Update on Interim Zika Virus Clinical Guidance and Recommendations

Coordinator:       
Thank you for standing by. At this time all participants are in a listen-only mode. After the presentation we’ll conduct a question and answer session. To ask a question please press the Star 1 and please record your name. Today’s conference is being recorded. If you have any objections you may disconnect at this time. I would like to introduce your host for today’s conference (Ashley Ghaffarzadeh). Please begin.

Ashley Ghaffarzadeh:
Thank you Kathy. Good afternoon I’m Ashley Ghaffarzadeh. And I’m representing the Clinician Outreach and Communication Activity, COCA for the Emergency Risk Communication Branch at the Centers for Disease Control and Prevention. I’m delighted to welcome you to today’s COCA call: Update on Interim Zika Virus Clinical Guidance and Recommendations.

You may participate in today’s presentation by audio only via Webinar or you may download the slides if you are unable to access the Webinar. The PowerPoint slide set and the Webinar link can be found on our COCA webpage at emergency.cdc.gov/coca. Click on February 25 COCA call. The slide set is located under Call Materials.

There is no continuing education provided for this call. CDC, our planners, presenters and their spouses/partners wish to disclose they have no financial interest or other relationships with the manufacturers of commercial products, suppliers of commercial services or commercial supporters. Planners have reviewed the content to ensure there is no bias. This presentation will not include any discussion of the unlabeled use of a product or products under investigational use.

 At the end of the presentation you will have the opportunity to ask the presenters questions. On the phone dialing Star 1 will put you in the queue for the questions. You may submit questions through the Webinar system at any time during the presentation by selecting Q&A Tab at the top of the Webinar screen and typing in your question.

Questions are limited to clinicians who would like information related to Zika virus disease. For those who have media 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.

Our first presenter is Dr. Emily Petersen. Dr. Petersen is a Medical Officer in the Division of Reproductive Health at the Centers for Disease Control and Prevention, CDC. Dr. Petersen is an Obstetrician/Gynecologist and has focus on maternal mortality during her career CDC.

Our second presenter is Dr. Katherine Fleming-Dutra is a Medical Epidemiologist with the National Center for Emerging and Zoonotic Infectious Diseases at CDC. Dr. Fleming-Dutra is a Pediatrician and Pediatric Emergency Medicine Physician and has focused on infectious diseases epidemiology in her career at CDC.

Our third presenter, Dr. Alexa Oster is a Medical Epidemiologist with the Division of HIV/AIDS Prevention at CDC. Dr. Oster is an Internist and has focused on HIV in her career at CDC. At this time please welcome Dr. Emily Petersen.

Dr. Emily Petersen:  
Thank you. Good afternoon. Thank you for this opportunity to speak with you today. We would like to share some brief background about what we know about Zika virus and then describe CDC’s inter - updated interim guidelines for healthcare providers.

Zika virus disease is spread to people primarily through the bite of an infected Aedes species mosquito. These mosquitoes are aggressive daytime biters but they also bite at night. Symptoms of Zika virus are generally mild and last for several days to a week.

Other documented modes of Zika virus transmission include intrauterine and perinatal transmission, sexual transmission and laboratory exposures. Additionally there have been reports of Zika virus transmission through blood transfusion in Brazil. Zika virus in breast milk and sexual transmission of Zika virus will be discussed later in the presentation.

The majority of patients with Zika virus infections are asymptomatic. When symptoms are present, the most common signs and symptoms of Zika virus disease include fever, rash, joint pain and conjunctivitis. Other symptoms include muscle pain and headache.

There are 29 countries or territories currently reporting Zika virus transmission. Updates on areas with active Zika virus transmission are available online. Local vector-borne transmission of Zika virus has not been reported in the continental United States but local transmission has been reported in US territories.

With the current outbreak in the Americas, the number of cases of Zika virus infection in US travelers will likely increase. Imported cases may result in virus introduction to the continental United States and local vector-borne transmission might occur in some areas of the US.

There is limited information available on Zika virus in pregnancy. Existing data show no evidence of increased susceptibility to Zika virus in pregnant women. Zika virus infection can occur in any trimester, but the incidence of Zika virus infection and pregnant women is not known. There is no evidence that pregnant women have more severe disease compared with non-pregnant people.

From October 2015 to January 2016, over 5200 cases of infants born with suspected microcephaly have been identified in Brazil. These cases have been temporally linked with the current Zika virus outbreak, although over 3900 are still under investigation. In French Polynesia, a retrospective study found 17 cases of neurologic malformation among fetuses and newborns that were temporally linked to a 2013 to 14 Zika virus outbreak. Investigations are ongoing.

Laboratory tests of a small number of cases in Brazil suggest a link between Zika during pregnancy and microcephaly. The pattern of microcephaly is consistent with fetal brain disruption sequence based on photos and scans of a small number of affected infants in Brazil and findings from retrospective investigation of the Zika outbreak in French Polynesia. The pattern that has been seen in infants with other intrauterine infections such as - has been seen in other uterine infections such as cytomegalovirus.

CDC continues to evaluate all available evidence to determine if there is a causal relationship between the reported cases of microcephaly and Zika virus infection in pregnancy. We are also working to understand the full spectrum of phenotypes that might be related to Zika infection. We are working hard to understand the factors that may influence the risk of birth defects. For instance, how the impact of timing of infection and pregnancy or severity of illness may increase or decrease the risk of microcephaly and other adverse pregnancy outcomes. In addition to these what we know, there are also recent reports on Zika virus and pregnancy outcomes which are building evidence for the link between Zika virus infection and microcephaly or other adverse outcomes. I will review these now.

Calvet et al recently reported two cases in Brazil. The first is a pregnant woman who developed a rash, fever and myalgia at 18 weeks’ gestation. She did not have Zika virus testing at this time. She had previously had a normal ultrasound at 16 weeks but a 21 week ultrasound indicated a fetal microcephaly diagnosis with moderate ventriculomegaly and partial agenesis of the cerebellar vermis. A 22 week ultrasound confirmed the microcephaly with ventricular dilation, asymmetry of the hemispheres, hypoplastic cerebellum and absence of cerebellar vermis. At 40 weeks, microcephaly and calcifications were detected by ultrasound prior to delivery. An amniocentesis was performed at 28 weeks and amniotic fluid was positive for Zika virus RNA. Serum and urine were negative for Zika virus by RT-PCR. The infant was born at 40 weeks with a head circumference less than the 1st percentile.

The second case is a pregnant woman residing in Brazil who had developed symptoms of Zika virus disease at ten weeks’ gestation. A 22 week ultrasound revealed mild hypoplasia of the cerebellar vermis and fetal head circumference at this time was below the 10th percentile. A 25 week ultrasound demonstrated fetal microcephaly and severe hypoplasia of the cerebellar vermis and enlargement of the posterior fossa. Amniotic fluid was positive for Zika virus RNA and serum and urine tests were negative. The infant was born with severe ventriculomegaly, microphthalmia, cataracts and severe arthrogryposis.

Mlakar and colleagues reported - recently reported the case of a pregnant woman who resided in Brazil until 29 weeks’ gestation. She developed symptoms of Zika virus at 13 weeks. Ultrasound reports at 14 and 20 weeks indicated normal fetal growth and anatomy, however an ultrasound at 29 weeks had evidence of fetal anomaly. A 32 week ultrasound showed intrauterine growth restriction, microcephaly and other brain abnormalities.
After termination at 32 weeks, fetal autopsy showed a brain weight four standard deviations below normal. Zika virus RNA was detected in the fetal brain tissue. There was - on exam there was almost complete agyria and internal hydrocephalus of the lateral ventricles.

In a recent article, Martines and colleagues reported cases of two pregnant women in Brazil who had clinical signs of Zika virus disease during their first trimesters. Their infants were born with microcephaly at 36 and 38 weeks and both infants died within 20 hours of birth. CDC received tissue samples in December 2015 and performed laboratory testing and histopathologic evaluation. Zika virus RNA was detected in only the brain tissue of both infants and there were significant histopathologic changes in the brain including parenchymal calcification and necrosis.

Martines et al also reported the cases of two pregnant women from Brazil with clinical signs of Zika virus disease during the first trimester who had fetal losses at 11 and 13 weeks. Zika virus RNA was detected in products of conception in both cases. Zika viral antigen was detected by immunohistochemical staining in the chorionic villi in one case and histopathologic changes consistent with calcification and fibrosis were seen in this case. These cases and their clinical presentations, sonographic, laboratory and pathologic findings are building the link between Zika virus and adverse pregnancy outcomes. Further studies are currently under way.

Now I would like to switch gears and discuss CDC’s updated interim guidance for healthcare providers caring for pregnant women and women of reproductive age with possible Zika virus exposure. Until more is known, CDC recommends that pregnant women should consider postponing travel to areas where Zika virus transmission is ongoing.

Pregnant women who are considering travel to one of these areas should talk to their healthcare providers and strictly follow steps to prevent mosquito bites during the trip. CDC recommends taking the following measures to prevent mosquito bites: Use EPA-registered insect repellents. These repellents, including DEET and permethrin, are safe and effective for pregnant women when used in accordance with the product label. Pregnant women should wear long-sleeved shirts and pants to cover exposed skin and wear permethrin-treated clothes. Pregnant women should stay and sleep in screened-in or air-conditioned rooms if possible. People should practice mosquito prevention strategies indoors and outdoors throughout the entire day.

Healthcare providers should ask all pregnant women about their travel history. If a pregnant woman has a history of travel to an area with Zika during pregnancy, her health care provider should evaluate her for symptoms of Zika virus infection including fever, rash, arthralgia or conjunctivitis, and test for Zika virus infection according to the testing algorithm. Pregnant women with male partners who have Zika virus infection or potential exposure should use condoms or abstain from sexual activity for the duration of pregnancy.

 On February 5, CDC updated its interim guidelines for US healthcare providers caring for pregnant women during a Zika virus outbreak. The updated guidance includes a new recommendation that serologic testing can be offered to asymptomatic pregnant women with a travel history to areas with ongoing Zika virus transmission. It also provides updates on screening, testing and management of pregnant women and it provides recommendations on counseling of women of respective age residing in areas of ongoing Zika virus transmission.

 CDC recommends the following Zika virus diagnostic testing for symptomatic persons. Reverse transcription-polymerase chain reaction or RT-PCR detects viral RNA in serum and should be collected within seven days after illness onset. Serologic testing for Zika virus immunoglobulin M or IgM may be collected four or more days after illness onset. IgM testing can be complicated by cross-reactivity among related flaviviruses such as dengue and yellow fever; plus a positive IGM result can be difficult to interpret.

Plaque Reduction Neutralization Test or PRNT can be performed to measure virus specific neutralizing antibodies to Zika virus and other flaviviruses. The levels of neutralizing antibodies can then be compared between the flaviviruses; while results might be difficult to interpret in person with previous infection or vaccination. Healthcare providers should work with their state, local or territory health departments for the facilitation and interpretation of testing.

Serologic testing for Zika virus can be offered to asymptomatic pregnant women with possible Zika virus exposure, including travel to or residence in an area with ongoing Zika virus transmission. A negative IgM result could suggest that a recent infection did not occur and could obviate the need for serial ultrasounds. However, a negative serologic result cannot definitively rule out Zika virus infection as information about the performance of the serologic testing of asymptomatic persons is limited.

I will now review Zika testing algorithms; first for pregnant women with history of travel to areas with Zika transmission, and second for women residing in these areas. Here is the updated testing algorithm for pregnant travelers. I will now go through it in further detail.

Symptomatic pregnant women with a history of travel to areas with Zika are women who experienced two or more of the following signs or symptoms within two weeks of travel: acute onset of fever, maculopapular rash arthralgia or conjunctivitis. RT-PCR should be performed during the first week of clinical illness. IgM testing may be indicated depending on the timing of the test in relation to symptom onset. Testing should be coordinated through the state, local or territorial health department.

For asymptomatic pregnant women with a history of travel to areas with ongoing Zika virus transmission, serologic testing with IgM can be offered. This test should be performed between 2 and 12 weeks after return from travel. A positive Zika virus test is defined as either Zika virus RNA detected on RT-PCR or Zika virus IgM positive with confirmatory neutralizing antibody titers that are greater than or equal to 4 folds higher than dengue virus neutralizing antibody titers. An inconclusive test is defined as Zika virus IgM positive with neutralizing antibody titers that are less than four-fold higher than dengue virus neutralizing antibody titers.

For pregnant women with a positive or inconclusive test result, healthcare providers should consider serial fetal ultrasounds for every three to four weeks and could consider amniocentesis for Zika virus testing. Referral to maternal-fetal medicine specialist is recommended. If the maternal test is negative, a fetal ultrasound should be performed to detect microcephaly or intracranial calcification. If one or both findings of microcephaly or intracranial calcification are present, the pregnant woman should repeat serologic testing and amniocentesis could be considered for Zika virus testing with RT-PCR. Consultation with the maternal-fetal medicine specialist would be recommended. If microcephaly and intracranial calcifications are not (present) routine prenatal care is appropriate.

Now I will discuss the recommendations for pregnant women who reside in areas with ongoing Zika transmission. Healthcare providers should evaluate pregnant women for symptoms of Zika virus infection and perform appropriate testing according to the algorithm. Local health officials should determine when to implement testing of asymptomatic pregnant women based on information about levels of Zika virus transmission and laboratory capacity. If testing is recommended healthcare providers can offer serologic testing at the initiation of prenatal care and perform a follow-up test in the mid-second trimester due to the ongoing risk of Zika virus exposure and infection. Routine ultrasound screening is recommended for all pregnant women at 18 to 20 weeks gestation. Again, pregnant women with male partners who have or are at risk of Zika virus infection should use condoms or abstain from sexual activity for the duration of pregnancy. Recommendations will be updated as more information becomes available.

On February 5, CDC issued this testing algorithm for pregnant women residing in an area with ongoing Zika virus transmission. It is more complex due to the ongoing risk of Zika virus exposure and infection for residents of these areas. First I will talk about the testing of symptomatic pregnant women residing in areas with Zika.

For pregnant women experiencing clinical illness consistent with Zika virus disease, RT-PCR testing should be performed during the first week of illness. IgM testing may also be indicated depending on the timing of the test in relation to the onset of illness. Testing should be coordinated through the state, local or territorial health department. For woman with positive or inconclusive test results, healthcare providers should consider performing serial fetal ultrasounds every three to four weeks and could consider amniocentesis for Zika virus testing. Referral to maternal-fetal medicine specialist is recommended if available.

If a symptomatic pregnant woman has a negative test result, a fetal ultrasound should be performed to detect microcephaly or intracranial calcifications. Either finding should prompt healthcare providers to retest for maternal Zika virus infection with serologic testing and consider the testing of amniotic fluid with RT-PCR depending on the clinical scenario. If microcephaly and intracranial calcifications are not present, routine prenatal care should be continued.
 

For a pregnant women residing in areas with ongoing Zika virus transmission, routine care might include testing for Zika virus in the mid-second trimester and an additional fetal ultrasound.

I will now talk about testing for asymptomatic pregnant women residing in areas with ongoing Zika virus transmission. Local health officials should determine when to implement testing of asymptomatic pregnant women based on levels of Zika virus transmission and laboratory capacity. If local health officials implement testing, serologic testing can be offered upon initiation of prenatal care.

In the case of a positive or inconclusive Zika virus test result, consider serial fetal ultrasounds every three to four weeks and amniocentesis. Referral to a maternal-fetal medicine specialist is recommended if available.

It is important to note that false positive IgM result is more likely among women residing in areas with ongoing Zika virus transmission than among travelers because of a higher likelihood of a previous exposure to a related flavivirus, for example, dengue virus. Interpretation of testing should be coordinated through state, local or territorial health department.

Pregnant women with negative Zika virus IgM test should receive routine prenatal care including fetal ultrasound at 18 to 20 weeks to assess fetal anatomy. The ultrasound should include careful evaluation of the fetus for brain anomalies including microcephaly and intracranial calcifications. Repeat IgM testing can also be offered in the mid-second trimester because of the ongoing risk for Zika virus exposure and infection.

Findings of microcephaly or intracranial calcifications on ultrasound, or a positive or inconclusive test for Zika virus infection on repeat testing, should prompt healthcare providers to consider serial fetal ultrasound and potentially consider testing of amniotic fluid with RT-PCR. If there are no findings of fetal microcephaly or intracranial calcifications, and tests are negative for Zika virus infection, routine prenatal care is appropriate. Because fetal microcephaly is most easily diagnosed in the late second and early third trimesters of pregnancy and because of ongoing potential exposure to Zika virus, healthcare providers might consider an additional fetal ultrasound later in pregnancy. Again, findings of microcephaly or intracranial calcifications should prompt healthcare providers to repeat serologic testing and consider testing of amniotic fluid.

To summarize, in pregnant women with positive or inconclusive Zika virus testing results, serial ultrasounds should be considered to monitor fetal anatomy and growth every three to four weeks. Referral to maternal-fetal medicine specialist is recommended. Testing is recommended at the time of delivery including: histopathologic examination of the placenta and umbilical cord; testing of growth and placental tissue and cord tissue for Zika virus RNA; and testing of cord serum for Zika and dengue virus IgM and neutralizing antibodies.

Lastly, I will talk about care for women of reproductive age who are not pregnant who are residing in areas with ongoing Zika virus transmission. Healthcare providers should counsel women regarding mosquito bite prevention. Additionally, they should discuss reproductive life plans and preconception care. Decisions regarding the timing of pregnancies are personal and complex. Reproductive life plans can assist in making these decisions. Healthcare providers should discuss patient age, fertility, reproductive and medical history as well as the values and purposes of the woman and her partner during discussions regarding pregnancy intentions and timing.

In the context of the ongoing Zika virus outbreak, preconception care should include a discussion of the signs and symptoms of Zika virus disease and when to seek care, and the potential risk of Zika virus infection during pregnancy and how to prevent Zika virus infections. For women of reproductive age who do not desire pregnancy, healthcare providers should provide counseling on family planning and contraceptive methods. Approximately half of US pregnancies each year are unintended. Patients should be counseled to use the most effective contraceptive method that can be used correctly and consistently. Additionally, healthcare providers should recommend condom use to reduce risk of contracting sexually transmitted infections.

For women of reproductive age residing in areas of ongoing Zika virus transmission who desire pregnancy, healthcare providers should emphasize mosquito prevention strategies. These interventions are known to reduce the risk of Zika virus infection and other vector borne diseases. Healthcare providers should provide preconception counseling and review the risks of Zika virus disease transmission during pregnancy. Women of reproductive age with current or prior Zika virus infection should be informed that there is no evidence that prior Zika virus infection poses a risk of birth defects for future pregnancies. Viremia is expected to last approximately one week in patients after the onset of illness and there is no evidence that a fetus conceived after maternal viremia has resolved would be at risk for fetal infection.

I would like to know pass it over to Dr. Katherine Fleming-Dutra who will discuss CDC’s recommendations for infants and children in the setting of Zika virus outbreak.

Dr. Katherine Fleming-Dutra:        
Thank you. As Dr. Petersen has already provided an overview of Zika virus and microcephaly I would like to start by reviewing the evidence for acute Zika virus disease in infants and children. Perinatal transmission of Zika virus infection to infants from mothers infected near the time of delivery has been reported in two cases.

During the Zika virus outbreak in French Polynesia in 2013 and 2014, two pregnant women with signs and symptoms of Zika virus infection around the time of delivery were tested and Zika virus RNA was detected by RT-PCR in both mothers. Their neonates were subsequently diagnosed with Zika virus infection within one to three days after delivery. One of these infants was asymptomatic and the other had thrombocytopenia and a diffuse rash.

It is unlikely that these neonates were exposed to mosquitoes, and it’s presumed that the transmission occurred during the time of delivery. Both babies recovered but the long-term follow-up was not reported. The spectrum of clinical features that might be observed in neonates who acquire Zika virus during the perinatal period are currently unknown.

Available evidence regarding the spectrum of Zika virus disease in infants and children who are affected through mosquito bites indicates that most children are asymptomatic or have mild illness similar to the findings seen in adults infected with Zika virus disease. In Zika virus outbreak in Yap Island, Micronesia in 2007, clinical illness was reported in persons 1 to 76 years of age. The most common signs and symptoms of illness reported were rash, either macular or papular, fever, arthralgia and conjunctivitis.

In that outbreak children aged 0 to 19 years have lower attack rates of confirmed and probable Zika virus disease then did adults aged 20 to 59 years. Among eight recent travel related cases of Zika virus disease among children in the United States, all had rash and at least one other sign or symptom: fever, arthralgia and non-purulent conjunctivitis.

Additionally Guillain-Barre syndrome or GBS has been reported after Zika virus infection but a causal link has not been established. It is unclear how many children have been affected. A report from Brazil indicated that six patients aged 2 to 57 years during the current outbreak have developed neurologic syndromes including Guillian-Barre and acute disseminated encephalomyelitis after laboratory-confirmed Zika virus infection. In French Polynesia among 38 reported cases of Guillain-Barre syndrome after Zika virus infection none were among children. Overall GBS incidence from any cause appears to increase with increasing age.

And deaths associated with Zika virus are very rare.

Now that I have provided that review I’d like to provide the CDC recommendations for the evaluation of infants and children with possible Zika virus infection. These are interim guidelines and CDC continues to evaluate all available evidence to update recommendations as new information becomes available.

CDC’s updated guidelines have been informed by our close collaboration with clinicians, professional organizations, state and local health departments and many other stakeholders. These updated guidelines contain a new recommendation to provide routine care to infants without microcephaly or intracranial calcifications who have no abnormal findings on prenatal or postnatal ultrasound, normal physical examination and whose mothers travel to or resided in areas with Zika virus transmission during pregnancy but whose mothers were not previously tested for Zika virus infection. These guidelines also have been expanded to include infants and children with possible acute Zika virus disease.

Let’s walk through the updated algorithm for the evaluation and management of infants whose mothers traveled to or resided in an area with ongoing Zika virus transmission during pregnancy. The first step is to determine whether or not the infant has microcephaly or intracranial calcification detected prenatally or at birth. For infants with microcephaly or intracranial calcification the evaluation and management remains the same as the guidelines released on January 26, 2016. This infant should be tested for Zika virus and further clinical evaluation and laboratory testing is also recommended for the infant.

For infants with any positive or inconclusive test findings for Zika virus infection, healthcare providers should report the case to the local, state or territorial health department and assess the infants for possible long term sequelae. For infants who have negative test results on all Zika virus tests performed, healthcare providers should evaluate the infant for other possible etiologies for the infant signs and symptoms and treat as indicated.

For an infant without microcephaly or intracranial calcifications born to a mother who was potentially infected with Zika virus during pregnancy, subsequent evaluation depends on results of maternal Zika virus testing. I will now go through this evaluation pathway in more detail.

If the mother received positive or inconclusive test for Zika virus infection, a thorough physical exam of the infant should be conducted and the infant should be tested for possible congenital Zika virus infection. If any of the infant’s samples tests positive or inconclusive, then the infant should undergo clinical evaluation as outlined in more detail in the interim guideline. The infant should also be followed to assess for possible long term sequelae and the infant’s case should be reported to the local, state or territorial health department. If the results of all of the infant’s tests are negative for evidence of Zika virus infection, then no further Zika virus testing or evaluation is recommended and this infant should undergo routine care.

Finally for infants without microcephaly or intracranial calcification whose mothers have negative Zika virus test results or who were not tested for Zika virus the infant should receive routine care.

I want to take a moment to talk more about how to manage infants without microcephaly or intracranial calcification whose mothers traveled to or resided in areas with ongoing Zika transmission during pregnancy but were not previously tested for Zika virus, as this recommendation has been updated from the previous version of the guidelines. If the infant has normal head circumference, normal prenatal ultrasound, normal postnatal ultrasound (if any are performed), and normal physical examination, we recommend routine care.

It is important to note that because information on the effects of congenital Zika virus infection is limited, healthcare providers should use clinical judgment in the assessment of newborns with abnormalities other than microcephaly or intracranial calcifications who were born to mothers who travel to or resided in an area with active Zika virus transmission during pregnancy. For these infants health care providers should consider testing the mother before testing the infant. These guidelines will be updated as additional information becomes available.

An example of a situation in which clinical judgment should be used is for an infant without microcephaly or intracranial calcification who fails the newborn hearing screen and whose mother travel to or resided in areas with ongoing Zika virus transmission but was not tested for Zika virus. In this situation the provider could consider testing the mother for Zika virus prior to testing the infant.

So to reiterate Zika virus testing of infants is recommended for infants with microcephaly or intracranial calcification born to women who travel to or resided in an area with Zika virus transmission while pregnant and for infants born to mothers with positive or inconclusive test results for Zika virus infection.

Next I will address the evaluation of infants and children aged less than 18 years with possible acute Zika virus disease.

Acute Zika virus infection should be suspected in infants and children less than 18 years of age who travel to or resided in an infected area within the past two weeks and have at least two of the following clinical manifestations -- fever, rash, conjunctivitis or arthralgia.

While infants and older children can acquire Zika virus through mosquito-borne transmission, infants can also be infected perinatally. Therefore acute Zika virus disease should be suspected in infants in the first two weeks of life if the mother traveled to or resided in an area with Zika virus transmission within two weeks of delivery and the infant has two or more of the following manifestations: fever, rash, conjunctivitis or arthralgia

Infants whose mothers reported illness consistent with Zika virus disease near the time of delivery should be monitored for signs and symptoms of Zika virus disease. If an infant shows signs and symptoms of acute Zika virus disease within the first two weeks of life, both the mother and infant should be tested for Zika virus infection. It’s important to note that arthralgia can be difficult to detect in infants and young children and can manifest as irritability, walking with a limp for ambulatory children, difficulty moving or refusing to move an extremity, pain on palpation, or pain with active or passive movement of the affected joints.

Zika virus testing for infants and children for acute Zika virus disease includes serum and (if obtained for other reasons) cerebrospinal fluid. If symptoms have been present for less than seven days, Zika virus RNA should be tested by RT-PCR. If Zika virus RNA is not detected and symptoms have been present for four or more days, serum may be tested for Zika and dengue virus IgM and neutralizing antibodies. Healthcare providers should contact their state, local or territorial health departments to facilitate testing. And more information about laboratory testing can be found at the Web address listed here.

Laboratory evidence for infants and children with possible acute Zika virus disease is the same as for children with possible congenital Zika virus infection. And laboratory evidence for- of Zika virus infection in an infant or child would include in any clinical specimen detectable Zika virus in cultures, Zika virus RNA by RT-PCR, or antigen by immunohistochemistry, or a clinical specimen positive for Zika virus IgM with confirmatory neutralizing antibody titers greater than or equal to four-fold higher than dengue virus neutralizing antibody titers. An inconclusive result would be Zika virus neutralizing antibodies less than four-fold higher than dengue virus neutralizing antibodies.

Illness associated with Zika virus is usually mild in infants and children with acute Zika virus disease. There is no specific antiviral treatment, and treatment involves supportive care. Healthcare providers should avoid the use of nonsteroidal anti-inflammatory drugs (or NSAIDs) until dengue virus has been ruled out and in all children less than 6 months of age. Aspirin should be avoided in children with suspected viral infections because of the association with Reye’s Syndrome.

Next I will address the guidelines for breastfeeding for mothers with Zika virus infection. Zika virus RNA has been identified in breast milk but attempts to culture the virus have been unsuccessful. At this time no cases of Zika virus transmission associated with breastfeeding have been reported, and, based on the current evidence, mothers with Zika virus infection and living in areas with ongoing Zika virus transmission are encouraged to breastfeed their infants because the benefits of breastfeeding outweigh the theoretical risk of Zika virus transmission through breast milk.

Finally I would like to talk about prevention of Zika virus disease in infants and children. Prevention of mosquito bites is the primary means of preventing Zika virus infection in persons of all ages traveling to or residing in areas with local Zika virus transmission. Mosquito bite prevention includes using air-conditioning or window and door screens when indoors, wearing long-sleeve shirts and long pants, using permethrin treated clothing and gear, and using insect repellent. When used as directed on the product label, most Environmental Protection Agency-registered insect repellents can be used to protect children age 2 months or greater against mosquito bites. Oil of lemon eucalyptus should not be used in children aged less than 3 years. Mosquito netting can be used to cover infants in carriers, strollers or cribs to protect them from mosquito bites.

Healthcare providers should educate parents and caregivers about mosquito bite prevention in infants and children if they are traveling to or residing in areas affected by Zika virus. It is important to note that mosquitoes also carry other viruses in addition to Zika.

Parents and caretakers should protect infants and children with Zika virus from mosquito bites for at least one week after illness onset to decrease the risk of transmission to others.

At this time I would like to turn it over to Dr. Alexa Oster.

Dr. Alexa Oster:
Hello. I will now provide an update on interim guidelines for prevention of sexual transmission of Zika virus in the United States. These recommendations were published in the MMWR Weekly on February 12. They apply to men who resided or have traveled to areas with active Zika virus transmission and their sex partners and they will be revised as more information becomes available.

I’d like to start by describing what we know and what we do not know about sexual transmission of Zika virus. We know that Zika virus can be sexually transmitted by a man to his sex partners, and this is of particular concern during pregnancy. All reported cases of sexual transmission involved sex without a condom with men who had or later develop symptoms. We also know the sexual transmission of many infections, including those caused by other viruses, is reduced by consistent and correct use of latex condoms.

We do not know whether infected men who never develop symptoms can transmit Zika virus to their sex partners or how long the Zika virus persists in the semen. One report found the virus in semen at least two weeks symptoms of infection began and another report found the virus in semen at least 62 days after symptoms of infection began. We also don’t know whether women with Zika virus infection can transmit Zika virus to their sex partners or whether Zika can be transmitted from oral sex. It is known that Zika virus is infectious in semen but it is unknown if Zika is infectious in other body fluids exchanged by oral sex including saliva and vaginal fluids.

This slide summarizes our recommendations for men who live in or traveled to an area of active Zika virus transmission. Men who - the first section pertains to men who have pregnant sex partners. They should abstain from sexual activity or consistently and correctly use condoms during sex including vaginal and anal intercourse or fellatio for the duration of pregnancy. Pregnant women should discuss their male partner’s potential exposures to mosquitoes and history of Zika-like illness with their healthcare provider. And providers can consult CDC’s guidelines for evaluation and testing of pregnant women which have just been summarized earlier in this call.

For men and their non-pregnant sex partners, if concerned about sexual transmission of Zika virus, they might consider abstaining from sexual activity or using condoms consistently and correctly during sex. When making this personal decision couples should take several factors into account. Most infections are asymptomatic and when illness does occur it is usually mild. Severe disease requiring hospitalization is uncommon. Risk for acquiring vector-borne Zika virus in areas of active transmission depends on the duration and extent of exposure to infected mosquitoes and the steps taken to prevent mosquito bites. And after infection Zika virus might persist in semen when it is no longer detectable in blood. At this time testing of men for the purpose of assessing sexual risks - sorry, for the purpose of assessing risk for sexual transmission is not recommended. Thank you.

Ashley Ghaffarzadeh: Thank you presenters for providing our COCA audience with a wealth of information. We will now open up the lines for the question and answer session. Questions are limited to clinicians who would like information related to Zika virus disease. 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.

When asking a question please state your organization and also remember you can submit questions through the Webinar system as well. Kathy do we have any questions in queue?

Coordinator:       
And yes we do. And at this time we are ready to begin the question and answer session. If you would like to ask a question please press the Star 1 and please record your first and last name. To withdraw your question press Star 2. Again press Star 1 to ask a question and our first question comes from Dr. (Arlio) from Cornell.

Dr. (Arlio):          
Yes. Hi. Can I be heard? Am I heard?

Hello? Can you hear me?

Ashley Ghaffarzadeh:         
Yes we hear you.

Dr. (Arlio):          
Okay great. Hi. Thank you for taking the question and for that informative presentation. For couples residing in the in the Continental US with the recent travel history to an area with active Zika transmission and active mosquito bites who desire a future pregnancy how long should they wait to try to conceive given evidence of Zika in the semen persisting for at least at ten weeks and that the CDC recommendations that pregnant women with male partners at risk of Zika should use condoms or abstain from sex for the duration of the pregnancy?

Dr. Emily Petersen:  
That’s a great question. Unfortunately we don’t have a great answer yet as we are still getting more information about Zika virus in semen and sexual transmission. Semen testing as Dr. Oster said is not currently available and we do not know how long Zika is present in semen in men who have had Zika. We also don’t know if men who have had Zika but never developed any symptoms can have Zika in their semen.

Dr. (Arlio):          
Right.

Dr. Emily Petersen:  
So we are undergoing studies to try to identify more information about this. And but unfortunately it is a case by case recommendation between the healthcare provider and the couple. And, you know, as you know the decision should include the patient’s age, fertility, reproductive life plan, personal values and preferences and so it’s a very complex decision at this time.

Dr. (Arlio):          
Is there any place where semen could be tested at this time to gain more information?

Dr. Emily Petersen:  
No.

Dr. (Arlio):          
So they - where are they testing it in academic like academic papers saying semen was documented, you know, is that positive Zika virus documented in the semen ten weeks afterwards? Where are they doing that sort of testing?

Dr. Emily Petersem: 
Dr. Oster do you have information on that?

Dr. Alexa Oster: 
Yes. I mean those tests are not available publicly at this point. And if we were able to do those tests we really have a limited understanding of how to interpret the results of such tests and that’s why we’re not recommending the testing at this time. As we learn more in the future tests may become available or may be helpful but at this time they’re just not.

Dr. (Arlio):          
As an overview and how long would you counsel someone to wait - three, six months, 12? I mean I just based on other, you know, I guess experience with other viruses since there’s no way of testing?

Dr. Alexa Oster: 
Unfortunately we don’t have any information that allows us to make a recommendation on that at this time. I’m really sorry.

Dr. (Arlio):          
Okay. Thank you for your time.

Coordinator:       
The next question is from Dr. Warner Hudson with UCLA. Your line is open.

Dr. Warner Hudson:
Hi. Thank you for a great presentation. I’m an Occupational Medicine Physician here and the question has to do with lab worker exposure where you’re working with live Zika virus, not mosquito borne. In the event of a blood-borne exposure to the material or the live Zika virus material or a splash I suppose we would treat this as is if somebody was exposed by a mosquito bite which it would not be. And so the question then becomes would it have been a good idea to have a baseline titer on such individuals since the titers are kind of variable, if the person was pregnant referral to perinatology?

If you have mosquitoes in your area should they be tested? Is there testing available? I know the Navy can do testing but I don’t know where to run for, you know, I caught some mosquitoes in the lab can I test them kind of thing? Would love your thoughts on that and now you’re handling it at CDC maybe. Thank you.

Dr. Emily Petersen:  
Thank you. We do not currently recommend baseline titers for pre-exposure testing. And I think that the question about the mosquitoes being tested is probably answered by our vector-borne colleagues or our vector control colleagues. I know that it is a challenging issue from discussions that they’ve been involved in but if you would want to email us we can get you in contact with them.

Dr. Fleming-Dutra:  
And then additionally I’d just like to add if someone has Zika virus infection acquired in any manner. It is important that that person protect themselves from mosquito bites for the week following, you know, that’s after infection so that they can try to prevent transmission to others as well. And then of course the case should be reported for local, state, or territorial health department.

Dr. Warner Hudson:
Great, okay thanks. That was very helpful.

Coordinator:
And the next question is from Dr. Sarah Lynn Mark with NASA. Your line is open.

Dr. Sarah Lynn Mark:        
Great. Thank you very much for a very informative presentation. Your guidelines really had a reference more for individuals who are overseas and residing in areas. As we come into the springtime and mosquitoes become more endemic here and it really becomes more of a situation that we will face on a daily basis when do you anticipate changing your guidelines or will they stay the same?

Dr. Katherine Fleming-Dutra:
And this is Dr. Fleming-Dutra. I just want to reiterate that we continue to evaluate all the evidence as it comes out and we’ll be updating the guidelines as more evidence and as we gain more information in collaboration with our partners. So there’s not a firm timeline set but it’s really about as new evidence comes that necessitate a need for updated guidelines we will continue to update them.

Dr. Sarah Lynn Mark:        
And I have one more question. You mentioned saliva and potential for transmission. Has there been any evidence for example through kissing?

Dr. Petersen:       
We’re not aware of any evidence for that. We know that the RNA can be detected in saliva but are not aware of transmission through saliva.

Dr. Sarah Lynn Mark:        
Thank you.

Coordinator:       
And the next question is from Marian Melish from the University of Hawaii. Your line is open.

Marian Melish:   
I have a question about when in pregnancy whether we have any information on about when in pregnancy the transmission to the infant is most likely?

Dr. Emily Petersen:  
Sure. Unfortunately we do not have information on that at this time. We are establishing a pregnancy- a voluntary pregnancy registry in the United States for pregnant women with Zika virus infection and this should help us to determine that.

In addition we’re working with in collaboration with other countries and organizations to further study Zika virus infection and timing in pregnancy and outcome.

Marian Melish:   
Thank you.

Coordinator:       
The next question is from Marisa Montecalvo. Your line is open.

Marisa Montecalvo: 
Yes hello. I’m from New York Medical College. And my question has to do with laboratory workers working with said Zika virus. So some of my questions were addressed with the previous question that was asked. But I was curious whether one would consider not allowing pregnant women to work in such a laboratory to risk a laboratory accident and...

Dr. Emily Petersen:  
I cannot answer that question at this time but my understanding is that we are working on developing guidance for occupational health and can follow-up with you on that question.

Marisa Montecalvo: 
Okay. That would be great. Should I send you an email because I think that there’s it’s really the pregnant woman and then of course...

Dr. Emily Petersen:  
That would be great.

Marisa Montecalvo:
how best to advise women of childbearing age and or who will become pregnant who are childbearing.

Dr. Emily Petersen:  
Right.

Marisa Montecalvo:
Okay very good. Thank you....

Coordinator:       
The next question is from Dr. Robert Ball. Your light is open.

Dr. Robert Ball:  
Thank you. Good data especially on OB. Dr. Robert Ball here, Medical University of South Carolina Public Health. Most questions that I had have been answered but the big picture question is this. What is your best guess or data for population attack rates? Your last Webinar on January 26 showed 73% of population attack rates with only 18% of cases asymptomatic which means at least four out of five are asymptomatic. Do you have any updates on those data?

Dr. Emily Petersen:  
We don’t have any updates from the current outbreaks, no, but we hope to have more data on that.

Dr. Robert Ball:  
Keep working. Thank you.

Coordinator:       
And our next question is from Michael Brady. Your line is open.

Michael Brady:   
Yes. You talked about individuals who are contemplating pregnancy and the inability to use semen. But if somebody has returned from an area where Zika virus has been and is considering pregnancy in the two to seven week period after that what would be the value of doing the IGM testing in trying to counsel them as to whether or not the likelihood that they acquired Zika while residing in an area was limited?

Dr. Alexa Oster: 
This is Alexa Oster. Right now we’re not recommending any kind of testing for asymptomatic people who are returning. And there are a variety of issues related to understanding how to interpret the results as well as laboratory capacity that are guiding this decision at this point. Again as we’ve said, you know, this is an evolving situation and so recommendations may change as capacity and our understanding evolves.

Ashley Ghaffarzadeh:         
Okay operator I think we have time for one more question and we have one from the Webinar. Presenters, the question is are you able to comment on the sensitivity and specificity of serological tests? Thank you.

Dr. Emily Petersen:  
Unfortunately we don’t have information in particular about the sensitivity and specificity about the serological test, in particular with asymptomatic persons and don’t have that data at this time.

Ashley Ghaffarzadeh:         
Okay. On behalf of COCA I would like to thank everyone for joining us today with a special thank you to our presenters Drs. Petersen, Fleming-Dutra and Oster. We invite you to communicate to our presenters after the Webinar if you have any questions for today’s presenters. Please email us at coca@cdc.gov. Put February 25 COCA call in the subject line of the email and we will ensure that your question is forwarded to your presenters. Again the email address is coca@cdc.gov.

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. There are no continuing education credits for this call. To receive information on upcoming COCA calls subscribe to COCA by going to the COCA Web page at emergency.cdc.gov/coca and clicking on the Join the COCA Mailing List link.

Join us for our next COCA call on March 31 at 2:00 PM Eastern Time on care for synthetic cannabinoids users. Get detailed information about this call about this call by visiting the COCA Web page emergency.cdc.gov/coca. You can connect with COCA on Facebook. Like our page on Facebook.com CDC Clinician Outreach and Communication Activity to stay connected to the latest news from COCA. Thank you again for being part of today’s COCA call. Have a great day.

Coordinator:       
Thank you. And this does conclude today’s conference. All parties may disconnect. Speakers please stand by.