Zika VirusSujata Ambardar MD. FACP

September 14, 2016

Zika Virus: Introduction

In 1947 isolated in Zika forest of Uganda First major infectious disease linked to human birth

defects in last half century WHO declared a Public Health Emergency of

International concern Introduced to Brazil from Pacific islands spread

rapidly to America within span of 1 year

NEJM 374:16

Zika : Epidemiology

Flavivirus in family Flaviviridae1953 First recognized in Nigeria ; mild febrile illnessOnly 13 natural acquired cases during next 57 years2007 Outbreak on several islands in State of Yap, Micronesia: 5000 infections in 67002013/2014 Outbreak French Polynesia involved 32,0002014/2015 Pacific islands, Easter Island, Cook Islands, Samoa

In Africa, Zika virus circulates in a sylvatic transmission cycle between nonhuman primates and certain forest-dwelling species of aedes mosquitoes. In this setting, sporadic human infections may occur. In suburban and urban settings, Zika virus is transmitted in a human–mosquito–human transmission cycle, mostly involving A. aegypti mosquitoes.

Petersen LR et al. N Engl J Med 2016;374:1552-1563.

Areas in Which Zika Virus Infections in Humans Have Been Noted in the Past Decade (as of March 2016).

Microcephaly Associated with Maternal Zika Virus Infection

Zika Virus:Complications

Increasing incidence of microcephaly, other neurologic findings prompted evaluation

Fetal abnormalities estimated at 29 % in ultrasounds done in Brazil

Findings of Zika virus RNA in amniotic fluid of fetuses with microcephaly

Early fetal loss and death Ocular abnormalities

NEJM 374: 16

Expected and Observed Numbers of Cases of the Guillain–Barré Syndrome

CDC Zika Case Counts in the US ( As of Sept 7,2016) US States Locally acquired mosquito-borne cases reported: 43 Travel-associated cases reported: 2,920 Virginia 78 (3) ; all travel Florida 571  (20) ; travel 43    (100)

mosquito -borne

Laboratory acquired cases reported:  1 Total: 2,964

Sexually transmitted: 24 Guillain-Barré syndrome: 7

Case Counts in the US

US Territories Locally acquired cases reported: 15,809 Travel-associated cases reported: 60 Total: 15,869*

Guillain-Barré syndrome: 31 *Sexually transmitted cases are not reported for US

territories because with local transmission of Zika virus it is not possible to determine whether infection occurred due to mosquito-borne or sexual transmission.

Local transmission of Zika virus

The Florida Department of Health has identified two areas of Miami-Dade County where Zika is being spread by mosquitoes. In addition to the previously identified area in the Wynwood neighborhood, there is now mosquito-borne spread of Zika virus in a section of Miami Beach

Zika: Screening Questions for every pregnant woman to assess risk

1) Have you traveled to a Zika-affected area within the past 12 weeks?

2) Have you had possible sexual exposure to Zika virus within the last 12 weeks?

3) Do you have ≥ 2 symptoms* of Zika and had mosquito bite(s) in the 2 weeks before symptom onset?

Revised Algorithm on Inova Net 8/2016

*Symptoms of Zika

Fever ( 65% ) Rash ( 90%) Arthralgia (65%) Conjunctivitis ( 55%) Pregnancy complication (fetal loss, fetus or

neonate with congenital microcephaly, intracranial calcifications, other structural brain or eye abnormality, or other congenital central nervous system related abnormality)

Zika Testing: Pregnant patient

Test for Zika if patient has at least one risk factor listed above 1. Provider should contact the local health department to

request Zika testing.

2. Upon approval, the local health department will FAX or e-mail the following two forms to the requesting provider. These two forms must accompany the sample(s) at all times and be filled out completely. The laboratory will not accept samples unless these two forms are provided.

a. ZIKA VIRUS CASE REPORT FORM b. DCLS MICRO/VIRO TEST REQUEST FORM

Zika Screening: Non-pregnant

Non‐pregnant individuals who did not travel to a Zika‐affected area :have ≥1 symptom of Zika and had possible sexual exposure to Zika virus*have ≥3 symptoms of Zika not explained by another etiology and had mosquitobite(s) in the 2 weeks before symptom onsetNon‐pregnant individuals who traveled to a Zika‐affected area: have ≥2 symptoms of Zika during orwithin 2 weeks of travel A person diagnosed with Guillain‐Barré Syndrome not known to be associated with another etiology

Zika Screening: Infants

Infants who: have ≥2 symptoms of Zika in the first 2 weeks of

life not explained by another etiology were born to mothers with laboratory evidence of

confirmed or possible Zika virus infection have fetal abnormalities consistent with congenital

Zika virus infection were diagnosed with microcephaly, intracranial

calcifications, brain or eye abnormality

Zika Testing

rRT-PCR testing for Zika virus is available through some commercial laboratories but VDH and Inova strongly recommend that providers caring for pregnant women pursue Zika virus laboratory testing through public health (at no cost to the patient).

Public health testing more timely combinations of rRT-PCR and serological (IgM) testing with appropriate reflex testing performed without need for additional orders or samples.

Providers may contact their local health department with any questions or to request Zika virus testing

Local Health Departments: Contact InformationHealth Department Electronic Approval Form Contact Number Alexandria https://www.alexandriava.gov/health/info/default.aspx?id=65006 571.259.8549

Arlington https://health.arlingtonva.us/zika-resources-clinicians/ 703.228.5200,

Fairfax http://go.usa.gov/cGuZ4 703.246.2433

Loudoun https://www.loudoun.gov/index.aspx?NID=3843 703.771.5936

Prince William - Manassas http://www.vdh.virginia.gov/lhd/PrinceWilliam/resources.htm 703.792.6301

Prince William - Woodbridge http://www.vdh.virginia.gov/lhd/PrinceWilliam/resources.htm

703.792.7301

Zika Testing

Patients presenting at physician offices without blood draw capabilities may be directed to an Inova Patient Service Location for blood collection (see attached for a list of facilities). Locations available on Inovanet Zika page NOTE: Patients who present at an Inova Patient Service

Location WITHOUT the required 2 FORMS completed will not have specimens collected and will be directed back to their provider. .

Zika Testing: Registration and Ordering Patient Presents at Facility for specimen collection. Patient will be registered in EPIC following normal registration

procedures. If possible, patient forms should be scanned into EPIC as part of patient record.

Staff will collect specimen using guidelines for acceptable specimens below.

If being collected by NON-Laboratory Staff- Order in EPIC “ZIKA-Health Department Lab Test (DCLS)” or LAB 12932 If being collected by Inova Laboratory Staff- Order in SOFT “ZIKA”, collect and verify. **Laboratory staff should monitor pending for ZIKA test and

verify accordingly to complete test. Laboratory staff will package specimens and paperwork for

transport to the health department

Zika Testing : Background Zika virus is a single-stranded RNA virus in the genus Flavivirus and is

closely related to dengue, West Nile, Japanese encephalitis, and yellow fever viruses . Among flaviviruses, Zika and dengue virus share similar symptoms of infection, transmission cycles, and geographic distribution

Zika virus antibody test results can be difficult to interpret because of cross-reactivity with other flaviviruses, which can preclude identification of the specific infecting virus, especially when the person previously was infected with or vaccinated against a related flavivirus

Interim Guidance for Interpretation of Zika Virus Antibody Test Results. MMWR Morb Mortal Wkly Rep 2016;65. DOI: http://dx.doi.org/10.15585/mmwr.mm6521e1

Zika Virus Infection and Immune Response Most Zika virus infections are asymptomatic Viremia is expected to occur from several days before illness

onset until a week after illness onset Zika virus–specific IgM antibodies develop during the first

week of illness Data on duration of IgM antibody persistence following Zika

virus infection are limited IgM antibodies against West Nile virus, a closely related

flavivirus, have been detected in asymptomatic, infected blood donors for at least 3 months after their viremic donation, and almost half of tested patients with West Nile virus neuroinvasive disease had detectable serum IgM antibodies >1 year after illness onset

Zika Virus Antibody Testing

An enzyme-linked immunosorbent assay (ELISA) can be used to detect anti-Zika virus IgM antibodies in serum or cerebrospinal fluid; however, the Zika virus IgM ELISA can provide false-positive results because of cross-reacting IgM antibodies against related flaviviruses or nonspecific reactivity

The plaque reduction neutralization test (PRNT) measures virus-specific neutralizing antibody titers and should be performed against various related flaviviruses to rule out false-positive ELISA results.

Zika Testing: Symptomatic patients For symptomatic women with exposure to Zika virus, rRT-PCR

testing of serum and urine is recommended up to 2 weeks after symptom onset.

Urine should always be collected with a patient-matched serum specimen

A positive rRT-PCR result on any sample confirms Zika virus infection and no additional testing is indicated. A negative rRT-PCR result does not exclude Zika virus infection and serum should be analyzed by IgM antibody (serological) testing.

Zika Testing: Asymptomatic pregnant patients with travel historyrRT-PCR testing is recommended on serum and urine within 2 weeks of the date of last possible exposure.rRT-PCR testing is also indicated for pregnant women who present for care ≥ 2 weeks after exposureIn areas with active ZIKV transmission, asymptomatic pregnant women should undergo IgM testing as part of routine obstetric care in the 1st and 2nd trimester.Reflex rRT-PCR testing is included as a subsequent test for women who are IgM positive

Interpretation of Zika Virus Testing Results Serum IgM antibody testing for Zika and dengue virus

infections should be performed if rRT-PCR is negative. For serum specimens collected <7 days after onset of

symptoms, the combination of a negative rRT-PCR result and negative IgM antibody testing suggests that there was no recent infection.

A negative IgM antibody test, in the absence of rRT-PCR testing, might reflect specimen collection before development of detectable antibodies and does not rule out infection with the viruses for which testing was performed

Zika : Pregnancy

In addition to microcephaly, other problems have been detected among fetuses and infants infected with Zika virus before birth, such as eye defects, hearing loss, and impaired growth.

Researchers are collecting data to better understand the extent Zika virus impact on mothers and their children.

Pregnant women with laboratory evidence of Zika virus infection should be evaluated and managed for possible adverse pregnancy outcomes and be reported to the U.S. Zika Pregnancy Registry or the Puerto Rico Zika Active Pregnancy Surveillance System for clinical follow-up

Prevention: Insect Repellents

Zika: Travel guidance in Pregnancy CDC recommends that pregnant women not travel to an area

with active Zika virus transmission. If a pregnant woman must travel to one of these areas, she

should talk to her healthcare provider. If she travels, she should be counseled to strictly follow steps

to avoid mosquito bites and prevent sexual transmission during the trip.

Zika:Transmission through Blood Transfusions Zika virus currently poses a low risk to the blood supply in the

continental US Cases of Zika transmission through blood transfusion in Brazil.

During the previous French Polynesian Zika virus outbreak, 2.8% of blood donors tested positive for Zika

On August 26, 2016, the US Food and Drug Administration (FDA) issued revised guidance to prevent the spread of Zika virus through the blood supply. This new FDA guidance calls for blood collection centers in the United States to screen all donated blood for Zika virus.

Additional resources: Centers for Disease Control and Prevention: http://www.cdc.gov/zika/ About Zika: http://www.cdc.gov/zika/about/index.html Interim Guidance for Interpretation of Zika Virus Antibody Test Results (6/4/16):

http://www.cdc.gov/mmwr/volumes/65/wr/mm6521e1.htm CDC for Providers Interim Guidance for Healthcare Providers Caring for Pregnant Women with Possible Zika

Virus Exposure Clinical Guidance for Healthcare Providers Caring for Pregnant Women Clinical Guidance for Healthcare Providers Caring for Infants & Children MMWR, Interim Guidelines for Pregnant Women During a Zika

Virus Outbreak — United States, 2016 CDC Pregnancy Registry CDC Guidance for Travel and Testing of Pregnant Women and Women of Reproductive Age for Zika

Virus Infection Related to the Investigation for Local Mosquito-borne Zika Virus Transmission in Miami-Dade and Broward Counties, Florida

Additional Resources:

Division of Consolidated Laboratory Services (Virginia Department of General Services)

DCLS - Chikungunya, Dengue and Zika Virus Testing VDH Health Commissioner Zika Virus Update #4 (Aug. 1, 2016)

Guide to Interpreting Zika Virus Test Results Zika Virus Disease Information for Clinicians Zika Checklist for Clinicians Chikungunya, Dengue and Zika Virus Infections - Cheat Sheet for Healthcare Providers

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