Zika Virus: Impact, Issues and Updates Moderator: Chris Campanile, MD, Family Physician at Coastal Hillside Family Medicine, Pawtucket, RI, NE QIN-QIO Consultant Clinical Director, Healthcentric Advisors Professor of Medicine Panelists: Jef Bratberg Pharm.D., BCPS Clinical Professor at University of Rhode Island, Specialties: Infectious Disease, Emergency Preparedness, Public/Population Health Erica Hardy MD, MA, MMSc Woman & Infants Hospital, Specialties: Infectious Disease and Obstetric Medicine Michael Smit MD, Hasbro Children's Hospital, Specialties: Pediatric Infectious Disease Medicine Audio Call In Number: 888-895-6448 Code: 5196001 This material was prepared by the New England Quality Innovation Network-Quality Improvement Organization (QIN-QIO), the Medicare Quality Improvement Organization for New England, under contract with the Centers for Medicare & Medicaid Services (CMS), an agency of the U.S. Department of Health and Human Services. The contents presented do not necessarily reflect CMS policy. 11SOWQIN_F1_201607_0664.
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Conflict of Interest Statement This notice confirms that there were not relevant conflicts of interest reported from either today s speakers or planning members of this learning activity. 3
Approval Statement for Individual CNE Activities This activity has been submitted to Northeast Multi-State Division (NE-MSD) for approval to award contact hours. Northeast Multistate Division (NE-MSD) is accredited as an approver of continuing nursing education by the American Nurses Credentialing Center s Commission on Accreditation. (Questions regarding CE status may be submitted to Sue Midwood, smidwood@healthcentricadvisors.org) 4
CME and CEU s At the end of the presentation a survey will appear where you can provide required information to receive 1.0 credits. Reminder: To qualify you must attend the full session 5
Overview and Disease Prevention in the Community Jef Bratberg Pharm.D., BCPS Clinical Professor at University of Rhode Island 6
Disclosures None of the individuals in a position to control the content of the CME activity have any relevant financial relationships to disclose. 7
Objectives Describe the epidemiology, clinical manifestations, testing, reporting, management, and prevention of Zika virus disease Provide recommendations to patients about possible Zika virus exposure and implications Discuss evaluation of infants with microcephaly and the relationship of Zika and microcephaly Identify pharmacist-driven interventions that will increase awareness of and promote Zika virus disease prevention in the community. 8
What is Zika Virus? Single-stranded RNA arbovirus Isolated in 1947 in Zika Forest, Uganda Flavivirus similar to Dengue Yellow fever West Nile Japanese encephalitis Sirohi, D.; Chen, Z.; Sun, L.; et al. (31 March 2016)."The 3.8 Å resolution cryo-em structure of Zika virus". Science. doi:10.1126/science.aaf5316. ISSN 0036-8075. 9
Modes of transmission Bite from an infected mosquito Maternal-fetal Intrauterine Perinatal Sexual transmission from infected male partners Laboratory exposure Theoretical: blood transfusion, organ and tissue transplant, fertility treatment, and breast feeding http://www.cdc.gov/zika/comm-resources/clinicianppt.pptx
What we do not know about sexual transmission We do not know how often men with Zika who never develop symptoms can have the virus in their semen or if they can pass Zika through sex. We do not know if sexual transmission of Zika virus poses a different risk of birth defects than mosquito-borne transmission. If a woman with Zika can pass the virus to her sex partners. http://www.cdc.gov/zika/comm-resources/clinicianppt.pptx
Possible Zika exposure (Travel or unprotected sex) Women Men Zika symptoms No symptoms Condoms / Abstain at least 8 weeks after symptoms start Condoms / Abstain at least 8 weeks after exposure Condoms / Abstain at least 6 months after symptoms start Condoms / Abstain at least 8 weeks after exposure. People who live in areas with Zika transmission (i.e. Puerto Rico, American Samoa, Virgin Islands) Zika symptoms Condoms / Abstain at least 8 weeks after symptoms start Condoms / Abstain at least 6 months After symptoms start No symptoms Condoms / Abstain Condoms / Abstain Highest Risk: Couples of a man and a pregnant woman should abstain from sex or use condoms consistently and correctly each time they have sex 12
Sexual transmission causes a marked increase in the incidence of Zika in women in Rio de Janeiro, Brazil. first posted online May. 26, 2016; doi: http://dx.doi.org/10.1101/055459. 13
Sexual transmission causes a marked increase in the incidence of Zika in women in Rio de Janeiro, Brazil. first posted online May. 26, 2016; doi: http://dx.doi.org/10.1101/055459. 14
Transmission Zika Virus Mosquito Vectors Show where mosquitoes have been found Do NOT show concentrations of mosquitoes Do NOT show risk of Zika spread A. albopictus A. aegypti http://www.cdc.gov/zika/vector/range.html 15
http://www.cdc.gov/zika/ geo/united-states.html http://www.cdc.gov/zika/geo/united-states.html US Zika Virus Case Count 7/13/2016 5 am EST 1/1/2015-7/13/2016 Zika virus disease & congenital infection are notifiable conditions in US US States Travel-associated: 1305 Locally acquired : 0 Lab-acquired: 1 Sexually transmitted: 14 Guillain-Barré syndrome (GBS): 5 US Territories Travel-associated: 11 Locally acquired: 2905 Sexually-transmitted (unknown- local transmission) GBS: 12 16
http://www.cdc.gov/zika/geo/pregwomen-uscases.html. 17
Symptoms Many infections asymptomatic. Most common symptoms Acute onset of fever Maculopapular rash Joint pain Conjunctivitis Other symptoms include muscle pain and headache. http://www.cdc.gov/zika/comm-resources/clinicianppt.pptx
Clinical features: Zika virus compared to dengue and chikungunya Rabe, Ingrid MBChB, MMed Zika Virus- What Clinicians Need to Know? (presentation, Clinician Outreach and Communication Activity (COCA) Call, Atlanta, GA, January 26 2016) http://www.cdc.gov/zika/comm-resources/clinicianppt.pptx
Diagnosis / Testing 20
Recommendations CDC recommends Zika virus testing for symptomatic people living in an active Zika transmission area, or who have recently traveled to an area with Zika, or who have had unprotected sex with a man confirmed to have Zika virus infection. Testing blood, semen, or urine is not recommended to determine how likely a man is to pass Zika virus through sex. Available tests may not accurately identify the presence of Zika or a man s risk of passing it on through sex. http://www.cdc.gov/zika/comm-resources/clinicianppt.pptx
Laboratories for diagnostic testing Testing performed at CDC, select commercial labs, and a few state health departments. CDC is working to expand laboratory diagnostic testing in states. Healthcare providers should contact their state health department to facilitate diagnostic testing. http://www.cdc.gov/zika/comm-resources/clinicianppt.pptx
Treating patients who test positive There are no vaccine or medicine Zika. Treat the symptoms of Zika Rest Drink fluids to prevent dehydration Take acetaminophen (Tylenol ) to reduce fever and pain Do not take aspirin or other non-steroidal anti-inflammatory drugs (NSAIDS) until dengue can be ruled out to reduce the risk of bleeding. http://www.cdc.gov/zika/comm-resources/clinicianppt.pptx
http://emergency.cdc.gov/coca/ppt/2016/coca-call-april12-zika-virus-clinical-guidelines_508.pdf 24
http://emergency.cdc.gov/coca/ppt/2016/coca-call-april12-zika-virus-clinical-guidelines_508.pdf 25
Do your homework before traveling wwwnc.cdc.gov/travel/page/zika-travel-information Pregnant women should not travel to areas with Zika. If they must travel to areas with Zika, tell pregnant patients to protect themselves from mosquito bites and take steps to prevent sexual transmission during and after travel. http://www.cdc.gov/zika/comm-resources/zika101slides.pptx
All Countries and Territories with Active Zika Virus Transmission 6/30/2016 http://www.cdc.gov/zika/geo/active-countries.html 27
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Zika Virus and Pregnancy Erica J. Hardy, MD Assistant Professor of Medicine Divisions of Infectious Disease and Obstetric Medicine Warren Alpert Medical School of Brown University Associate Director Women s Infectious Disease Consultation Service Women & Infants Hospital of Rhode Island
Disclosures None of the individuals in a position to control the content of the CME activity have any relevant financial relationships to disclose. 30
Objectives Prevention Impact on pregnancy Screening and testing recommendations Areas of uncertainty 31
Who is at risk in pregnancy? Travel or residence in area with active Zika transmission Sexual transmission Other (lab, organ transplant, blood transfusion) 32
What is the risk of Zika in pregnancy? Zika can be passed from mother to fetus during pregnancy and around the time of birth Infection around time of conception unknown No reports of transmission during breastfeeding Infection in pregnancy can cause Microcephaly, severe brain defects Growth restriction Eye defects, hearing loss Fetal loss 33
Preconception counseling Because of the uncertainty surrounding transmission, timing, & fetal effects, counseling is complex No evidence that Zika causes congenital infection after maternal viremia Incubation period: 3-14 days After symptom onset, Zika viremia lasts a few days to 1 week, longest in literature is 11 days 34
Preconception counseling should include: Signs and symptoms of Zika disease Potential outcomes of Zika infection in pregnancy Women should wait at least 8 weeks after symptoms before attempting conception No data available for women with asymptomatic infection, however: Based on longest incubation period (14 days), longest time of viremia (11 days), women with asymptomatic infection should wait at least 8 weeks from last date of possible exposure before attempting conception MMWR April 1, 2016, Vol 65, No 12 35
Preconception counseling should include: Provide information and strategies to prevent unintended pregnancy Effective contraception CDC has info sheets Consistent and correct condom use can decrease risk of sexual transmission Other prevention strategies Areas of risk awareness DEET (safe in pregnancy) Mosquito nets, permethrin-treated clothing MMWR April 1, 2016, Vol 65, No 12 36
Preconception counseling: Recommendations for men Sexual transmission can occur Data are limited CDC reported 7 lab confirmed cases of sexual transmission In all cases, the male had symptoms All have occurred within 3 weeks of symptoms (up to 10 weeks from symptoms) The duration and pattern of Zika in semen not well understood Oster AM, Russell K, Stryker JE, et al. Update: Interim Guidance for Prevention of Sexual Transmission of Zika Virus United States, 2016. MMWR 2016;65:323 325 37
Preconception counseling: Recommendations for men If male had confirmed or suspected Zika (based on clinical illness) Consider abstaining from sex or using condoms for 6 months after illness onset If male had travel risk but no symptoms of Zika Consider abstaining from sex or using condoms for at least 8 weeks after departure from Zika area If male resides in Zika risk area but no symptoms Consider abstaining from sex or using condoms while active transmission persists Oster AM, Russell K, Stryker JE, et al. Update: Interim Guidance for Prevention of Sexual Transmission of Zika Virus United States, 2016. MMWR 2016;65:323 325 38
Who to test? Testing for risk of sexual transmission prior to conception: Not recommended because duration and pattern of shedding not well understood A pregnant partner with possible sexual exposure should be tested if either she or her male partner developed symptoms consistent with Zika 1 or more of the following symptoms within 2 weeks of possible exposure (acute onset of fever, rash, arthralgia, conjunctivitis) Couples in which a woman is pregnant and male partner has traveled to or resides in Zika risk area, should use condoms for the duration of the pregnancy Oster AM, Russell K, Stryker JE, et al. Update: Interim Guidance for Prevention of Sexual Transmission of Zika Virus United States, 2016. MMWR 2016;65:323 325 39
What testing is available? rrt-pcr for viral RNA collected <7 days (serum) or <= 14 days (urine) after illness onset IgM and neutralizing antibodies in serum collected up to 12 weeks after illness onset Plaque reduction neutralization test (PRNT) for virusspecific neutralizing antibodies in paired serum Immunohistochemical staining for viral antigens or RT- PCR on fixed tissues State Department of Health approves and sends testing CDC working to expand testing sites 40
Who to test in pregnancy? Women who DO NOT reside in area with active Zika transmission Testing recommended for pregnant women with clinical illness (1 or more: fever, rash, arthralgia, conjunctivitis) during or within 2 weeks of travel or possible sexual exposure Possible exposure includes (while pregnant or within 8 weeks prior to conception [6wk before LMP]): Travel to an area with active Zika transmission Sex (vaginal or anal) without a condom with male who traveled to or resided in an area with active Zika transmission Testing not recommended for pregnant women with possible sexual exposure if both partners are asymptomatic Petersen EE, Polen KN, Meaney-Delman D, et al. Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure United States, 2016. MMWR 2016;65:315 322 41
Who to test in pregnancy? Pregnant women who RESIDE in area with active Zika transmission If one or more signs/symptoms of Zika virus disease, testing should be performed at presentation If a woman does not report symptoms, serum IgM testing can be offered: Upon initiation of prenatal care and, if negative In mid-second trimester Repeat testing if symptoms develop 43
Fetal testing during pregnancy Fetal ultrasound abnormalities consistent with Zika disease include: Microcephaly Intracranial calcifications Brain or eye abnormalities Fetal ultrasounds might not detect abnormalities until late 2 nd or 3 rd trimester Serial ultrasounds consider every 4 weeks 45
CDC US Zika Pregnancy Registry CDC established the US Zika Pregnancy Registry to collect information and learn more about pregnant women in the US with Zika and their infants Data collected will be used to update recommendations for clinical care, plan for services for pregnant women and families affected by Zika, and improve prevention of Zika infection during pregnancy CDC maintains a 24/7 consultation service for health officials and healthcare providers caring for pregnant women. To contact the service, call 770-488-7100 or email ZIKAMCH@cdc.gov CDC also established a similar system, the Zika Active Pregnancy Surveillance System, in Puerto Rico https://www.cdc.gov/zika/hc-providers/registry.html 46
Pregnant women A negative IgM result obtained 2-12 weeks after known exposure would suggest that a recent Zika infection did not occur and could obviate the need for serial ultrasounds Testing of amniotic fluid should be individualized Sensitivity of PCR on AF is unclear Optimal time for amniocentesis not known Zika RNA has been detected in amniotic fluid as early as 4 weeks after maternal symptoms and as early as 17 weeks gestation Petersen EE, Polen KN, Meaney-Delman D, et al. Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure United States, 2016. MMWR 2016;65:315 322 47
Areas of uncertainty Characteristics and duration of viral shedding, especially in sequestered sites such as semen More data needed in order to understand sexual transmission risk Performance of testing in amniotic fluid If testing is pending at time of delivery, placenta and cord blood samples may be important 48
Conclusions Preconception counseling important Understanding is changing Counseling for men and women is important Has become part of routine prenatal care Global village, screening for exposure is important Not just for Zika but for other illnesses 49
Zika Virus Update on an Emerging Infectious Disease Affecting Newborns Michael Smit, MD, MSPH, FAAP Pediatric Infectious Diseases Alpert Medical School of Brown University 50
Disclosures: None of the individuals in a position to control the content of the CME activity have any relevant financial relationships to disclose. 51
Zika virus: diagnosis in newborns Staples JE, Dziuban EJ, Fischer M, et al. Interim Guidelines for the Evaluation and Testing of Infants with Possible Congenital Zika Virus Infection United States, 2016. MMWR Morb Mortal Wkly Rep 2016;65place_Holder_For_Early_Release:63 67. DOI: http://dx.doi.org/10.15585/mmwr.mm6503e3 52
Abnormally small head Head Circumference <3%tile < 2 std dev Adjusted for gest age Microcephaly 53
Causes Genetic Disruptive (stroke) Infection CMV Toxoplasmosis Rubella Microcephaly 54
Zika virus diagnosis in newborns Molecular: reverse transcription-polymerase chain reaction (RT-PCR) for viral RNA Serologic: immunoglobulin (Ig) M ELISA and plaque reduction neutralization test (PRNT) Staples JE, Dziuban EJ, Fischer M, et al. Interim Guidelines for the Evaluation and Testing of Infants with Possible Congenital Zika Virus Infection United States, 2016. MMWR Morb Mortal Wkly Rep 2016;65place_Holder_For_Early_Release:63 67. DOI: http://dx.doi.org/10.15585/mmwr.mm6503e3 55
Staples JE, Dziuban EJ, Fischer M, et al. Interim Guidelines for the Evaluation and Testing of Infants with Possible Congenital Zika Virus Infection United States, 2016. MMWR Morb Mortal Wkly Rep 2016;65place_Holder_For_Early_Release:63 67. DOI: http://dx.doi.org/10.15585/mmwr.mm6503e3 56
Recommended clinical evaluation and laboratory testing for infants with possible congenital Zika virus infection Comprehensive physical examination. Evaluation for neurologic abnormalities, dysmorphic features, splenomegaly, hepatomegaly, and rash or other skin lesions. Cranial ultrasound, unless prenatal ultrasound results from third trimester demonstrated no abnormalities of the brain. Evaluation of hearing. Ophthalmologic evaluation before discharge from the hospital or within 1 month after birth. Staples JE, Dziuban EJ, Fischer M, et al. Interim Guidelines for the Evaluation and Testing of Infants with Possible Congenital Zika Virus Infection United States, 2016. MMWR Morb Mortal Wkly Rep 2016;65place_Holder_For_Early_Release:63 67. DOI: http://dx.doi.org/10.15585/mmwr.mm6503e3 57
Recommended clinical evaluation and laboratory testing for infants with possible congenital Zika virus infection For infants with microcephaly or intracranial calcifications, additional evaluation includes the following: Consultation with a clinical geneticist. Consultation with a pediatric neurologist re: brain imaging. Testing for other congenital infections Consider consulting a pediatric infectious disease specialist. Complete blood count, platelet count, and liver function and enzyme tests. Consideration of genetic and other teratogenic cause. Staples JE, Dziuban EJ, Fischer M, et al. Interim Guidelines for the Evaluation and Testing of Infants with Possible Congenital Zika Virus Infection United States, 2016. MMWR Morb Mortal Wkly Rep 2016;65place_Holder_For_Early_Release:63 67. DOI: http://dx.doi.org/10.15585/mmwr.mm6503e3 58
Microcephaly in Brazil Between 22 October 2015 and 12 March 2016 6480 cases of microcephaly and/or central nervous system (CNS) malformation were reported by Brazil including 182 deaths. 2001 to 2014: average of 163 microcephaly cases was recorded nationwide per year Prevalence of microcephaly among newborn children 15 states with laboratory-confirmed Zika virus transmission 2.8 cases per 10 000 live births Four states without confirmed Zika virus transmission 0.6 cases per 10 000 live births 59
Microcephaly in Infants Pernambuco State, Brazil, 2015 EID, Volume 22, Number 6 June 2016 60
Microcephaly in Infants Pernambuco State, Brazil, 2015 EID, Volume 22, Number 6 June 2016 61
N=104 Microcephaly in Infants Pernambuco State, Brazil, 2015 EID, Volume 22, Number 6 June 2016 Mean head circumference: 29cm Mother mean age: 25 years (15-43) 59 recall rash during pregnancy Neuroimaging (N=58) Calcifications (93%) Malformations of cortical development (69%) Lissencephaly Pachygyria Agyria 62
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Potential complications Severe intracranial calcifications Severe cortical malformations Ventriculomegaly Cerebellar hypoplasia Abnormal hypodensity of white matter Ocular findings 66
Chorioretinal scarring: Ventura CV et al. Zika: neurological and ocular findings in infant without microcephaly. 67 Lancet. 2016 Jun 18;387(10037):2502.
Potential complications Guillain-Barre Syndrome From: CDC responds to Zika: Zika 101. April 29, 2016 68
Guillain-Barre Syndrome outbreak associated with Zika virus infection in French Polynesia October 13-April 2014 Guillan-Barre Syndrome + Zika virus reported Case-control study 42 patients with GBS 41 (98%) with anti-zika IgM or IgG 54/98 (56%) in controls (p<0.001) First evidence of Zika virus causing GBS From: Lancet, Vol 387, April 9, 2016 69
Zika: Mortality Can cause fetal loss Mortality varies Certainty of diagnosis Gestational age of infection 70
Recommended long-term follow-up for infants with possible congenital Zika virus infection Report case to state, territorial, or local health department Conduct additional hearing screen at age 6 months appropriate follow-up of hearing abnormalities Evaluate occipitofrontal circumference and developmental characteristics and milestones throughout the first year of life Use of appropriate consultations with medical specialists Pediatric neurology Developmental and behavioral pediatrics Physical and speech therapy Staples JE, Dziuban EJ, Fischer M, et al. Interim Guidelines for the Evaluation and Testing of Infants with Possible Congenital Zika Virus Infection United States, 2016. MMWR Morb Mortal Wkly Rep 2016;65place_Holder_For_Early_Release:63 67. DOI: http://dx.doi.org/10.15585/mmwr.mm6503e3 71
Treatment No treatment No vaccine Repurposed West Nile virus vaccine under development 72
Discussion and Q&A Jef Bratberg Pharm.D., BCPS Clinical Professor at University of Rhode Island, Specialties: Infectious Disease, Emergency Preparedness, Public/Population Health Erica Hardy MD, MA, MMSc Woman & Infants Hospital, Specialties: Infectious Disease and Obstetric Medicine Michael Smit MD, Hasbro Children's Hospital, Specialties: Pediatric Infectious Disease Medicine To ask a question please press #6 to unmute yourself, or you can pose a question in the chat box 73