Dahiana Marcela Gallo Gordillo, MD, PhD

Especialista en Ginecología y Obstetricia

Sub-especialista Medicina Materno Fetal, Fetal Medicine

Foundation, UK

Doctorado en Medicina perinatal, Universidad de Granada

Qué conocemos y qué no

conocemos sobre la infección

por Zika.

FUNDARED-MATERNA

(Colombia)

http://espanol.cdc.gov/img/cdc/ES

http://espanol.cdc.gov/img/cdc/ES

http://espanol.cdc.gov/img/cdc/ES

Zika Virus

• Virus RNA

• Familia de los Flavivirus

ZIKA – NUEVOS AVANCES

Transmisión

• A. aegypti y A. Albopictus:

AMERICA

• < 2.000 m sobre el nivel del

mar

• Capacidad vectorial alta

• Virus en saliva

• Pica principalmente de día

• Vive en estrecha relación con

los humanos

Petersen LR, et al. Zika virus. N Engl J Med. March 2016

Pacheco O. Zika Virus Disease in Colombia — Preliminary

Report. N Engl J Med. June 2016

ZIKA – NUEVOS AVANCES

Transmisión

TRANSMISIONES:

• VERTICAL: Virus en líquido amniótico

• SEXUAL: virus en semen

• TRANSFUSIONES: Virus en sangre

producto de donación (Polinesia

Francesa)

• ACCIDENTE BIOLOGICO

J. Lessler et al., Science 10.1126/science.aaf8160 (2016)

AISLAMIENTO:

• SEMEN: Hasta 6 meses ORINA: Hasta

12 días

SANGRE: Hasta 10 días

Epidemiologia

ZIKA – NUEVOS AVANCES

Comportamiento Mundial

1947 Aislamiento del virus en mono Rhesus en el Bosque Zika de Uganda

2013 – 2014

Epidemia en la Polinesia Francesa

2014 Chile

2015 Brasil

Alerta OMS

Incidencia de

microcefalia en Brasil

2010-14: 6/100.000 NV

2015: 117/100.000 NV

Copa Mundial FIFA 2014

Va’a World Sprint Canoe World

Championships

Extensión a países

vecinos

COLOMBIA

(Octubre2015)

45 países Enero-

Agosto 2016

Malone RW, et al. Zika Virus: Medical Countermeasure Development Challenges. PLOS Neglected Tropical Diseases. March

2016

Petersen LR, et al. Zika virus. N Engl J Med. March 2016

2007 brote en

islas del estado

de Yap -

Micronesia

Manifestaciones clínicas

SINTOMAS

ZIKA

Erupción

macular/papular

90%

Fiebre 65%

Artritis/Artralgia 65%

Conjuntivitis no

purulenta

55%

Mialgias 48%

Cefalea 45%

Dolor retro-

orbital

39%

Edema 19%

Vómitos 10%Petersen LR, et al. Zika virus. N Engl J Med. March 2016

Centers for Disease Control and Prevention. Zika virus –What clinicians need to

know?. Clinician Outreach and Comunication Activity (COCA). Jan 2016

SINTOMA ZIKA DENGUE CHIKUNGUNYA

FIEBRE ++ +++ +++

RASH +++ + ++

CONJUNTIVITI

S

++ - -

ARTRALGIA ++ + +++

MIALGIA + ++ +

CEFALEA + ++ ++

HEMORRAGIA - ++ -

SHOCK - + -

INFECCIÓN POR EL VIRUS DEL ZIKA

Se deben realizar otros estudios complementarios para

paciente con síndrome febril : Hemograma, Parcial de orina,

PCR

Faye O.»One Step RT-PCR for detection of Zika virus. Journal of clinical virology 43 (Mayo 2008)

Diagnostico

Suero y orina principales especímenes diagnósticos para Zika para

pacientes sintomáticos

Muestras menores a 14 días desde el inicio de los síntomas: RT-PCR

• Cualquiera positivo: Dx

• Si ambos negativos: Deteccion de anticuerpos

Muestras >2ss: Determinar IgM en suero (Embarazada tomar tambien

muestra de orina)

• Adulto con IgM positivo: : Prueba de Neutralización por reducción

en Placa PRNT

• Embarazada con IgM positivo: RT-PCR en suero y orina. Si es

negativo PRNT

Considerar RT-PCR en

liquido amniótico.

El tiempo para realizarlo no

ha sido determinado.

Se deja a criterio del medico

tratante

July 26, 2016 Page 1 of 12

Guidance for U.S. Laboratories Testing for Zika Virus Infection

July 26, 2016

Table of Contents

Overview .....................................................................................................................................................................1

Specimen Referral ......................................................................................................................................................3

Specimen Type ...........................................................................................................................................................3

Use of CDC Assays by Qualified Laboratories .............................................................................................................4

Biological Safety .........................................................................................................................................................5

Methods .....................................................................................................................................................................5

Molecular testing ....................................................................................................................................................5

Antibody detection methods..................................................................................................................................6

Reporting ....................................................................................................................................................................9

References ..................................................................................................................................................................9

2016 Zika Response: Algorithm for U.S. Testing of Symptomatic Individuals ......................................................... 10

2016 Zika Response: Algorithm for U.S. Testing of Symptomatic Individuals ......................................................... 11

2016 Zika Response: Algorithm for U.S. Testing of Asymptomatic Pregnant Women ........................................... 12

Overview

Testing of specimens within the United States to determine possible Zika virus infection should be limited to

specimens collected from patients meeting  CDC’s  clinical  an d  epidemiological  criteria  fo r  testing1. Clinical signs

and symptoms associated with Zika virus infection are discussed here:

http://www.cdc.gov/zika/symptoms/index.html. It is important to note that Zika virus infection can cause signs

and symptoms similar to those seen in patients with dengue and chikungunya virus infections.

Current information and guidance for the U.S. Zika response is available on CDC’s Zika website:

http://www.cdc.gov/zika/index.html. Information specific to state and public health laboratory response:

http://www.cdc.gov/zika/laboratories/index.html.

Full testing algorithms are presented at the end of this document.

NOTE: Serum and urine are the primary diagnostic specimens for Zika virus infection.

Symptomatic individuals meeting epidemiological criteria:

Serum and urine collected from symptomatic patients < 14 days post onset of symptoms (DPO) should

be tested by Zika virus real time reverse transcriptase-polymerase chain reaction (rRT-PCR). A positive

1 The  term  “clinical  and  ep idemiological  critera”  refers  to  fa ctors  su ch  as  symptoms,  pregnancy  and  ex p osure  risk.     Please  refer to current CDC clinical guidance: http://www.cdc.gov/zika/hc-providers/index.html

CDC

ZIKA – NUEVOS AVANCES

Definiciones de Caso

CASO SOSPECHOSO:

Erupción cutánea y/o fiebre y al menos 2 de los siguientes:

- Artralgias

- Artritis

-Conjuntivitis hiperemica no purulenta

CASO PROBABLE:

- Caso sospechoso

-Ig M (+) Zika

- Vinculo epidemiológico

CASO CONFIRMADO:

-ARN virus Zika o Antígeno en suero u otras

muestras

- Ig M (+) Zika y PRNT Zika(+) ≥ 20 copias

la exclusión de otros flavivirus

Pero Que Tan Cierto Es

Tanto Terror ?

ZIKA – NUEVOS AVANCES

Sd. Zika congénito

• Circulación del Virus Zika en 25 estados de Brasil

• 7.343 casos de microcefalia sospechosos de ser producidos por el virus del Zika

• 1.271 niños con microcefalia, hijos de madre con síntomas de Zika en el

embarazo

• 5 casos: 3 Muertes perinatales tempranas y 2 abortos espontáneos primer

trimestre

• Sin exposiciones a medicamentos o tóxicos

• TORCH, VIH, Serología, TR- PRC Dengue: Negativos

• Muestras de órganos, placenta y cordón enviados al CDC de Atlanta para

estudio

• RT-PCR virus Zika (+) en SNC y Placenta; Tipificación mostro compatibilidad 99-

100% con las cepas que circularon en Brasil 2015

Zika virus impairs growth inhuman neurospheres and brainorganoidsPatricia P. Garcez,1,2*ErickCorreia Loiola,2† RodrigoMadeiro daCosta,2† LuizaM.

Higa,3† PabloTrindade,2† RodrigoDelvecchio,3 JulianaMinardi Nascimento,2,4Rodrigo

Brindeiro,3Amilcar Tanuri,3 StevensK.Rehen2,1*

1Inst itute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 2D'Or Inst itute for Research and Education (IDOR),

Rio de Janeiro, Brazil.3Inst itute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 4Inst itute of Biology, State University of Campinas, Campinas,

Brazil.

*Corresponding author.Email:ppgarcez@icb.ufrj.br (P.P.G.);srehen@lance-ufrj.org (S.K.R.)

Miner JJ, et al. Zika Virus Infection

during Pregnancy in Mice Causes

Placental Damage and Fetal

Demise. Cell. 2016 May.

The Brazilian Zika virus strain causes

birth defects in experimental models.

Cugola FR, et al. Nature, 2016.

Sd. Zika congénito

• SNC:

Microcefalia

Craneocinostosis

Liscencefalia

Holoproscencefalia

alobar

Hipertelorismo

Hipoplasia cerebelosa

Ventriculomegalia

• Criptorquidia

• Hipoplasia pulmonar

• Artrogriposis

Histopatología SNC:

• Calcificaciones del

parenquima

• Degeneración de

células neuronales y

gliales

• Necrosis

Comportamiento en Humanos

Prevenir ?

• Viajar: www.cdc.gov/travel

• Usar repelente de insectos: DEET, Picaridina, aceite

de eucalipto de limón, IR3535

• Vestir con blusas de manga larga y pantalón largo

• Vaciar el agua acumulada en recipientes

• Instalar mallas en ventanas y puertas

• Si tiene fiebre, permanecer en un lugar aislado para

evitar picadura de mosquitos y transmisión a otras

personas

• Uso del Condón para evitar la transmisión sexual

• Vacunación en desarrollo

1

Prevention of sexual transmission of Zika virus

Interim guidance update 6 September 2016

WHO/ZIKV/MOC/16.1 Rev.3

1. Introduction

1.1 Background

This document is an update of guidance published on 7

June 2016 to provide advice on the prevention of sexual

transmission of Zika virus.

The primary transmission route of Zika virus is via the

Aedes mosquito. However, mounting evidence has shown

that sexual transmission of Zika virus is possible and more

common than previously assumed.1 This is of concern due

to an association between Zika virus infection and adverse

pregnancy and fetal outcomes, including microcephaly,

neurological complications and Guillain-Barré syndrome.

This review comprises recent evidence on sexual

transmission of Zika virus which includes sexual

transmission from

Asymptomatic males to their female partners,

Symptomatic female to her male partner,

Longer shedding of Zika virus in semen.

Based on this new evidence, the recommended length of

time for safer sex practices for asymptomatic males

returning from areas with active Zika virus transmission

was extended from 8 weeks to 6 months. This is the same

length of time as is recommended for symptomatic males.

This recommendation now also applies to females, whether

or not they have had symptoms. The 6 month duration of

safer sexual practice upon return has not changed. (Please

see footnote c).

The current evidence on persistence of Zika virus in semen,

its infectiousness and impact on sexual transmission

remains limited. This guidance will be reviewed and the

recommendations updated as new evidence emerges.

1.2 Target audience

This document is intended to inform the general public,

and to be used by health care workers and policy makers to

provide guidance on appropriate sexual practices in the

context of Zika virus.

2. Sexual transmission of Zika virus

2.1 Current evidence

2.1.1 Summary of publications

As of 26 August 2016, a total of 17 studies or reports have

been published on sexual transmission of Zika virus,

including the following:

• Seven studies on symptomatic male to female

transmission2-8

• One study on male to male transmission9

• One study on female to male transmission10

• Two studies on asymptomatic male to female

transmission11-12

• Four case-reports reported by International Health

Regulations National Focal Points13-16

• Two case-reports described through government/news

media17-18

In addition, eight studies have been published on the

presence of Zika virus in semen.19-26

2.1.2 Modes of sexual transmission

Zika virus transmission by sexual intercourse was first

suggested by Foy et al.2 Published in 2011, this study

described the case of a male patient infected with Zika

virus in south-eastern Senegal in 2008 who infected his wife

via sexual intercourse upon return to the United States of

America. Since then, and up to 26 August 2016, sexual

transmission of Zika virus has been reported in eleven

countries (United States of America3, Italy4, France5,

Germany6, New Zealand8, Argentina13, Chile14, Peru15,

Portugal16, Canada17, and Spain18) and referred mainly to

vaginal intercourse. On 2 February 2016, the United States

Centers for Disease Control and Prevention (CDC)

announced the first documented case of a man infected

with Zika virus through anal sex.9 Soon after, a case report

published in April 2016 raised the suspicion of Zika virus

transmission through oral sex.5 The case had sexual contact

with a partner with symptoms of Zika virus infection.

Transmission via oral sex was suspected as the sexual

activity involved vaginal intercourse, with no condom and

no ejaculation, and oral sex with ejaculation. Up to June

2016, cases of sexual transmission were reported only from 1

Prevention of sexual transmission of Zika virus

Interim guidance update 6 September 2016

WHO/ZIKV/MOC/16.1 Rev.3

1. Introduction

1.1 Background

This document is an update of guidance published on 7

June 2016 to provide advice on the prevention of sexual

transmission of Zika virus.

The primary transmission route of Zika virus is via the

Aedes mosquito. However, mounting evidence has shown

that sexual transmission of Zika virus is possible and more

common than previously assumed.1 This is of concern due

to an association between Zika virus infection and adverse

pregnancy and fetal outcomes, including microcephaly,

neurological complications and Guillain-Barré syndrome.

This review comprises recent evidence on sexual

transmission of Zika virus which includes sexual

transmission from

Asymptomatic males to their female partners,

Symptomatic female to her male partner,

Longer shedding of Zika virus in semen.

Based on this new evidence, the recommended length of

time for safer sex practices for asymptomatic males

returning from areas with active Zika virus transmission

was extended from 8 weeks to 6 months. This is the same

length of time as is recommended for symptomatic males.

This recommendation now also applies to females, whether

or not they have had symptoms. The 6 month duration of

safer sexual practice upon return has not changed. (Please

see footnote c).

The current evidence on persistence of Zika virus in semen,

its infectiousness and impact on sexual transmission

remains limited. This guidance will be reviewed and the

recommendations updated as new evidence emerges.

1.2 Target audience

This document is intended to inform the general public,

and to be used by health care workers and policy makers to

provide guidance on appropriate sexual practices in the

context of Zika virus.

2. Sexual transmission of Zika virus

2.1 Current evidence

2.1.1 Summary of publications

As of 26 August 2016, a total of 17 studies or reports have

been published on sexual transmission of Zika virus,

including the following:

• Seven studies on symptomatic male to female

transmission2-8

• One study on male to male transmission9

• One study on female to male transmission10

• Two studies on asymptomatic male to female

transmission11-12

• Four case-reports reported by International Health

Regulations National Focal Points13-16

• Two case-reports described through government/news

media17-18

In addition, eight studies have been published on the

presence of Zika virus in semen.19-26

2.1.2 Modes of sexual transmission

Zika virus transmission by sexual intercourse was first

suggested by Foy et al.2 Published in 2011, this study

described the case of a male patient infected with Zika

virus in south-eastern Senegal in 2008 who infected his wife

via sexual intercourse upon return to the United States of

America. Since then, and up to 26 August 2016, sexual

transmission of Zika virus has been reported in eleven

countries (United States of America3, Italy4, France5,

Germany6, New Zealand8, Argentina13, Chile14, Peru15,

Portugal16, Canada17, and Spain18) and referred mainly to

vaginal intercourse. On 2 February 2016, the United States

Centers for Disease Control and Prevention (CDC)

announced the first documented case of a man infected

with Zika virus through anal sex.9 Soon after, a case report

published in April 2016 raised the suspicion of Zika virus

transmission through oral sex.5 The case had sexual contact

with a partner with symptoms of Zika virus infection.

Transmission via oral sex was suspected as the sexual

activity involved vaginal intercourse, with no condom and

no ejaculation, and oral sex with ejaculation. Up to June

2016, cases of sexual transmission were reported only from

Hasta el 26 de Agosto del 2016

Existen 17 estudios reportando

transmisión sexual.

• 7 Estudios: Hombres sintomáticos

– Mujeres

• 1 estudio: Hombre – Hombre

• 1 estudio: Mujer – Hombre

• 2 estudios: Hombres asx – Mujer

• 6 reportes de casos

• Reporte de casos: Presencia del

virus hasta 188 días despues del

inicio de los sintomas.

• Carga viral 100.000 veces más

alta que la carga sanguínea

• Qué tan probable es que la infección por Zika afectará el

embarazo ?

• Existiran defectos en el bebe si se adquiere la infección

por Zika durante el embarazo ?

• Variedad de efectos en la salud cuando se adquiere la

infección por Zika durante el embarazo ?

• Aparición de un nuevo brote

Cual es el riesgo de afección según

edad gestacional ?

• Epidemia agosto 2015 – abril 2016

• 11,944 embarazadas – 1484 (12%) PCR positivo

• 532 en 1 trimestre 84% embarazadas al corte

• 702 en 2 trimestre 71% embarazadas al corte

• 612 en 3 trimestre

• 82 % peso normal

• 2% bajo peso

• 8% pretermino

• 1% muerte fetal

• No microcefalia en ninguna PCR positiva

• Registro nacional de Microcefalia 4 casos con ZIKA fetal positivo –

madres asintomaticas !!!!!! No estaban en el registro del estudio

• Estudio de cohorte de mujeres embarazadas que

presentaron Rash durante el embarazo 345 pacientes

• 134 positivas para ZIKA

• Búsqueda de Síndrome de Zika Congenito

• 3,4% 4 RN microcefalia

• Infección en primer trimestre

• 42% 43 pacientes anormalidades al 1 mes de vida

• Calcificaciones – anormalidades migracion SNC , ocular, auditivo

Conclusiones

• Estamos ante una epidemia de una enfermedad nueva, que estamos estudiando, por lo que no hay verdades absolutas

• La nueva evidencia apunta a que el virus del Zika produce el Síndrome de Zika Congénito y Sd. De Guillain Barré

• La Afección por ZIKA – compromete múltiples lesiones Síndrome ****Búsqueda Activa *****

• Existen Factores Predisponentes desconocidos para la aparición de Lesiones

Conclusiones

• Debemos hacer énfasis en la prevención,

predominantemente en mujeres en edad reproductiva

• Realizar Seguimiento de Mujeres gestantes en Riesgo

según protocolos nacionales

• Debemos contribuir con el reporte y estudio de TODOS

los posibles casos de infección por virus del Zika

MUCHAS GRACIAS damargago@hotmail.com

FUNDARED-MATERNA

(Colombia)