Zika Virus: What Chicago Providers Need to Know

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Zika Virus: What Chicago Providers Need to Know Stephanie R. Black, MD, MSc Medical Director, Communicable Disease Program Lisa Masinter, MD, MPH, MS Medical Director, Bureau of Maternal, Infant, Child and Adolescent Health February 19, 2016

Overview Epidemiology and clinical manifestations Infants with microcephaly/relationship to Zika Management and recommendations for pregnant women with possible Zika virus exposure Diagnostic testing and CDPH s role Reporting

Zika Virus Single stranded RNA virus Genus Flavivirus, Family Flaviviridae Closely related to dengue, yellow fever, Japanese encephalitis and West Nile Virus Transmission primarily by Aedes species mosquitoes

Feb 1: Zika Declared Public Health Emergency of International Concern Dr. Margaret Chan, director-general of the World Health Organization, and Dr. David L. Heymann, WHO assistant director-general, announce the global emergency during a news conference Monday in Geneva. Fabrice Coffrini/AFP/Getty Images An "extraordinary event" that is "serious, unusual or unexpected. Much is unknown about Zika virus: Degree of risk for development of complications, such as microcephaly? Is there a period of highest risk to the fetus during pregnancy? Does symptomatic disease reflect a higher viral burden and what consequences could this have? How long does Zika virus last in semen?

Epidemiology: Transmission Primarily Aedes Mosquitoes Aedes mosquitoes efficient human vectors - Also transmit dengue and chikungunya viruses - Lay eggs in standing water - Aggressive daytime biters, but can also bite at night, dawn, and dusk Aedes aegypti of greater epidemiologic concern than Aedes albopictus - A. aegypti preferentially bite humans and prefer city/urban habitats near humans - A. albopictus have no preference for biting humans over animals and prefer less urban habitats

Aedes aegypti and Aedes albopictus Geographic Distribution in the United States Aedes aegypti Aedes albopictus

Photo courtesy of Claudia Blanco Seasonal CDPH Mosquito Abatement Activities Primarily control West Nile Virus (WNV), carried by Culex mosquitoes (not Aedes) Larvicide in >100,000 Chicago catch basins Collect mosquitoes, record species and sex, test female Culex for WNV In 2015, tested 16,997 mosquitoes Map locations of mosquitoes positive for WNV to consider targeted spraying Can expand surveillance if increasing number of Aedes mosquitoes All can help by emptying standing water, removing old tires left outside, cleaning yards

Epidemiology: Other Modes of Transmission Maternal-fetal Other Sexual Blood transfusion Laboratory exposure Theoretical Organ or tissue transplantation *http://ecdc.europa.eu/en/publications/publications/zika-virus-french-polynesia-rapid-risk-assessment.pdf

Epidemiology: istoric Areas of Zika Transmission http://www.npr.org/sections/goatsandsoda/2016/02/05/464442791/mapping-zika-from-a-monkey-in-uganda-to-a-growing-global-concern

Epidemiology: Yap Island Incidence and Attack Rates Infection rate: 73% (95% CI: 68 77%) Symptomatic attack rate among infected: 18% (95% CI: 10 27%) All age groups affected Adults more likely to present for medical care No severe disease, hospitalizations, or deaths Note: Rates based on serosurvey on Yap Island, 2007 (population 7,391) Duffy M. N Engl J Med 2009

Areas of Zika Transmission http://www.npr.org/sections/goatsandsoda/2016/02/05/464442791/mapping-zika-from-a-monkey-in-uganda-to-a-growing-global-concern

http://www.cdc.gov/zika/geo/united-states.html. As of Feb 17, 2016 Zika Virus Disease in U.S. 2015-2016 No local vector-borne transmission seen yet in continental U.S. US States Travel assoc = 84 Local vector-borne = 0 US Territories Travel assoc = 1 Local = 9

Clinical Manifestations http://www.memeornah.com/trending/zika-virus-rash/887/# Duffy MR, Chen T, Hancock WT et al. N Engl J Med 2009;160:2536-43; Thomas DL, Sharp TM, Torres J et al. MMWR Feb 12, 2016 65

Complications: Guillain-Barre Syndrome Case report of GBS occuring immediately after Zika virus infection in French Polynesia Brazilian MOH reporting increased number of people who have been infected with Zika virus and also have GBS Reports of GBS among US cases Potential link is being investigated Oehler et al. Euro Surveill. 2014 Mar 6;19(9). pii: 20720.; feb 5, 2016 CDC transcript telebriefing

Why the Public Health Emergency? Microcephaly and maternal-fetal transmission AP Photos/Felipe Dana scattered intracranial calcifications enlarged ventricles and volume loss

What is Microcephaly? Small head; often smaller brains and abnormal brain development Other associated issues How Common is Microcephaly? RARE 2-12 cases per 10,000 live birth in US Chicago 2015: 4.6 per 10,000 live birth (18 cases)

Maternal-Fetal Transmission: French Polynesia 2013 2014 Two pregnant women with signs and symptoms consistent with Zika infection around the time of delivery Both mothers tested positive for Zika virus RNA by RT- PCR Zika virus infection was confirmed in the neonates, 1-3 days after delivery RNA noted in breastmilk from both mothers, BUT nonreplicative in cell culture Besnard, M., et al., Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014. Euro Surveill, 2014. 19(14): p. 1-5.

Maternal-Fetal Transmission: Brazil 2015: Epidemiology Rates of Microcephaly Over Time: the Americas and the Caribbean Comparison of the rates of microcephaly in the Americas and Caribbean from 2010-2014 and 2015 Updated as of Epidemiological Week 52 (December 27, 2015 January 2, 2016) Microcephaly rates by state in Brazil (cases per 1,000 live births) 0.1-1.0 1.1-15.0 15.1-30.0 30.1-45.0 45.1-88.6 Countries Countries with Zika confirmed cases Epi Week 52 2015 Country limits Brazil State Boundaries Data Source: Reported from the IHR National Focal Points and through the Ministry of Health websites. Map Production: PAHO-WHO AD CHA IR ARO Source: Pan American Health Organization, Epidemiological update, 17 January 2016

http://www.paho.org/ ; MMWR Morb Mortal Wkly Rep 2016;65:59 62 Martines RB MMWR Morb Mortal Wkly Rep 2016;65:159 160 ; Mlakar J N Engl J Med. 2016 Feb 10; Maternal-Fetal Transmission: Brazil 2015: Lab Specimens PAHO epidemiological alert Dec 2015 RNA in amniotic fluid of two pregnant women whose fetuses were diagnosed with microcephaly by ultrasound MMWR 1/29/16 35 LP samples pending from infants with microcephaly MMWR 2/10/16 RNA in fetal brain of two neonatal losses with microcephaly RNA in products of conception of two early miscarriages NEJM 2/10/16 RNA in fetal brain with microcephaly of European woman who had lived in Brazil

Foy et al. Probable non vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis. 2011;17:880 2 Musso et al. Potential sexual transmission of Zika virus. Emerg Infect Dis 2015;21:359 61. Sexual Transmission Wife of Colorado scientist developed compatible symptoms and had positive serologies for Zika virus after sexual contact Presence of hematospermia complicates interpretation Replication-competent Zika virus isolated from semen 10 weeks after illness onset in Tahitian male; blood collected at same time as semen negative by PCR Dallas health officials reported case of Zika in a person whose only exposure was sexual contact with a returned traveler

Zika Virus Identified in Blood and Urine Gourinat et al. Detection of Zika Virus in Urine. Emerg Infect Dis. 2015 Jan; 21(1): 84 86.

http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm486359.htm Guidelines for Blood Banks In areas without active Zika virus transmission, donors at risk for Zika virus infection should be deferred for 4 weeks: Those who had symptoms suggestive of Zika virus in 4 weeks prior Those with sexual contact with a person or traveled to or resided in an area with active transmission during the prior 3 months Those who have traveled to area with active Zika virus transmission in the 4 weeks prior In areas with active Zika virus transmission FDA recommends that whole blood and blood components for transfusion be obtained from areas of the US without active transmission Blood establishments may continue to collect platelets and plasma if an FDA-approved pathogen-reduction device is used Ask potentially affected donors to refrain from giving blood

Zika Management No specific antiviral therapy Treatment is supportive (i.e., rest, fluids, analgesics, antipyretics) Suspected Zika virus infections should be evaluated and managed for possible dengue or chikungunya virus infections Aspirin and other NSAIDs should be avoided until dengue can be ruled out to reduce the risk of hemorrhage Acetaminophen for pregnant women

Prevention for Pregnant Women 1. Pregnant women should consider postponing travel to affected countries http://wwwnc.cdc.gov/travel/page/zika-travel-information 2. Pregnant women should consider using condoms or abstaining from sex throughout the pregnancy with partners who have traveled to affected countries 3. If travelling to an affected area, use mosquito bite prevention http://www.cdc.gov/chikungunya/pdfs/fs_mosquito_bite_prev ention_travelers.pdf http://www.cdc.gov/media/releases/2016/s0315-zika-virus-travel.html; MMWR 2/12/16

Prevention

http://www.cdc.gov/zika/pdfs/zika-pregnancytravel.pdf

Testing and Surveillance for Pregnant Women with Possible Zika Virus Exposure Offer test if symptomatic within 2 weeks of travel or if asymptomatic, from 2 to 12 weeks after travel If positive: Refer MFM Ultrasound exam 3-4 weeks; consider amnio Zika testing at delivery: placenta, umbilical cord, fetal tissue if loss Zika testing of infant If negative or testing declined: Ultrasound 18-20 weeks and routine prenatal care Consider repeat ultrasound later in pregnancy Continue breastfeeding MMWR 2/12/16; ACOG SMFM Practice Advisory Update 2/12/16

Management of Non-Pregnant Women of Reproductive Age Prevention: Prevent unintended pregnancies Women who are trying to become pregnant: Before you or your male partner travel, talk to your doctor about your plans to become pregnant and the risk of Zika virus infection. You and your male partner should strictly follow steps to prevent mosquito bites during travel. Counsel of women with current or previous infection: no evidence of increased risk for birth defect in future pregnancy http://www.cdc.gov/media/releases/2016/s0315-zika-virus-travel.html; MMWR 2/12/16

Diagnostic Testing Reverse transcriptase-polymerase chain reaction (RT-PCR) for viral RNA in serum collected 7 days after illness onset Serology for IgM and neutralizing antibodies in serum collected 4 days after illness onset Plaque reduction neutralization test (PRNT) for 4-fold rise in virus-specific neutralizing antibodies in paired sera Immunohistochemical (IHC) staining for viral antigens or RT-PCR on fixed tissues

Serology Cross-Reactions with Other Flaviviruses Zika virus serology (IgM) can be positive due to antibodies against related flaviviruses (e.g., dengue, yellow fever) Neutralizing antibody testing may discriminate between cross-reacting antibodies in primary flavivirus infections Difficult to distinguish infecting virus in people previously infected with or vaccinated against a related flavivirus

Laboratory Testing Priorities 1. Pregnant women with symptom onset (fever, rash, arthralgias, conjunctivitis) within 2 weeks of returning from an area with active Zika virus transmission 2. Asymptomatic pregnant women with a history of travel to an area with active Zika virus transmission; specimen should be collected between 2 and 12 weeks after returning from the area 3. Infants with microcephaly or intracranial calcifications or born to mothers with positive or indeterminate Zika virus testing during pregnancy 4. Men or nonpregnant women with a history of travel to an area with active Zika virus transmission and symptom onset during travel or within 2 weeks of return

Laboratories for Diagnostic Testing No commercially available diagnostic tests Testing performed at CDC and a few state health departments CDC is working to expand laboratory diagnostic testing in states Healthcare providers should contact their local health department (in Chicago, CDPH) to facilitate diagnostic testing

What Your Local Health Department Can Do For You Conducts disease surveillance Ensures standard application of case definitions Responds to emerging infectious disease threats with guidance about infection control and diagnostic testing Coordinates with and reports to state health dept and CDC Approves your Zika virus testing For Chicago: Get started by calling our Zika line: 312-746-4835

1. Complete Test Authorization form and fax to CDPH Communicable Disease Program at 312-746-4683

Serum Collection Collect blood in a serum separator tube Store by refrigerating at 4 C Specimens along with both IDPH test requisition form and CDC-DASH form should be sent to IDPH laboratory in Chicago Specimens must be transported on icepacks

AUTH #

Chicago providers should register for Chicago s Health Alert Network (HAN) to receive important public health alerts tailored to providers by specialty To register, go to HAN page (https://www.chicagohan.org) and click in upper right corner (or call 312-747-7987) https://www.chicagohan.org/zika

Acknowledgements CDPH Sarah Kemble Massimo Pacilli Allison Arwady Shamika Smith Usha Samala Loretta Miller Damian Plaza Janetta Prokopowicz Saul Ayala Laura Sparrow Charlayne Guy Vilma Alicea Annette Jones Julio Fernandez Jen Levy Karin Hearin Dianna LaPorte Claudia Blanco Shannon Xydis Jose Gonzalez Chris Shields Liza Pilch IDPH Debbie Freeman Connie Austin Fred Echols CDC OUR PROVIDERS!!!

Thank You. Questions? Chicago Zika call line 312-746-4835 CDPH Zika info site: https://www.chicagohan.org/zika