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Zika virus is a mosquito-borne flavivirus closely related to dengue, West Nile, Japanese encephalitis, and yellow fever viruses. Diagnostic testing for Zika virus infection can be accomplished using both molecular and serologic methods. However, results of Zika virus antibody testing can be difficult to interpret because of cross-reactivity with related flaviviruses, which can preclude identification of the specific infecting virus, especially when the person previously was infected with or vaccinated against a related flavivirus.

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All patients with clinically suspected dengue should receive appropriate management to reduce the risk for hemorrhagic medical complications. Pregnant women with laboratory evidence of a recent Zika virus infection or flavivirus infection should be evaluated and managed for possible adverse pregnancy outcomes and reported to the appropriate Zika virus pregnancy registry. Health care providers should consult with state or local public health authorities for assistance in interpreting test results.

For persons with suspected Zika virus disease, a positive rRT-PCR result confirms Zika virus infection, and no antibody testing is indicated (3,4,7). However, because of the decline in the level of viremia over time and possible inaccuracy in reporting of dates of illness onset, a negative rRT-PCR result does not exclude Zika virus infection. Therefore, serum IgM antibody testing for Zika and dengue virus infections should be performed if rRT-PCR is negative. For serum specimens collected

All patients with clinically suspected dengue virus infection should receive appropriate management to reduce the risk for hemorrhagic complications (11). Symptomatic and asymptomatic pregnant women with serologic or molecular evidence of recent Zika virus infection should be evaluated and managed for possible adverse pregnancy outcomes and reported to the U.S. Zika Pregnancy Registry or the Puerto Rico Zika Active Pregnancy Surveillance System (9,10). Among persons for whom serologic testing is unable to determine the most recent infecting flavivirus, an epidemiologic link to a laboratory-confirmed case of dengue or Zika virus disease can be considered in determining the most likely infecting virus (22). In addition, data on the epidemiology of viruses known to be circulating at the location of exposure and clinical features of these viral infections should be considered. If serologic testing is inconclusive or there is evidence of recent infection with either Zika or dengue virus, patients should be clinically managed for both infections because they might have been infected with either virus. Health care providers with questions about test result interpretation should consult with state or local public health authorities for assistance.

CDC has developed interim guidelines for health care providers in the United States who are caring for infants born to mothers who traveled to or resided in an area with Zika virus transmission during pregnancy. These guidelines include recommendations for the testing and management of these infants. Guidance is subject to change as more information becomes available; the latest information, including answers to commonly asked questions, can be found online ( ). Pediatric health care providers should work closely with obstetric providers to identify infants whose mothers were potentially infected with Zika virus during pregnancy (based on travel to or residence in an area with Zika virus transmission [ ]), and review fetal ultrasounds and maternal testing for Zika virus infection (see Interim Guidelines for Pregnant Women During a Zika Virus Outbreak*) (1). Zika virus testing is recommended for 1) infants with microcephaly or intracranial calcifications born to women who traveled to or resided in an area with Zika virus transmission while pregnant; or 2) infants born to mothers with positive or inconclusive test results for Zika virus infection. For infants with laboratory evidence of a possible congenital Zika virus infection, additional clinical evaluation and follow-up is recommended. Health care providers should contact their state or territorial health department to facilitate testing. As an arboviral disease, Zika virus disease is a nationally notifiable condition.

Zika virus is a mosquito-borne flavivirus primarily transmitted by Aedes aegypti mosquitoes (2,3). Aedes albopictus mosquitoes also might transmit the virus. Ae. aegypti and Ae. albopictus mosquitoes are found throughout much of the Region of the Americas, including parts of the United States, and also transmit dengue and chikungunya viruses (4). Zika virus infections have also been documented through both intrauterine transmission resulting in congenital infection and intrapartum transmission from a viremic mother to her newborn (5,6). Zika virus RNA has been detected in breast milk, but Zika virus transmission through breastfeeding has not been documented (5).

The diagnosis of Zika virus infection is made through molecular and serologic testing (2). This includes reverse transcription-polymerase chain reaction (RT-PCR) for viral RNA, and immunoglobulin (Ig) M ELISA and plaque reduction neutralization test (PRNT) for Zika virus antibodies. Because it is currently not known which type of testing most reliably establishes the diagnosis of congenital infection, CDC recommends both molecular and serologic testing of infants who are being evaluated for evidence of a congenital Zika virus infection (Box 1). No commercial tests for Zika virus are available; Zika virus testing is performed at CDC and some state and territorial health departments. Health care providers should contact their state or territorial health department to facilitate testing.

Zika virus RT-PCR testing should be performed on serum specimens collected from the umbilical cord or directly from the infant within 2 days of birth (12). In addition, cerebrospinal fluid (CSF) obtained for other studies, and frozen and fixed placenta obtained at delivery, should also be tested by RT-PCR. IgM ELISA for Zika virus and dengue virus should be performed on infant serum, infant CSF, and maternal serum; however, results of these assays can be falsely positive because of cross-reacting antibodies (9,12). PRNT can be performed to measure virus-specific neutralizing antibodies and to discriminate between cross-reacting antibodies from closely related flaviviruses (e.g., dengue or yellow fever viruses). Finally, immunohistochemical staining to detect Zika virus antigen on fixed placenta and umbilical cord tissues can be considered.

When an infant is born with microcephaly or intracranial calcifications to a mother who was potentially infected with Zika virus during pregnancy, the infant should be tested for Zika virus infection (Figure 1) (Box 1). In addition, further clinical evaluation and laboratory testing is recommended for the infant (Box 2). The mother should also be tested for a Zika virus infection, if this testing has not already been performed during pregnancy. An ophthalmologic evaluation, including retinal examination, should occur during the first month of life, given reports of abnormal eye findings in infants with possible congenital Zika virus infection (11).

For infants with any positive or inconclusive test findings for Zika virus infection, health care providers should report the case to the state, territorial, or local health department and assess the infant for possible long-term sequelae (Box 3). This includes a repeat hearing screen at age 6 months, even if the initial hearing screening test was normal, because of the potential for delayed hearing loss as has been described with other infections such as cytomegalovirus (14).

For infants with microcephaly or intracranial calcifications who have negative results on all Zika virus tests performed, health care providers should evaluate for other possible etiologies and treat as indicated.

If the mother has not undergone any previous testing for Zika virus infection during pregnancy, CDC recommends that she receive testing only if she reported symptoms consistent with Zika virus disease during or within 2 weeks of any time spent in an area with ongoing Zika virus transmission while she was pregnant (1,15). If the mother has any positive or inconclusive findings from tests for Zika virus infection, then the infant should undergo testing for evidence of a congenital Zika virus infection (Box 1). If the mother has not received any previous testing for Zika virus, and did not report clinical illness consistent with Zika virus disease during pregnancy, no further testing of the mother or infant is recommended (Figure 2).

The only way to prevent congenital Zika virus infection is to prevent maternal infection, either by avoiding areas where Zika virus transmission is ongoing or strictly following steps to avoid mosquito bites (15,18). Mosquito-bite prevention includes using air conditioning or window and door screens when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear, and using insect repellents. When used according to the product label, U.S. Environmental Protection Agency-registered insect repellents are safe for pregnant women (18).

*Indications for testing include 1) infants with microcephaly or intracranial calcifications born to women who traveled to or resided in an area with Zika virus transmission while pregnant, or 2) infants born to mothers with positive or inconclusive test results for Zika virus infection. 2351a5e196