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THE ZIKA VIRUS PANDEMIC A LESSON IN EPIDEMIOLOGY AND GLOBAL HEALTH ADRIAN GARCIA MD


OBJECTIVES

Describe the epidemiology, clinical manifestations, and prevention of Zika virus disease

Discuss the current recommendations for men and women attempting to conceive with suspected Zika virus exposure

Discuss the current recommendations and diagnostic evaluation for pregnant women with suspected Zika virus exposure

Discuss the relationship of Zika and microcephaly


ZIKA VIRUS

On March 2nd, 2015 Brazil notified the WHO of an illness characterized by skin rash. Zika not suspected at the time

February 1st, 2016: After local spread in >20 countries, WHO declares that recent association of Zika with microcephaly and other neurological disorders constitutes a Public Health Emergency of International Concern

http://www.who.int/mediacentre/news/statements/2016/1st-emergency-committee-zika/en/


ZIKA VIRUS

Epidemiology

Transmission

Clinical manifestations

Diagnosis

Complications

Prevention and current recommendations

Future outlook


ZIKA VIRUS

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A mosquito-borne ssRNA flavivirus

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Members of Flaviviridae family includes yellow fever, West Nile virus, dengue, and tick-borne encephalitis


ZIKA VIRUS TIMELINE

Kindhauser MK, Allen T, Frank V, Santhana RS & Dye C. Zika: the origin and spread of a mosquito-borne virus


ZIKA VIRUS TIMELINE

Kindhauser MK, Allen T, Frank V, Santhana RS & Dye C. Zika: the origin and spread of a mosquito-borne virus


ZIKA VIRUS TIMELINE

Kindhauser MK, Allen T, Frank V, Santhana RS & Dye C. Zika: the origin and spread of a mosquito-borne virus


ZIKA - CURRENT STATUS

All Countries & Territories with Active Zika Virus Transmission - CDC - August 11th, 2016


ZIKA - CURRENT STATUS

Maps of Zika in the United States - CDC - August 10th, 2016


ZIKA IN CONTINENTAL US

As of August 10th, 2016 there have been 1962 cases (going back to 2011), but only 6 locally acquired mosquito borne

15 live-born infants with birth defects and six pregnancy losses with birth defects with laboratory evidence of Zika virus infection thus far

Cases expected to increase in current outbreak

Virus introduction and local spread in more areas is likely

Maps of Zika in the United States - CDC - August 10th, 2016


ZIKA IN PUERTO RICO

http://wwwnc.cdc.gov/travel/notices/alert/zika-virus-puerto-rico


ZIKA PUBLIC HEALTH RESPONSE

Puerto Rico as case example (under guidance of CDC) -

Protecting pregnant women

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Controlling the mosquito vector

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Expanding full range of voluntary contraceptive options for men and women

Zika Active Pregnancy Surveillance System (PRDH and CDC)

65 infants born to women with active Zika infection during pregnancy: no cases of congenital Zika virus infection among live births detected thus far

Update: Ongoing Zika Virus Transmission — Puerto Rico, November 1, 2015–July 7, 2016. MMWR Morb - CDC


TRANSMISSION

Mosquito-borne (Aedes species)

Non-mosquito transmission:

1. Intrauterine 2. Peri-partum 3. Sexual

4. Other routes


MOSQUITO-BORNE TRANSMISSION


AEDES MOSQUITO US DISTRIBUTION


INTRAUTERINE TRANSMISSION

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Several case reports of Zika virus RNA detected in the amniotic fluid of fetuses that had cerebral abnormalities detected by US

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ZIKV RNA and viral antigens have been detected post-mortem in infants born with microcephaly who died soon after birth, as well is in placental tissue


SEXUAL TRANSMISSION

Several case reports show high viral load in semen of infected male7, which makes it a viable sexual pathogen

One case reports ZIKV RNA in semen 2 months after symptom onset8

One more recent case report showed presence of virus in semen after 182 days!

Limited data about risk of transmission


OTHER ROUTES OF TRANSMISSION

Blood transfusion: No documented cases, though transmission is likely based on data from other arboviruses 9

Breast milk: No documented cases so far

Bite from infected monkey: One case documented in Indonesia. Monkeys are natural reservoirs. http://wwwnc.cdc.gov/travel/notices/alert/zika-virus-puerto-rico


CLINICAL PRESENTATION

Incubation period 3-14 days

Infection rate ~ 75% (from previous outbreaks)

Serosurveys in YAP and French Polynesian outbreaks show symptoms in ~ 20% of infected individuals

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SYMPTOMS

Macular/papular rash (90%)

Fever (65%)

Arthralgia (65%)

Conjunctivitis (55%)

Myalgia (48%)

Headache (45%)

Retroorbital pain (39%)

Vomiting (10%) CDC: Information for Clinicians


FLAVIVIRUSES WITH SIMILAR FEATURES

CDC: Information for Clinicians


DIAGNOSIS

During first two weeks after the start of illness, Zika virus infection can often be diagnosed by performing real-time reverse transcriptase polymerase chain reaction (rRT-PCR) on serum and urine.

Serology for IgM and neutralizing antibodies in serum collected up to 12 weeks after illness onset

Serologic cross-reactivity between closely related flaviviridae (dengue, Chinkungunya). PRNT is a differentiating test, but costly, not widely available


REPORTING CASES

Reportable disease to ODH and CDC (arbovirus)

Voicemail message on the reportable diseases hotline with the case information

US Zika Pregnancy Registry


ACUTE ZIKA DISEASE MANAGEMENT PEARLS

No antiviral treatment

Treatment supportive (rest, fluids, analgesics, antipyretics)

If Zika suspected, need to rule out dengue

No NSAIDs/ASA until dengue ruled out


NEUROLOGIC COMPLICATIONS

Temporal and geographic relationship observed with GBS and Zika virus infection

Case control study from French Polynesia Zika outbreak: 42 GBS cases (98% with positive Zika serology, odds ratio > 34) 12 .

In current outbreak, increased incidence of GBS in 16 countries

Case reports of meningoencephalitis and acute myelitis


FETAL COMPLICATIONS

Full spectrum of fetal complications yet to be determined. They include fetal death, placental insufficiency and CNS injury.

Microcephaly is the most worrisome complication and the reason why Zika has been declared a Public Health Emergency by the WHO


MICROCEPHALY

http://www.cdc.gov/zika/pdfs/microcephaly_measuring.pdf


MICROCEPHALY

Prevelance: 6/10,000 live births in US

Etiologies: Genetic>prenatal/perinatal brain injury

A retrospective analysis of the 2013–2014 Zika outbreak in French Polynesia estimated that 1% of the fetuses and neonates who were born to mothers infected with Zika virus in the first trimester had microcephaly, a prevalence 50 times higher than what would be expected. 13

A cohort study published in NEJM from Brazil indicated that fetal abnormalities detected by ultrasonography were present in 29% of women with Zika virus infection during pregnancy. 10

These studies led the CDC to publish an article in NEJM “Zika Virus and Birth Defects — Reviewing the Evidence for Causality” where it concluded that ZIKV was a cause of microcephaly in April 2016


MICROCEPHALY MORBIDITY

Seizures

Developmental and motor delay

Intellectual disabilities

Problems with hearing and vision

Severe microcephaly can lead to death from feeding/swallowing difficulty, status epilepticus


TESTING INFANTS

CDC: Information for Clinicians


EVALUATING INFANTS

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CDC Recommendations on evaluation of infants with positive or inconclusive Zika test results: -

Physical exam, developmental assessment, measurement of head circumference

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Cranial Ultrasound

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Ophthalmologic evaluation within 1 month of birth

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Hearing screen within 1 month of birth

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Consult appropriate specialist for abnormal findings

CDC: Information for Clinicians


EVALUATING INFANTS

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Infants with Microcephaly and evidence of Congenital Zika Virus Infection: -

Consultation with Genetics and Neurology

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Testing for other congenital infections

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Considering other genetic/teratogenic causes

CDC: Information for Clinicians


EVALUATING INFANTS

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Long term follow-up for infants with suspected Zika infection: -

Additional hearing screen at 6 months

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Continual developmental assessment through 1st year of life

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Consultation with appropriate specialists if abnormalities are noted

CDC: Information for Clinicians


ZIKA AND PREGNANCY •

No evidence that previous infection will affect future pregnancies

All pregnant women should be asked a sexual and travel history at each prenatal visit

Who to test:

CDC Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure


CDC RECOMMENDATIONS: PREGNANT WOMEN

CDC Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure


CDC RECOMMENDATIONS: NON-PREGNANT ADULTS

Women with Zika virus disease should wait until at least 8 weeks after symptom onset before attempting conception.

Men with possible or confirmed Zika with pregnant partners should use barrier contraception or abstain from sex for remainder of pregnancy, and wait 6 months from time of exposure till conception

Routine testing is not currently recommended for women or men who are attempting conception who have possible exposure to Zika virus but no clinical illness.

CDC Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure


PREVENTION •

Travel advisories

Contraception

Vector Control

No vaccine available

CDC - Preventing Mosquito-Borne Illnesses


WHO RISK ASSESSMENT “Overall, the global risk assessment has not changed. Zika virus continues to spread geographically to areas where competent vectors are present. Although a decline in cases of Zika infection has been reported in some countries, or in some parts of countries, vigilance needs to remain high. At this stage, based on the evidence available, there is no overall decline in the outbreak.�

http://www.who.int/emergencies/zika-virus/situation-report/11-august-2016/en/


FUTURE OF CURRENT EPIDEMIC

Will likely get worse, some experts expect incidence >1 million

Further research needed in associations with adverse birth outcomes and GBS, as well as environmental factors that favor emergence of disease

Good news: Current virus strains in Americas 99% similar genetically - one vaccine to rule them all.


REFERENCES

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1. WHO statement on the first meeting of the International Health Regulations (2005) (IHR 2005) Emergency Committee on Zika virus and observed increase in neurological disorders and neonatal malformations http://www.who.int/mediacentre/news/statements/2016/1st-emergency-committee-zika/en/ 2. Kindhauser MK, Allen T, Frank V, Santhana RS & Dye C. Zika: the origin and spread of a mosquito-borne virus [Submitted]. Bull World Health Organ E-pub: 9 Feb 2016. 3 Zika Virus Microcephaly and Guillain-Barre Syndrome Situation Report 21 Apr 2016 4. Zika virus infection in French Polynesia Jouannic, Jean-Marie et al. The Lancet , Volume 387, Issue 10023 , 1051 - 1052 5. Effler PV, Pang L, Kitsutani P, et al. Dengue fever, Hawaii, 2001-2002. Emerg Infect Dis 2005;11:742-9. 6. Zika virus infection among U.S. preg- nant travelers — August 2015–February 2016. MMWR Morb Mortal Wkly Rep 2016;65:211-4. 7. Mansuy JM, Dutertre M, Mengelle C, et al. Zika virus: high infectious viral load in semen, a new sexually transmitted pathogen? Lancet Infect Dis 2016 March 3 (Epub ahead of print). 8. Atkinson B, Hearn P, Afrough B,et al. Detection of Zika virus in semen. Emerg Infect Dis 2016 May 9. Marano G, Pupella S, Vaglio S, Lium- bruno GM, Grazzini G. Zika virus and the never-ending story of emerging pathogens and transfusion medicine. Blood Transfus 2016;14:95-100. 10. Brasil P, Pereira JP Jr, Raja Gabaglia C, et al. Zika virus infection in pregnant women in Rio de Janeiro — N Engl J Med. DOI: 10.1056/ NEJMoa1602412.


REFERENCES

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12. Cao-Lormeau VM, Blake A, Mons S, et al. Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet 2016 February 29 (Epub ahead of print). 13. Sonja A. Rasmussen, Denise J. Jamieson, Margaret A. Honein, Lyle R. Petersen. Zika Virus and Birth Defects — Reviewing the Evidence for Causality. New England Journal of Medicine, 2016 14. CDC Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure — United States, 2016 Weekly / April 1, 2016 / 65(12);315–322 15. Adams L, Bello-Pagan M, Lozier M, et al. Update: Ongoing Zika Virus Transmission — Puerto Rico, November 1, 2015–July 7, 2016. MMWR Morb Mortal Wkly Rep 2016;65:774–779 16. WHO Situation Report - Zika Virus, Microcephaly, Guillain-Barre Syndrome, 11 August, 2016 17. Zika Virus: Information for Clinicians - CDC, 5 August 2016 18. Zika Virus - Lyle R. Petersen, M.D. et al, N Engl J Med 2016; 374:1552-1563April 21, 2016DOI: 10.1056/NEJMra1602113


THANK YOU


The zika virus pandemic