Zika Virus: Updates to Clinical Guidance and Recommendations for Pregnant Women and Infants

Moderator: Marcy Friedman

Presenters: Dana Meaney-Delman, MD, MPH; Sasapin Grace Prakalapakorn, MD, MPH; Titilope Oduyebo, MD, MPH

Date/Time: July 27, 2017, 2:00 – 3:00 pm ET

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>> Good afternoon.I am Marcy Friedman and I’m representing the ClinicianOutreach and Communication Activity,COCA with the Emergency Risk Communication Branchat the Centers for Disease Control and Prevention.I’m happy to welcome you to today’s COCA call,Zika virus updates to clinical guidance and recommendationsfor pregnant women and infants.You may participate in today’s presentation via webinaror you may download the slides if you are unableto access the webinar.The PowerPoint slide set and the webinar link can be foundon 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 beprovided at the end of the call.CDC, our planners, presenters and their spouses,partners which to disclose they have no financial interestor other relationships with the manufacturersof commercial products, suppliers of commercial servicesor commercial supporters.Planners have reviewed content to ensure there is no bias.At the end of the presentation, you will have the opportunityto ask the presenters questions.You may submit questions through the webinar systemat any time during the presentation by selecting the”questions tab” on the webinar’s screenand typing in your question.Questions are limited to clinicians who wouldlike information related to Zika virus.For those who have media questions,please contact CDC Media Relations at 404-639-3286or send an email to media@cdc.gov.If you are a patient, please refer your questionsto your healthcare provider.At the conclusion of today’s session,the participant will be able to understandand apply the updated interim guidance for pregnant womenwith possible exposure to Zika virus and practice,understand the latest estimatesfrom the United States territories regarding pregnancyoutcomes associated with Zika virus infection duringpregnancy, and apply knowledgeof pediatric ophthalmologic findings in infantswhen evaluating and managing infantswith possible congenital Zika virus infection.Today’s first presenter is Dr. Titilope Oduyebo.Dr. Oduyebo is an obstetrician gynecologistin the clinic Team Leadwith the Pregnancy and Birth Defects Task Forcefor CDC’s Zika Virus Response.She is involved in developing clinical guidancefor healthcare providers caring for pregnant women and womenof reproductive age with possible exposure to Zika virus.Dr. Oduyebo is also involvedwith the U.S. Zika Pregnancy Registryand provides technical assistance and support to state,tribal, local and territorial health departments collectinginformation about pregnancyand infant outcomes following laboratory evidence,or confirmed, or possible Zika virus infectionduring pregnancy.Dr. Oduyebo is also a subject matter expertand provides clinical consultationto healthcare providers in state, tribal,local and territorial health departmentsthrough the CDC Zika Pregnancy Hotline.Today’s second presenter is Dr. Dana Meaney-Delman.Dr. Meaney-Delman is currently serving as the Pregnancyand Birth Defects Task Force Co-Leadfor the CDC’s Zika Response.She is a Senior Medical Advisor in the National Centerfor Emergency, correction Emergingand Zoonotic Infectious Diseases at the CDCwhere she is extensively involvedin Infectious Disease Public Health Response.In her career at CDC, she has focused on the developmentof evidence-based clinical guidelinesfor infectious diseases.Her contributions have included the developmentof clinical guidelines for anthrax,small pox, Ebola and botulism.She has co-authored numerous articles including systematicliterature reviews and clinical guidelinesfor anthrax prevention and treatmentfor pregnant and postpartum women.Dr. Meaney-Delman is an obstetrician and gynecologistwith over 15 years of clinical experience.She holds board certification in obstetrics and gynecologyand serves as a board examiner for the American Boardof Obstetrics and Gynecology.She is an Adjunct Assistant Professor of Obstetricsand Gynecology at Emory University School of Medicineand continues to be clinical active.Our third and final presenter is Dr. Grace Prakalapakorn.Dr. Prakalapakorn is an Assistant Professorof ophthalmology and pediatrics at Duke University.She is fellowship trained pediatric ophthalmologistand a board-certified ophthalmologist.Dr. Prakalapakorn’s interests liein public health ophthalmology and international health.She was a formal Fulbright scholar and has workedwith the CDC and Orbis International.At this time, please welcome our first presenter, Dr. Oduyebo.

>> Okay, so thank you everyone for joining and we apologizefor the technical difficulties.I also want to thank the COCA staff organizing this call.I would like to start off with the topicsthat will be discussed in today’s presentation.First, I will discuss the updated intern Zika guidancefor pregnant woman including some of the rationalfor the changes and updates of the testing of women.Next, my colleague Dr. Dana Meaney-Delmanand Dr. Grace Prakalapakorn will discuss pregnancy outcomesafter maternal Zika virus exposureand the pediatric ophthalmologic findings among infantswith congenital Zika virus infection.Well, we’ll start with emerging data and the current stateof epidemic that prompted the guidance updates.I would like highlight two key points to set the stage; first,epidemiologic data shows a decrease in the numberof Zika cases in the Americans.When this occurs, pretest probability goes downand the probabilityof false-positive test results increase.Second, Zika virus IgM antibodies can persistfor months in some people making it difficultfor healthcare providers to use Zika IgM test resultsto determine whether infection occurred during the currentpregnancy versus prior to conception.Now, I’m going to briefly review the common trendsof Zika virus epidemiology in the Americans and in the U.S.From 2015 to 2017, local transmissionof Zika virus has been identified from 48 countriesand territories in the Americans.This graph shows data from the Pan American Health Organizationor PAHO and includes confirmed and specific casesof Zika reported from different regions overtime;the highest number of cases according in 2016with decreasing numbers [inaudible] and May 2016.A much smaller number of cases have been reported to datein 2017 with most cases from the South American region.This graph shows the numberof Zika virus disease cases reported from the U.S. statesin Washington, D. C. from 2016 to 2017.The highest number of cases was reported from Julyand August 2016 with decrease in numbersin late 2016 and into 2017.Since the last guidance was released in July of 2016,the number of travel-associated cases reported,have declined sharply.This trend reflects the overall declinein Zika transmission in the Americas.The change in epidemiology of Zika virusin the Americas has indications for the interpretationof test results particularly for serologic tests.This picture shows an example of a populationwhere the disease is common where 40out 100 people have disease.People shown in red have the disease and people shownin blue do not have the disease.The two boxes below show categorizationby hypothetical diagnostic tests with given characteristics.In this example, 98% specificity and 98% sensitivity.In a populationwith a relatively high disease prevalence,most people will be categorized correctly.Looking at the box on the right, most of the peoplewith positive test results will be true positiveswith only 3% classified as positivewhen they are truly negative or false-positives.This slide shows the same diagnostic test performancewith a different disease prevalence.In this example, the disease is rare with only 1out of a 100 people truly having disease.The test correctly classifies most peopleas negative as seen on the left.However, when looking at the group on the right classifiedas positive, I high proportion 67% are actuallyfalse-positives, meaning they do not actually have the disease.This shows a hypothetical test with near optimal sensitivityand specificity and does not represent the characteristicsof currently available diagnostic tests for Zika.As Zika transmission declines in the Americas,the lower prevalence increases the probabilitythat positive test results are false-positives.Emergent epidemiologic and laboratory data and a kickbackas of the case with other flaviviruses,Zika virus IgM can persist beyond 12 weeks after infection.A number of unpublished studies have identified persistenceof Zika IgM in some people for several months after infection.Unpublished and preliminary datafrom the Zika virus persistence study or Zika study of personswith not confirmed Zika virus disease recently reporteddetection of IgM response at 8 to 15 days after symptom onsetin almost all participants.The percent of participants with detectable IgM levels decreasedover time, but some participants remain IgM-positive for morethan 210 days or several months after symptom onsets.It is important to notethat this data are still being collected and analyzedand may represent underestimateof the true duration of Zika IgM.Because Zika IgM antibodies can persist,a positive Zika IgM antibody test among pregnant womenwith recent possible Zika virus exposure during the currentpregnancy and before the current pregnancy result could meanseveral things.It could indicate an infection during the current pregnancymeaning the pregnancy is likely at risk from Zika,or an infection that occurred before the current pregnancymeaning the current pregnancy is likely not at risk from Zika.Alternatively, a positive result could actually be falsewhich could, would mean the fetus is likely notat risk from Zika.In light of the emerging data, on July 24th, 2017,the CDC updated its intern clinical guidancefor healthcare providers care for pregnant womenwith possible Zika virus exposure.The updated guidance emphasizes a shared decision-making modelfor testing and screening pregnant women.One in which patientsand providers work together to make decisionsabout testing and care plans based on the patient preferencesand values, clinical judgments and a balance assessmentof risks and expected outcomes.During this process,the healthcare provider’s clinical judgment is imperativeand when deciding whether to advise testing,factors such as length of possible exposure,type and location of possible exposure,intensity of Zika virus transmission at the locationof travel, as well as, the presence of symptoms,prevention measures taking, the patient’s preferencesand concerns, and the jurisdictional recommendationsshould all be considered.There are now two algorithms; one for pregnant womenwith symptoms of Zika virus diseaseand one for those without.Here is an image of the algorithmfor symptomatic pregnant women.This algorithm also applies to pregnant womenwith possible Zika virus exposure who have a fetuswith prenatal ultrasound findings consistentwith possible Zika virus associated birth defects.In the updated guidance, each algorithm begins with a reminderfor healthcare providers to ask patientsabout possible Zika exposure beforeand during the current pregnancy,a diagnosis of laboratory confirmed Zika virus diseaseand the presence of Zika symptoms.Before deciding whether it’s a test, we have included a promptfor healthcare providers to discuss the limitationsof the testing and potential riskof misinterpretation of test results.CDC has developed samples scriptsthat can guide healthcare providers during this complexconversations and provide ideas about how to expand thingsin a way that can be understood by patients.From there, the algorithm outlines who to test,when to test, which tests to order,and how to interpret test results.To begin, healthcare providers should ask about the typeand duration of possible Zika virus exposure beforeand during the current pregnancy.This includes travel or residents in areas with riskfor Zika virus transmission, as well as,possible sexual exposure to Zika virus, true unprotected sexwith a person who travels to or livein an area with risk for Zika.Knowledge of a pregnant women’s possible exposureto Zika virus before and during pregnancies critical contextualinformation that should be used to tailor the preand post-test counseling and the interpretation of test results.They should also ask about a diagnosisof laboratory confirmed Zika virus infection before thecurrent pregnancy.Based on experience with other flaviviruses,previous Zika virus infection is likely to confer prolonged,possibly lifelong immunity.Testing is not routinely recommended for pregnant womenwith a previous diagnosisof laboratory confirmed Zika virus infectionby either the nucleic acid test, NAT or serology.If a woman does not have any symptoms,the asymptomatic algorithm should be usedwhich I will describe later.In the updated guidance, testing is recommendedfor symptomatic pregnant womenwith possible Zika virus exposure as soon as possibleto 12 weeks after symptom onset.Concurrent testing by NAT on serum urine and serologyon serum is recommended.Reports of prolonged detection of Zika virus RNAin symptomatic pregnant women support longer timeframesfor the performance of molecular diagnostic testing.However, by extending the window for NAT testing, the potentialfor false-positive may increase.The concurrent testing with IgM and the recommendationsfor repeat testing in certain scenarios should address this.Performing the concurrent Zika virus IgM antibody testing canhelp to confirm the diagnosis of active Zika virus infectionwith more than one test.Next, I will just briefly discuss NATand serology test results and interpretation.In both serum and urine specimens are NAT positive,regardless of the IgM antibody results,the results should be interpreted as evidenceof acute Zika virus infection.For interpretation of other combinationsof positive NAT results and serology, please referto the table on the interpretation of NAT serologyin the MMWR and this is in table-1.The Laboratory Interpretation Tablefor Zika virus testing was also updatedto incorporate the emerging data.If the NAT results are negative on both urine and serumand the IgM antibody results are negative, this interpretedas no evidence of Zika virus infection.However, if the NAT test results are negativeand the IgM results is a non-negative,then a plaque reduction neutralization testor PRNT should be ordered.PRNT measures the virus specific neutralizing antibody titersand should be performed for Zika/dengue virusesin NAT’s-negative IgM non-negative specimens.Of note, currently PRNT confirmation is not routinelyrecommended for individuals living in Puerto Rico.For laboratory interpretation in the absence of PRNT testing,please refer to the Interpretation Tablewhich is table-1 in the MMWR.If the Zika PRNT results is greater than or equal to 10and the dengue PRNT results is less than or equal to 10,this should be interpreted as Zika virus infection;timing of infection cannot be determined.However, for pregnant womenwithout Zika virus exposure before the current pregnancy,a positive IgM result represent a recent Zika virus infection.If the Zika PRNT results is greater or equal to 10and dengue PRNT results is also greater than or equal to 10,this should be interpreted as Flavivirus infection,the specific virus and the timingof infection cannot be determined.However, again for pregnant womenwithout Zika virus exposure before the current pregnancy,a positive IgM in this setting would represent recentunspecified Flavivirus infection.Last, if the Zika virus PRNT results is less than 10,the results should be interpreted as no evidenceof Zika virus infection.Switching gears to the asymptomatic pregnant women,the testing recommendations here differ basedon the circumstances of possible exposure.Here is an image of the algorithm.The left arm of the algorithm contains guidancefor testing asymptomatic pregnant womenwith ongoing possible exposure, meaning, they live inor frequently travel to an area with risk for Zika.The right arm contains guidancefor testing asymptomatic pregnant womenwith recent possible exposure to Zikabut without ongoing exposure.As with symptomatic pregnant women,healthcare providers should ask asymptomatic pregnant womenabout possible Zika virus exposure beforeand during the current pregnancy, about a diagnosisof laboratory confirmed Zika virus infection before pregnancyand the presence of symptomsof Zika during this current pregnancy.If the woman reports possible Zika virus exposureand symptoms, the asymptomatic; excuse me,the symptomatic algorithm should be usedand that’s the algorithm we just went over.Before testing, the testing limitations and potential risksfor misinterpretation of results including the false-positivesand false-negatives should be discussed.Previously, CDC’s guidance recommendedthat asymptomatic pregnant women with ongoing possible exposureto any area with risk for Zika before their current pregnancy;excuse me, during their current pregnancy receive IgM testingwith reflex NAT testingif indicated during the first and second trimester.In the updated guidance, testing for Zika virus should continueto be offered to asymptomatic pregnant womenwith ongoing possible exposure,because it might identify infection during pregnancyand provide information that can be used to guide clinical care.NAT testing should be offered 3 times during pregnancy.Zika IgM testing is no longer recommendedor routinely recommended,because of the emerging data indicating challengesin determining whether the positive results represents aninfection that occurred during the current pregnancyversus prior to conception.For pregnant women who tested not positive any time beforeor during pregnancy, additional NAT testing is not recommended.There is limited data to inform timing of testing by NAT alone.So for the pregnant women without a previous diagnosisof laboratory confirmed Zika virus infection,testing at the initiation of prenatal careand 2 additional tests during the courseof the pregnancy coincidingwith prenatal visits should be considered.For interpretation of the NAT test results, please referto the table on the Interpretation of NATand Serology in the MMWR which is in table-1.Next, I will discuss the recommendationsfor asymptomatic pregnant womenwith recent possible Zika exposureor without ongoing exposure.Here is an image of the algorithm.Previously, CDC’s guidance recommendedthat an asymptomatic pregnant womanwith recent possible Zika virus exposure,but without ongoing exposure be offered testing with either NATor IgM based on timing of last possible exposure.In the updated guidance, testing asymptomatic pregnant womenwith recent possible Zika exposure,but without ongoing exposure is not routinely recommended.Testing should be considered using the shared thedecision-making model that we discussed earlier.The updated guidance is intended to reduce the possibilityof false-positive results in the settingof the low pretest likelihood.We acknowledge that these changes will have implicationsfor surveillance information from asymptotic pregnant women.However with the decline in prevalence of Zika,the probabilityof false-positive test results increases and the changein epidemiology further limits the diagnostic capabilityof currently available Zika tests.There is also the possibility that the lack of routine testingof asymptomatic pregnant womenwith recent possible Zika exposure, but not ongoingor without ongoing exposure with effective detection of infantswithout obvious birth abnormalitiesfor whom may have complications from congenital Zika infection.To address this, the updated guidance emphasizesthat pediatric healthcare providers should inquireabout possible maternalor congenital Zika exposure for every newborn.Infants born to motherswith possible Zika virus exposure during a pregnancywho did not receive testing,should have a comprehensive physical examinationwhich would include standardized measurementof the head circumference , neurologic assessmentand standard newborn hearing screening which is all partof the routine newborn care.Based on the level of possible Zika virus,maternal Zika virus exposure, the healthcare provider,pediatric healthcare provider should consider whether furtherevaluation of the newbornfor possible congenital Zika virus infection is warranted.In which case, a head ultrasoundand ophthalmologic assessment should be considered.Based on the results of those evaluations,testing of the infant for Zika could be considered.Moving forward, AAP, the American Academyof Pediatricians and the American College of Obstetricsand Gynecology will be working closely togetherto follow-up on this guidance.Specifically, they will be assessing the needfor additional guidance for infants and children in termsof diagnostic and developmental assessments and updated guidanceas anticipated this fall.Again, we want to emphasizethat additional recommendations may takeinto account the epidemiology of Zika virus transmissionand other considerations in areas with risk of Zikaand therefore, might include a routine recommendationto test asymptomatic pregnant womenwith possible recent exposure, but without ongoing exposurefor either clinical care or as part of Zika virusof infection surveillance.The comprehensive approach to testing placentaland fetal tissues have also been updated.Testing of the placentaland fetal tissues specimens can be performedfor diagnostic purposes in certain scenarios.For example, if a woman does not have definitive Zika virus testresults and has a fetus or infantwith possible Zika virus associated birth defects.However, testing of placental testingfor Zika virus infection is not routinely recommendedfor asymptomatic pregnant womenwho have recent possible Zika virus exposure,but without ongoing exposure and who have a fetus or infantwithout possible Zika virus associated birth defects.Because of the severe effectsof Zika virus infection during pregnancy, CDC continuesto recommend that pregnant women who travelto any area with risk for Zika.If a pregnant woman must travel to these areas,they should be counseled about the risk of Zika,ways to protect themselves, and the limitationsof Zika testing upon their return.If a pregnant woman lives in or travels to an area with riskfor Zika, she should take steps to prevent mosquito bitesand also sexual transmission.Steps should also be taken by pregnant women’s partnerswho live in or travel to areas where riskfor Zika virus transmission to avoid becoming infectedwith Zika and steps should be taken by both the partnerand the pregnant woman to prevent sexual transmission.CDC has developed many tools to assist cliniciansin the preventing the guidance I have described.There are tools to assist with screening, counseling,and we also have a helpline for clinical inquiries.There are also fact sheets that can be provided to patientsthat explains Zika testing and test results.In addition, CDC continuesto maintain the Zika pregnancy hotline for healthcare providersof pregnant women and also of infantswith possible Zika virus infection.Through this service, CDC scientistsand clinicians are available for any concernsabout clinical managements and to answer questionsabout the U.S. Zika pregnancy registry.I will now turn it over to Dr. Dana Meaney-Delmanwho will discuss the pregnancy outcomesafter maternal Zika virus infectionin the United States and territories.

>> Thank you Dr. Oduyebo.Good afternoon.My name is Dana Meaney-Delman and I serve as the co-leadfor the CDC’s Pregnancy and Birth Defects Task Force.I’d like to welcome you again to this call and thank you allfor taking the time to be on the call today.Please let us know if there are ongoing autiologic problemsby Chat Box.Today, I’d like to provide an updateon a report recently published in CDC’s morbidityand mortality weekly report.This publication was released on June 8th,2017 and is the first report on territorial datafrom the Zika Pregnancy and Infant Registries.CDC established the Zika Pregnancyand Infant Registries early in 2016to monitor possible Zika virus infectionin women during pregnancy.These registries include the U.S. Zika Pregnancy Registry,or USZPR and the Puerto Rico Zika Active PregnancySurveillance System or ZAPSS.Both are a collaboration between CDC and the state, tribal,local, and territorial health departments.The Pregnancy and Infant Registries collect informationabout women with laboratory evidenceof possible Zika virus infection during pregnancy and,most importantly, their infants.The shared goals of these registries areto better understand the effectsof Zika virus infection during pregnancy on infants.These pregnancies, pregnancy registries can estimate thenumber of infants with birth defectsand other pregnancy outcomes, provide datato inform the spectrum of outcomes associatedwith maternal Zika virus infection,and can be a local resource to assistwith linking infants to care.Pregnant women in the 50 U.S statesand U.S. territories are included in the registriesif they have laboratory evidenceof possible Zika virus infection regardless of whetheror not they have symptoms.Infants born to these women are also included in the registry.Additionally, infants who are identified at birthwith laboratory evidence of congenital Zika virus infection,and whose mothers were not identifiedwith Zika during pregnancy are included.Of note, the goal of these surveillance registriessystems is to follow-up on all infants born to womenwith laboratory evidence of Zika for with exposureto Zika during pregnancy and includes surveillance of infantswithout laboratory confirmation of Zika at birth.This slide demonstrates a comparison between the two partsof the pregnancy and infant registries.The U.S. ZPR captures data on pregnant womenand infants affected by Zika in the 50 U.S. statesand all territories except Puerto Rico.ZAPSS is unique to Puerto Rico,but the data elements captured are aligned to allowfor comparisons between the registries.Aside from location, the registries differand that the U.S. Zika Pregnancy Registry follows infantsfor a shorter period of time than infants in Puerto Rico.The report published includes data from American Samoa,the commonwealth of Puerto Rico, the federated statesof Micronesia, the Republic of Marshall Islands,and the U.S. Virgin Islands and represents the dedicationand commitment of many people in many locations.Along with our partners in the U.S. territories,CDC scientists have analyzed 3900 pregnancies reportedto the Zika Pregnancy and Infant Registries.It reported to the registriesbetween January 1st, 2016 and April 25th of this year.The peak in the number of pregnancieswith possible Zika virus infection reportedto these registries had laboratory evidenceor symptom onset during July through September 2016and this was demonstrated by Dr. Oduyebo.Of the total of 3930 pregnancieswith possible Zika virus infection reportedto the Zika Pregnancy and Infant Registries, 2500 pregnant womenwith evidence of Zika virus infection had completedtheir pregnancies.Of these, 122 or about 5% reported Zika associated birthdefects in infants that coincidewith the CDC surveillance case definition.This is consistent with what was reported from the 50 statesand District of Columbia during 2016.Of note, this is based on surveillance data capturedat birth and does not include the longitudinal follow-up dataof these infants for which data collection is ongoing.Among the 122 fetuses and infants reported to the registrywith Zika associated birth defects,108 or almost 90% were classifiedas having a brain abnormality and/or microcephaly.There are several other findings I would like to highlight;surveillance data from the territories shown hereon the far right column, demonstrates similar numbersof infants with reported birth defects that were born to womenwith symptomaticand asymptomatic confirmed Zika virus infection.In the U.S. territories,women with confirmed Zika virus infections documentedin the first trimester had the highest proportion of infantswith reported Zika associated birth defects,with 8% of pregnancies resulting in a fetus or babywith a possible Zika virus infection compared to 5%in the second trimester and 4% in the third.In previously published data from the U.S. statesand District of Columbia, about 15% of pregnant womenwith confirmed Zika virus infectionin their first trimester had a fetus or babywith a Zika associated birth defect.It is important to note that these estimates for the impactof Zika virus infection during the first trimester are basedon relatively small numbers.These numbers 8% for first trimester infectionin the U.S. territories and 15% for U.S. statesand D.C. may seem different, but the confidence intervalsfor these estimates overlap,meaning that this is not a statisticallysignificant difference.And again, we have not yet analyzed data on older infantsand it is important that we monitor the long-term outcomesof these infants to assess the impact of infectionsat different points in pregnancy.Among women diagnosed in the third trimester, 34% or about 1in 3 had reported symptoms of Zika virus infection.Among women with third trimester infection or those diagnosedwith infection in the third trimester,4% resulted in an infant or a fetuswith the Zika associated birth defects basedon the CDC surveillance case definition.These findings highlight the factthat birth defects can be detected following a diagnosisof Zika virus infection detected in any trimester; however,it is important to note that these, the exact timingof infection is not known for all of these women.This report also highlights potential gaps in the evaluationof infants at birth with possible Zika virus infection.Last year.Can we do a sound check?I think we lost sound for a moment.Great, we’re going to start over on the slide.So, this report also highlights potential gaps in the evaluationof infants at birthwith possible congenital Zika virus infectionin the U.S. territories.Last year, CDC released updated recommendationsfor healthcare providers caring for babies born to motherswith evidence of Zika virus infection during pregnancyincluding a comprehensive physical exam, brain imaging,newborn hearing screening and Zika lab tests.In this territorial report, nearly 60% of infantswith possible congenital Zika had test resultsfor Zika virus infectionat birth reported to the registries.Based on data reported to the Zika Pregnancyand Infant Registries, over half of the babieswith possible congenital infection have received brainimaging at birth which is higher than the 1 out of 4 basedon data reported to the registries from the 50 statesby March and D. C. by March of this year.Of note, follow-up information is reported on a regular basis.Brain imaging, for example a head ultrasound, is importantto look for brain abnormalities at birthbecause babies may have brain defectsthat are not otherwise evident without imaging.We are continuing to outreach to healthcare providersto ensure the registry captures the results of brain imagingand we are also continuing to emphasize the importanceof brain imaging for babieswith possible congenital Zika infection.In this report, nearly 80% of infantswith possible congenital Zika infection,reported to have received the recommended hearing screening.While we expect that all infants would have an hearing screenat birth, this might not have been documentedin the medical record when informationabout the birth hospitalization was collected.While this information is encouraging,there might still be opportunitiesto ensure every clinician is aware of how to screenfor exposure to possible Zika infection, how to diagnose it,and how to monitor for follow-up care.In the coming months we will be interested in also lookingat the ophthalmologic manifestations of these infantswhich you will hear about from Dr. Prakalapakorn.These reports have important public health implications.Current data suggests that the risk for birth defects is higherwhen infection occurs early in pregnancy.However, birth defects have been identified among pregnanciesthat have been diagnosed with Zika virus infectionin the third trimester.Therefore, Zika virus infection during any trimesterof pregnancy might result in Zika associated birth defectsand further study is needed.Identification and follow-up care of infants born to womenwith laboratory evidence of recent Zika virus infectionor those with exposure can facilitate timelyand appropriate clinical intervention servicesand assessment of future needs.The continued follow-up care of infants is criticalto elucidate the impact of Zika virus infection during pregnancybeyond the abnormalities detected at birth.Monitoring of ongoing pregnancieswith laboratory evidenceof possible recent Zika virus infectionand the continued follow-up of infant status beyond birth,hospitalization can inform public health recommendationsfor testing, evaluation and care.Healthcare providers and public health officials can helpcommunities by educating familieson Zika virus prevention and encouraging pregnant womento avoid travel to areas with Zika.Healthcare providers should tell women and men howto protect themselves from Zika virus infection.Ask me about possible exposure and providing testsand follow-up care as outlinedby Dr. Oduyebo is very important.Guidance is updated as we learn more about Zika virus infection.So it’s important to check on current recommendations.Supporting babies and familiesby developing a coordinated care plan for babies affectedby Zika virus infection including ongoing support,follow-up care, and linkingto local health department resources is alsovery important.And of course, continued reporting of pregnant womenand infants with possibleor confirmed congenital Zika virus infectionto the registries is an important thing as well.In summary, Zika virus infection diagnosed during any trimesterof pregnancy may be associated with the birth defectsthat meets the CDC case surveillance definition.The absence of presence of symptoms in pregnant womenwith confirmed Zika virus infection does not appearto impact the number of infants with birth defects.Healthcare providers can educate patients,consider the CDC recommendations for screening and testing,support infants and families, and again,report to the registries.There is much left to learn about Zika virus infectionand this report adds to our growing knowledge,but there remains many,many unanswered questions.CDC will continue to work diligentlywith our public health and clinical partnersto help us all learn more.Thank you for your attention today.I will now turn it over to Dr. Prakalapakorn who will presenton pediatric ophthalmologic findings associatedwith congenital Zika.

>> She has the remote control.

>> Thank you Dr. Meaney-Delman.Good afternoon and thank you for joining us.My name is Dr. Grace Prakalapakorn and today I wouldlike to talk to you about pediatric eye findingsthat have been reported in infantswith Zika virus infection.Before we delve into the ocular findings reported in infantswith Zika virus infection, let’s do a brief reviewof the ocular anatomy.Here is a cross-sectional image of the eye.Light normally travels through the front clear surfaceof the eye known as the cornea, through the openingin the colored part of the eye known as the pupil,through the normally clear lens of the eye and is focusedon the back light sensing surfaceof the eye known as the retina.The retina then transmits signals through the optic nerveto the brain which interprets these signals as images.These images are of the normal retina of a right eye.The retina is the light sensing part of the back of the eye.The photograph on the left shows just a smallbut important section of the overall retina depictedin the image on the right.The photograph on the left is centered on the maculawhich the area of your retina responsiblefor your central vision.On the right of this photograph is the optic nervewhich is responsible for carrying informationfrom the retina to the brain.Note here that the optic nerve looks pink and healthy.Next, I will describe ocular findings reported in the settingof congenital Zika infection.Our knowledge of the effectsof Zika virus infection during pregnancy is evolving.While most ocular abnormalities have been reported in infantswith microcephaly, ocular abnormalities have been donein infants both with and without microcephaly.Abnormalities have been found both in the anteriorand posterior parts of the eye.A couple of studies have evaluated the visual functionamong cohorts of infants with microcephaly dueto suspected congenital Zika syndrome.Both studies found that while about 40%of their cohorts have ocular abnormalities,a100% are children tested had visual impairment.This cortical visual impairment might be the most common causeof blindness among children with congenital Zika syndrome.Among infants with microcephalyand presumed congenital Zika virus infection,the most commonly reported structural ocular abnormalitiesinvolved the macula and the optic nerve.The macula is the area of the retina responsiblefor central vision, and the optic nerve is the structureresponsible for sending informationfrom the eye to the brain.Commonly reported macular findings include;macular motting, loss of foveal light reflex,and chorioretinal atrophy depictedby the short green arrow in the image on the left.Commonly reported optic nerve findings include optic nervehypoplasia which is a small optic nervewith a double ring sign seen in the image on the left depictedby the long white arrow.Optic nerve cupping, which is an increase in the ratiobetween the size of the depression and the optic nerveand the size of the optic nerve, and optic nerve pallorwhich is a sign of insult or damage to nerve.Other posterior eye findings that have been reportedin infants with microcephalyin presumed Zika virus congenital infection include;retinal lesions that are not purely confined to the macula,but can located in other parts of the retina.The image on the right shows pigmentary clumping depictedby the blue arrowand a subretinal hemorrhage depicted by the yellow arrow.There is also vascular tortuosity,meaning the vessels have many curves and in the periphery,the long white arrows depict areas of abnormal terminationof the vessels and the short white arrow shows a focal areaof vascular dilation.Other ocular findings have also been reported in infantswith presumed congenital Zika syndromeand microcephaly including; congenital glaucoma,a disease in which the pressure in the eye is too highand can cause damage to the optic nerve which can resultin severe vision loss.Some common symptomsin congenital glaucoma are excessive tearing,light sensitivity, and large cloudy corneas,the normally clear front surface of the eye as shownin the image on the left.Iris colobomas shown here on the top rightwhere there is a defect in the colored part of the eye knownas the iris, most likely causes by the failureof some structures of the eyeto close during gestational development; microphthalmia,an abnormally small eye shown on the image on the bottom right.Other abnormalities not pictured include subluxationor displacement of the lens, cataracts;a clouding of the normally clear lens of the eye,and intraocular calcifications.Studies have found that risk factorsfor ocular abnormalities among infantswith presumed congenital Zika infection included a smallerhead circumference, microcephaly,other central nervous system abnormalities,earlier trimester infection in pregnancyand joint contractures.While most reported cases of infantswith ocular findings have microcephaly,infants with possible Zika virus infectionwithout microcephaly have also been reportedto have both anteriorand posterior ocular findings including; microophthalmia,iris colobomas, optic nerve and retinal abnormalities.The image on the left shows a hypopigmented retinal lesionabove the optic nerve and in the image on the right,a chorioretinal scar in the macula.Our knowledge of the effects of Zika virus infection on the eyeand on vision with or without concomitant structural anomaliesis still growing.A recent study of infants born or motherswith Zika virus infection during pregnancy identified 8 infantswithout central nervous system findingswho had eye abnormalities.In addition to previously reported eye findings,researchers also reported an infant with a colobomaof the optic nerve and retina.Ocular manifestations are not uniqueto congenital Zika infection.This table compares ocular findings reported in infantswith congenital Zika infection to thosein other common congenital infections.As you can see, there is some overlap across the diseasesin ocular manifestations such as the presence of microphthalmia,cataracts, and optic nerve pallor.To date, no active inflammatory lesions have been reportedin infants with congenital Zika infection, whereas,they have been reported in other diseases.As with the other congenital infections,not only does the presence of ocular manifestations varybetween infants, but also the severity of these findings.Now I will speak about CDC’s current recommendationsregarding clinical management of infantswith possible congenital Zika virus infectionwhich were published in August 2016.Currently, the CDC recommendsthat infants who’s mothers have risk factorsfor maternal Zika virus infection that has traveledto a residence in an area of Zika virus transmission,or sex with a partner who traveled to or residedin such an area, and maternal test results are not availableand there is concern about infant follow-up,that these infants be seen before hospital discharge.All infants with laboratory evidenceof congenital Zika virus infectionor with abnormal findings consistentwith congenital Zika syndrome,should be seen before 1 month of age.If the ophthalmologic examinationwithin the first month of life is normal,another complete examination is recommended at 3 months of age.Referral for ophthalmologic screening maybe consideredin other clinical scenarios outside those I’ve justdescribed including when mothers have not been tested.The ocular examination by an eye care professional shouldinclude; visual acuity assessment,intraocular pressure measurements,slit lamp examination and a dilated fundus examination.Children who experience visual impairmentor loss should be referred to a low-vision specialistand developmental services early in life knownas early intervention to help babies improveand maximize their abilities.Because Zika virus testing is not perfect,for infants without laboratory evidence of Zika virus infectionbut for whom suspicionfor congenital Zika virus infection remains,primary care providers can help by considering a referralto an ophthalmologist before hospital dischargeor within 1 month of birth.For the outpatient management of infants with laboratory evidenceof Zika virus infection, but without abnormalities consistentwith congenital Zika syndrome,a visual screening including assessmentof visual regard should be performedat each well-child visit and referralto an ophthalmologist should be madefor any caregiver or provider concerns.Here are some tips for screening vision in infants.The simplest and most convenient ways to assess visionin a preverbal child is a Wince to Light Testand the Fix and Follow Test.For very young infants, 1 to 2 months of age, you can testif they wince to light.This can even be tested through closed eyelids using a verybright light such as a penlight.If you don’t have a bright light to shine, you can turn onand off the room lights to see if you elicit a reaction.Infants may wince with the light onand their eyes may widen in the darkness.At about 3 months of age, you should be able to testif they are able to fix and follow.You just need an object that grabs their attentionand you see if they are able to look at the object and follow itas you move it around.Start off by checking their vision with both eyes open,then try to test one eye at a time by covering one eyewith your hand while you assess visionin the other uncovered eye.Today, we have covered several topics related to Zika.What we’ve learned in the past yearand how we are changing guidanceto address these new developments.In summary, declining Zika virus transmission in the Americasand new data on the Zika virus persistence,have increased the complexity of testing prompting CDCto update its guidance for the clinical managementof pregnant women with possible Zika virus exposure.This updated guidance emphasizes a shared decision-making modelfor the testing and screening of pregnant women.One in which patients and providers work togetherto make decisions about testing and care plans basedon a balanced assessment of risks and expected outcomes,clinical judgment, patient preferences and values,and incorporates state or local area recommendations.A recent report detailing pregnancy outcomesof Zika virus infectionin the U.S. territories supports the claimthat Zika virus infection poses a riskto all pregnancies regardless of timing of possible exposure,and congenital Zika virus infection can leadto poor ophthalmologic outcomes in the presence and absenceof other birth defects.All of this is the work of many people.Many thanks to all of our collaboratorsand thank you all for listening today.

>> Thank you presenters for providing or COCA audiencewith such a wealth of very important information regardingZika virus.We will not move on to the questionand answer portion of the call.We have additional CDC Zika experts who will join usfor this part of the call.Due to time constraints, it’s possible we may not be ableto address your question.If this occurs, please email your question to coca@cdc.gov,again, coca@cdc.gov and we’ll forward your questionto the appropriate presenter for an answer.Again, questions are limited to clinicians who wouldlike information related to Zika virus.For media questions, please contact CDC Media Relationsat 404-639-3286 or send an email to media@cdc.gov.If you’re a patient, please refer your questionsto your healthcare provider.Our first question that came in through the webinar system is,what percentage of patients in this studyso far have shown positive IgM persistencein the past 12 weeks?

>> Can you hear me?This is Dr. AddisHello.

>> We can hear you Eddy.

>> Oh, okay thank you.I’m sorry.I didn’t realize.Okay. So, I think that the answerto the question is very difficult.We don’t have a good denominator.We have looked at several studies longitudinallyin patients who were PCR-positive and then test,and then bled them out over serial bleedsover a consistent period of time almost as long as a year now.In all of those patients, we do see in the majorityof those, a long-term IgM.We’ve also noticed that there are several individualsand several papers that have been published recentlythat demonstrate longevity of IgM beyond the 10 dayor a 30-day window that one would normally expectfor an IgM response.Some say that with Orbivirus you can expect responsesup to 90 days because of that’s what’s been seen with someof the other arboviruses.So, in this particular case, the problem isthat we do see patients beyond 90 days with IgM,but like I said, it’s very difficultto determine the percentage simplybecause we don’t have a good denominator.We just have a large number of individuals who we have seenwho demonstrate long-term or persistent IgM.Thank you.

>> Thank you Dr. Addis.The next question is, is there concernthat decreasing testing now at the heightof mosquito season will fail to provide surveillancethat would provide an indication of increasing casesin susceptible since most cases are asymptomatic?

>> This is Dr. Oduyebo speaking.Thank you for your question.As was discussed during the presentation,it’s really important to know that the reported incidenceof Zika virus disease in the Americas has declinedand which this implications for interpretationof Zika virus test results.With declining prevalence of the Zika virus disease,the probabilityof a false-positive test result increases and this could leadto a negative repercussion for pregnant women and their care.In addition, the limitations of the currently available test,the lack of vaccine or effective therapy underscores theimportance of shared patient-providerdecision-making.You know, making the decision about Zika virus testingand whether to advise you takeinto account the patient’s unique circumstancesand should allow pregnant women to make an informed decisionby the utility of testing in the contextof the local jurisdictional recommendations.

>> Okay, thank you Dr. Oduyebo.The next question is, if after the shared decision-makingdiscussion, an asymptomatic patient desires testing,should this be sent through the Health Departmentor will this have to be sent to commercial labs?

>> So, our; I want some people to make note that this;these guidance are recommendationsand local state health departments view ourrecommendations and may adapt based on their local context.So given this, it’s very important for you to reachout to your local or state health departmentsto discuss this and where the procedures will beas these recommendations and guidance are adapted or adopted,because it’s most likely to deferby the jurisdiction you’re in.

>> Thank you Dr. Oduyebo.The next question is, what is the estimated false-positiverate in an asymptomatic patient?

>> Thank you so much for that question.I’d like to invite our epidemiology and surveillancecolleague from Fort Collins to respondto that question Dr. Ingrid Rabe.

>> Hi. Thanks very much.So, they are, there’s difficultyin quantifying the actual false-positive rates.I think it’s just important to take a step back and rememberthat they, there are different issues at have been mentionedin this presentation already with regard to false-positives,so we know that inherent in the [inaudible] has been publishedin the [inaudible] documents for the respected assays themselvesthat there will be some false-positive test resultsoccurring, but as was described in the presentation itself,as we do get decreasing numbersof true positive infections occurring that among peoplewho are tested,the false-positive rate will increase.So, to put a number on it would not be possible at this time,but we know that as the prevalence continuesto decrease, that that percentage will increase.Of note as well, for many who are familiar during the courseof the outbreak, there have been cautions issuedaround the IgM results and the possibilityof false-positives dueto various reasons including cross-reactivity,but also in non-specific reactivity in assays well,hence, the repeated causefor basically appropriate conformity testingwere indicated.So, not a specific number to put on there,but we do from a mathematicaland epidemiologic standpoint expect that that proportionof false-positives will increase among positive tests.

>> Thank you so very much Dr. Rabby.The next question is, does sex with a male partnerwho was possibility exposed to Zika qualifyas repeated exposure for a pregnant woman i.e. both wenton vacation to a Zika endemic country with no plans to return?And the second portion of that question is,what is the definition of ongoing?

>> Thank you.This is Dr. Oduyebo speaking.So, here at CDC we define ongoing possible Zika virusexposure and referring to a person who lives in an areawith risk for Zika and who has frequent exposureto area with Zika.For example, living in the U.S. Mexico borderwith regular travel into Mexico.So, for a pregnant woman with a partner which frequent,and we mean daily or weekly travel to an area with riskfor Zika, we would recommend that condoms are usedor the couples abstain from sexfor the duration of the pregnancy.In the event that this advice is not followedand there’s recurrent unprotected sex,then it will be reasonable to follow the guidancefor asymptomatic pregnant women with ongoing possible exposure.On the other hand, for a pregnant woman with a partnerwho traveled once to an area with the risk for Zika,we would recommend that condoms again are usedor the couple abstain from sexfor the duration of the pregnancy.If the recommendations are not followed,the situation possibly could be consideredas having an ongoing possible exposure.

>> Thank you Dr. Oduyebo.Next question is, is there a recommendationon how long pregnancy should be postponedafter possible Zika exposure in an endemic area?

>> Thank you for the question.This is Dr. Oduyebo speaking again.So, women and partners wishingto conceive should receive preconception counselingabout how to minimize riskfor Zika virus transmission during pregnancyand this includes before they travel,they talk to their doctorabout whether they should postpone their travel.And if they do travel,the recommended waiting period after travel.This recommendation was published in September,I believe 2016 that has not changed.If only the woman traveled or had exposure, possible exposureto an area with risk, the recommendation is to waitat least 8 weeks after symptom onset of Zika virus diseaseor 8 weeks after, you know, the last possible exposure.If it was a male, it was a male who had exposure to an areawith risk for Zika, the recommendation is to waitat least 6 months after his symptom onsetor possible exposure.

>> Okay, thank you so much Dr. Oduyebo;Oduyebo corrected, excuse me.On behalf of COCA, I would like to thank everyonefor joining us today and thank you so muchfor your patience while we experienced someaudio difficulties.We would like to especially thank our presenters,Dr. Oduyebo, Dr. Meaney-Delman and Dr. Prakalapakorn.The recording of this call and the transcript will be postedto the COCA website at emergency.cdc.gov/cocawithin the next few days.All Continuing Educationfor COCA calls are issued online through TCE online.The CDC Training and Continuing Education online systemat www.cdc.gov/tceonline.Those who participated in today’s COCA call and wouldlike to receive continuing education,should complete the online evaluation by July 26th,2018 and use course code, WC2286.Those who will review the call and demand and wouldlike to receive continued education,should complete the online evaluation by May 24th,2018 also using course code, WC2286.To receive information on upcoming COCA calls,subscribe to COCA by going to the COCA webpageat emergency.cdc.gov/coca and clicking on the”join the COCA mailing list” link.Please join us for our next COCA call which will take placeon August 15th where the topic will be Candida auris .Also, you’re invited to like our Facebook pageat facebook.com/cdc outreach and communication activityto stay connected to the latest news from COCA.Again, we will; if we did not get to your question today,we would appreciate your sending your questions to COCAat cdc.gov, again, it’s coca@cdc.govand we will be happy to respond to your question and get backto you just as quickly as possible, and thank you againso much for being a part of today’s COCA call.We hope you have a great day.

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