Emerging Infectious Diseases: Preliminary Observations on the Zika Virus Outbreak
Published: 2016-03-02T00:00:00

Fast Facts:

Highlights:
section_title: Why GAO Did This Study
paragraphs: Emerging infectious diseases constitute a clear and persistent threat to the health and well-being of people and animals around the world. The Zika virus, which at present appears to be primarily transmitted to humans by infected mosquitos, can cause symptoms including fever, rash, and joint pain. A large ongoing outbreak is occurring in Brazil that started in May 2015. As of February 24, 2016, over 100 cases of U.S. travel-associated Zika virus disease cases have been reported.
Due to concerns about its potential impact, you asked GAO to present preliminary observations on the Zika virus. This statement addresses (1) the epidemiology and transmission of the Zika virus disease, including reporting on the incidence of disease and what is known about its link to microcephaly; (2) detection and testing methods; (3) methods for mosquito control; and (4) the proposed federal research agenda as it relates to the Zika virus and Zika virus disease.
To report on these questions, GAO reviewed relevant peer-reviewed scientific literature, epidemiological alerts, agency documents, and prior GAO work from 2003-2016 on related topics; consulted experts in the fields of virology, infectious diseases, and vector control, including industry representatives; and interviewed officials of the CDC and NIH.
section_title: What GAO Found
paragraphs: While several countries have reported outbreaks of Zika virus disease—which appear to be primarily transmitted to humans by mosquitos—unanswered questions remain regarding the epidemiology and transmission of the disease. Many factors—including a large number of asymptomatic patients and patients with mild symptoms, and a lack of a consistent international case definition of Zika virus disease—complicate understanding of the virus and may hinder responses to the current outbreak. For example, an estimated 80 percent of individuals infected with the Zika virus may not manifest clinical symptoms. As a result, incidence of the infection may be underestimated. Questions also remain regarding the strength of the association between Zika virus infection and two other conditions: microcephaly and Guillain-Barré syndrome.
A lack of validated diagnostic tests, consistent international case definitions, and trend information may also contribute to difficulty in estimating the prevalence of the virus. The United States uses two diagnostic tests for Zika, and according to the U.S. Centers for Disease Control and Prevention (CDC), while there are no commercially-available diagnostic tests for Zika, an antibody-based test for Zika virus was recently authorized for Emergency Use by the U.S. Food and Drug Administration. Diagnosing Zika virus infection is also complicated because it is difficult to differentiate it from other similar diseases, such as dengue or yellow fever. For example, a person previously infected with dengue could be falsely identified as also having been exposed to the Zika virus (and vice-versa). Moreover, the World Health Organization has acknowledged the need for a consistent case definition—that is, a set of uniform criteria to define the disease for public health surveillance and to determine who is included in the count and who is excluded. Additionally, a lack of pattern and trend data has made surveillance challenging.
Because Zika virus disease cannot yet be prevented by drugs or vaccines, vector (mosquito) control remains a critical factor in preventing and mitigating the occurrence of this disease. There are three methods for mosquito control: (1) standing water treatment, (2) insecticides, and (3) emerging technologies. Mosquito control has been achieved in some locations by methods such as reducing or chemically-treating water sources where mosquitoes breed or mature, or by insecticide dispersal. Emerging technologies, including biological control methods—such as infecting mosquitoes with bacteria— genetically-modified mosquitoes, and auto-dissemination traps, show some promise but are still in development and testing phases.
The National Institutes of Health (NIH) and the CDC have identified several high priority areas of research. Research priorities include basic research to understand viral replication, pathogenesis, and transmission, as well as the biology of the mosquito vectors; potential interactions with co-infections such as dengue and yellow fever viruses; linkages between Zika and the birth defect microcephaly; improving diagnostic tests; vaccine development; and novel vector control methods. These efforts are ambitious, and agencies may face challenges in implementing this agenda.
section_title: What GAO Recommends
paragraphs: GAO is not making recommendations at this time.

section_title: Letter
paragraphs: I am pleased to be here today to discuss our preliminary observations on  Zika virus disease. Zika virus—which at present appears to be primarily  transmitted to humans by infected mosquitoes—can cause symptoms  including fever, rash, conjunctivitis (red eyes), and joint and muscle pain.  Although a possible link between Zika virus disease and microcephaly in  newborn babies, as well as a link with Guillain-Barré syndrome in infected  adults has been hypothesized, to date, the link has not been firmly  established. The Government Accountability Office (GAO) has issued  several reports dealing with preparedness for, detection of, and response  to emerging infectious diseases domestically and internationally, as well  as pandemics. (See appendix 1 for a listing of these reports).
Emerging infectious diseases represent an ongoing threat to the health  and livelihoods of people and animals worldwide. Many advances in  medical research and treatments have been made during the last century,  but infectious diseases are nevertheless a leading cause of death  worldwide. In addition to causing nearly one in five human deaths  worldwide, infectious diseases impose a heavy societal and economic  burden on individuals, families, communities, and countries. Infectious  diseases are a continuous threat for reasons that include: (1)  emergence—at times rapid—of new infectious diseases; (2) re- emergence of previously-known infectious diseases; and (3) persistence  of intractable infectious diseases. According to the National Institutes of  Health (NIH), infectious diseases continue to emerge and evolve.  Changes in human demographics, behavior and land use—among other  factors—bring people into closer and more frequent contact with  pathogens and are contributing to infectious disease emergence. This  may involve exposure to animal or insect carriers of disease. There is  also an increase in the opportunities for pathogens to jump between  animal and human reservoirs. In addition to Zika, other examples of  emerging infectious diseases include: Ebola virus disease, severe acute  respiratory syndrome (SARS), influenza, dengue, and chikungunya,  among others.
Due to concerns about the potential impact of Zika virus disease, you  asked us to present our preliminary observations on several issues  associated with Zika virus disease. This statement addresses issues, if  any, associated with (1) the epidemiology and transmission of the Zika  virus disease, including reporting on the incidence of disease and what is  known about its link to microcephaly; (2) detection and testing methods;  (3) methods for mosquito control; and (4) the proposed federal research  agenda as it relates to the Zika virus and Zika virus disease.
To report on these questions, we reviewed relevant peer-reviewed  scientific literature, epidemiological alerts, agency documents, and prior  GAO work from 2003-2016 on related topics such as disease surveillance  and emerging infectious diseases; consulted experts in the fields of  virology, infectious diseases, and vector (mosquito) control, including  industry representatives; and interviewed officials of the Centers for  Disease Control and Prevention (CDC) and the National Institutes of  Health (NIH).
The work upon which this testimony is based was conducted from  February through March 2016 in accordance with generally accepted  government auditing standards. Those standards require that we plan  and perform the audit to obtain sufficient, appropriate evidence to provide  a reasonable basis for our findings and conclusions based on our audit  objectives. We believe that the evidence obtained provides a reasonable  basis for our findings and conclusions based on our audit objectives.
subsections: section_title: Background
paragraphs: 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).
subsections: section_title: U.S. Role in Global Disease Surveillance
paragraphs: 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.
section_title: The Epidemiology and Transmission of the Zika Virus are Not Fully Understood and Accurate Information on the Incidence is Lacking
paragraphs: 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.
subsections: section_title: Several Countries Have Reported Outbreak of Zika Virus Disease
paragraphs: 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.
section_title: A Number of U.S. Travelers Have Been Infected with the Zika Virus
paragraphs: 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.
section_title: Questions Remain about the Transmission of the Zika Virus
paragraphs: 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.
subsections: section_title: Questions Remain Regarding the Link between Zika Virus Infection and Neurological and Auto-Immune Disorders
paragraphs: 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. According to the  European Center for Disease Control, over 8,000 suspected cases of  Zika Virus infection had been reported by February 2014. Notably, there  were nearly 40 cases of Guillain-Barré syndrome reported, with all cases  following disease episodes compatible with Zika virus infection.  Historically, there had been 10 or fewer cases of Guillain-Barré syndrome  in Polynesia annually. The European Center for Disease Control stated  that further investigations could be conducted to establish the relationship  between neurological and auto-immune complications and Zika virus  infection.
section_title: Mild Symptoms and Asymptomatic Cases May Lead to Underestimation
paragraphs: Researchers have reported that an estimated 80 percent of the  individuals infected with the Zika virus are asymptomatic, that is, they  have the virus but do not manifest clinical symptoms. Since diagnosis of  suspected Zika virus disease is often based on clinical symptoms, and in  light of the fact that clinical symptoms are usually non-existent or mild,  experts told us that many individuals who are infected with the Zika virus  may not seek medical care, and thus are not counted as a case, resulting  in significant underestimation of the true incidence of infection.
section_title: Lack of Consistent International Case Definitions May Lead to Inaccurate Count
paragraphs: An accurate count of the number of Zika virus disease cases requires a  consistent case definition, or set of uniform criteria to define the disease  for public health surveillance and to determine who is included in the  count and who is excluded. However, establishing a definition is  problematic for Zika virus disease. If Zika cases are diagnosed based on  serology data, then the incidence count may include people who have  been infected with the virus, but do not show clinical symptoms. On the  other hand, if cases are defined by clinical symptoms only, with no  serology testing, then the incidence could be higher or lower than that  count obtained from serology testing only, because people who present  with clinical symptoms may or may not actually test positive for Zika virus.
According to the WHO Zika Response Strategy, there is currently a need  to establish a uniform case definition for Zika virus disease, as well as  historical rates, or baselines, for associated conditions. The Council of  State and Territorial Epidemiologists currently has a case definition for  Zika virus disease—under arboviral diseases—with two tiers: a “probable  case” definition based on clinical signs and symptoms as well as the  presence of certain anti-Zika antibodies, and a “confirmed case” definition  for laboratory-confirmed cases based on laboratory analysis. However,  because other countries may be using different testing protocols, it is  unclear whether their results would be consistent with the CDC case  definitions, complicating epidemiological analysis. Engaging international  cooperation to establish uniform case definitions and baselines for  diagnosing Zika virus disease and microcephaly can facilitate discovery of  modes of transmission and causal links between Zika virus disease and  microcephaly or Guillain-Barré syndrome.
section_title: Lack of a Case Definition of Microcephaly May Complicate Linkage with Zika Virus Disease
paragraphs: When the WHO declared a Public Health Emergency of International  Concern on February 1, 2016, it acknowledged that there was no  international standard surveillance case definition for microcephaly.  Problems with changing case definitions, lack of sufficient information on  underlying causes and brain pathology, and lack of baseline data make it  difficult to accurately determine the level of increase of microcephaly in  Brazil, and how much is due to the Zika virus.
Some researchers offered several possible explanations for the observed  increase in microcephaly cases, other than actual increase of cases as a  result of Zika virus infection. First, because of the recent attention,  newborn babies with visible cranial deformities are likely to be fast- tracked for in-depth examination. This temporal increase in suspected  cases of microcephaly could also be distorted given both raised  awareness with more children than usual being measured and reported,  and the changing definition of microcephaly over time. Although there is  evidence of an increased number of cases of microcephaly in Brazil,  these authors demonstrated that the number of suspected cases relied on  a screening test that had very low specificity and therefore overestimated  the actual number of cases.
section_title: Lack of Validated Diagnostics Tests May Mask the Incidence of Zika Virus Disease
paragraphs: According to the CDC, there are currently two Zika diagnostic tests  available in the United States: reverse transcription polymerase chain  reaction (RT-PCR) and Immunoglobulin M (IgM) followed by the Plaque  Reduction Neutralization Test (PRNT) test. The current RT-PCR test  can detect infection only during the period of illness when the virus is  present. According to an NIH official, the PRNT diagnostic test is the most  specific for antibody detection, but is cumbersome and not suitable for  screening a large number of individuals.
When detecting antibodies, diagnosing cases of Zika virus disease and  differentiating it from other diseases caused by other flaviviruses, such as  dengue or yellow fever, is difficult if someone has been infected by  another flavivirus. Some tests for Zika virus antibodies suffer from cross- reactivity with antibodies to similar viruses, such as from dengue virus  disease, meaning that tests using these antibodies for detection are not  specific for the Zika virus. For example, a person previously infected with  another flavivirus such as dengue could be falsely identified as also  having been exposed to the Zika virus (and vice-versa). In addition, new  outbreaks like Zika may not have known patterns or trends, making  effective surveillance challenging. For example, after the onset of illness,  Zika virus remains in the blood for about 5-7 days, according to the CDC.  After this period, called viremia, diagnosis of Zika virus disease at this  time relies on detection of antibodies against the Zika virus. Since  antibodies in the blood may persist longer than the virus, a positive result  for antibodies against the Zika virus indicates only that the patient was  previously exposed to the Zika virus. Thus, the window for detecting the  actual virus is small. It is not clear whether an antibody test could  determine how long ago the patient was exposed.
According to the CDC, while there are no commercially-available  diagnostic tests for Zika, an antibody-based test for the Zika virus (Zika  MAC-ELISA) was recently authorized for Emergency Use by the FDA.  One of the main limitations of this test, among others, is its inability to  differentiate between infection with Zika and other closely related  flaviviruses such as dengue. This test in its current form may confuse the  practitioners because of its lack of specificity. Since closely related  flaviviruses such as dengue may also be present in Zika outbreak  countries, the utilization of this assay could wrongly identify non-Zika- virus associated infections, thus putting extra burden on the laboratory  and health care systems, and distort the epidemiological analyses.
Adding to the limitations of these diagnostic systems are limited numbers  of facilities able to perform definitive confirmatory testing, particularly in  the developing world. The WHO is undertaking an analysis of diagnostics  under development, developing target product profiles, facilitating the  preparation and characterization of reference reagents, and setting up an  Emergency Use Assessment and Listing mechanism for priority Zika  diagnostics.
section_title: Various Methods of Mosquito Control Exist and Novel Approaches Are Underway
paragraphs: Because Zika virus disease cannot yet be prevented by drugs or  vaccines, vector (mosquito) control remains a critical factor in mitigating  risks associated with this disease. The Aedes aegypti and Aedes  albopictus mosquitoes are present around the world, as well as in the  United States. Figure 3 shows a predicted distribution and intensity of the  Aedes aegypti and Aedes albopictus mosquitoes, respectively, and  indicates that the southeastern United States, particularly the Gulf Coast  states, could be at risk of exposure in the near future. Figure 4 shows the  approximate distribution of Aedes aegypti and Aedes albopictus  mosquitoes in the United States in more detail.
There are both large scale and personal methods for mosquito control.  We provide a brief preliminary overview of some population-scale control  methods identified in the literature, agency documents, and interviews  with industry officials and academicians, which include three potentially- overlapping categories: (1) standing water treatment, (2) insecticides, and  (3) emerging technologies. For some of these emerging techniques, their  effectiveness remains to be demonstrated, but they have the potential to  be additional tools in mosquito control. Personal methods, such as use of  repellents, nets or long-sleeved clothing and staying indoors in air- conditioned locations are out the scope of this report.
subsections: section_title: Standing Water Treatment
paragraphs: Standing water treatment for mosquito control can be achieved by the  physical reduction of bodies of water or by treating the water with  chemicals that kill mosquito larvae or interfere with their development.  According to CDC documentation, these treatments include use of certain  bacteria or insecticides that mimic mosquito hormones, which prevents  mosquitoes from maturing or kills them as larvae. Another method  involves coating water with a thin film of oil to suffocate immature larvae.
section_title: Insecticide Dispersal
paragraphs: According to CDC documentation, insecticide dispersal relies on various  techniques such as space spraying by trucks or aircraft, or residual  spraying, which entails coating surfaces with insecticide. Spraying is one  method currently used in the United States. CDC documentation and  scientific literature have established that in the long-term, the  effectiveness of spraying may be diluted due to insecticide resistance,  concerns over environmental exposure, and questionable efficacy of  externally-delivered wide-area fogging or spraying. Additionally, the WHO  notes that reactive space spraying during emergencies has a low impact  unless integrated with other control strategies. Researchers are  developing new chemicals that are more targeted towards mosquitoes,  and are attempting to alleviate human toxicity issues.
The use of insecticides as control methods effectively reduced mosquito- borne diseases, including malaria and yellow fever, in most of the world in  the 1940s-1960s. The WHO determined that maintaining vector control  after a disease subsides is complicated by dwindling resources. Indeed,  by the 1980s-1990s, many dangerous vector-borne diseases re-emerged  or spread to new regions.
Additionally, the spread of some diseases, such as dengue virus disease,  can be attributed to a combination of mosquito, viral, and human factors.  To address the resulting complexities of such disease transmissions, the  WHO uses “Integrated Vector Management,” which leverages multiple  control methods based on surveillance and evaluation of involved insects  and disease epidemiology.
section_title: Emerging Technologies
paragraphs: Emerging technologies include (1) use of biological control methods, (2)  genetically-modified mosquitoes, and (3) auto-dissemination traps. Based  on scientific literature, these technologies show some promise in studies  to overcome issues associated with use of insecticides, such as  insecticide resistance. Many of these methods have been tested in  smaller-scale controlled field trials internationally. We have not done an  independent, comprehensive evaluation of these technologies, due to  time limitations.
subsections: section_title: Biological Control Methods
paragraphs: Biological control methods include introducing natural predators of  mosquitoes or their eggs and using bacteria to prevent disease  transmission to humans. For example, certain small crustaceans and  certain fish eat mosquito larvae. The suitability of this approach for the  Zika virus is uncertain because the primary mosquito species identified  for Zika transmission are the Aedes aegypti and Aedes albopictus, which  can breed in very small volumes of water, such as those found in tin cans  or in plates under potted plants.
Scientific literature has identified another approach—using bacteria to  reduce disease transmission from mosquitoes to humans. This bacteria,  called Wolbachia, can be transferred from mosquitoes to their eggs,  thereby propagating this effect to future generations. This tactic has been  demonstrated in laboratory environments and is undergoing field trials  internationally, particularly in areas affected by the dengue virus.
section_title: Genetically Modified Mosquitoes
paragraphs: Control of the disease-transmitting mosquito population using genetically  modified mosquitoes can be potentially achieved in different ways.  Some genetically-modified mosquitoes are engineered with a “lethal”  gene that constantly makes a protein that kills the mosquito larvae.  According to one company creating these mosquitoes, the use of  genetically modified mosquitoes allows for population control by  introducing male genetically-modified mosquitoes that transfer this lethal  gene to the female mosquito’ s eggs. As a result, mosquito larvae with the  inherited lethal gene die. The company claims it has achieved a 90  percent reduction in mosquito populations using its method of releasing  the modified male mosquitoes 1-3 times weekly over a period of months.  The modified mosquitoes do not persist in the environment, as released  mosquitoes generally die out on their own. Given the estimated 200- meter range of a male mosquito during its lifetime, scalability may be  challenging. Another genetically-modified mosquito method incorporates  viral resistance into mosquitoes, with the goal of replacing existing  populations of mosquitoes with one less capable of disease transmission,  rather than reducing the number of mosquitoes. Scientific literature  indicates there may be public opposition to release of genetically-modified  mosquitoes for either procedure due to uncertainties about their effect on  people and the environment, or other unknown consequences.
section_title: Auto-dissemination Traps
paragraphs: Mosquito control by auto-dissemination traps functions similarly to  insecticides, but relies on containers coated with similar chemicals. After  a mosquito lands on these containers, they are contaminated with the  chemicals and subsequently transfer them to the location where they lay  eggs, which may result in larval death. In the case of the Aedes aegypti  mosquito, WHO documentation indicates these locations tend to be small  containers, so auto-dissemination is particularly suited to these  mosquitoes. Auto-dissemination traps have shown 42-98 percent  decreases in Aedes aegypti mosquito population in field trials.
section_title: Federal Priority Research Agenda is Ambitious and Implementation of Some Research May be Challenging
paragraphs: NIH and CDC have identified areas of high priority for research related to  the Zika virus. In addition, the Administration’s $1.9 billion emergency  funding request to combat the spread of the Zika virus is intended to  provide resources to both NIH and CDC to this end. If approved, the NIH  would receive $130 million to support vaccine development and other  work related to Zika and other mosquito-borne diseases such as  chikungunya. The CDC would receive $828 million, including $225 million  for grants and technical assistance, in part to expand mosquito or vector  control. The FDA would receive $10 million, in part to support the  approval of new diagnostic tests and evaluation of treatment efficacy.
NIH has identified areas of high priority including:
Basic research to understand viral replication, pathogenesis, and  transmission, as well as the biology of the mosquito vectors; potential  interactions with co-infections such as dengue and yellow fever  viruses; animal models of Zika virus infection; and novel vector control  methods; and
Pursuing Zika virus research to develop sensitive, specific, and rapid  clinical diagnostic tests; drug treatments for Zika virus as well as  broad spectrum therapeutics that treat multiple flaviviral infection; and  effective vaccines and vaccination strategies.
On February 5th, 2016, several NIH institutes issued a notice to  researchers indicating NIH’ s interest in supporting research to  understand transmission of the Zika virus, optimal screening and  management in pregnancy, and the mechanisms by which the Zika virus  affects the developing nervous system, including potential links to  microcephaly. This notice was followed by a Funding Opportunity  Announcement issued on February 19th, 2016, to create an expedited  mechanism for funding exploratory and developmental research projects  on these topics.
The CDC has identified priority areas of research focus on Zika including:
Determining the link between Zika virus infections and the birth defect  microcephaly and measuring changes in incidence rates of the birth  defect over time; Improving diagnostics for the Zika virus, including advanced methods  to refine tests and support advanced developments for vector control;  and
Enhancing international capacity for virus surveillance, expanding  laboratory testing, and health care provider testing in countries at  highest risk of Zika virus outbreaks.
These research activities are intended to supplement other activities for  response, readiness and surveillance.
The priority research areas identified by NIH and CDC are ambitious and  agencies may face some challenges in implementing this agenda,  including:
Given that there are few known cases in the United States, NIH and  CDC may have to rely on the cooperation of other countries with  sufficient number of cases in order to carry on the proposed research.  However, data from other countries may be different due to different  definitions of Zika virus disease and microcephaly.
Demonstrating the link between the Zika virus and microcephaly may  depend not only on the presence of the virus, but also on  environmental and nutritional factors. In addition, shifting case  definitions and a lack of baseline data makes it difficult to determine  the increase, if any, in microcephaly and how much can be attributed  to the Zika virus.
The presence of a high percentage of asymptomatic cases makes it  difficult to conduct epidemiological studies, both in identifying exposed  and unexposed individuals for case control studies.
Prior infection or co-infection with another virus such as dengue may  complicate any analyses.
NIH officials told us that prior work on similar viruses has allowed them to  make rapid progress on both a DNA-based vaccine (based on prior work  on West Nile Virus), and a live attenuated virus vaccine modeled after the  dengue virus vaccine that is currently in phase 3 clinical trials in Brazil.  NIH officials told us that prior “platform” work on similar viruses has  expedited response to the Zika outbreak, and in the development of  diagnostic tests and vaccines.
With regard to the dengue vaccine, NIH provided us with the following  timeline:  It has taken more than 16 years, and trials are not yet complete. NIH  officials told us that given their past experience with the development of  vaccine for dengue fever, a vaccine for Zika could be ready for use in an  emergency situation in three to four years, in the best case scenario.  However, when we asked NIH about this estimate, NIH stated that the  National Institute of Allergy and Infectious Diseases plans to begin a  Phase I clinical trial within this calendar year. If a candidate vaccine  shows promise in Phase I testing, additional clinical testing could begin by  2017 in countries where the disease is found, if the outbreak is still  ongoing. The progress of these additional tests, and whether they can  contribute to successful licensure, depends on a number of factors,  including scientific and technical progress, as well as the size of any  ongoing Zika outbreaks during clinical testing. For this reason, it is difficult  to provide an exact estimate for the time it will take to develop a Zika  vaccine from preclinical studies through clinical testing and licensure.
Zika virus disease poses new challenges to vaccine development and  testing. This disease has specific and important implications for pregnant  women. There are substantial knowledge gaps in current understanding  of Zika, irrespective of the affected population. Since Zika virus disease is  associated with, and may cause, adverse fetal outcomes, pregnant  women are at particular risk and may benefit from measures such as  vaccines. There are several current scientific and structural barriers to  developing and testing vaccines for pregnant women. Overcoming  these barriers may extend timeframes for vaccine testing and approval.  The information we have from NIH and our prior work suggests that  development of a Zika virus vaccine may take longer than anticipated by  NIH.
section_title: Appendix I: Related GAO Work
paragraphs: Biosurveillance: Ongoing Challenges and Future Considerations for DHS  Biosurveillance Efforts. GAO-16-413T. Washington, D.C.: February 11,  2016.
Air Travel and Communicable Diseases: Comprehensive Federal Plan  Needed for U.S. Aviation System’s Preparedness. GAO-16-127.  Washington, D.C.: December 16, 2015.
Emerging Animal Diseases: Actions Needed to Better Position USDA to  Address Future Risks. GAO-16-132. Washington, D.C.: December 15,  2015.
Climate Change: HHS Could Take Further Steps to Enhance  Understanding of Public Health Risks. GAO-16-122. Washington, D.C.:  October 5, 2015.
Biosurveillance: Challenges and Options for the National Biosurveillance  Integration Center. GAO-15-793. Washington, D.C.: September 24, 2015.
Biosurveillance: Additional Planning, Oversight, and Coordination Needed  to Enhance National Capability. GAO-15-664T. Washington, D.C.: July 8,  2015.
Federal Veterinarians: Efforts Needed to Improve Workforce Planning.  GAO-15-495. Washington, D.C.: May 26, 2015.
Biological Defense: DOD Has Strengthened Coordination on Medical  Countermeasures but Can Improve Its Process for Threat Prioritization.  GAO-14-442. Washington, D.C.: May 15, 2014.
National Preparedness: HHS Has Funded Flexible Manufacturing  Activities for Medical Countermeasures, but It Is Too Soon to Assess  Their Effect. GAO-14-329. Washington, D.C.: March 31, 2014.
National Preparedness: HHS Is Monitoring the Progress of Its Medical  Countermeasure Efforts but Has Not Provided Previously Recommended  Spending Estimates. GAO-14-90. Washington, D.C.: December 27, 2013.
Homeland Security: An Overall Strategy Is Needed to Strengthen Disease  Surveillance in Livestock and Poultry. GAO-13-424. Washington, D.C.:  May 21, 2013.
National Preparedness: Efforts to Address the Medical Needs of Children  in a Chemical, Biological, Radiological, or Nuclear Incident. GAO-13-438.  Washington, D.C.: April 30, 2013.
Influenza: Progress Made in Responding to Seasonal and Pandemic  Outbreaks. GAO-13-374T. Washington, D.C.: February 13, 2013.
Homeland Security: Agriculture Inspection Program Has Made Some  Improvements, but Management Challenges Persist. GAO-12-885.  Washington, D.C.: September 27, 2012.
Biosurveillance: Nonfederal Capabilities Should Be Considered in  Creating a National Biosurveillance Strategy. GAO-12-55. Washington,  D.C.: October 31, 2011.
National Preparedness: Improvements Needed for Acquiring Medical  Countermeasures to Threats from Terrorism and Other Sources.  GAO-12-121. Washington, D.C: October 26, 2011.
Homeland Security: Challenges for the Food and Agriculture Sector in  Responding to Potential Terrorist Attacks and Natural Disasters.  GAO-11-946T. Washington, D.C.: September 13, 2011.
Homeland Security: Actions Needed to Improve Response to Potential  Terrorist Attacks and Natural Disasters Affecting Food and Agriculture.  GAO-11-652. Washington, D.C.: August 19, 2011.
Influenza Vaccine: Federal Investments in Alternative Technologies and  Challenges to Development and Licensure. GAO-11-435. Washington,  D.C.: June 27, 2011.
Influenza Pandemic: Lessons from the H1N1 Pandemic Should Be  Incorporated into Future Planning. GAO-11-632. Washington, D.C: June  27, 2011.
Live Animal Imports: Agencies Need Better Collaboration to Reduce the  Risk of Animal-Related Diseases. GAO-11-9. Washington, D.C.:  November 8, 2010.
Biosurveillance: Efforts to Develop a National Biosurveillance Capability  Need a National Strategy and a Designated Leader. GAO-10-645.  Washington, D.C.: June 30, 2010.
Veterinarian Workforce: The Federal Government Lacks a  Comprehensive Understanding of Its Capacity to Protect Animal and  Public Health. GAO-09-424T. Washington, D.C.: February 26, 2009.
Influenza Pandemic: Sustaining Focus on the Nation’s Planning and  Preparedness Efforts. GAO-09-334. Washington, D.C: February 26,  2009.
Veterinarian Workforce: Actions Are Needed to Ensure Sufficient  Capacity for Protecting Public and Animal Health. GAO-09-178.  Washington, D.C.: February 4, 2009.
Influenza Pandemic: HHS Needs to Continue Its Actions and Finalize  Guidance for Pharmaceutical Interventions. GAO-08-671. Washington,  D.C.: September 30, 2008.
Emergency Preparedness: States Are Planning for Medical Surge, but  Could Benefit from Shared Guidance for Allocating Scarce Medical  Resources. GAO-08-668. Washington, D.C.: June 13, 2008.
Influenza Pandemic: Efforts Underway to Address Constraints on Using  Antivirals and Vaccines to Forestall a Pandemic. GAO-08-92.  Washington, D.C.: December 21, 2007.
Influenza Vaccine: Issues Related to Production, Distribution, and Public  Health Messages. GAO-08-27. Washington, D.C: October 31, 2007.
Global Health: U.S. Agencies Support Programs to Build Overseas  Capacity for Infectious Disease Surveillance. GAO-08-138T. Washington,  D.C.: October 4, 2007.
Agricultural Quarantine Inspection Program: Management Problems May  Increase Vulnerability of U.S. Agriculture to Foreign Pests and Diseases.  GAO-08-96T. Washington, D.C.: October 3, 2007.
Global Health: U.S. Agencies Support Programs to Build Overseas  Capacity for Infectious Disease Surveillance. GAO-07-1186. Washington,  D.C.: September 27, 2007.
Influenza Pandemic: DOD Combatant Commands’ Preparedness Efforts  Could Benefit from More Clearly Defined Roles, Resources, and Risk  Mitigation. GAO-07-696. Washington, D.C.: June 20, 2007.
Influenza Pandemic: Efforts to Forestall Onset Are Under Way; Identifying  Countries at Greatest Risk Entails Challenges. GAO-07-604. Washington,  D.C.: June 20, 2007.
Avian Influenza: USDA Has Taken Important Steps to Prepare for  Outbreaks, but Better Planning Could Improve Response. GAO-07-652.  Washington, D.C.: June 11, 2007.
Influenza Pandemic: DOD Has Taken Important Actions to Prepare, but  Accountability, Funding, and Communications Need to be Clearer and  Focused Departmentwide. GAO-06-1042. Washington, D.C.: September  21, 2006.
Homeland Security: Management and Coordination Problems Increase  the Vulnerability of U.S. Agriculture to Foreign Pests and Disease.  GAO-06-644. Washington, D.C.: May 19, 2006.
Influenza Vaccine: Shortages in 2004-05 Season Underscore Need for  Better Preparation. GAO-05-984. Washington, D.C.: September 30, 2005.
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