Zika Virus Infection and Pregnancy

Helen V. Madamba, MD MPH-TM FPOGS FPIDSOG
February 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 and
Zika 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.

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 abnormalities

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
outdoors
r

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

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.

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 recommended

On January 26, 2016, this report was posted as an MMWR

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

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.

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.

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 ZIKV
Peterson 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.

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
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/PM
C4378478/

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_f7624
2858baeb56d6bb8ee290f6ec1da

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
http://www.actamedicaportuguesa.com/revi
sta/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/m
m6503e2.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
m6505e2.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
m6505e2.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
m6503e3.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
C3321795/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
C4313657/

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

#HealthXPH tweetchat
Let’s talk about ZIKA!
Saturday, February 27, 2016
9:00 p.m. to 10:00 p.m. MLA
@helenvmadamba
https://www.facebook.com/Helen-V-Madamba
http://www.slideshare.net/HelenMadamba
INFECTION IN PREGNANCY

Zika Virus Infection and Pregnancy

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