...

“Introduction of Zika in Brazil: A personal perspective

by user

on
Category:

aids and hiv

11

views

Report

Comments

Transcript

“Introduction of Zika in Brazil: A personal perspective
“Introduction of Zika in Brazil:
A personal perspective
Maurício Lacerda Nogueira, MD, PhD
Associate Professor
Department of Microbiology and Infectious Diseases
Faculdade de Medicina de São José do Rio Preto
Senior Visiting Scientist
Virology Section
Fundação de Medicina Tropical – Doutor Heitor Vieira Dourado
Manaus
International Faculty
Center for Tropical Diseases
University of Texas Medical Branch
Galveston, TX, USA
[email protected]
Arboviruses
•
Over 210 species were isolated in Brazil
– 36 causes human diseases in sporadic, endemic or epidemic forms
– Mostly were identified in the 60´s and 70´s
Togaviridae - Alphavirus
Flaviviridae –Flavivirus
 Bunyaviridae –Orthobunyavirus
VASCONCELOS, 2005; FIGUEIREDO, 2007
The Brazilian Flaviviruses
• 14 were known in Brazil:
–
–
–
–
–
Dengue 1 to 4
SLEV, WNV
YF
Bussuquara, Cacipacoré, Iguape, Ilheus, Rocio
Zika
Nhumirim (?)
Cause: Hemorrhagic diseases (DEN and YF) and/or encephalitis
(Rocio and SLEV)
Bussuquara, Cacipacoré, Iguape, Ilheus - ?????
VASCONCELOS, 2005; FIGUEIREDO, 2007
▪ São José do Rio Preto
→ Hyperendemic for DENV
Size: 432 km² (20°49'12" S 49°22'44" O)
Estimated population: 442.548 hab. (2015)
Weather: Tropical Humid
Annual medium temperature: 23.6 °C
Annual average rainfall: 1400 mm
IDHM: 0,797
IBGE, 2010.
▪ Dengue cases in SJRP since 2006
Years
Official data:
Divisão de Zoonoses, CVE and SINAN
2014
15381
DENV-1/4
2013
33772
DENV-4
2012
773
2011
3834
2010
36133
2009
2097
2008
621
2007
9346
2006
24108
DENV-1
DENV-2
DENV-3
DENV by serotype during 2006 to 2014 in
SJRP
Yellow Fever
Yellow Fever in Sao Paulo and
Brazil
• 1990 to 2007 – only 2cases in SP
– “2008 - Mendonça (NHP) and Human Cases in
Ribeirao Preto and Sao Carlos Region
• 2009 – Outbreak in Botucatu (over 20 human
cases)
• After 2010 – Increase # cases and distribution
– Rio Grande do Sul
• 2015 - NHP cases in Brasilia
YF Vaccine Coverage 2012
Different Viruses – Same
symptoms: The SLEV –Dengue cocirculation in SP
SLEV in SP
• Several isolations in 1967 to 1969
– Rodents, sentinels and birds
• Itapetininga, Casa Grande e Guaratuba
• Isolated in 1993 - Pereira Barreto
• Anopheles
• Isolated in Araçatuba
– Culex
– 5% ab prevalence in the region (no dengue at the time)
• High level of circulation between 2005-2006(IAL)
SLEV in Ribeirão Preto, 2009
Felipe Gonçalves M. Maia,
Juliana Helena Chavez,
Benedito Antonio L. Fonseca,
Luiz Tadeu M. Figueiredo
The clinical epidemiological
diagnosis in a outbreak – our
experience in sjrp
Sample Processing
Amostra (soro)
Extração de RNA
RT-PCR
Duplex-RT-PCR
Primers gênero-específico para
Orthobunyavirus
Primers gênero-específicos para
Alphavirus e Flavivirus
Multiplex-Nested-PCR
Nested-PCR
Primers espécie-específicos para DENV 1-Primer espécie-específico SLEV
3, YFV
Nested-PCR
Nested-PCR
Primer espécie-específico para
DENV-4, ROCV, ILHV, WNV, BSQV
Primer espécie-específico para
OROV
Multiplex-Nested-PCR
Primers espécie-específicos para MAYV,
VEEV, WEEV, EEEV
Eletroforese em gel de agarose
+
-
Bronzoni et al, 2004 e 2005
Analyzed samples that were considered dengue only by clinical
and epidemiological criteria
M
São José do Rio Preto
413 samples
325 +
C+
C+
DENV-2
DENV-3
600 pb
300 pb
• 320 (77,5%) DENV-3
• 3 (0,7%) DENV-2
M
C+
C+
SLEV
DENV-3
• 6 (1,4%) SLEV
600 pb
200 pb
 Co infection
• 1 DENV-2 e DENV-3
• 3 DENV-3 e SLEV
Terzian et al, 2010 – Vector Borne and Zoonotic Diseases
C-
West nile in brazil – another piece
to the flavivirus puzzle
RT-PCR and Viral Isolation negative
PRNT90 with High titer to WNV and low to SLEV
Other sorological tests + for WNV
Flavivirus
Rocio
 neurotropic and associate to oubreak
 birds - Aedes sp. and Psorophora sp.
1973 to 1977: outbreak in Vale do Ribeira -1000 cases and 10% fatality rate
Ab in population
Some unpublished reports
Bussuquara
Just 1 human case
Iguape and Cacipacoré
?
Lopes, 1978; Lopes, 1979; Iversson, 1989; Iversson, 1992; Straatmann, Santos-Torres et al., 1997; Travassos Da Rosa, 1997; Figueiredo, 2000; Figueiredo, 2007
ZIKA: A NEW FLAVIVIRUS IN BRAZIL
GENETIC AND GEOGRAPHICAL
ANALYSIS OF ZIKA VIRUS (ZIKV)
ISOLATED FROM AN
AUTOCHNOUS CASE IN SÃO
PAULO STATE, BRAZIL, 2015
Presenting author: Mariana Sequetin Cunha
Núcleo de Doenças de Transmissão Vetorial – Instituto Adolfo Lutz - SP
Blood donor, male, 52 years,
from Sumaré (SP) with no travel
reported
10/03/2015
11/03/2015
18/03/2015
Blood donation
1º Hospital Care
2º Hospital Care
HEMOCENTRO UNICAMP
HOSPITAL DE CLÍNICAS UNICAMP
HOSPITAL DE CLÍNICAS UNICAMP
• Asymptomatic
• Symptomatic
(dengue like
illness)
• Asymptomatic
• DENV IgM MAC EIA
• DENV RT-qPCR
• Virus isolation
• IH
NDTV/IAL:
20/03
Receptor, male, 55 years
13/03/2015
14/03/2015 – 21/03/2015
Liver Transplant
Intensive Care
HOSPITAL DE CLÍNICAS UNICAMP
UTI HOSPITAL DE CLÍNICAS
UNICAMP
Blood Transfusion
• Asymptomatic
30/03/2015
Non-Intensive Care
GASTROCENTRO UNICAMP
• Asymptomatic
• Asymptomatic
• NS1 strap
• MAC EIA
• DENV RT-qPCR
• Virus isolation
• HI
• MAC EIA
• DENV RT-qPCR
• Virus isolation
• HI
NDTV: 27/03
NDTV: 17/04
Results
Blood Donor
D-1
This sample was
retrieved from
HC/UNICAMP and
was sent later to
NDTV
D6
DENV IgM MAC EIA
Negative
Negative
DENV RT-qPCR
Negative
Negative
IFA
POSITIVE
Negative
IH
-
Negative
Receptor
D0 (transfusion)
D17
IgM MAC EIA
Negative DENV, ROCV,
SLEV, YFV
DENV POSITIVE
DENV RT-qPCR
Negative
Negative
IFA
POSITIVE
Negative
IH
Anti-Flavi atb
Anti-Flavi atb
NS1
Negative
-
Receptor Sample
IFA Anti-flavivirus
Positive
RT-PCR/IFA Anti-DENV
Negative
RT-PCR SLEV
RT-PCR WNV
Zika Virus RT-PCR Positive
(Lanciotti et al., 2008)
RT-PCR YFV
NSP5 sequenced
Applied Biosystems
377 DNA sequencer
Dengue kills, so lets assume that all cases
are dengue and treat them like it until
prove otherwise. What about the $
impact?
CHIKV en Las Américas
42
2 POINTS BEFORE THE END
1 - Arboviruses surveillance in
Brazil (and SA?)
• Only data from official labs (IEC, IAL, etc..) are considered as
real
• Patients with encephalitis or hemorrhagic fever only get to
medical attention after the viremia is over (only serology for
diagnosis)
• Most if not all arbovirus suspected infections will be
considered dengue (or now Zika or CHIKV) in the initial
approach, and will be tested only for this (if tested at all)
• There will be a large number of cross reaction for dengue as
the population is mostly YF vaccinated and dengue exposed
• Brazil has a strong network of university based labs, that have
capacity and technology to do virus surveillance
• It HAS to be used (and funded)
2 - Public Health X Individual care
• Brazil has a large number of health insurance
covered population
• They (and their doctors) don’t accept clinicalepidemiological diagnosis
• There will be a pressure for private and university
labs to develop and use molecular tests for ZKV and
CHKV
– Lack of “controls” : eg: My lab (I will not have a
Zika control, until I isolate and sequence a Zika
virus as I did with CHKV….)
– Data will be not officially counted as cases
Flavivirus challenges in Brazil
• Co circulation of several viruses
• Lack of RT-PCR or viral isolation in large majority of
the cases
– No PCR in prodromal phases , except in
universities* or by chance in dengue surveillance *They do NOT exist officially
• Diagnosis made by either serology or clinical
epidemiological data
• Lack of confidence in flavivirus serology in a
population YF vaccinated and dengue primed
• Low levels of diagnosis of SLEV, WNV, Rocio, etc… Everything is DENGUE!!
Take home....
• DENGUE is not the only arbovirus causing diseases in
Brazil.
• Mayaro, SLEV and Oropouche are being detected in
Brazil.
• YFV is going to the south of brazil and to new areas.
• WNV, CPC, ILHV, etc…
• Introduction of ZIKA and CHKV
– The number of Zika cases are not known? They
probaly are in several thousand cases
• Surveillance is mandatory, but it has to be
decentralized and shared with university and private
labs
LPV-FAMERP
Maurício L Nogueira, MD, PhD
Roberta V M Bronzoni, DVM, PhD
Adriano Mondini, MSc, PhD
Eliane Fávaro, PhD
Alessandra Vidotto, PhD
Danila Vedovello, PhD
Joice Biseli, PhD
Carolina Pacca, PhD
Ana Carolina Terzian, DVM, PhD
Ana Theresa Morais, PhD
Danilo Vilas Boas Duarte, MSc
Ariele Gavioli, DVM, MSc
Daiane Machado
Faculdade de Saúde Pública - USP
Francisco Chiaravalloti Neto, PhD
ICB/USP
Paolo Zanotto, PhD
Marcelo Urbano Ferreira, MD, PhD
UFJF
Betania Drummond, PhD
FMRP – USP
Luiz Tadeu Moraes Figueiredo, MD, PhD
IBILCE-UNESP
Paula Rahal, PhD
UFPE
Ana Cristina Lima Leite, PhD
UQ - Australia
Alex Kromikh, PhD
CDC
Nick Komar, PhD
MSSM
Ana Sesma, PhD
MIT
Lee Gerkh, PhD
Irene Bosch, PhD
UTMB
Nikkos Vasilakis, PhD
Scott Weaver, PhD
Jonatham Auguste, PhD
UFMG
Erna Kroon, PhD
Alvaro Eiras, PhD
Mauro M Teixeira, MD, PhD
https://www.facebook.com/#!/groups/205746489469432/
Fly UP