SUCCESSFUL EXPERIENCES AND CHALLENGES FOR SURVEILLANCE AND RESPONSE IN BRAZIL ZIKA ... · 2016-12-30 · ZIKA VIRUS DISEASE AND ITS COMPLICATIONS SUCCESSFUL EXPERIENCES AND CHALLENGES

ZIKA VIRUS DISEASE AND ITS COMPLICATIONSSUCCESSFUL 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 [email protected]

Epidemiologist - DVM, MSc

Bali, Indonesia on 17-18 November 2016

ROUNDTABLE MEETING ON ZIKA VIRUS: IMPROVING DETECTION, PREPAREDNESS, AND RESPONSE, THROUGH SURVEILLANCE AND RESEARCH

mailto:[email protected]


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 confirmedcases 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 cases2016= 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






INFECTION


ZIKA VIRUS DISEASE (ZIKV) - BACKGROUND


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

• Men Infertility? Under studying in mices

• 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.






INFECTION


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

SÍNDROME DE GUILLAIN BARRÉ - ZIKA


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.






INFECTION


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


CLINICAL DESCRIPTION OF THE CONGENITAL SYNDROME ASSOCIATED WITH ZIKA (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


CLINICAL DESCRIPTION OF THE CONGENITAL SYNDROME ASSOCIATED WITH ZIKA 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


SÍNDROME CONGÊNITA ASSOCIADA AO ZIKA

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 vermianhypoplasia, 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 SYNDROMEDigestive:• 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.



SURVEILLANCE OF THE CONGENITAL SYNDROME ASSOCIATED WITH ZIKA VIRUS 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



SURVEILLANCE OF THE CONGENITAL SYNDROME ASSOCIATED WITH ZIKA VIRUS 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 neurodevelopmentalassessment, and supportive therapy should be put in place for any difficulties notedincluding 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 duringpregnancy, even without microcephaly or disproportionately small head relative to the faceor body, should be followed up to detect, manage and investigate signs ofneurodevelopmental abnormality including feeding difficulties, hearing or vision problem andpoor head growth. Follow-up visits should occur at 3 months, 9 months and 24 months of ageas 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

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SUCCESSFUL EXPERIENCES AND CHALLENGES FOR SURVEILLANCE AND RESPONSE IN BRAZIL ZIKA ... · 2016-12-30 · ZIKA VIRUS DISEASE AND ITS COMPLICATIONS SUCCESSFUL EXPERIENCES AND CHALLENGES