Qué conocemos y qué no conocemos sobre la infección por Zika. · •Adulto con IgM positivo: :...
Transcript of Qué conocemos y qué no conocemos sobre la infección por Zika. · •Adulto con IgM positivo: :...
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:[email protected] (P.P.G.);[email protected] (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