Article : Zika Virus 6 Months Later

Thomas R. Frieden, MD, MPH; Anne Schuchat, MD; Lyle R. Petersen, MD, MPH


On January 15, 2016, the Centers for Disease Control and Prevention advised pregnant women not to travel to areas where the Zika virus was spreading. Six months later, more than 60 countries or territories have reported new local transmission of Zika. By August 4, 2016, nearly 1700 cases of travel-associated Zika infection, including 479 in pregnant women, had been reported in the continental United States; Puerto Rico is experiencing rapid and extensive spread of the epidemic.1 Florida has documented 5 symptomatic and 8 asymptomatic locally acquired Zika infections in a 6-block area north of downtown Miami. Comprehensive mosquito control efforts, including reduction of standing water, provision of repellants containing diethyltoluamide (DEET), and application of pyrethroid insecticides and larvicides using backpack sprayers and trucks to eliminate adult and larval forms of mosquitoes, were initiated on confirmation of the first cases. Persistent findings of Aedes aegypti mosquitoes led to a decision to also use aerial spraying with naled and larvicide within 3 days of documentation of the risk of ongoing Zika transmission.

The association between Zika infection (both symptomatic and asymptomatic) and serious birth defects, including microcephaly, has been confirmed.2 Sexual transmission of Zika from both male and female partners can occur, and the virus may be able to remain viable in semen for months. The competent vectors—A aegypti as well as the less efficient vector Aedes albopictus—put 30 and 41 US states, respectively, at risk for local mosquito-borne transmission of Zika. Risk of microcephaly after Zika infection early in pregnancy may range from 1% to 13%; the full spectrum of congenital Zika virus syndrome is not known, nor is it known whether infants exposed to Zika during pregnancy who appear healthy at birth will have neurologic or other problems.

Infection can also rarely be associated with other complications, including Guillain-Barré syndrome and severe thrombocytopenia, although causality is uncertain. In July 2016, report of an elderly man’s death in Utah after infection by Zika during travel was soon followed by the recognition of Zika infection in a family member who helped care for the individual shortly before the relative’s death. Transfusion-associated Zika virus transmission reported in Brazil has prompted blood donation screening in selected areas of the United States.

Almost as surprising as the rapid growth in knowledge about Zika is the disparity in presentation of Zika infection and concern about the virus. For the public health community, Zika represents an unprecedented emergency. Never before, to our knowledge, has a mosquito-borne virus been associated with human birth defects or been capable of sexual transmission. The effects of brain damage due to microcephaly and consequences of other Zika-related birth defects are likely devastating, lifelong, and costly. However, most people infected with Zika have no symptoms, and concern among the general public has been muted even in some affected locales. Zika is a silent epidemic. Other vector-borne pathogens—dengue virus and chikungunya virus—cause painful symptoms and are easily recognized by affected communities. The consequences of widespread Zika transmission only become evident many months after infection, when women infected with Zika earlier in their pregnancies deliver infants with severe neurologic complications. Northeastern Brazil has now recorded more than 1700 cases of microcephaly attributed to Zika,3 and women infected in other Latin American areas are just starting to deliver infants with evidence of Zika-related complications.4

Puerto Rico is in the midst of a large epidemic of Zika. Experience with chikungunya, another newly introduced virus spread by A aegypti, as well as blood screening, case reports, and testing of pregnant women, suggest that 25% of Puerto Rican individuals, including an estimated 6000 to 11 000 pregnant women, may be infected by Zika this year. The approach to prevent harm from Zika requires action at both individual and community levels and includes protection against mosquito bites; screening the blood supply; ensuring access to voluntary, effective contraception; and effective vector control. Effective action in Puerto Rico has been complicated by lingering suspicions related to historical activities, competing priorities, and the speed needed to bring integrated vector management to scale. Misinformation has clouded public understanding of the best ways to protect individuals and communities.

Pregnant women should avoid travel to areas with Zika transmission. People can reduce the risk of mosquito bites (including during travel and for the 3 weeks after return to reduce the risk of local spread from asymptomatic infection) by wearing long-sleeved shirts and long pants and using a US Environmental Protection Agency–registered insect repellent, such as those containing DEET. When used as directed, these repellents are safe and effective, including for pregnant women and infants as young as 2 months. In areas where Zika is spreading and where feasible, pregnant women should be protected from mosquitoes by air conditioning or at least screens. Homeowners, neighbors, and municipalities should remove standing water where mosquitoes can breed. Women who want to avoid pregnancy should be offered voluntary, effective contraception. Because Zika virus is present in semen, men who live in or have traveled to Zika-affected areas should use a condom every time they have sex with a woman who is or may be pregnant.

With Zika infection, as with other emerging infections, astute clinicians have been critical to recognition of new patterns of disease. Keeping up with rapidly changing guidance amid multiple clinical demands is difficult. Obstetricians and gynecologists should ensure access to contraception on request and provide sensitive care and counseling for women with laboratory evidence of Zika infection. The Centers for Disease Control and Prevention (CDC) updates travel alerts and interim guidance for clinicians, including recently updated guidance on diagnostic testing.5 Clinicians need to know how and for whom to test for Zika infection and how to interpret results. Laboratory algorithms have evolved as new information emerges, including the utility of testing urine specimens up to 2 weeks after symptoms appear. Further and frequent enhancements to laboratory testing guidelines are likely as the CDC and others conduct rapid-cycle research to optimize detection of Zika infection. To detect local transmission of Zika, clinicians in areas at risk need to test patients without travel to Zika-affected areas, such as patients with fever, rash, joint pain, or conjunctivitis. The CDC is working with the American Academy of Pediatrics to provide interim guidance for evaluation, monitoring, and treatment of infants born following Zika-affected pregnancies.

Control of mosquito-borne diseases in the contiguous United States has largely focused on Culex mosquito species that are the vector for West Nile virus infection. Integrated vector management activities—mosquito surveillance, reducing mosquito larval habitats, and applying products that control mosquito larvae and adults—are relevant for both Culex and Aedes vector species, but important differences require retooling mosquito control programs. While systematic mosquito monitoring provides early warning of impending West Nile virus outbreaks, human infections are the best early indicator of Zika virus circulation in a community. In addition, the day-biting A aegypti and A albopictus mosquitoes are not strongly attracted to the CDC light traps commonly used for Culex surveillance; other surveillance methods such as ovicups and autocidal gravid traps are required.

Control measures also differ. Community cleanup has a more prominent role for A aegypti because larvae hatch in small containers of water. Labor-intensive house-to-house application of products to kill adult and larval mosquitoes, using backpack sprayers, may be required for control. Aerial spraying of insecticide is used routinely and safely for mosquito control when no other options are available to rapidly reduce the mosquito population. Ultra–low-volume aerial application of insecticide uses very small droplets (<100 μm) that kill mosquitoes on contact; this method allows for application of very small amounts of insecticide over large geographic areas (<1 oz/acre). Ultra–low-volume aerial pesticide application against A aegypti was evaluated in New Orleans, Louisiana, and reduced caged A aegypti by more than 90% in both open and sheltered areas (B. Carter, MSPH, unpublished data, 2015). Further evaluation of efficacy of aerial applications using modern spray technology as part of comprehensive mosquito control is needed as this may be the only feasible method to reach large urban populations at the speed and scale required to ablate sudden outbreaks. Monitoring insecticide resistance in the United States is necessary to guide selection of pesticides.

Progress has already been made, but new tools are needed to better address Zika and other vector-borne threats. Newly developed tests diagnose current and recent infections for clinical care, and high-throughput, sensitive nucleic acid detection methods have been developed to screen the blood supply. The US Food and Drug Administration has issued multiple Emergency Use Authorizations for use of these tests in public health and other laboratories. Available tools can be improved for greater specificity (eg, differentiating antibody against Zika from other flaviviruses). Innovation in insect repellents could give more options to consumers. Further exploration of new classes of insecticides and novel approaches to vector control is important for Zika as well as other mosquito-borne diseases.6 Effective community engagement is needed to promote understanding and support for interventions and participation in research planning. Development of safe and effective vaccines against this virus could protect travelers and residents in areas where the virus may spread. Development of vaccines will require a race against viral spread during the current epidemic. Experience with the recurrence of other flavivirus epidemics (eg, dengue and yellow fever) suggests that large populations will be susceptible to Zika for years to come. Implementing comprehensive research efforts today can yield substantial returns.

There is much left to learn about Zika, but no time to waste in scaling control efforts. The months ahead require urgent action in Puerto Rico, vigilance within southern parts of the United States where local transmission remains a risk, and continued caution among pregnant women, their partners, and health care professionals regarding travel and mosquito protection. An improved mechanism to respond to emergencies is also crucial, with bipartisan calls for an infectious disease rapid response fund to speed implementation of emergency response.


JAMA

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