Zika virus - SGB - SZC PE Brazil

ZIKA VIRUS DISEASE AND ITS COMPLICATIONS
SUCCESSFUL EXPERIENCES AND CHALLENGES FOR SURVEILLANCE AND RESPONSE IN BRAZIL
ZIKA VIRUS DISEASE AND ITS COMPLICATIONS:
SUCCESSFUL EXPERIENCES AND CHALLENGES
FOR SURVEILLANCE AND RESPONSE IN BRAZIL
George Santiago Dimech
gsdimech@gmail.com
Epidemiologist - DVM, MSc
Recife – Pernambuco - December 2016

BACKGROUND (2015) – PERNAMBUCO - BRAZIL
• February / March: outbreak of an exanthematic disease without a diagnostic hypothesis
established, later (July) confirmed as Zika virus disease
• July: increase in the number of cases (from May) of Síndrome de Guillain-Barré (SGB)
• October 2015: increase (since August) in the prevalence of microcephaly
• It coincided temporarily with an epidemic of the Zika virus ~ 6-7 months earlier
• Subsequently, other congenital anomalies, placental insufficiency, fetal growth
retardation and fetal death associated with Zika virus infection during pregnancy were
described.

SITUATION REPORT – MYCROCEPHALY - PERNAMBUCO - BRAZIL
Pernambuco: 21,5% of reported cases and 18% of confirmed
cases among the 27 states of Brazil.

Reported cases of dengue, chikungunya, zika and microcephaly (reported and confirmed) in the second epidemiological
week. Pernambuco, 2015-2016
Source: Planilha de Acompanhamento Semanal Dengue (GCDFA/DGCDA), Sinan Online e CIEVS/SEVS/SES-PE
Outbreak of
exanthematic disease of
unknown etiology
Congenital syndrome
associated with Zika
virus infection
Triplice Epidemic: Zika,
Dengue, Chikungunya
Zika Virus:
2015=~80.000 cases
2016= 11.500 cases

Estimated cases of dengue, Zika, and reported cases of chikungunya and microcephaly (reported and confirmed) in the second
epidemiological week. Pernambuco, 2015-2016
Source Planilha de Acompanhamento Semanal Dengue (GCDFA/DGCDA), Sinan Online e CIEVS/SEVS/SES-PE
Estimated cases of
Zika: 81.000 reports*
Congenital syndrome
associated with Zika
virus infection

PERNAMBUCO: 185 cities distributed by 12 Health Regions

• ZIKA VIRUS DISEASE (ZIKV)
• GUILLAIN-BARRÉ SYNDROME (GBS) AND OTHER
NEUROLOGICAL COMPLICATIONS
• CONGENITAL SYNDROME ASSOCIATED WITH ZIKA VIRUS
INFECTION

ZIKA VIRUS DISEASE (ZIKV) - BACKGROUND

Zika virus (ZIKV)
• Transmission:
• Mosquitoes – Genus Aedes – More Important
• Others:
• Sexual
• man => woman / woman => man / man => man
• It seems more common than expected
• Confirmed elimination by semen for up to 6 months
• Pregnant women: Indication for use of condoms or sexual abstinece
• Vertical (mother-to-child): Malformations
• Blood transfusion
• Occupational (laboratorial accident)
Obs #1: Non confirmed means: urine, saliva.
Obs #2: Breast milk: particles were identified, but no evidence of transmission of the
disease to the baby.
Fuente: http://agenciabrasil.ebc.com.br/ - Arquivo/Agência Brasil/

Clinical description: 80% asymptomatic
• Sudden onset of rash, which is usually maculopapular
• Spreads in a cephalocaudal (cerebro-caudal) manner (head, trunk, and upper and
lower extremities, frequently affecting the palmar and plantar Surfaces - in the
convalescent stage, there may be laminar desquamation)
• Pruritic: often inteferes with the patient’s daily activities, even hindering sleep
• Non-purulent conjunctival hyperemia.
• Low-grade fever (< 38.5◦C)
• Adenopathy or lymphadenopathy is rare, and when it occurs, the retroauricular ganglia
lymph nodes are affected.

Source: revistavivelatinoamerica.comhttp://medicinapreventiva.info/

• In some cases, articular impairment is observed:
• Usually polyarthralgia with bilateral, symmetrical periarticular edema
• Mild articular edema, without hyperemia or local heat
• The joints of the hands and wrists are most frequently affected, followed by the
knees and ankles
• Zika x Chikungunya: pain associated with ZIKV disease tends to be milder and is
not debilitating
• Infertilidad de los hombres? Bajo estudio en ratones
• Other possible manifestations include headache, myalgia, nausea, diarrhea, and Vomiting
• No instances of hemodynamic impairment have been observed as is seen in severe
dengue cases

Surveillance:
• Syndromic Surveillance: rash
• Pre-event Phase
• Travelers Health
• Mass Gathering; commercial or touristic zones; other
• Universal Surveillance: Notification of all Suspect Cases
• Sentinel Surveillance: Laboratory investigation of cases in selected health
services;

Surveillance:
• Pregnant women with exanthema Surveillance
• Notification and follow-up of all pregnant women with Exanthema
• Laboratory monitoring - Differential Zika x arboviruses x other STORCH
• Follow-up: Women's Health - Ultrasound and psychological support
• Results 2016: ~4.200 reports:
• Chikungunya: 929 (22.0%)
• Dengue 144 (3.4%)
• Zika 64 (1.5%)
• Coinfection/Cross Reaction: Chikungunya and Zika: 6 (0.1%)
• Coinfection/Cross Reaction: Dengue e Chikungunya: 143 (3.4%)
• Non realized: 1,558 (37,0%)
• Negative: 1,648 (39.3%)

Pregnant woman with exanthematic disease is a priority for Zika's diagnosis
• Definition: Pregnant woman, regardless of gestational age, with acute exanthematic disease and
excluded non-infectious causes.
• It will only be possible to identify the etiologic agent considered acute exanthematic
disease in the first five days of the eruption
• For pregnant women with exanthema, ultrasound is indicated between the 32nd and 35th
gestational weeks (~ 7 months).

• The criteria for ultrasonically suspected congenital syndrome associated with zika infection
in the fetus meet similar definitions of the newborn:
• Decreased cranial circumference (CC <2 SD) below the mean for gestational age;
• Presence of cerebral calcifications AND / OR
• Presence of ventricular changes E / OR
• At least two of the following signs of posterior fossa alterations: cerebellar hypoplasia,
posterior fossa widening greater than 10mm and agenesis / hypoplasia of corpus
callosum.

CASE DEFINITION:
Suspected case of Zika virus disease: Patient with rash* with at least two or more of the
following signs or symptoms:
• fever, usually <38.5 °C
• conjunctivitis (non-purulent/hyperemic)
• arthralgia
• myalgia
• peri-articular edema
* usually maculopapular and pruritic
Probable case of Zika virus disease
• Patient who meets the criteria of a suspected case AND also has anti-ZIKV IgM
antibodies, without laboratory results indicating infection by other ﬂaviviruses.

CASE DEFINITION:
Confirmed case of Zika virus disease: Patient who meets the criteria for a suspected case
AND has laboratory confirmation of recent ZIKV infection, with presence of:
• RNA or ZIKV antigen in any serum sample or other type (for example, urine, saliva, tissue
or whole blood); OR
• Positive anti-ZIKV IgM antibodies AND plaque reduction neutralization plate (PRNT90) for
ZIKV titers ≥ 20 and four or more times higher than for other ﬂaviviruses; and
exclusion of other ﬂavivirus;* OR
• In deceased individuals, molecular detection of the viral genome in autopsy tissue (fresh or
in paraffn), or specifc viral antigen detection by immuno-histochemistry testing.

Diagnostic indications, according to day of symptom onset and sample type.

• Detection of ZIKV IgM antibodies is an important tool in confirming Zika virus infection
associated to complications, including neurological and congenital syndromes.
• ZIKV serological diagnosis can be performed by ELISA IgM starting from the 6th day of
onset of symptoms through several months after the infection.
• Serological diagnosis In primary infections with flaviviruses have shown that there is no
cross-reactivity of antibodies (or very low) with other antigenically related virus.
• In individuals with a previous history of infection by other flaviviruses (dengue, sylvatic
yellow fever or vaccine yellow fever, West Nile Virus, etc.) the possibility of cross-reactivity
is high.
• For this reason, the use of serology for routine surveillance (outpatients with suspected
ZIKV infection) in endemic areas for different flavivirus is limited.

GUILLAIN-BARRÉ SYNDROME (GBS)
• In its typical form, GBS occurs as an ascending, progressive, symmetrical,
subacute muscular paralysis that reaches peak severity by 4 weeks and is
accompanied by areﬂexia (absence of reﬂexes).
• It may be preceded by a history of infection: Zika (including asymptomatic),
Chikungunya, Campylobacter (bacteria found in poultry farming), influenza virus,
Epstein-Barr virus, HIV, after pneumonia, other

ARBOVIROSIS X SGB 2015
Distribution of cases of GBS, Dengue, Chikungunya and zika by date of onset of
symptoms. Pernambuco, 2015 - 2016

Outbreak investigation of Guillain-Barré syndrome with pre zika virus infection,
Metropolitan Region of Recife, Pernambuco, Brazil, january-june 2015:
• Fifty-five patients were investigated and 40 (72%) were confirmed for GBS according to
Brighton criteria.
• 18 (45%) had symptoms up to 35 days before GBS: Rash 15 (83%); arthralgia 13
(72%); Fever 11 (61%); headache 11 (61%); myalgia 9 (50%) and pruritic 9 (50%)
• Discharged: 17 patients / Died: 01
• Median: 8 (0 to 35) days between the suspected viral previous infection and the
neurologic symptoms.
Observation:
• No increase in hospitalizations for GBS in previous epidemic years of dengue
• No records of chikungunya transmission until the end of the investigation
• Temporal relation with the zika epidemic

SENTINEL SURVEILLANCE OF NEUROLOGICAL MANIFESTATIONS - ARBOVIRORES
• HOSPITALAR UNIT - NEUROLOGY AND NEUROPEDIATRY
• Investigate the complete medical history for all patients with suspected GBS;
• Detailed neurological examination;
• Information on previous diseases, triggering factors, and progression of neurological
symptoms

SENTINEL SURVEILLANCE OF NEUROLOGICAL MANIFESTATIONS - ARBOVIRORES
• HOSPITALAR UNIT - NEUROLOGY AND NEUROPEDIATRY
Complementary Sources:
• Review of existing sources of information (clinical records, data from tertiary referral
hospitals, and others) in order to establish a baseline incidence of GBS.
• Monitoring of immunoglobulin dispensing and administration as a proxy indicator of an
increase in incidence of GBS.
• Review of surveillance data on acute ﬂaccid paralysis, which can also be used as a proxy
indicator of GBS.

SURVEILLANCE OF CASES OF NEUROLOGICAL MANIFESTATIONS WITH PREVIOUS
VIRAL INFECTION HISTORY
What to watch:
• Suspected case of arbovirus-related neuroinvasive disease admitted to the Hospital
(Sentinel Unit)
• History viral infection consistent with symptoms of dengue fever or Chikungunya or Zika up
to 30 days before onset of neurological symptoms
Neuroinvasive disease: encephalitis, meningoencephalitis, myeloradiculitis, myelitis,
myeloneuropathy, encephalous disseminated acute myelitis (ADEM), Guillain-Barré syndrome
and its variants of undetermined origin.

• Laboratorial Diagnosis:
• Serological diagnosis of ZIKV in Guillain-Barré and other neurological complications
generally, suspicion of a neurological syndrome occurs outside the viremia period;
• Accordingly IgM antibody detection by ELISA in serum sample (or cerebrospinal fluid
collected -LCR- under medical supervision) is recommended.

SURVEILLANCE OF CONGENITAL SYNDROME ASSOCIATED WITH ZIKA VIRUS
INFECTION

NEWBORN (RN) WITH MICROCEPHALY
October/15 first cases 27/Oct/15 Protocol #1 02/December
Protocol #2
33 cm 32 cm
17/march
Technical Report
SEVS/PE March/2016
31,9 – 31,5 cm
-(2SD)
SURVEILLANCE OF CONGENITAL SYNDROME ASSOCIATED WITH ZIKA VIRUS
INFECTION

• Zika virus is an intensely neurotropic virus
that particularly targets neural progenitor
cells but also – to a lesser extent –
neuronal cells in all stages of maturity.
Viral cerebritis can disrupt cerebral
embryogenesis and result in microcephaly
and other neurological abnormalities
2175
Adaptado de Tang et al., 2016, Cell Stem Cell

CLINICAL DESCRIPTION OF THE CONGENITAL SYNDROME ASSOCIATED WITH ZIKA
(CSZ) VIRUS INFECTION**
• Presence of microcephaly:
• Head circumference below -2 standard deviations measured at 24 hours after birth
according to the standardized guidelines for gestational age and sex. A new
measurement of HC should then be obtained, preferably during the first week of life
• Its correct use requires having reliable data on gestational age (from first-trimester
ultrasound or date of last menstrual period
• Premature and full-term newborns: Intergrowth-21st standards growth curve
• https://intergrowth21.tghn.org/site_media/media/articles/newbornsize.pdf
• Full-term newborns for whom reliable information on gestational age at birth is
unavailable, it is recommended to use the standards from the WHO Multicentre
Growth
• http://www.who.int/childgrowth/standards/es/
2175

(CSZ) VIRUS INFECTION**
• Presence of microcephaly:
• Pernambuco: 2.175 reports of (CSZ):
• 393 (18%) Confirmed (with congenital malformations especially of the central
nervous system, auditory, and visual that could be associated with ZIKV)
• 72 (18%) without microcephaly
• 1433 (66%) Discarded
• 351 (16%) Under investigation
2175

VIRUS INFECTION
• Presence of microcephaly with other signs, such as:
• Facial or other disproportionality cranial-facial disproportion
• Anthropometric disproportions
• Redundant scalp with roughness
• Irritability: hypertonia/spasticity and epileptic / seizures -
• Joint disorders: artrogriposis
• Severe central nervous system compromise - presence of: cerebral calcifications
(mainly cortical and subcortical), cerebral ventricles, anomalies abnormalities of the
posterior fossa, and lissencephaly
• Auditory (hearing loss) and visual abnormalities

SPECTRUM OF SYMPTOMS:
(a) Axial transabdominal US performed at 36
weeks shows ventriculomegaly, calcifications
in the thalamus and basal ganglia, and
enlarged cisterna magna.
(b) Soft-tissue
(c) Body bone reconstruction - The postnatal
bone reconstruction image showed the severe
joint contractures, similar to those observed
on (f)
(d) and (e) axial postmortem CT images show an
abnormal profile, moderate ventriculomegaly,
parenchymal atrophy, splaying of the
cerebellar hemispheres, inferior vermian
hypoplasia, and calcifications in the
subcortical white matter, thalamus, and basal
ganglia. The corpus callosum is not
visualized. The gyral pattern is abnormally
smooth for a term neonate.
(f) a photograph of the neonate.
SPECIAL REPORT: Congenital Brain Abnormalities and Zika Virus: What
the Radiologist Can Expect to See Soares de Oliveira-Szejnfeld et al -
Radiology: Volume 281: Number 2, 2016 n radiology.rsna.org

BMJ 2016;354:i3899 | doi: 10.1136/bmj.i3899
Congenital Zika syndrome with arthrogryposis: retrospective - case series study. Vanessa
van der Linden et al.

Fundus Photographs of a 2-Month-Old Girl
The right eye has granular, pigmentary mottling in the
macula (A), and the left eye has a chorioretinal lobulated
atrophic lesion and slight pigmentary mottling (B).
OCULAR FINDINGS IN INFANTS WITH PRESUMED ZIKA VIRUS INFECTION
Fundus Photographs of a 1-Month-Old Boy
The right (A) and left (B) eyes have paramacular
superotemporal round chorioretinal atrophy surrounded
by a hyperpigmented halo and hyperpigmented mottling
Bruno de Paula Freitas et al JAMA Ophthalmology May 2016 Volume 134, Number 5

OCULAR FINDINGS IN INFANTS WITH PRESUMED ZIKA VIRUS INFECTION
Bruno de Paula Freitas et al JAMA Ophthalmology May 2016 Volume 134, Number 5

UPDATES THE CHARACTERIZATION OF ZIKA CONGENITAL SYNDROME
Digestive:
• Gastroesophageal reflux (due to trunk-brain dysfunction);
• Dysphagia and other severe deglutition and suctioning problems
• Some babies have a need for gastrostomy
• Placing a feeding tube directly into the stomach, through the abdominal wall.
Respiratory:
• Respiratory infection secondary to dysphagia - aspiration pneumonia
• Pulmonary hypoplasia?
• Laryngomalacia?
Cardiac:
• Cardiac dysautonomia
Others:
• Hernias (umbilical / inguinal)
• Change in genitalia (cryptorchidism / hypospadias
• Hormonal disorders: the early pubic

SURVEILLANCE OF THE CONGENITAL SYNDROME ASSOCIATED WITH ZIKA VIRUS
INFECTION – PRINCIPAL OBJECTIVES
• Establish the baseline and monitor the prevalence of births and trends of the congenital
syndrome associated with ZIKV infection, with microcephaly as a tracer event.
• Investigate any increase in the prevalence of microcephaly at birth or other associated
conditions.
• Detect and investigate all new cases of congenital malformations (including microcephaly)
not explained by other known causes.
• Detect the presence of infection in newborns of pregnant women who are receiving follow-
up due to detection of ZIKV.

INFECTION:
• Step #1 Design an ad hoc subsystem specifically for the detection of newborns with
congenital syndrome, and miscarriage, and fetal deaths
• Reports from sonographers, obstetricians, and maternal and child hospitals
• Step #2 Establish case definitions
• Step #3 Establish protocols

INFECTION – CASE DEFINITION
Suspected case of congenital syndrome associated with Zika virus infection: Live
newborn who presents with:
• Microcephaly: head circumference below -2 standard deviations measured at 24 hours
after birth according to the standardized guidelines for gestational age and sex; OR
• Other congenital malformation of the central nervous system;
AND whose mother during pregnancy:
• resided in or traveled to an area with the presence of ZIKV vectors; OR
• had unprotected sex with a partner who resided in, or traveled to, an area with the
presence of ZIKV vectors.

Probable case of congenital syndrome associated with Zika virus infection:
Live newborn who meets the criteria for a suspected case of congenital syndrome associated
with ZIKV AND
• who has intracranial morphological alterations diagnosed by any imaging method,
and excluding other known possible causes; OR
• whose mother had rash during pregnancy.

Confirmed case of congenital syndrome associated with Zika virus infection
• Live newborn of any gestational age who meets the criteria for a suspected case of
congenital syndrome associated with ZIKV, AND with laboratory confirmation of ZIKV
infection, independent of the detection of other agents.

Summary of the recommendations for specifcally diagnosing Zika among newborns
Source: Falcao et al. Ann Clin Microbiol Antimicrob (2016) 15:57

Suspected Zika-virus-associated abortion or stillbirth: Abortion or stillbirth in a woman,
who during her pregnancy:
• presented rash AND
• resided in or travelled to an area where ZIKV vectors were present;
• OR
• had unprotected sex during pregnancy with a partner who resided in or travelled to an area
where ZIKV vectors were present.
Confirmed Zika-virus-associated abortion or stillbirth
• All suspected cases where ZIKV infection is confirmed from blood or urine samples from
either the mother or puerperal or abortion or fetal death tissue.

• Families of neonates with congenital Zika virus syndrome should be informed about the
diagnosis and advised regarding management and prognosis
• Psychosocial support and advice should be provided to families of neonates with congenital
Zika virus syndrome
• Infants with congenital Zika syndrome should receive a comprehensive neurodevelopmental
assessment, and supportive therapy should be put in place for any difficulties noted
including irritability, seizures, swallowing difficulties, early onset spasticity and hip dysplasia.
• Multidisciplinary approaches should be adopted to provide early interventions and support
to promote neurodevelopment, prevent contractures and manage early complications
• Infants with congenital Zika virus syndrome should be followed up at 1 month, 3 months, 6
months, 9 months, 12 months, 18 months and 24 months of age. Additional follow-up should
be provided if there are other complications. Further follow-up beyond 24 months of age will
be required depending on the child’s condition and needs.

• At each visit, head circumference should be measured in order to monitor postnatal brain
growth
• Developmental and neurological assessments should be performed with the full engagement
of caregivers to identify developmental delays and other neurological abnormalities including
epilepsy and disorders of movement, posture and swallowing.
• Hearing should be screened in the first month of life as early as possible before discharge
from hospital and further audiological evaluation and services should be provided
• There should be comprehensive ophthalmological assessment.
• The health and well-being of the families and caregivers, including their psychological well-
being should be assessed. Families and caregivers should be provided psychosocial support
and parenting advice.

• Infants born to mothers with suspected, probable or confirmed Zika virus infection during
pregnancy, even without microcephaly or disproportionately small head relative to the face
or body, should be followed up to detect, manage and investigate signs of
neurodevelopmental abnormality including feeding difficulties, hearing or vision problem and
poor head growth. Follow-up visits should occur at 3 months, 9 months and 24 months of age
as a minimum.

Psychosocial support for pregnant women and for families with microcephaly and other
neurological complications in the context of Zika virus - Interim guidance for health-care providers
http://apps.who.int/iris/bitstream/10665/204492/1/WHO_ZIKV_MOC_16.6_eng.pdf?ua=1
1. Accurate Information
2. Conveying health information
3. Supportive communication
4. Common reactions
5. Basic psychosocial support
6. Strengthening social support
7. Stress reduction
8. Advice on parenting

• Risk communication: Health Care Workers / Pregnant
Women / General Public:
• Promote protective behaviors
• Community Engagement
• Reduce Anxiety
• Address Stigma
• Dispel rumors
• Counter Cultural miscaptions
https://youtu.be/MMmzmgxzCMQ

RUMORS

• Risk communication: http://www.who.int/risk-communication/zika-virus/en/

• More information:
• Protocols: https://goo.gl/hMTlq9
• Congenital syndrome associated with zika virus: https://goo.gl/gt9a6i
• Zika Virus Disease: https://goo.gl/OmVsEK
Copy short URL
goo.gl/w09f4q
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Thank You!
gsdimech@gmail.com

Zika virus - SGB - SZC PE Brazil

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