Zika Update: Findings from the U.S. Zika Pregnancy Registry and Updated Clinical Guidance

Moderator: Kondra Williams

Presenters: Sonja Rasmussen, MD, MS; Emily Petersen, MD

Date/Time: May 4, 2017, 2:00 – 3:00 pm ET

>> Good afternoon. I’m Kondra Williams, and I’m representing the Clinician Outreach and Communication Activity, COCA, with the emergency risk communication branch at the Centers for Disease Control and Prevention. I’m happy to welcome you to today’s COCA call: Zika Update, Findings from the US Zika Pregnancy Registry and Updated Clinical Guidance. You may participate in today’s presentation via webinar, or you may download the slides if you’re unable to access the webinar. The PowerPoint slides set and the webinar link can be found on our COCA webpage at emergency.cdc.gov/coca. Free continuing education is offered for this COCA call. Instructions on how to earn continuing education will be provided at the end of the call. CDC, our planners, presenters, and their spouses or partners, wish to disclose they have no financial interests or other relationships with the manufacturer’s or commercial products, suppliers of commercial services, or commercial supporters. Planners have reviewed content to ensure there is no bias.

>>At the end of the presentation, you will have the opportunity to ask the presenters questions. You may submit questions to the webinar system at any time during the presentation by selecting the questions tab on the webinar screen and typing in your question. Questions are limited to clinicians who would like information related to Zika. For those who have media questions, please contact CDC Media Relations at 404-639-3286 or send an email to media@cdc.gov. If you are a patient, please refer your questions to your healthcare provider.

>>At the conclusion of today’s session, the participant will be able to: understand the latest estimates for birth defects associated with Zika virus infection during pregnancy,discuss additional considerations for evaluating and managing infants with possible congenital Zika virus infection, and apply the updated recommendations outlined in the additional considerations for the evaluation and management of infants with possible congenital Zika virus infection.

>>Today’s first presenter is Dr. Emily Peterson. Dr. Peterson is a medical officer in CDC’s Division of Reproductive Health and she also leads the US Zika virus Pregnancy Registry team on the Pregnancy and Birth Defects Taskforce for CDC’s Zika response. Dr. Peterson completed her medical degree at the University of Iowa. Our second presenter is Dr. Sonja Rasmussen. Dr. Rasmussen is a pediatrician and clinical geneticist and director of CDC’s Division of Public Health Information Dissemination. She is a senior subject matter expert on pregnancy and birth defects. She is also editor-in-chief of CDC’s Morbidity and Mortality Weekly Report. Dr. Rasmussen completed her medical degree at the University of Florida. At this time, please welcome our first presenter, Dr. Peterson.

>> Good afternoon, thank you. Today I would like to talk to you about a recent Vital Signs article published in CDC’s Morbidity and Mortality Weekly Report with accompanying communications materials. This report updates what we know about Zika in the United States and provides a more comprehensive picture of how Zika infection during pregnancy is affecting families.

>>CDC established the US Zika Pregnancy Registry in collaboration with state, tribal, local and territorial health departments and healthcare providers in the United States and US territories, excluding Puerto Rico, which has its own pregnancy registry, the Zika Active Pregnancy Surveillance System. The US Zika Pregnancy Registry collects data to monitor pregnancy and infant outcomes in pregnancies with laboratory evidence of possible Zika virus infection. The data are collected– the data collected are used to inform and update recommendations for clinical guidance and inform public health response. Data have been used to estimate the number of fetuses and infants with birth defects potentially related to Zika, provide information on the phenotype of congenital Zika syndrome, and plan for services for pregnant women, their infants, and families affected by Zika to ensure infants are linked to care.

>>This slide provides an overview of the inclusion criteria of the US Zika Pregnancy Registry. Pregnant women in the United States with laboratory evidence of possible Zika virus infection regardless of whether or not they have symptoms, and their exposed infants are included in the US Zika Pregnancy Registry. Additionally, infants identified at birth with laboratory evidence of congenital Zika virus infection and their mothers are included in the US Zika Pregnancy Registry.

>>As background, in January 2017, the US Zika Pregnancy Registry data-use working group published an article describing the proportion of fetuses or infants with birth defects potentially related to Zika virus in pregnancies with laboratory evidence of possible Zika virus infection. This article included the initial 442 completed pregnancies reported by September 22, 2016. This study found 6% of fetuses or infants had birth defects potentially related to Zika and this was a similar proportion of pregnancies whether or not the pregnant women experienced symptoms of Zika virus disease. This helped dispel a hypothesis that only women who had symptoms of Zika virus disease during pregnancy would have adverse outcomes and provided further evidence for the current recommendations of testing pregnant women with possible Zika virus exposure without symptoms, in addition to those with symptoms of Zika virus disease. This study showed that among women with Zika virus infection in the first trimester of pregnancy, birth defects potentially related to Zika were reported in 11% of the fetuses or infants.

>>Moving on to the updated report we will talk about today, on April 4, 2017, we published a Vital Signs report in CDC’s MMWR detailing data in the US Zika Pregnancy Registry. I will be discussing these findings today. The report updates the previously published estimates using data collected from January to December 2016. In the [inaudible] article, initial estimates were based on 442 completed pregnancies reported to the registry by September 22, and the updated Vital Signs report analyzed data on 972 completed pregnancies reported between January and December 27, 2016. Completed pregnancies included pregnancies of any length of gestation that ended in a live born infant or pregnancy loss. Additionally, in this report, we analyzed the subgroup of pregnancies with confirmed Zika virus infection. This is the largest series of infant outcomes among pregnancies with lab evidence of possible Zika virus infection that has been reported and is critical to CDC’s effort to better understand the impact of Zika during pregnancy.

>>Before we look at the findings of the report, I would like to discuss how the US Zika Pregnancy Registry defines laboratory confirmed recent Zika virus infection. And then define how we define a possible recent Zika virus infection. Laboratory-confirmed, recent Zika virus infection is relatively straightforward. It includes Zika virus RNA in any maternal or fetal infant specimen detected by a nucleic acid test, or NAT, such as RT-PCR. Or includes a positive or equivocal Zika or dengue virus IgM result with Zika virus plaque reduction neutralization test or PRNT titer greater than or equal to 10 and dengue virus PRNT titer less than 10. The US Zika Pregnancy Registry also includes pregnancies in which there were possible recent Zika virus infections. Due to the limitations of serologic testing, recent Zika virus infection cannot always be confirmed and the results may indicate recent unspecified flavivirus infection, which might be Zika virus infection or another flavivirus infection such as dengue virus. In the US Zika Pregnancy Registry, possible recent Zika virus infection includes laboratory confirmed Zika virus infection as described on the previous slide including the detection of Zika virus RNA and specific serologic test results, and we also include other serologic results, which indicate recent unspecified flavivirus infection. This includes either positive or equivocal Zika virus IgM and Zika virus PRNT titer greater than or equal to 10 regardless of the dengue virus PRNT or negative Zika virus IgM and positive or equivocal dengue virus IgM and Zika virus PRNT greater than or equal to 10 regardless of the dengue PRNT. Again, the US Zika Pregnancy Registry laboratory inclusion criteria are specified as possible recent Zika virus infection because the registry includes mother-infant pairs with a serologic evidence of recent unspecified flavivirus infection as well as those with laboratory confirmed recent Zika virus infection.

>>Moving on to our results. From January 15 through December 27, 2016, a total of 1,297 pregnancies with possible recent Zika virus infection were reported to the US Zika Pregnancy Registry from 44 states. We analyzed the completed pregnancies during this period to determine the number of fetuses or infants with birth defects potentially related to Zika. In the same method as the previous article, we classified birth defects potentially related to Zika as brain abnormalities and/or microcephaly, neural tube defects and other early brain malformations, eye defects, and consequences of central nervous system dysfunction, such as arthrogryposis and congenital deafness.

>>Among 972 completed pregnancies with possible recent Zika virus infection, birth defects potentially related to Zika were reported for 51, or 5%, of these fetuses or infants. Brain abnormalities and/or microcephaly were the most common birth defect identified, reported in 43 of 51 fetuses or infants with birth defects, or 84%. Birth defects were reported in similar proportions of fetuses and infants whose mothers did and did not report symptoms of Zika virus disease during pregnancy, similar to the previous findings.

>>Looking at the data by trimester of symptom onset or Zika virus exposure in completed pregnancies with possible recent Zika virus infection, among these 147 pregnancies, 14, or 9%, of the fetuses or infants had birth defects. Looking specifically at completed pregnancies with confirmed recent Zika virus infection, the proportion of fetuses or infants with birth defects in this population was higher. With 24 of 250 pregnancies affected by birth defects potentially related to Zika, or 10%. Again, the majority of birth defects identified were brain abnormalities and/or microcephaly with 18 of 24 of the fetuses or infants with brain abnormalities and/or microcephaly. Looking at completed pregnancies with confirmed Zika virus infection, with first trimester symptom onset or exposure, nine of 60 completed pregnancies, or 15%, had recorded birth defects potentially related to Zika.

>>We also analyzed the postnatal imaging and infant testing practices reported among 895 live born infants in the registry who had possible congenital Zika virus infection. Postnatal neuroimaging results were reported for 221 infants, or 25%. When we looked at the rate before and after CDC’s updated infant guidance, which was published in late August 2016, prior to the guidance, 20% of infants were reported to have received postnatal imaging compared to 20% of infants born after the updated CDC guidance was released. Zika virus testing results of any infant tested– any infant specimen – were reported for 585, or 65%, of the infants with mothers with possible Zika virus infection. Lastly, we compared our data to the baseline prevalence of birth defects potentially related to Zika as reported in a previous publication in the MMWR.

>>This detailed data from pre-Zika years from three birth defect surveillance systems in the United States. This report estimated the prevalence of Zika-related birth defects before Zika in the Americas to be three out of every 1000 births, and we compared this with our data, which was 24 fetuses and infants with the same birth defects among the 250 completed pregnancies with confirmed Zika virus infection in 2016. This translated to an estimated 30-fold increase in birth defects potentially related to Zika and pregnancies with confirmed Zika virus infection compared with pre-Zika years.

>>As part of Vital Signs communications materials, we highlighted our key findings from this article in the Vital Signs fact sheet, which is available online, and print copies can be available upon request. The following findings, which were previously discussed, were highlighted. Nearly 1,300 pregnant women with evidence of possible Zika virus infection were reported in 44 states in 2016. About one in 10 pregnancies with confirmed recent Zika virus infection had a fetus or infant with birth defects potentially related to Zika. Only one in four infants with possible congenital Zika virus infection were reported to have received neuroimaging after birth, which is recommended by CDC.

>>Neuroimaging is critical to identify infants who may appear healthy but have underlying brain abnormalities to ensure they receive care that is needed. We also highlighted the following findings related to the proportion of fetuses and infants with birth defects potentially related to Zika among the almost 1,000 completed pregnancies with evidence of Zika in 2016. Five percent of these pregnancies with possible Zika virus infection had fetuses or infants with birth defects. Ten percent of the pregnancies with confirmed Zika virus infection had fetuses or infants with birth defects and then looking at the pregnancies in the first trimester, 15% with confirmed Zika virus infection in the first trimester of pregnancy had fetuses or infants with birth defects.

>>As part of the Vital Signs communication efforts, we developed a graphic of an infant with congenital Zika syndrome, which was based on a photo of an actual infant with congenital Zika syndrome. Findings include microcephaly, brain abnormalities, seizures, eye and hearing abnormalities, difficulty swallowing, and joint contractures.

>>So what can be done to reduce the risk of Zika-related birth defects? There are basic steps that people, especially pregnant women and their male partners, can take to protect themselves from Zika and protect their infants from the potentially negative health effects of Zika during pregnancy.

>>Healthcare providers play a key role in prevention and care. This includes educating pregnant women and their families on Zika prevention, asking about recent– about possible Zika exposure when caring for pregnant women or infants, providing testing and follow-up care to affected infants to ensure appropriate intervention services are available, and supporting affected infants and families by creating coordinated care plans and monitoring the infant’s development. CDC recommends that healthcare providers advise pregnant women not to travel to areas with risk of Zika.

>>CDC has developed an interactive map, which details recommendations regarding travel. Areas in purple include countries and territories with CDC travel notices and other areas with Zika risk. Countries with endemic Zika. Today, in the United States, Florida and Texas are the only states that have had local transmission, which has occurred in small discrete areas only. If a pregnant woman must travel or lives in an area with Zika virus infection, CDC recommends she talk with her healthcare provider before she travels, strictly follow steps to prevent mosquito bites during the trip, and take steps to prevent sexual transmission as well as talk with her healthcare provider after she returns even if she does not feel sick.

>>To prevent mosquito bites, healthcare providers should advise pregnant women to wear long-sleeve shirts and pants, stay and sleep in places with air conditioning or that use window and door screens, use EPA-registered insect repellent with one of the following active ingredients: DEET, picaridin, IR3535, oil of lemon eucalyptus, para-menthane-diol, or 2-undecanone. CDC– once a week for people living in an area with Zika transmission, it’s recommended they empty, scrub, turn over, cover, or throw out items that hold water such as trash containers, tires, buckets, toys, planters, flower pots, birdbaths, or pools. CDC recommends healthcare providers advise pregnant women whose partners live in or travel to an area with risk of Zika, that they should use condoms every time they have sex or not have sex, and perform these practices for the duration of the pregnancy even if the partner does not have symptoms or feel ill.

>>Healthcare providers caring for pregnant women and infants should also ask about Zika virus exposure during pregnancy including some of the questions listed here on the slide. Have you traveled to an area with risk of Zika during pregnancy or just before you became pregnant? Do you live in or do you travel frequently, daily or weekly, to an area with risk of Zika? Have you had sex without a condom with a partner who lives in or has traveled to an area with Zika? This slide addresses the question of who should be tested for Zika.

>>All pregnant women, regardless of symptoms, who live in or have recently traveled to an area with risk of Zika that has a CDC travel notice, or has had unprotected sex with a partner who lives in or traveled to an area with a CDC Zika travel notice, should be tested for Zika. Women who live in or recently traveled to an area with risk of Zika but without CDC Zika travel notice should be tested if they develop symptoms or if their fetus has abnormalities on ultrasound that may be related to Zika infection. Further information on testing is available on CDC’s website, including a widget to help identify if testing is indicated for a pregnant woman.

>>Dr. Sonja Rasmussen will be talking about updates on evaluation and management of infants with possible congenital Zika virus infection and thus I will skip this slide as she will cover it more completely. But I do want to say that further information materials are available on CDC’s website for the care of both pregnant women and infants, including clinical decision-making tools.

>>Finally, we ask healthcare providers to contribute to the knowledge about Zika virus and pregnancy and to help inform clinical guidance and public health actions by reporting to the US Zika Pregnancy Registry. Healthcare providers should notify their health departments of pregnant women and/or infants with Zika virus infection and more available– more information is available online on the US Zika Pregnancy Registry website and CDC registry staff can be reached via phone or email as listed here. It is because of the national aggregated data that we know what we know about Zika virus infection in pregnancy and are able to produce updated recommendations based on current information available. We thank you for your partnership. I would now like to introduce Dr. Sonja Rasmussen, who will speak about additional considerations on infant guidance. Thank you.

>> Thank you so much, Dr. Peterson. And thank you to everyone here today for the opportunity to speak with you about the additional considerations for evaluation and management of infants with possible congenital Zika infection. As a reminder, in August 2016, in collaboration with the American Academy of Pediatrics, CDC published updated interim guidance for healthcare providers caring for infants with possible congenital Zika virus infection in the Morbidity and Mortality Weekly Report, or MMWR. Based on new information that has accumulated since then, last month in April 2017, CDC published a web update entitled Additional Considerations for the Evaluation and Management of Infants with Possible Congenital Zika Virus Infection regarding neuroimaging and Zika virus testing. These considerations do not replace the previously published guidance but instead offer additional information to clarify the recommendations in the existing guidance.

>>The interim guidance from August 2016 defines infants with possible congenital Zika virus infection as infants born to mothers with laboratory evidence of Zika virus infection during pregnancy, or infants with abnormal clinical or neuroimaging findings suggestive of congenital Zika syndrome and a maternal epidemiologic link suggesting possible transmission regardless of maternal Zika virus test results. These infants should all receive a comprehensive physical exam, which includes head circumference, weight, and length measurements and a careful neurologic assessment. In addition, infants should receive a standard newborn hearing assessment. A head ultrasound is also recommended to detect brain abnormalities that may not be apparent at birth or may not be detected on prenatal ultrasound.

>>Zika virus leads to a distinct pattern of birth defects among fetuses or infants born to women infected during pregnancy and this has been defined as the congenital Zika syndrome. These birth defects include severe microcephaly with partially collapsed skull, a thin cerebral cortex with calcifications particularly noted in the sub cortical region, macular scarring and focal pigmentary retinal mottling, and other abnormalities on ophthalmologic examination of the retina, congenital contractures, and these can be in a single joint or in multiple joints as in arthrogryposis, and then finally marked early hypertonia and symptoms of extrapyramidal involvement such as tremors, posturing, and spasticity.

>>It is important to note that microcephaly at birth is not a necessary feature of congenital Zika syndrome and this MMWR report describes infants in Brazil with laboratory evidence of congenital Zika virus infection who had a normal head size at birth. All 13 infants had brain anomalies consistent with congenital Zika syndrome but they also showed a decrease in the rate of head circumference growth postnatally and microcephaly was diagnosed in 11 of 13 infants by the end of the year. This case series illustrates that the full spectrum of poor outcomes caused by Zika virus infection during pregnancy remains unknown. It also emphasizes the importance of neuroimaging in evaluating infants with possible congenital Zika virus infection.

>>Early neuroimaging might identify brain abnormalities related to congenital Zika infection even among infants who have a normal head circumference at birth. However, as you heard from Dr. Peterson, a recent CDC Vital Signs report of mother-infant pairs included in the US Zika Pregnancy Registry demonstrated that only one in four babies with possible congenital Zika virus infection in the United States were reported to have received neuroimaging at birth. Neuroimaging at birth is critical to identify babies who may appear healthy but have underlying brain defects to ensure that they receive the care that they need.

>>CDC recommends that a head ultrasound be performed before hospital discharge for infants with possible Zika virus infection. However, as our experience with infants with congenital Zika syndrome from Brazil has shown, head ultrasound may be technically difficult in some infants. Thus, for infants who have a small or even absent anterior fontanelle making it difficult to visualize the intracranial anatomy by ultrasound, we now recommend that advanced imaging such as MRI or CT be considered.

>>In addition to neuroimaging, the initial evaluation for infants with possible congenital Zika virus infection also include Zika virus laboratory testing. The interim guidance released in August 2016 recommended laboratory testing for infants born to moms with laboratory evidence of Zika virus infection and infants with clinical or neuroimaging findings suggestive of congenital Zika syndrome and a maternal epidemiologic link suggesting possible transmission. In addition to these two groups of infants, CDC now recommends that healthcare providers consider testing for Zika virus infection for infants born to mothers with an epidemiologic link for whom there may be a concern for infant follow-up care in babies where the mom was not tested before delivery and the exposure is more than 12 weeks before delivery, or for mothers where the testing was negative and the setting of where an exposure had occurred more than 12 weeks earlier. For these infants, head ultrasound and ophthalmologic assessment should also be considered before hospital discharge in addition to the laboratory testing. For infants that meet testing criteria, it is recommended that infant specimens are collected within two days after birth because if collected later, it may be difficult to distinguish between congenital and postnatally acquired infection, particularly in areas with risk of Zika transmission.

>>We have received many inquiries about infant testing after two days of life. There are no available data on the performance of Zika RNA nucleic acid testing and IgM ELISA tests over time among infants to help guide what might be the maximum number of days or weeks after birth when specimen collection and testing may be helpful. We do expect that both viral RNA and IgM anybody levels will decline over time, making negative test results difficult to interpret. However, despite this limitation, if the recommended testing window within the first two days of life is missed it is still reasonable to test the infants– infant as soon as is feasible using specimens collected within the first few weeks to months after birth to help guide further evaluation and follow up for infants with possible congenital Zika virus infection. And this is particularly among infants born in areas without the risk of Zika. In addition to Zika virus testing of serum and urine, the current guidance– the guidance that we published in August– mentioned that Zika virus testing could also be performed on CSF, on cerebral spinal fluid, if it was collected for other reasons.

>>There are now limited reports from Brazil of congenital Zika virus infection in which CSF was the only sample that tested positive. Therefore, healthcare providers should consider obtaining and testing CSF for Zika virus RNA and IgM antibody in infants with clinical findings of possible congenital Zika syndrome but for whose initial laboratory tests are negative on serum and urine. The image on this slide is a table that summarizes the interpretation of laboratory test results of infants with possible congenital Zika virus infection. Infants with confirmed or probable congenital Zika virus infection both meet the clinical case definition of congenital Zika virus infection. A positive nucleic acid test, or NAT, regardless of IgM results is classified as a confirmed congenital Zika virus infection, while test results with a negative nucleic acid test but positive IgM in the setting of Zika-specific neutralizing antibodies in either the infants’ or mothers’ sample is considered a probable congenital infection because a positive IgM could be due to nonspecific immune reactivity.

>>CDC recommends plaque reduction neutralization testing, or PRNT, testing at 18 months. After maternal antibodies– after that maternal IgM is expected to have waned to confirm a probable congenital infection. At this time, the optimal methods to test for congenital Zika virus are unknown. Because data on testing for congenital Zika virus infection are limited, current CDC infant testing guidance is based on experience with other congenital infections. Two recent studies describe a small number of infants with clinical findings consistent with congenital Zika syndrome on whom results of laboratory testing for Zika virus infection were negative. Negative test results might occur in an infant with clinical findings of possible congenital Zika syndrome for several reasons. The first, the clinical findings may be due to another cause to another infection or a genetic cause. The testing could possibly be incomplete – either RNA test wasn’t performed without antibody testing or was– the testing was performed on sub optimal specimens, for example in cord blood rather than blood obtained from the infant. Or it could have been obtained too late after RNA and IgM antibodies had cleared or waned, or a negative test might be because the fetus failed to mount an IgM antibody response.

>>It is unknown if all fetuses infected, especially those early in gestation, mount an IgM antibody response. At this time, we do not know the sensitivity and specificity of currently available Zika virus testing in infants. Thus, for instance without laboratory evidence of Zika virus infection but for whom suspicion of congenital Zika virus infection remains, healthcare providers should evaluate for other causes of congenital infection, consider obtaining an ophthalmology exam and auditory brainstem response, or ABR, hearing test before hospital discharge or within one month of birth to check for findings that could provide additional clinical information. In addition, providers should consider performing other evaluation and follow up in accordance with CDC interim guidance for the evaluation and management of infants with possible congenital Zika virus infection.

>>CDC has developed an algorithm, or a job aid, that summarizes the clinical management of infants with possible Zika virus infection to assist healthcare providers as they care for these infants. This is available on the CDC website. Infants with possible congenital Zika infection may need to see many specialists, which includes neurologists, ophthalmologists, hearing and developmental specialists, among others, and it is critical that their care is well coordinated. To facilitate coordination of care for families and help improve access to the necessary services, CDC in collaboration with McKing Consulting Corporation and with March of Dimes, established Zika Care Connect. Central to Zika Care Connect is a provider network accessible through a website and helpline, and you can see the website address here, which will help connect pregnant women and families to specialty healthcare professionals listed on the slide and from the US states colored purple who have agreed to care for families affected by Zika. The program will be expanded in mid-2017 to include additional jurisdictions and the addition of a laboratory testing web portal for healthcare providers to identify laboratories that are offering Zika virus testing.

>>In summary, the additional considerations provide clarification for several issues including the importance and types of neuroimaging based on the infant phenotype, timing, and specimens for Zika virus testing and possible limitations of infant Zika virus laboratory testing. And in that context, clinicians should remain– should maintain a level of suspicion in the case of infants with abnormalities consistent with congenital Zika syndrome whose test results have been negative. All of this is the work of many people. Many thanks to all of our collaborators inside and outside CDC and thank you for listening on this call today.

>> Thank you presenters for providing our COCA audience with a wealth of information. We will now move on to the question and answer portion of this call. Please remember you may submit questions to the webinar system at any time during the presentation by selecting the questions tab at the bottom of the webinar screen and typing in your question. Questions are limited to clinicians who would like information related to Zika. For those who have media questions, please contact CDC Media Relations at 404-639-3286 or send an email to media@cdc.gov. If you are a patient please refer your questions to your healthcare provider. At this time, we’ll go ahead and take our first question. What is the CDC currently doing to increase the number of infants with possible congenital Zika virus infection who receive neuroimaging?

>> Yes. We do feel that this is really an important issue that only 1 in 4 babies who needed to have a head ultrasound at birth were getting it and so this is something that we’ve been really working hard on. One of the ways is trying to reach out to clinicians, for example, through this COCA call. We are also working with professional organizations. We’ve been working with the American Academy of Pediatrics. We’ve been presenting at several national meetings trying to get the word out about this. And we’re trying to make it so that our infant tool aid or algorithm that’s available on our website is easy for people to follow – as easy as possible for people to follow so that they’re aware that this is really important for infants.

>> Thank you. Our second question: what is the definition of recently traveled? Eight weeks or six months?

>> Thank you. For the purposes of CDC guidance, we defined recent travel for pregnant women as travel during pregnancy or in the periconceptional period, and for nonpregnant women as travel within the past eight weeks and for men travel within the past six months due to the possibility of the virus to remain in the semen for up to six months.

>> Thank you. How will USA providers and CDC prevent epidemic proportions of spread in the US without testing all travelers from infected areas?

>> So CDC recommends the testing of symptomatic non-pregnant persons who have symptoms of Zika virus infection. We recommend the use of personal protective measures such as insect repellent for individuals with a diagnosis of Zika to reduce the further transmission. And additionally, recommend enhanced surveillance and diagnostic testing for those with symptoms.

>> Thank you. Why is there a crossover in the testing with West Nile virus results.

>> In persons previously infected with the flavivirus or who have been vaccinated against a flavivirus such as yellow fever, Japanese encephalitis, or tickborne encephalitis, subsequent exposure to a related flavivirus can result in rapid and brisk rise in neutralizing antibodies against multiple flaviviruses. Additionally, neutralizing antibody titers against the? flavivirus to which the person was previously exposed might be higher than the titer of the virus which they were recently infected. So for instance, if they previously had a dengue infection and are having a recent Zika virus infection, then the dengue titer might be higher initially. And when performing serologic testing the presence of these neutralizing antibodies against multiple flaviviruses can preclude a conclusive determination of which flavivirus was responsible for the recent infection, so that’s why we include pregnancies with possible Zika virus infection.

>> Thank you. Can you address laboratory testing at private clinical laboratories versus laboratories in the LRN? Is the sensitivity and specificity lower for testing at private clinical laboratories?

>> Private laboratories have been approved with EUA– use tests that are approved by the FDA Emergency Use Authorization. And that’s as far as we can comment on that.

>> Thank you. Do we know if a baby can have birth defects from father’s sperm only without the mother catching the virus?

>> We aren’t aware of that being possibly happening. Of course the father’s sperm can affect the mother and then the mother could be infected could be in the mom’s blood. We aren’t aware of it being possible of just being the father’s sperm infecting the mother– infecting the fetus, I’m sorry.

>> Thank you. For possible maternal infection, if the IgM is negative, PRNT testing is not routinely done. So would you recommend that all pregnant women with IgM testing have PRNT testing whether or not it is initially negative to make sure not a false-negative screen?

>> CDC’s recommendations recommend PRNT testing is performed when IgM is positive or equivocal. PRNT is not recommended by CDC when IgM is negative.

>> Thank you. What is the progress of the vaccine against Zika virus infection?

>> There is currently no vaccine for Zika virus, however, several vaccine candidates are currently in development. It may take several years before an effective vaccine is developed and ready for distribution.

>> Thank you. Will there be more specific guidance on indications for infant PRNT testing at 18 months to confirm congenital Zika infections? Should this be ordered in any infant with a compatible syndrome and inclusive prior testing of mother and infant?

>> Yeah. We will continue to update our guidance as more information is available. Right now all? we have is really limited information and as we get more information, and we’re starting to get more information, especially through the US Zika Pregnancy Registry. That’s why we feel so strongly about the importance of people reporting to our US Zika Pregnancy Registry and as we get more information we will update our guidance.

>> Thank you. What is CDC’s best hypothesis regarding whether– what percent of Zika exposed fetuses might have defects that actually go undetected at delivery?

>> You know, I think that’s really an important question. I think we don’t have the answer right now. I’m concerned about the data that we have from the US Zika Pregnancy Registry because so many– you heard– 3 in 4 babies didn’t have a head ultrasound done, didn’t have any neuroimaging. And so we could be underestimating that number at this time and we are continuing to encourage people to do that full workup so that we can do the best we can. Also it’s possible that some of these kids may develop problems after birth. We know that from other infections like CMV that a baby can have normal hearing at birth and develop hearing loss later on. So we’re also looking for those sorts of issues in the US Zika Pregnancy Registry and the pregnancy surveillance system that’s being used in Puerto Rico.

>> Okay. At this time we have time for our last question. If a child is Zika infected is there drug treatment?

>> No, unfortunately there is no medication at all. So, I’m not sure if the person asking the question is asking about a baby who had Zika– the mom had Zika during pregnancy or the baby had Zika after the baby has been born, but unfortunately in neither case is there any medication that can be used to treat Zika.

>> Thank you. On behalf of COCA, I would like to thank everyone for joining us today. With a special thank you to our presenters, Dr. Emily Peterson and Dr. Sonja Rasmussen. The recording of this call and the transcript will be posted to the COCA website at emergency.cdc.gov/coca within the next few days. All continuing education for COCA calls are issued online through TCE online. The CDC training and continuing education online system at www.cdc.gov/tceonline. Those who participated in today’s COCA call and would like to receive continuing education should complete the online evaluation by June 5, 2017, and use course code WC2286. Those who will receive a call on demand and would like to receive continuing education should complete the online evaluation by May 4, 2018, also using course code WD2286. To receive information on upcoming COCA calls subscribe to COCA by going to the COCA webpage at emergency.cdc.gov/coca and clicking on the join the COCA mailing list link. Also, you are invited to like our page at facebook.com/cdc clinician outreach and communication activity to stay connected to the latest news from COCA. Thank you again for being a part of today’s COCA call. Have a great day.

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