zika virus infection

Helen V. Madamba, MD MPH-TM FPOGS FPIDSOGFebruary 26, 2016

POGS Cebu Chapter

INFECTION IN PREGNANCY

@helenvmadamba POGS CEBU 2016

Zika virus• Zika virus, a flavivirus

transmitted by Aedes mosquitoes.

Schuler-Faccini et al 2016 at http://www.cdc.gov/mmwr


CLINICAL ILLNESS CONSISTENT WITH ZIKA VIRUS DISEASE

• Two or more of the following signs or symptoms:– Acute onset of fever–Maculopapular rash– Arthralgia– Conjunctivitis


• Zika virus (ZIKV), a mosquito-borne flavivirus, was first isolated from a rhesus monkey in Uganda in 1947.

Hayes EB 2009 at http://wwwnc.cdc.gov/eid


• ZIKV was isolated from humans in Nigeria during studies conducted in 1968 and during 1971-1975.



• From 1951 through 1981, serologic evidence of human ZIKV infection reported

• African countries such as Uganda, Tanzania, Egypt, Central African Republic, Sierra Leone, and Gabon

• Parts of Asia including India, Malaysia, Philippines, Thailand, Vietnam, and Indonesia


@helenvmadamba POGS CEBU 2016@helenvmadamba POGS CEBU 2016

• Discovery of ZIKV on the physically isolated community of Yap island is testimony to the potential for travel or commerce to spread the virus across large distances.


• The outbreak on Yap island, Micronesia in 2007 shows that ZIKV illness has been detected outside of Africa and Asia.


Since January 2012, the Pacific Region has experienced 28 new documented outbreaks and circulation of dengue, chikungunya and

Zika virus.

Roth A et.al. 2016 at http://www.eurosurveillance.org


Map of newly reported dengue, chikungunya and Zika virus infection outbreaks or new virus circulation, Pacific Region,

January 2012–17 September 2014 (n=28)



Map of the known distribution of Aedes (Stegomyia) mosquitoes, vectors of dengue and possible vectors of chikungunya andZika viruses, Pacific Region as of beginning October 2014



• Largest ZIKV outbreak occurred in French Polynesia during 2013-2014.

Musso 2016 at http://wwwnc.cdc.gov/eid


Brazil strain = French Polynesia

• Imported cases from French Polynesia

• Occurred among attendees of the annual Tapati festival

• World Cup Soccer competition in 2014

• Va’a World Sprint Championship canoe race in Rio de Janeiro

Musso 2016 at http://wwwnc.cdc.gov/eid


ZIKA VIRUS INFECTION, PHILIPPINES, 2012


MARCH 2012• A prospective longitudinal

cohort study, which included active surveillance for acute febrile illness, was initiated in Cebu City, Philippines.– 270 acute febrile illnesses– 267 samples for serologic testing

for evidence of influenza, dengue, chikungunya, Japanese encephalitis, and Zika virus infections

Alera MT et.al. 2015 at http://wwwnc.cdc.gov/eid


MAY 2012• A 15-year old boy in Cebu City• subjective fever, headache,

conjunctivitis, sore throat, myalgias, stomach pain, anorexia, nausea and vomiting, but no rash

• The boy recovered fully by the 3-week study follow up visit.

• ZIKV RNA was detected in the patient’s serum sample



• It is possible that the ZIKV strain was introduced into the Philippines before 2012 and remained undetected.



Why the fuss now?• Rapid spread since its first

detection in May 2015 in Brazil to 22 other countries and other territories in the Americas

• Possible association with a significant rise in the number of babies born with microcephaly and neurological disorders

• “Global Emergency” by the WHO

Petersen E et.al. 2016 at http://wwwnc.cdc.gov/eid


In Brazil November 2014: great outbreak of a new exanthematic disease

characterized by early onset exanthema, no or little fever, arthraligia, articular edema and conjunctivitis Zika virus confirmed through PCR in April 2015.


On January 22, this report was posted as an MMWR Early Release on the MMWR website


September 2015

• Increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge. Schuler-Faccini et al 2016 at http://www.cdc.gov/mmwr


Microcephaly• Head circumference ≥ 2

standard deviations [SD] below the mean for sex and gestational age at birth



October 2015• The Ministry of Health (MoH)

confirmed an increase in birth prevalence of microcephaly in northeast Brazil, compared with previously reported estimates (approx 0.5/10,000 LB)

• 58 cases in a single month from different cities

• MICROCEPHALY REGISTRY in Brazil established

Brito C. 2015 at http://www.actamedicaportuguesa.com


Brazilian Society of Medical Genetics

• Zika Embryopathy Task Force (SBGM-ZETF) includes clinical geneticists, obstetricians, pediatricians, neurologists and radiologists

• Objective: to review all incident cases of microcephaly as well as infants born to mothers with suspected Zika virus infections during pregnancy



Brazil Ministry of Health

• Cohort of 35 infants with microcephaly born August to October 2015– 35 mothers lived in or visited Zika

virus-affected areas during pregnancy

– 25 infants had severe micrcephaly– 17 had at least one neurologic

abnormality– 27 infants who had neuroimaging

studies, all had abnormalitiesSchuler-Faccini et al 2016 at http://www.cdc.gov/mmwr


Brazil Ministry of Health

• Pregnant women should protect themselves from mosquito bites:– By using airconditioning, screens,

or nets when indoors– Wearing long sleeves and pants– Using permethrin-treated clothing

and gear– Using insect repellants when

outdoorsr



Increase in microcephaly associated with ZIKV

• Outbreak of many cases in short space of time in different cities high attack rates and rapid dispersion transmitted by arthropods




• Microcephaly, periventricular and cortical microcalcifications, vernix cerebellar hypoplasia and lisencephaly compatible with congenital infections




• Diseases associated with TORCH not associated with large outbreaks

• Negative for TORCH infections• 70% mothers reported

compatible features of Zika disease in first trimester of pregnancy (during outbreak)



Zika virus genome was detected in amniotic fluid samples from two pregnant women in Brazil whose fetuses had been diagnosed with microcephaly.

Calvet et al 2016 at http://www.thelancet.com


Zika Viral RNA and antigens were detected in brain tissues from infants with microcephaly and placental tissues from early miscarriages.

Martines et al 2016 at http://www.cdc.gov/mmwr


On January 19, 2016 this report was posted as an MMWR Early Release on the MMWR website


Health care providers should ask all pregnant women about recent travel.• (+) symptoms consistent

with Zika virus transmission with ultrasound findings of fetal microcephaly or intracranial calcifications test for Zika

Petersen et.al. 2016 at http://www.cdc.gov/mmwr


• Testing is not indicated for women without travel history to an area with Zika virus transmission.

Petersen et.al. 2016 at http://www.cdc.gov/mmwr


Pregnant women with laboratory evidence of Zika

virus infection • serial ultrasound

examination to monitor fetal growth and anatomy

• referral to maternal-fetal medicine or infectious disease specialist.– There is no specific antiviral

treatment for Zika virus, supportive care is recommendedPetersen et.al. 2016 at http://www.cdc.gov/mmwr


On January 26, 2016, this report was posted as an MMWR Early Release on the MMWR website


Zika virus testing• Infants with microcephaly or

intracranial calcifications born to women who traveled to or resided in an area with Zika virus transmission while pregnant

• Infants born to mothers with positive or inconclusive test results for Zika virus infection

Staples JE et.al. 2016 at http://www.cdc.gov/mmwr


Zika virus testing

• Molecular• serologic



Zika virus testing

• As an arboviral disease, Zika virus disease is a nationally notifiable condition.



On February 5, 2015, this report was posted as an MMWR Early Release on the MMWR website


UPDATED RECOMMENDATIONS FOR TESTING PREGNANT WOMEN WITH A HISTORY OF TRAVEL TO AREAS WITH ONGOING ZIKA VIRUS TRANSMISSION


With clinical illness consistent with Zika virus

disease• Reverse transcription-PCR

testing (RT-PCR)• Immunoglobulin M (IgM)

Oduyebo et al 2016 at http://www.cdc.gov/mmwr


Asymptomatic pregnant women

• Serologic testing for Zika virus– Consider cross-reactivity

among dengue, yellow fever and West Nile viruses

– Negative IgM obtained 2-12 weeks after travel would suggest a recent infection did not occur and could obviate need for serial ultrasounds.Oduyebo et al 2016 at http://www.cdc.gov/mmwr


Recommendation• Includes recommendations for

screening, testing, and management of pregnant women and recommendations for counseling women of reproductive age (15–44 years)



GUIDELINES FOR PREGNANT WOMEN RESIDING IN AREAS WITH ONGOING

ZIKA VIRUS TRANSMISSION


• Pregnant women who reside in areas with ongoing Zika virus transmission have an ongoing risk for infection throughout their pregnancy and should be evaluated for symptoms of Zika virus disease.



(+) clinical illness• Testing by

RT-PCR on serum collected within 7 days of symptom onset


Women who report clinical illness consistent with Zika virus disease• A negative RT-PCR result

from serum collected 5-7 days after symptom onset does not exclude Zika virus infection

• Serologic testing should be performed.



• A false positive IgM result is more likely among women residing in areas with ongoing Zika virus transmission than among travelers because of a higher likelihood of previous exposure to a related flavivirus.

Serologic testing



(-) clinical illness• Testing

recommended at the initiation of prenatal care with follow-up testing mid-second trimester– Local levels of Zika

virus transmission– Laboratory

capacity


Pregnant women with negative Zika virus IgM

• Routine prenatal care• Ultrasound should include

careful evaluation of the fetus for brain anomalies, including microcephaly and intracranial calcifications (late second and early third trimesters of pregnancy)



Pregnant women with positive or inconclusive Zika virus IgM

• Referral to maternal-fetal medicine specialist

• Serial fetal ultrasounds to monitor fetal anatomy and growth every 3-4 weeks



At the time of delivery• histopathologic examination

of the placenta and umbilical cord,

• testing of frozen placental tissue and cord tissue for Zika virus RNA, and

• testing of cord serum



• To prevent human-to-mosquito-to-human transmission, persons infected with Zika, dengue, or chikungunya virus should protect themselves from mosquito exposure during the first week of illness.



SPECIAL CONSIDERATIONS FOR WOMEN OF REPRODUCTIVE AGE RESIDING IN AREAS OF

ONGOING ZIKA VIRUS TRANSMISSION


• Health care providers should discuss reproductive life plans, including pregnancy intention and timing, with women of reproductive age in the context of the potential risks associated with Zika virus infection.



Pregnancy intentions and timing

• Patient age• Fertility• Reproductive and medical history• Values and preferences of the woman

and her partner• Discussion of the signs and symptoms

and potential risks associated with Zika virus infection



Strategies to prevent unintended pregnancy

• Counseling on family planning• Safety, effectiveness,

availability, acceptability considered when selecting a contraceptive method

• Correct and consistent use of condoms reduces the risk for sexually transmitted infections



• Women of reproductive age with current or previous laboratory-confirmed Zika virus infection should be counseled that there is no evidence that prior Zika virus infection poses a risk for birth defects in future pregnancies.



• Viremia is expected to last approximately one week in patients with clinical illness.

• There is no current evidence to suggest that a fetus conceived after maternal viremia has resolved would be at risk for fetal infection.



On February 5, 2015, this report was posted as an MMWR Early Release on the MMWR website


Sexual transmission of Zika virus is possible

• From man to woman in Colorado, USA

• From man to woman in Dallas County Health and Human Services

• Replication-competent Zika virus isolated from semen

Oster AM et al 2016 at http://www.cdc.gov/mmwr


• Clinical and serologic evidence indicate that 2 American scientists contracted Zika virus infections while working in Senegal in 2008.

• One of the scientists transmitted this arbovirus to his wife after his return home.

• Direct contact is implicated as the transmission route, most likely as a sexually transmitted infection.

Foy et.al. 2011 at http://www.ncbi.nlm.nih.gov


On February 2, 2016 News reports of a Dallas County

case of sexually transmitted Zika virus

https://www.youtube.com/watch?v=ubEfwHM0mlA


• In December 2013, during a Zika virus (ZIKV) outbreak in French Polynesia, a patient in Tahiti sought treatment for hematospermia, and ZIKV was isolated from his semen.

• ZIKV transmission by sexual intercourse has been previously suspected.

• This observation supports the possibility that ZIKV could be transmitted sexually.

Musso et.al. 2015 at http://www.ncbi.nlm.nih.gov


• Men who reside in or have traveled to an area of active Zika virus transmission who have a pregnant partner should abstain from sexual activity (i.e. vaginal intercourse, anal intercourse, or fellatio) for the duration of the pregnancy.

Oster AM et al 2016 at http://www.cdc.gov/mmwr


• Pope Francis says contraception is the lesser of

two evils.https://www.youtube.com/watch?v=64ZhdDd6FH4


IMPLICATIONS FOR PUBLIC HEALTH PREPAREDNESS FOR MASS

GATHERINGS AT THE 2016 BRAZIL OLYMPICS


Mode of Transmission of ZIKV

• Mosquito-borne ZIKV transmission

• Sexual transmission• Blood transfusion and

transmission of ZIKVPeterson et.al. 2016 at http://ac.els-cdn.com


Brazil reports Zika infection from blood transfusions

http://www.reuters.com/article/us-health-zika-brazil-blood-idUSKCN0VD22N


Reduce risk of acquiring ZIKV

• Measures to avoid mosquito bites include wearing long-sleeved shirts, use of insect repellant and staying in screened or air-conditioned accomodations.

• Any travelers who are pregnant or planning to become pregnant, should avoid travelling to areas with ZIKV outbreaks.

Peterson et.al. 2016 at http://ac.els-cdn.com


Reduce risk of acquiring ZIKV

• Pregnant women should wear protective clothing, apply a U.S. Environmental Protection Agency (EPA)-approved insect repellant, and sleep in a screened room or under a mosquito net.



WHO Emergency Committee on Zika virus

• A coordinated international response is needed to improve surveillance, the detection of infections, congential malformations, and neurological

complications, to intensify the control of mosquito populations, and to

expedite the development of diagnostic tests and vaccines to protect people at

risk, especially during pregnancy



DOH, Philippines• Metro Manila (CNN

Philippines): The Department of Health (DOH) said it is ready to handle cases of Zika virus, which is "relatively milder compared to dengue."

"Yes we are ready," said DOH spokesman Dr. Lyndon Lee-Suy.


DOH, Philippines• He added: "But let us clear that

not all pregnant women naman with Zika would really have babies with microcephaly.”

• The last recorded Zika virus victim in the Philippines was in 2012, and he survived the disease.


Dr Willie Ong on facebook at https://www.facebook.com/drwillieong?fref=ts


References• Hayes EB. Zika Virus Outside Africa.

Emerging Infectious Diseases Vol. 15, No. 9, September 2009. page 1347-1350. Accessed on February 23, 2016 at http://wwwnc.cdc.gov/eid/pdfs/vol15no9_pdf-version.pdf

References• Roth A, Mercier A, Lepers C, Hoy D,

Duituturaga S, Benyon E, Guillaumot L, Souarès Y. Concurrent outbreaks of dengue, chikungunya and Zika virus infections – an unprecedented epidemic wave of mosquito-borne viruses in the Pacific 2012–2014. Euro Surveill. 2014;19(41):pii=20929. Accessed on February 23, 2016 at http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20929

References• Musso. Zika Virus Transmission from

French Polynesia to Brazil. Emerging Infectious Diseases Vol. 21, No. 10, October 2015, page 1887. Accessed on February 23, 2016 at http://wwwnc.cdc.gov/eid/article/21/10/15-1125_article

References• Alera MT, Hermann L, Tac-An IA,

Klungthong C, Rutvisuttinunt W, Manasatienkij W, Villa D, Thisomboonsuk B, Velasco JM, Chinnawirotpisan P, Lago CB, Roque VG Jr, Macareo LR, Srikiatkhachorn A, Fernandez S, Yoon I. Zika Virus Infection, Philippines, 2012. Emerging Infectious Diseases Vol. 21, No. 4, April 2015 accessed on February 23, 2016 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378478/

References• Petersen E, et al. Unexpected and Rapid

Spread of Zika Virus in The Americas - Implications for Public Health Preparedness for Mass Gatherings at the 2016 Brazil Olympic Games. Int J Infect Dis (2016). Accessed on February 23, 2016 at http://ac.els-cdn.com/S1201971216000217/1-s2.0-S1201971216000217-main.pdf?_tid=a142cdc6-dc19-11e5-8574-00000aacb361&acdnat=1456444014_f76242858baeb56d6bb8ee290f6ec1da

References• Brito C. Zika Virus: a New Chapter in

the History of Medicine. Acta Med Port 2015 Nov-Dec; 28 (6):679-680. Accessed on February 23, 2016 at http://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/7341/4565

References• Schuler-Faccini L, Ribeiro EM, Feitosa

IM, et al. Possible Association Between Zika Virus Infection and Microcephaly — Brazil, 2015. MMWR Morb Mortal Wkly Rep 2016;65:59–62. Accessed on February 20, 2016 at http://www.cdc.gov/mmwr/volumes/65/wr/mm6503e2.htm

References• Petersen EE, Staples JE, Meaney-

Delman, D, et al. Interim Guidelines for Pregnant Women During a Zika Virus Outbreak — United States, 2016. MMWR Morb Mortal Wkly Rep 2016;65:30–33.accessed on February 23, 2016 at http://www.cdc.gov/mmwr/volumes/65/wr/mm6505e2.htm?s_cid=mm6505e2.htm_w

References• Oduyebo T, Petersen EE, Rasmussen

SA, et al. Update: Interim Guidelines for Health Care Providers Caring for Pregnant Women and Women of Reproductive Age with Possible Zika Virus Exposure — United States, 2016. MMWR Morb Mortal Wkly Rep 2016;65:122–127 accessed on February 23, 2016 at http://www.cdc.gov/mmwr/volumes/65/wr/mm6505e2.htm?s_cid=mm6505e2.htm_w

References• 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;65:63–67. Accessed on February 23, 2016 at http://www.cdc.gov/mmwr/volumes/65/wr/mm6503e3.htm

References• Foy BD, Kobylinski KC, Foy JLC, Blitvich

BJ, Travassos da Rosa A, Haddow AD, et al. Probable non–vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis. 2011 May. Accessed February 26, 2016 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321795/pdf/10-1939_finalD.pdf

References• Musso D, Roche C, Robin E, Nhan

T, Teissier A, Cao-Lormeau VM. 2015 Potential sexual transmission of Zika virus. Emerg Infect Dis. 2015 Feb;21(2):359-61. Accessed February 26, 2016 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313657/

References• DOH ready for Zika virus, February 2,

2016 on CNN Philippines accessed on February 23, 2016 at http://cnnphilippines.com/news/2016/02/01/doh-ready-zika-virus.html

Helen V. Madamba, MD MPH-TM FPOGS FPIDSOGFebruary 26, 2016

POGS Cebu Chapter



#HealthXPH tweetchatLet’s talk about ZIKA!

Saturday, February 27, 2016 9:00 p.m. to 10:00 p.m. MLA

@helenvmadambahttps://www.facebook.com/Helen-V-Madamba

http://www.slideshare.net/HelenMadamba



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