) physical control, or nonchemical mosquito control, (2) larval mosquito  control, (3) adult mosquito control, and (4) personal protection. Each of these physical control methods has strengths and limitations. According to this study, this method may reduce mosquito-borne dengue  transmission by about 90 percent. Surveillance Helps Inform Mosquito Control Efforts. According to  CDC documentation, the agency developed technical guidance and  provides funding and technical assistance to support state and local  mosquito control activities. In response to our recommendation to establish a transparent  process to provide CDC diagnostic tests to manufacturers, HHS  stated that CDC will work with its existing Technology Transfer  Office to implement a transparent process for providing  manufacturers with approved CDC diagnostic assays. Blow, Ph.D., Director, Armed Forces Pest Management Board,  Defense Pest Management, Department of Defense  Michael Callahan, M.D., M.S.P.H., Director of Translational Therapeutics,  Vaccine, and Immunotherapy Center, Massachusetts General Hospital,  Harvard Medical School  Joseph M. Conlon, M.Sc., BCE, Technical Adviser, American Mosquito  Control Association  Durland Fish, Ph.D., Honorary D.Sc., Emeritus Professor, Yale School of  Public Health  Eva Harris, Ph.D., Professor, Division of Infectious Diseases and  Vaccinology, School of Public Health and Director, Center for Global  Public Health, University of California at Berkeley  Anna M. Likos, M.D., M.P.H., State Epidemiologist and Interim Deputy,  Secretary for Health, Florida Department of Health  Jorge L. Munoz-Jordan, Ph.D., Chief, Molecular Diagnostics and  Research Laboratory, Division of Vector Borne Infectious Diseases,  Dengue Branch, Centers for Disease Control and Prevention  Benjamin Pinsky, M.D., Ph.D., Medical Director, Clinical Virology  Laboratory, Stanford University School of Medicine  Brenda Rivera-García, D.V.M., M.P.H., Territorial Epidemiologist, Puerto  Rico Department of Public Health  Alfonso J. Rodriguez-Morales, M.D., Ph.D., Chair, Colombian  Collaborative Network of Zika (RECOLZIKA)

Appendix II: Objectives, Scope, and Methodology

The objectives of this review were to (1) provide information on what is  known and not known about the epidemiology of the Zika virus and  determine the challenges, if any, in conducting surveillance and  epidemiological studies, (2) determine the characteristics of different Zika  virus authorized diagnostic tests and any challenges manufacturers and  users faced, and the extent to which Food and Drug Administration (FDA)  and Centers for Disease Control and Prevention (CDC) followed their own  communication guidance during the U.S. outbreak, and (3) identify  available mosquito control methods, describe their strengths and  weaknesses, and identify any challenges federal agencies and others  face in assisting mosquito control efforts. We reviewed relevant documentation such as, FDA’s guidance  to the manufacturers, product labels, and agencies reports on the  epidemiology of the Zika virus, and interviewed officials from key federal  agencies that are involved in the domestic Zika virus response. With the  assistance of the National Academy of Sciences, we convened a meeting  with 16 experts to discuss issues related to the Zika virus outbreak. Influenza: Progress Made in Responding to Seasonal and Pandemic  Outbreaks.
Why GAO Did This Study

Zika virus disease can cause adverse pregnancy and neurological outcomes. Given this ongoing threat, GAO was asked to evaluate progress made and challenges faced by federal agencies in responding to the Zika virus outbreak in the United States.
GAO examined (1) information on what is known and not known about the epidemiology of the Zika virus, and any challenges with conducting surveillance and epidemiological studies, (2) characteristics of different diagnostic tests authorized during the outbreak, challenges test manufacturers and users faced, and the extent to which FDA and CDC followed their own communication guidance, and (3) the strengths and limitations of available mosquito control methods, and challenges federal agencies face supporting these efforts.
GAO reviewed literature and agency documentation, and interviewed federal and state officials about the Zika virus and the U.S. response. GAO also convened an expert meeting with the assistance of the National Academy of Sciences to discuss various issues surrounding the response to the Zika virus.

What GAO Found

Since Zika virus disease was a newly emerging disease threat in the United States, and relatively little was known about the Zika virus prior to the 2016 U.S. outbreak, the Centers for Disease Control and Prevention (CDC), and the states were not fully equipped with needed information and resources at the beginning of the outbreak. This presented several challenges for Zika virus disease surveillance and research efforts, such as challenges related to establishing a national definition for reporting cases. Knowledge about Zika virus epidemiology has increased in the past year, including information about Zika virus disease incidence and distribution of cases, and its associated adverse health outcomes. Most of the 5,197 Zika virus disease cases reported by April 5, 2017 in the United States were associated with travel from affected areas outside the continental United States. Only two states had disease cases of local, mosquito-borne transmission—216 were in Florida and 6 in Texas. While much has been learned about the epidemiology of the Zika virus, many unknowns remain, including the actual number of infections and the full spectrum of outcomes.
The 16 Zika virus diagnostic tests authorized during the outbreak varied in their performance and operational characteristics. For example, they varied in their ability to detect the virus and provide accurate results. In developing the diagnostic tests, manufacturers faced challenges in several areas, including access to clinical samples and other authorized diagnostic tests for comparison purposes. Users of the tests also encountered challenges, including determining the most accurate test to use, and obtaining equipment needed to conduct the tests. Some manufacturers raised concerns about the difficulty in developing diagnostic tests that met the Food and Drug Administration's (FDA) requirements for Emergency Use Authorization and some users expressed concerns about selecting tests amongst those authorized. GAO also determined that CDC and FDA did not follow some of their guidance in communicating with users of diagnostic tests, including providing clear information that would have enabled users to more easily compare performance across different tests.
Mosquito control programs in the United States are implemented at state and local levels and are critical to mitigating the risks associated with the Zika virus. Control methods include applying pesticides, reducing available water sources for breeding, and using personal protection. Each method has its strengths and limitations. For example, some control methods are more effective at reducing mosquito populations while others help prevent individuals from mosquito bites. Similarly, each method has some limitations, for example, there is varied public opposition to the use of certain pesticides. CDC supports state and local mosquito control activities primarily by providing guidance on mosquito control methods and funding to support certain mosquito control efforts. Challenges federal agencies faced in supporting these activities include sustaining staff expertise in mosquito control during periods when there are no outbreaks, funding constraints, and effectively communicating information about the geographical distribution of mosquitoes that transmit the Zika virus.

What GAO Recommends

GAO is making five recommendations to FDA and CDC, including that CDC establish a transparent process for providing test manufacturers access to diagnostic tests and FDA and CDC provide information to help ensure that users of diagnostic tests can compare performance. Agencies agreed with four recommendations but raised some concerns with the fifth. GAO has addressed these concerns in the report.