Zika Virus Robert Wittler, MD Disclosure I have no relevant financial relationships with the manufacturers(s) of any commercial products(s) and/or provider of commercial services discussed in this CME activity. I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation. Zika Virus Mosquito-borne virus in the Flavivirus genus closely related to Dengue, West Nile, and Yellow Fever viruses Discovered in 1947 (Africa) and known to cause sporadic cases of mild, self-limited illness in persons living in Africa and Asia First recognized widespread outbreak was on Yap Island in Micronesia in 2007 outbreaks in Southeast Asia and the western Pacific followed, including a large outbreak in French Polynesia in 2013-2014 1
Zika Virus Virus in the French Polynesia outbreak has been phylogenetically linked to the virus that emerged in Brazil in May 2015 first local transmission of Zika virus in the Americas 440,000 to 1.3 million suspected cases by the end of 2015 In Oct 2015, the Brazilian Ministry of Health reported increasing numbers of infants born with microcephaly On Feb 1, 2016 the WHO declared the ongoing Zika crisis and emergency and that the link between Zika virus and microcephaly was strongly suspected Zika Virus Transmission Primarily transmitted through the bite of Aedes species mosquitoes Other documented modes of transmission include intrapartum (congenital) transmission from a mother with viremia to her infant, perinatal transmission to infants from mothers infected near the time of delivery, sexual transmission, and laboratory exposures Theoretical risk for transmission from blood transfusion and organ or tissue transplantation Incubation period is thought to be in range of 3-14 days 2
Florida Mosquito-Borne Transmission CDC press release July 29, 2016 http://www.cdc.gov/media/releases/2016/p0729-floridazika-cases.html Four people likely infected by bites of local Aedes aegypti mosquitoes Miami Clinical Manifestations (not congenital) Most persons are asymptomatic (~80%) For those with symptoms illness is generally mild and self-limited Macular or papular rash, fever, arthralgia, and non purulent conjunctivitis are the most often observed features Symptoms typically last several days to one week All age groups are at risk for Zika virus infection In the Yap Island outbreak the attack rate for symptomatic infection among children (<19 years of age) was lower than that for adults Lab Testing for Possible Acute Zika Virus Disease If symptoms have been present for <7 days, test serum (and CSF if obtained for other reasons) for Zika virus RNA by RT-PCR If Zika virus RNA is not detected and symptoms have been present for 4 days, test serum (and CSF if obtained for other reasons) for Zika virus IgM and neutralizing antibodies 3
Mouse embryonic brain slices show a remarkable tropism of Zika virus infection for neural stem cells Zika virus impairs cell cycle progression of neural stem cells Congenital infection has been confirmed by reverse transcriptase-polymerase chain reaction testing or immunohistochemistry The incidence of congenital Zika virus infection and the frequency of adverse outcomes are currently unknown Microcephaly is the adverse outcome for which there is the most evidence Hydranencephaly, ventriculomegaly, cerebral calcifications, abnormally formed or absent brain structures (eg, corpus callous, thalami, pons, cerebellar vermis, brainstem) have been identified in congenitally infected fetuses and infants Postnatal exam findings included ophthalmologic (micropthalmia, cataracts, chorioretinitis) and neurologic (arthrogryposis, hypertonia, seizures) To date, postmortem examination has found no evidence of infection of organs other than the brain Information on long term outcomes not yet available 4
Preconception Counseling Recommendations for Women with Possible Exposure Who Do Not Reside in an Area with Active Zika Virus Transmission Incubation period is likely 3-14 days Based on limited data the duration of Zika viremia after symptom onset may range from a few days to one week; the longest duration of viremia in the published literature was 11 days Women with Zika virus disease should wait until at least 8 weeks after symptom onset before attempting conception No data are available regarding the risk for congenital infection among pregnant women with asymptomatic infection MMWR, April 1, 2016, Vol 65, pages 315-322 Preconception Counseling Recommendations for Women with Possible Exposure Who Do Not Reside in an Area with Active Zika Virus Transmission Asymptomatic women with possible Zika virus exposure should be advised to wait at least 8 weeks after the last date of exposure before attempting conception based on estimated upper limit of the incubation period and approximate tripling of longest published period of viremia after symptom onset MMWR, April 1, 2016, Vol 65, pages 315-322 5
Testing Pregnant Women with Possible Zika Exposure Who Do Not Reside In An Area With Active Transmission Testing is recommended for pregnant women with a clinical illness consistent with Zika virus disease One or more of the following: Acute onset of fever, rash, arthralgia, or conjunctivitis during or within 2 weeks of travel or possible sexual transmission If <2 weeks after symptom onset do rrt-pcr on serum and urine If 2-12 weeks after symptom onset perform Zika virus IgM and dengue virus IgM MMWR, April 1, 2016, Vol 65, pages 315-322 MMWR, July 29,2016, Vol 65, pages 739-747 Testing Pregnant Women with Possible Zika Exposure Who Do Not Reside In An Area With Active Transmission Testing can be offered to pregnant women without clinical illness consistent Zika virus disease Zika virus rrt-pcr on virus and urine if <2 weeks after possible exposure Zika virus IgM, and if the IgM is positive or indeterminate, neutralizing antibodies on serum should be performed, if 2-12 weeks after possible exposure MMWR, April 1, 2016, Vol 65, pages 315-322 MMWR, July 29,2016, Vol 65, pages 739-747 Laboratory Evidence of Maternal Zika virus infection Zika virus RNA detected by RT-PCR in any clinical specimen, or Positive Zika virus IgM with confirmatory neutralizing antibody titers in serum. Testing is considered inconclusive if Zika virus neutralizing antibody titers are <4-fold higher than dengue neutralizing antibody titers MMWR, April 1, 2016, Vol 65, pages 315-322 6
MMWR, July 29, 2016 MMWR, April 1, 2016 MMWR, July 29, 2016 7
Lab Testing for Possible Test infant serum for Zika virus RNA, Zika virus IgM and neutralizing antibodies, and dengue virus IgM and neutralizing antibodies initial sample should be collected either from the umbilical cord or direct from the infant with 2 days of birth, if possible If CSF is obtained for other studies, test for Zika virus RNA, Zika virus IgM and neutralizing antibodies, and dengue virus IgM and neutralizing antibodies Consider histopathologic evaluation of the placenta and umbilical cord with Zika virus immunohistochemijcal staining on fixed tissue and Zika virus RT-PCR on fixed and frozen tissue If not already performed during pregnancy, test mother s serum for Zika virus IgM and neutralizing antibodies, and dengue virus IgM and neutralizing antibodies Evaluation for Possible Comprehensive physical exam including careful measurement of head circumference, length, weight, and assessment of gestational age Evaluation for neurologic abnormalities, dysmorphic features, splenomegaly, hepatomegaly, and rash or other skin lesions. Full body photographs and photo documentation of any rash, skin lesions, or dysmorphic features should be performed. Cranial US, unless prenatal US results from third trimester were no normal 8
Evaluation for Possible Hearing evaluation by evoked otoacoustic emissions testing or auditory brainstem response testing, either before discharge or within one month after birth Ophthalmologic evaluation either before discharge from the hospital or within one month of birth Additional Evaluation for Infants with Microcephaly or Intracranial Calcifications Consultation with clinical geneticist or dysmorphologist Consultation with pediatric neurologist to determine appropriate brain imaging and additional evaluation Testing for other congenital infections to include syphilis, toxoplasmosis, rubella, CMV, and HSV. Consider consulting pediatric ID. CBC, AST, ALT, bilirubin 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 No cases of Zika virus infection associated with breastfeeding have been reported CDC encourages mothers with Zika virus infection and living in areas with ongoing Zika virus transmission to breastfeed their infants Current evidence suggests that the benefits of breastfeeding outweigh the theoretical risks of Zika virus transmission through breast milk 9
https://www.cdc.gov/zika/pdfs/pediatric-evaluation-follow-up-tool.pdf 10