Arbovírus PDF

Arbovírus
Prof. Dr. Luiz Fernando Almeida Machado
LFAM@UFPA.BR
Pathways to neuronal injury and
apoptosis in HIV-associated dementia CONCEITO DE ARBOVÍRUS
Marcus Kaul*, Gwenn A. Garden† & Stuart A. Lipton*
*Center for Neuroscience and Aging Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jol a, California 92037, USA
(e-mail: mkaul@burnham.org and slipton@burnham.org)
†Department of Neurology, University of Washington, Seattle, Washington 98195, USA (email: gagarden@u.washington.edu)
Human immunodeficiency virus-1 (HIV-1) can induce dementia with alarming occurrence worldwide. The
mechanism remains poorly understood, but discovery in brain of HIV-1-binding sites (chemokine receptors)
• Arthropod-borne = arbovírus
provides new insights. HIV-1 infects macrophages and microglia, but not neurons, although neurons are
injured and die by apoptosis. The predominant pathway to neuronal injury is indirect through release of
macrophage, microglial and astrocyte toxins, although direct injury by viral proteins might also contribute.
These toxins overstimulate neurons, resulting in the formation of free radicals and excitotoxicity, similar to
other neurodegenerative diseases. Recent advances in understanding the signalling pathways mediating
these events offer hope for therapeutic intervention.
T
independent risk factor for AIDS mortality9. These findings
• Vírus → transmissão biológica → vertebrados

he syndrome of cognitive and motor
dysfunction observed after infection with support the hypothesis that HAART does not provide
human HIV-1 has been designated HIV- complete protection from the development of HAD.
associated dementia (HAD). Although highly Unfortunately, HIV protease inhibitors and several of the
susceptíveis e artrópodes hematófagos (ou pela via

active antiretroviral therapy (HAART) has nucleoside analogues penetrate poorly into the CNS11, allow-
resulted in a decrease in the incidence of HAD1,2, it does ingearlyCNSinfectiontoevolveindependentlyovertimeina
not seem to provide complete protection from or reversal protected brain reservoir. Thus, despite the finding that
of HAD3,4, and the prevalence of the dementia may improved systemic control of viral replication is associated
transovariana)
eventually increase as people live longer with AIDS5,6. with a decrease in the incidence of HAD, whether this effect
Currently there is no specific treatment for HAD, mainly wil be long lasting is open to question4,12. In fact, distinct
because of an incomplete understanding of how HIV antiviral drug-resistance patterns in the plasma and
infection causes neuronal injury and apoptosis. The cerebrospinal fluid (CSF) compartments have recently been
principal pathway for HIV entry into the central nervous reported13. It is possible that the proportion of HIV-infected
system (CNS) is through infected monocytes. The individuals who develop disability secondary to HAD wil
predominant pathogenesis of HAD is believed to involve increase as improvements in control of peripheral viral
activation of monocytic cells (macrophages and replication and the treatment of opportunistic infections
microglia) and their subsequent release of toxins that lead continue to extend life expectancy, resulting in an increase in
to neuronal and astrocytic dysfunction. Macrophages and theoverallprevalenceofHAD.Amorecompleteunderstand-
microglia can be activated by HIV infection itself, by ing of the pathogenesis of HAD wil help identify therapeutic
• Multiplicam-se e produzem viremia em vertebrados

interaction with viral proteins, or by immune stimulation targets for its prevention and treatment.
due to concurrent infection or other factors7. It is possible
that direct effects of viral proteins on neurons may also HIV entry into the brain and initiation of HAD
contribute to neurodegeneration, although neurons HIV enters the CNS early in the course of infection, and the
themselves are not infected by HIV-1. Here we review the virus resides primarily in microglia and macrophages.
extracellular and intracellular signalling pathways leading However, infection of these cells may not be sufficient to ini-
to macrophage or microglial activation, as well as those tiate neurodegeneration12. It has been proposed that factors
induced in neurons and astrocytes. These pathways are of associated with advanced HIV infection in the periphery
potential therapeutic importance as targets for the (non-CNS) are important triggers for events leading to
prevention or treatment of HAD. dementia. One such factor could be the increased number
• Multiplicam-se em artrópodes → transmitidos pela

TheprevalenceofHADwasestimatedintheearly1990sto of circulating monocytes that express CD16 and CD69.
be as high as 20–30% of those patients with advanced HIV These activated cells adhere to the normal endothelium of
disease and low CD4 counts8. Many experts believe that HAD the brain microvasculature, transmigrate, and then trigger
is now the most common cause of dementia worldwide a number of deleterious processes12.
picada de artrópodes → período de incubação

among people aged 40 or less, and it is a significant indepen-
dent risk factor for death due to AIDS9. With the advent of
HAART, the incidence of HAD decreased to as low as 10.5%
The blood–brain barrier (BBB) is crucial in HIV infec-
tion of the CNS12,14. Microglial and astrocytic chemokines
(cell migration (chemotaxis)-inducing cytokines), such as
extrínseco (WHO, 1985).

(ref. 10), but in recent years its incidence as an AIDS-defining monocyte chemoattractant protein (MCP)-1, seem to
il ness has actually increased3. The proportion of new cases of regulate migration of peripheral blood mononuclear cells
HAD demonstrating a CD4 count greater than 200 !l"1 is through the BBB14. Histological studies in specimens from
also increasing10. Moreover, a less fulminant form of HIV-1-infected humans and simian immunodeficiency
neurological dysfunction, termed minor cognitive/motor virus (SIV)-infected rhesus macaques show that lympho-
disorder (MCMD), may be more prevalent than frank cytes and monocytes migrate into the brain15,16. However,
dementia in the HAART era, and remains a significant the pathophysiological relevance of CNS-invading
988 NATURE | VOL 410 | 19 APRIL 2001 | www.nature.com
Pathways to neuronal injury and Ciclo de transmissão
apoptosis in HIV-associScience
Forum: ated dementia & Society Trends in Microbiology August 2013, Vol. 21, No. 8
(e-mail: mkaul@burnham.org and slipton@burnham.org) (3) Spillback into
enzoo!c cycle
provides new insights. HIV-1 infects macrophages and microglia, but not neurons, although neurons are Control of urban
macrophage, microglial and astrocyte toxins, although direct injury by viral proteins might also contribute. transmission
T
Control of urban Control of
he syndrome of cognitive and motor independent vectors orfindings
risk factor for AIDS mortality . These 9 arboreal vectors
dysfunction observed after infection with supportmodula!on
the hypot h esis that HAART does not provide of or modula!on of
associated dementia (HAD). Although highly Unfurban
ortunately, HIV protease inhibitovectorial
rs and several of the their vectorial
active antiretroviral therapy (HAART) has nuclcapacity;
eoside analogues penetrate poorly into the CNS , allow- 11
capacity;
1,2
resulted in a decrease in the incidence of HAD , it does ingearlyCNSinfectiontoevolveindependentlyovertimeina
not seem to provide complete protection from or reversal protimmuniza!on
ected brain reservoir. Thus, despite the finding that of immuniza!on of
3,4
urban
of HAD , and the prevalence of the dementia may improved systemic control of viral replication is associated
5,6
eventually increase as people live longer with AIDS . with a decrease in the incidence of HAD, whether this effect
enzoo!c NHP
Currently there is no specific treatment for HAD, mainly wilpopula!ons
be long lasting is open to question . In fact, distinct 4,12
hosts
system (CNS) is through infected monocytes. The individuals who develop disability secondary to HAD wil Targeted
vaccina!on of
microglia) and their subsequent release of toxins that lead continue to extend life expectControl
ancy, resulting in an increase in of urban people exposed
microglia can be activated by HIV infection itself, by ing of the pathogenesis of HADvectors wil help identify therapeutic or
to enzoo!c
interaction with viral proteins, or by immune stimulation targets for its prevention andmodula!on
Aedes spp. spillover;
treatment. of
that direct effects of viral proteins on neurons may also HIV entry into the brain andurban initiation of HAD vectorial reduc!on of
contribute to neurodegeneration, although neurons HIV enters the CNS early incapacity; the course of infection, and the exposure to
themselves are not infected by HIV-1. Here we review the virus resides primarily in microglia and macrophages. A. aegyp! enzoo!c vectors
extracellular and intracellular signalling pathways leading However, infection of these celimmuniza!on of
A. albopictus
ls may not be sufficient to ini-
to macrophage or microglial activation, as well as those tiate neurodegeneration . Iturban12
has been proposed that factors
potential therapeutic importance as targets for the (non-CNS) are important popula!ons triggers for events leading to
among people aged 40 or less, and it is a significant indepen- The blood–brain barrier (BBB) is crucial in HIV infec- (2) Human urban amplifica!on (1) Spillover from enzoo!c cycle
dent risk factor for death due to AIDS9. With the advent of tion of the CNS12,14. Microglial and astrocytic chemokines
HAART, the incidence of HAD decreased to as low as 10.5% (cell migration (chemotaxis)-inducing cytokines), such as TRENDS in Microbiology
Figure
HAD demonstrating a CD42. count greaterCartoon
than 200 !l"1 is through the BBB14. Hisdepicting
tological studies in specimens from the emergence of urban transmission cycles for dengue virus (DENV), yellow fever virus (YFV), and chikungunya virus (CHIKV) from enzootic
10
al so increasi ng . Moreover , a less ful m inant form of HIV-1-in fe cte d humans and si m i an i m munodef ic i ency
cycles. Lines through arrows indicate potential points for intervention in enzootic circulation, spillover infections of humans, introductions into the urban cycle, and
spillback
disorder (MCMD), may be more prevalfrom ent than frank cytesurban
and monocytes migrate into thcycles e brain15,16. However, to initiate arboreal enzootic cycles. The line thickness reflects the likelihood of success of these interventions (a thicker line indicates a greater
dementia in the HAART era, and remains of
likelihood a significantsuccess).
the pathophysiological relevance of CNS-invading
Propriedades
Arboviruses
Single-stranded Single-stranded Double-stranded

positive-sense RNA negative sense RNA RNA
Family: Togaviridae Family: Bunyaviridae Family: Reoviridae

Genus: Alphavirus a) Genus: Orthobunyavirus a) Genus: Orbivirus
Nairovirus Coltivirus a)
Family: Flaviviridae Phlebovirus
Genus: Flavivirus a) Tospovirus CLINICAL
Family: Rhabdoviridae EXPERIMENT
Genus: Vesiculovirus
VACCINE
Family: Orthomyxoviridae
Genus: Thogotovirus
RESEARCH
Clin Exp Vaccine Res 2014;3:58-77
s e outros animais pela picada São transmitidas pelo sangue do Arbovírus
envelope
de pacientes do
virêm
no Brasil
ví
Quadro 1 Os
ematófagos. – Arbovírus
arbovírusemergentes
que pore insetos hematófagos,
reemergentes no provocando
o que não mudança
deixa de
m humanos e outrosBrasil7,8,9,10
animais de uma preocupação na doação para,deentão,
sangue liberar
em á
membros de cinco famílias virais: endêmicas2. Casos de transmissão Após a do vírus O
decapsidação
Família Vírus Sigla Doença
viridae, Flaviviridae, Reoviridae e do Nilo (WNV) entre seres humanos,
para por meio
o citoplasma 7
.
Dengue DENV transfusões de sangue e transplante de órgãos, têm
Febre hemorrágica
relatados, entretanto todos os As proteínas
arbovírus que virais
produ
haja mais de Encefalite
545 espécies
de Saint de
Louis
SLEV viremia
Meningite
são epotencialmente
encefalite uma única
passíveis de poliproteín
desencadea
s quais, mais de 150 relacionadas
infecções iatrogênicas 4,5
. que é clivada por
seres humanos, sendo a maioria
Rocio ROCV Encefalite
tidos em ciclo de transmissão entre do hospedeiro
O único continente onde os arbovírus não
e vir
e Flaviviridae
reservatórios vertebrados WNV endêmicos
Oeste do Nilo como Meningite ée encefalite codificadas
o Antártico. Estes na porção
vírus tendem a ter
os amplificadores2,3.Cacipacore proteínas não estrutura
CACV distribuição –geográfica e climática restrita, como p
de um subsistema ecológicoOs especial represen
flavivírus replic
Ilheus ILHV pelos
Doença febril, encefalite
vírus, vetores, hospedeiros amplificadore
às membranas, por m
rrespondence / Correspondencia: reservatórios
Doença. febril
1
Bussuquara BUSV as pequenas proteína
Centro de Ciências Biológicas
Iguape IGUV
O Brasil– é constituído e, por presumivelmente,
uma grande exte
Londrina, Campus Universitário terrestre (pouco mais de 8.500.000
, Pr 445 km 380. Bairro: Jardim Portal de Versal
A síntese kmde2),uma
situado
fita
drina-Paraná-Brasil
Mayaro MAYV uma área
Doença predominantemente
febril e artralgias é a tropical,
primeira com
etapa exted
7 Togaviridae florestas na Região Amazônica, que poralémsua
devezflorestas
serv
Encefalite Equina
ail.com EEEV leste, sudeste
Doença e litoral sul. Apresenta também
neurológica
do Leste RNA de polaridade p
Bunyaviridae Oropouche OROV
Febre hemorrágica, detectadas cerca de 3
doença neurológica Rev Pan-Amaz
do cicloSaude replicativo
2014; 5(3):55-64oc
Pathways to neuronal injury and Arbovírus no Brasil
apoptosis in HIV-associated dementia
Família Flaviviridae Togaviridae

T Gênero
he syndrome of cognitive and motor independent risk factor for AIDS mortality9. These findings
Flavivirus Alphavirus
Febre amarela
Mayaro
Espécies
Dengue
Chikungunya
Zika
among people aged 40 or less, and it is a significant indepen- The blood–brain barrier (BBB) is crucial in HIV infec-
HAART, the incidence of HAD decreased to as low as 10.5% (cell migration (chemotaxis)-inducing cytokines), such as
545 arbovírus já identificados

150 causam doenças em humanos

T
nucleoside analogues penetrate poorly into the CNS11, allow-
Arbovírus isolados na Amazônia Brasileira

active antiretroviral therapy (HAART) has
• 1954 – 2015: >10.000 isolamentos virais

• 186 tipos: 157 novos para o Brasil

• 84 novos para o mundo

disease and low CD4 counts8. Many experts believe that HAD
is now the most common cause of dementia worldwide
the brain microvasculature, transmigrate, and then trigger
a number of deleterious processes12.
• A maioria tem patogenicidade indeterminada para o homem

also increasing10. Moreover, a less fulminant form of
neurological dysfunction, termed minor cognitive/motor
disorder (MCMD), may be more prevalent than frank
HIV-1-infected humans and simian immunodeficiency
virus (SIV)-infected rhesus macaques show that lympho-
cytes and monocytes migrate into the brain15,16. However,
Epidemiologia
• Zoonoses com ampla distribuição geográfica

T
• Homem como hospedeiro acidental

eventually increase as people live longer with AIDS5,6.
• Hospedeiros de manutenção: aves, roedores,

with a decrease in the incidence of HAD, whether this effect
morcegos, répteis, etc

• Persistência de um arbovírus = verteb.

susceptíveis + vet. competentes

Patogenia
• Vírus - linfonodos satélites – replicação

T
(fagócitos) – viremia – órgão alvo

reported13. It is possible that the proportion of HIV-infected
• Período de incubação: 1-15 dias (3-7 dias)

principal pathway for HIV entry into the central nervous
Diagnóstico Laboratorial
• Isolamento Viral
T
• Deteção de antígenos
• - IFA, imunohistoquímica, RT-PCR

• Provas sorológicas
• IH, FC TN
• ELISA
Tratamento, Prevenção e Controle

Pathways to neuronal injury and Febre amarela
Febre Amarela
Família Flaviviridae
TGênero Flavivirus
RNAfs (+)
because of an incomplete understanding of how HIV
infection causes neuronal injury and apoptosis. The
system (CNS) is through infected monocytes. The
antiviral drug-resistance patterns in the plasma and
cerebrospinal fluid (CSF) compartments have recently been
individuals who develop disability secondary to HAD wil
70 nm
microglia can be activated by HIV infection itself, by
interaction with viral proteins, or by immune stimulation
that direct effects of viral proteins on neurons may also
ing of the pathogenesis of HAD wil help identify therapeutic
targets for its prevention and treatment.
HIV entry into the brain and initiation of HAD

Endêmica na América do Sul e África

induced in neurons and astrocytes. These pathways are of
potential therapeutic importance as targets for the
prevention or treatment of HAD.
TheprevalenceofHADwasestimatedintheearly1990sto
associated with advanced HIV infection in the periphery
(non-CNS) are important triggers for events leading to
dementia. One such factor could be the increased number
of circulating monocytes that express CD16 and CD69.
Mantidos em natureza entre primatas não

humanos
dementia in the HAART era, and remains a significant
Febre amarela
Ciclo urbano e silvestre

T
be as high as 20–30% of those patients with advanced HIV
is now the most common cause of dementia worldwide
Aedes aegypti
These activated cells adhere to the normal endothelium of
a number of deleterious processes12.
HAART, the incidence of HAD decreased to as low as 10.5%
(ref. 10), but in recent years its incidence as an AIDS-defining
il ness has actually increased3. The proportion of new cases of
Vetor urbano
(cell migration (chemotaxis)-inducing cytokines), such as
monocyte chemoattractant protein (MCP)-1, seem to
regulate migration of peripheral blood mononuclear cells
Vetor silvestre
T
Figura 6 - O “iceberg” da febre amarela. Distribuição das formas clínicas.
988
NATURE | VOL 410 | 19 APRIL 2001 | www.nature.com
Revista da Sociedade Brasileira de Medicina Tropical 36:275-293, mar-abr, 2003
s demais indivíduos desenvolvem formas clínicas quadros clássicos de febre amarela, graves e
Febre amarela
exuberantes e outros exibem quadro graves. Aí elevado percentual de fatalidade (Tabela 2).
Tabela 2 - Apresentações clínicas da febre amarela no homem 57.

Forma clínica Evolução (dias) Principais manifestações Grupos mais acometidos
Leve até 2 febre e cefaléia crianças com anticorpos maternos (IgG)
adquiridos
Moderada 2-3 sintomas anteriores e mais pessoas com imunidade para
mialgias, artralgias, náuseas, outros Flavivirus*
vômitos e astenia
Grave 3-5 além dos anteriores, icterícia, agricultor, pescador, caçador, lenhador,
hematêmese ou oligúria turista e outros suscetíveis com
imunidade cruzada para Flavivirus
Maligna ≥6 todos os sintomas clássicos Mesmo grupo de pessoas sem imunidade
Revista da Sociedade Brasileira de Medicina Tropical 36:275-293, mar-abr, 2003

são observados cruzada para outros Flavivirus
* A resposta sorológica para um dado vírus desse gênero, apresenta no indivíduo infectado certa imunidade cruzada, que é parcial e
se supõe conferir algum grau de proteção contra infecções provocadas por outros Flavivirus.
ormas leve e moderada: a sintomatologia observada o paciente se recupera inteiramente sem seqü
ormas leve e moderada revela-se incaracterística e Apresenta-se de forma silenciosa de difícil diagn
unde-se com a encontrada em outras doenças mesmo durante as epidemias de febre ama
ciosas comuns em áreas endêmicas entre as quais podendo ser confundida com mal estar passa
ais importantes são a malária, as hepatites virais, a resfriado e enxaqueca. Apenas as provas espec
tifóide e a mononucleose infecciosa. definem o diagnóstico.
m geral, os sintomas na forma leve restringem-se Na forma moderada, o quadro clínico mos
rícula ou febre moderada de início súbito que pode arrastado e conspícuo. O paciente refere início
ão vir acompanhada de cefaléia discreta, astenia com febre e cefaléia. Além desses sintomas ele
ndisposição passageira e tontura. Esse quadro apresentar náuseas com ou sem vômitos, mialg
Revista
ui por algumas horas até dois dias, da Sociedade
findos os quaisBrasileira
Figura 7- Febre amarela. Paciente em coma com
quadro maligno. Notar hemorragia.
de Medicina
artralgias Tropical
que não 36:275-293,
incomodam mar-abr, 2003
o paciente nem dific
Febre amarela
Áreas de risco
São Paulo (2008)

14 casos
8 óbitos
São Paulo (2009)

28 casos
11 óbitos
Journal of Clinical Virology 64 (2015) 160–173
vom
Febre amarela
hem
the
phy
sim
is g
(∼2
fact
furt
to Y
Afri
in t
mo
asso
hum
Afri
This
tho
Bas
Fig. 1. Cases of yellow fever in Africa and South America, 1985–2009, officially
into
notified to the World Health Organization. Journal of Clinical Virology 64 (2015) 160–173
Febre amarela
Diagnóstico Laboratorial
• Isolamento viral (cultura celular e camundongos)
• Sorologia (ELISA - IgM e IgG)
• Biologia molecular (PCR)
Prevenção e Controle
Cepa 17D
Pathways to neuronal injury and DENV, ZIKV, CHIKV
Vetores: Ae. aegypti e Ae. albopictus
Dengue
Família: Flaviviridae
Gênero Flavivirus
T Sorotipos 1, 2, 3 e 4 Zika
RNAfs (+)active antiretroviral therapy (HAART) has

resulted in a decrease in the incidence of HAD1,2, it does
not seem to provide complete protection from or reversal
nucleoside analogues penetrate poorly into the CNS11, allow-
ingearlyCNSinfectiontoevolveindependentlyovertimeina
protected brain reservoir. Thus, despite the finding that
Família: Flaviviridae
40-65 nm
Currently there is no specific treatment for HAD, mainly
wil be long lasting is open to question4,12. In fact, distinct
Chikungunya
Gênero Flavivirus
Envelopado
predominant pathogenesis of HAD is believed to involve
increase as improvements in control of peripheral viral
RNAfs (+)
to neuronal and astrocytic dysfunction. Macrophages and
theoverallprevalenceofHAD.Amorecompleteunderstand-
ing of the pathogenesis of HAD wil help identify therapeutic Família: Togaviridae
40-65 nm
contribute to neurodegeneration, although neurons
HIV enters the CNS early in the course of infection, and the Gênero Alphavirus
Envelopado
to macrophage or microglial activation, as well as those
tiate neurodegeneration12. It has been proposed that factors
associated with advanced HIV infection in the periphery RNAfs (+)
Isolado em 1947
These activated cells adhere to the normal endothelium of 65-70 nm
(Uganda)
dent risk factor for death due to AIDS9. With the advent of
tion of the CNS12,14. Microglial and astrocytic chemokines Envelopado
HAD demonstrating a CD4 count greater than 200 !l"1 is
through the BBB14. Histological studies in specimens from
Isolado em 1950
(Tanzânia)
Pathways to neuronal injury and DENV, ZIKV, CHIKV
Genoma dos Flavivírus
T
resulted in a decrease in the incidence of HAD1,2, it does
not seem to provide complete protection from or reversal
of HAD3,4, and the prevalence of the dementia may
Estruturais
ingearlyCNSinfectiontoevolveindependentlyovertimeina
improved systemic control of viral replication is associated
Não estruturais
Genoma dos Togavírus

activation of monocytic cells (macrophages and
microglia) and their subsequent release of toxins that lead
replication and the treatment of opportunistic infections
continue to extend life expectancy, resulting in an increase in
DENV, ZIKV, CHIKV
Genoma dos Flavivírus e Togavírus

DENV, ZIKV, CHIKV
Ciclo de replicação
Boletim Epidemiologia: DENV, ZIKV, CHIKV
Epidemiológico Volume 47
N° 18 - 2016
Secretaria de Vigilância em Saúde − Ministério da Saúde

ISSN 2358-9450
Dengue
Monitoramento dos casos de que as regiões Centro-Oeste e Sudeste apresentam
dengue, febre de chikungunya e as maiores taxas de incidências, mantendo-se a
Maisvírus
febre pelo deZika
390atémilhões
a Semanade novas infecções por ano
tendência de 2015: 613,1 casos/100 mil hab. e
Epidemiológica 13, 2016 540,9 casos/100 mil hab., respectivamente. Entre
as Unidades da Federação, destacam-se Minas
Dengue Brasil (2016) - 802.429 casos prováveis Gerais (1.332,5 casos/100 mil hab.), Rio Grande do
Em 2016, foram registrados 802.429 casos Norte (857 casos/100 mil hab.) e Mato Grosso do
prováveis de dengue no país até a Semana Sul (825,9 casos/100 mil hab.) (Tabela 1).
Entre os municípios com as maiores taxas
Sudeste (57,8%): 463.807 casos
Epidemiológica (SE) 13 (3/1/2016 a 2/4/2016)
(Figura 1). Nesse período, a região Sudeste de incidências no mês de fevereiro por estrato
registrou o maior número de casos prováveis populacional, em relação ao número de habitantes
Nordeste (19,7%): 158.235 casos
(463.807 casos; 57,8%) em relação ao total do (menos de 100 mil habitantes, de 100 a 499 mil, de
500 a 999 mil e acima de 1 milhão de habitantes),
país, seguida das regiões Nordeste (158.235 casos;
19,7%), Centro-Oeste (94.672 casos; 11,8%), Sul destacam-se Guamaré/RN, com 12.929,7 casos/100
Centro-Oeste (11,8%): 94.672 casos
(57.282 casos; 7,1%) e Norte (28.433 casos; 3,5%) mil hab. (população <100 mil hab.); Itabuna/BA,
(Tabela 1). Foram descartados 161.273 casos com 2.751,7 casos/100 mil hab. (população de 100
suspeitos de dengue no período. mil a 499 mil hab.); Contagem/MG, com 1.394,8
Sul (7,1%): 57.282 casos
A análise da taxa de incidência de casos casos/100 mil hab. (população de 500 mil a 999 mil
prováveis de dengue (número de casos/100 mil hab.); e Belo Horizonte/MG, com 1.547,4 casos/100
hab.), segundo regiões geográficas, demonstra Norte (3,5%): 28.433 casos
mil hab. (população >1 milhão de hab.) (Tabela 2).
Boletim Epidemiologia: DENV
N° 18 - 2016
Boletim Epidemiológ
Secretaria de Vigilância em Saúde − Ministério da Saúde − Br
ISSN 2358-9450
Tabela 1 – Comparativo de casos prováveis de dengue entre 2015a e 2016b, até a Semana Epidemiológica 13, por região e
Unidade da Federação
febre pelodavírus
Região/Unidade Zika até a Semana
Federação
tendência de 2015: 613,1 casos/100
Casos (n) Incidênciamil
(/100hab. e
mil hab.)
Epidemiológica 13, 2016 2015 a

540,9 2016
casos/100
b
mil hab., respectivamente.
2015 Entre
2016
Norte 13.853 as Unidades
28.433 da Federação, destacam-se
79,3 Minas162,7
Rondônia
Dengue 646 Gerais6.124
(1.332,5 casos/100 mil hab.), Rio Grande
36,5 do
346,3
Acre 4.344
Em 2016, foram registrados 802.429 casos Norte3.867 540,6
(857 casos/100 mil hab.) e Mato Grosso481,3 do
Amazonas 1.782 3.686 45,2 93,6
prováveis
Roraima de dengue no país até a Semana 226
Sul (825,9
121
casos/100 mil hab.) (Tabela 1).
44,7 23,9
Epidemiológica
Pará (SE) 13 (3/1/2016 a 2/4/2016)2.431 Entre os municípios com as
4.905 maiores taxas 60,0
29,7
(Figura
Amapá 1). Nesse período, a região Sudeste1.833 de incidências
558 no mês de fevereiro
239,1 por estrato 72,8
registrou
Tocantins o maior número de casos prováveis 2.591 populacional,
9.172 em relação ao171,0
número de habitantes 605,4
Nordeste
(463.807 casos; 57,8%) em relação ao total79.492
do (menos de 100 mil habitantes,
158.235 140,5de 100 a 499 mil, de
279,8
Maranhão 3.676 500 a10.083 53,2
999 mil e acima de 1 milhão de habitantes),146,0
país,
Piauí
seguida das regiões Nordeste (158.235 casos;
2.743 801 85,6 25,0
Ceará 244 casosmil
11.584 confirmados
10.888
hab. (população <100 mil
130,1 140 óbitos122,3
hab.); Itabuna/BA,
(57.282 casos;
Rio Grande 7,1%) e Norte (28.433 casos;10.960
do Norte 3,5%) 29.501 318,4 857,0
(Tabela
Paraíba 1). Foram
Dengue grave descartados
(2016) 161.273 casos3.750 com 18.402
2.751,7 casos/100 mil hab. 94,4(população de 463,3100
suspeitos
Pernambucode dengue no período. 26.004 mil a44.121
499 mil hab.); Contagem/MG,
278,3 com 1.394,8 472,1
Alagoas
A análise da taxa de incidência de casos 3.708 casos/100
5.522mil hab. (população111,0de 500 mil a 999165,3 mil
Sergipe 2.724
1.707 casos suspeitos
hab.); 2.726
e Belo Horizonte/MG,76,1 com 1.547,4 casos/100121,5
prováveis
Bahia
de dengue (número de casos/100 mil
15.360 36.191 101,0 238,0
hab.), segundo regiões geográficas, demonstra
Sudeste 503.254
mil hab. (população
463.807
>1 milhão
586,9
de hab.) (Tabela 2).
540,9
Minas Gerais 48.210 278.071 231,0 1.332,5
Epidemiologia: DENV
Manifestações clínicas do dengue
Exantemas
Pathways to neuronal injury and Dengue
Quadro clínico
Graus de gravidade da Febre hemorrágica do dengue/

Síndrome do choque do dengue (DHF/DSS)

T
Grau I: Trombocitopenia + hemoconcentração. Ausência de sangramento

Grau II: Trombocitopenia + hemoconcentração. Presença de sangramento

Grau III: Trombocitopenia + hemoconcentração. Insuficiência circulatória

Grau IV: Trombocitopenia + hemoconcentração. Choque profundo

extracellular and intracellular signalling pathways leading
However, infection of these cells may not be sufficient to ini-
Dengue
hemorrágica
O Ministério da Saúde informa: este medicamento é
contra-indicado em casos de suspeita de dengue
Boletim Epidemiologia: CHIKV
N° 18 - 2016

ISSN 2358-9450
Monitoramento dos casos de

Chikungunya
que as regiões Centro-Oeste e Sudeste apresentam
febre pelo vírus Zika até a Semana tendência de 2015: 613,1 casos/100 mil hab. e
Epidemiológica 13, 2016 38.332 casos 13.236 casos 696540,9 casos/100 mil hab., respectivamente. Entre
2015 as Unidades da Federação, destacam-se Minas
Dengue prováveis confirmados municípios
Gerais (1.332,5 casos/100 mil hab.), Rio Grande do
Brasil
Em 2016, foram registrados 802.429 casos
prováveis de dengue no país até a Semana
Norte (857 casos/100 mil hab.) e Mato Grosso do
Sul (825,9 casos/100 mil hab.) (Tabela 1).
39.017 casos
Epidemiológica (SE) 13 (3/1/2016 a 2/4/2016) 6.159 casos
1.126
2016
prováveis
registrou o maior número de casos prováveis
(463.807 casos; 57,8%) em relação ao total do
confirmados
populacional, em relação ao número de habitantes
municípios
(menos de 100 mil habitantes, de 100 a 499 mil, de
país, seguida das regiões Nordeste (158.235 casos; 500 a 999 mil e acima de 1 milhão de habitantes),
2015 - 6 óbitos
(Tabela 1). Foram descartados 161.273 casos
suspeitos de dengue no período.
2016 - 15 óbitos
com 2.751,7 casos/100 mil hab. (população de 100
mil a 499 mil hab.); Contagem/MG, com 1.394,8
(média
A análise da taxa dede 75 anos
incidência de idade)
de casos (média
casos/100 mil hab. (população de 500demil68
a 999anos
mil de idade)
3 Bahia
hab.), segundo regiões geográficas, demonstra 3 Bahia
mil hab. (população >1 milhão de hab.) (Tabela 2).
1 Sergipe 2 Paraíbaa
120.000
1 São Paulo 2 Rio Grande do Norte
100.000 1 Pernambuco 9 Pernambuco
Epidemiológica 13, Brasil, 2016
Boletim Epidemiologia: CHIKV
N° 18 - 2016

ISSN 2358-9450

Dengue Gerais (1.332,5 casos/100 mil hab.), Rio Grande do
Epidemiológica (SE) 13 (3/1/2016 a 2/4/2016) Entre os municípios com as maiores taxas
hab.), segundo regiões geográficas, demonstra mil hab. (população >1 milhão de hab.) (Tabela 2).
120.000
100.000
80.000
Número de casos
60.000
Sem registro
40.000
Casos confirmados
20.000 Casos notificados
0
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53
Semana Epidemiológica de Início de Sintomas

2014 2015 2016
Fonte: Sinan Online (atualizado em a13/07/2015; b04/01/2016; c04/04/2016).

Dados sujeitos a alteração.
Fonte: Sinan (atualizado em 07/04/2016).

Figura 1 – Casos prováveis e taxa de incidência de dengue, por semana epidemiológica de início de sintomas, Brasil, 2014a,
2015b e 2016c
Figura 3 – Casos prováveis e confirmados de febre de chikungunya por município de notificação, até a Semana
Pathways to neuronal injury and Chikungunya
Quadro clínico
quadros de febre associados à dor articular intensa e
T
he syndrome of cognitive and motor debilitante, cefaléia e mialgia
dysfunction observed after infection with
independent risk factor for AIDS mortality9. These findings
support the hypothesis that HAART does not provide
poliartrite/artralgia simétrica (principalmente punhos,

tornozelos e cotovelos)
não são comuns choque ou hemorragias importantes como

extracellular and intracellular signalling pathways leading
However, infection of these cells may not be sufficient to ini-
na dengue, mas podem surgir sintomas neurológicos

These activated cells adhere to the normal endothelium of
Boletim Epidemiologia: ZIKV
N° 18 - 2016

ISSN 2358-9450
Zika que as regiões Centro-Oeste e Sudeste apresentam

Monitoramento dos casos de
Brasil (2016) - 91.387
febre pelo vírus Zika até a Semana
casos
tendência de prováveis
2015: 613,1 casos/100 mil hab. e
31.616 casos confirmados 1.359 municípios
Gestantes
prováveis de dengue no país até a Semana
Epidemiológica (SE) 13 (3/1/2016 a 2/4/2016)
Sul (825,9 casos/100 mil hab.) (Tabela 1).
7.584 casos suspeitos
(463.807 casos; 57,8%) em relação ao total do 2.844 casos confirmados
(menos de 100 mil habitantes, de 100 a 499 mil, de
Óbitos
São Luís/MA Benevides/PA
prováveis de dengue (número de casos/100 mil Serrinha/RN 
hab.); e Belo Horizonte/MG, com 1.547,4 casos/100
hab.), segundo regiões geográficas, demonstra mil hab. (população >1 milhão de hab.) (Tabela 2).
300,0 --| 501,0
Boletim 501,0 --| 1.001,0

1.000,0 --| 4.843,5
Epidemiologia: ZIKV
Epidemiológico
Fonte: Sinan-NET (atualizado em 07/04/2016).

Figura 4 – Taxa de incidência (/100 mil hab.) de febre pelo vírus Zika por município de notificação, até a Semana
Volume 47
N° 18 - 2016

ISSN 2358-9450

Epidemiológica (SE) 13 (3/1/2016 a 2/4/2016) Entre os municípios com as maiores taxas
(57.282 casos; 7,1%) e NorteSem (28.433
registro casos; 3,5%) mil hab. (população <100 mil hab.); Itabuna/BA,
(Tabela 1). Foram descartados Casos161.273 casos
confirmados com 2.751,7 casos/100 mil hab. (população de 100
suspeitos de dengue no período. Casos notificados mil a 499 mil hab.); Contagem/MG, com 1.394,8
prováveis de(atualizado
Fonte: Sinan-NET dengue (número de casos/100 mil
em 07/04/2016). hab.); e Belo Horizonte/MG, com 1.547,4 casos/100
hab.), segundo
Figura regiõesdos
5 – Distribuição geográficas,
casos suspeitos demonstra mil
e confirmados de febre hab.
pelo (população
vírus >1 milhão
Zika por município de hab.) até
de notificação, (Tabela
a 2).
Semana Epidemiológica 13, Brasil, 2016
recent phylogeographic
Epidemiologia: ZIKV
May and December 201
virus is following a sim
(Musso et al., 2015a).
ZIKV has been isolat
2014), but virus has
Marchette et al., 1969
WHO Collaborating Ce
Viruses: Annual Report
but the current rapid sp
vector (Marcondes and
(Benedict et al., 2007; K
may also partially explai
virus transmission by Ae
small number of cases (K
limited transmission (Gr
bined with the frequent
2016; Morrison et al., 2
tor must therefore also b
The fact that ZIKV rep
that global risk mapping
ations with Guillain-Bar
mothers (World Health
Figure 1. lead to more severe co
(A) Map showing the distribution of the final set of 323 ZIKV occurrence locations entered into the ensemble Boosted Regression Tree modelling procedure.
Locations are classified by year of occurrence to show those which took place (i) prior to the 2007 outbreak in Federated States of Micronesia; (ii) between 2007–2014; and (iii) during the
2015–2016 outbreak; (B) the total number of locations reporting symptomatic ZIKV occurrence in humans globally over time.
Messina et al. eLife 2016;5:e15272. DOI: 10.7554/eLife.15272

Zika vírus e microcefalia:
verdade ou mentira
T
lineages of the virus,6 and the latter strains and Vapalahti contributed equally to this
Brief Report
ic and the Americas.7 As in the transmission article.
theZika main Virus transmission
Infection with cycle Prolonged of ZIKV Maternal occurs This article was published on March 30,
humans. Viremia and Fetal Brain Abnormalities 2016, at NEJM.org.
ZIKV outbreak is the apparentT increased h e n e w e ng lrisk
R.W. Driggers, C.-Y. Ho, E.M. Korhonen, S. Kuivanen, A.J. Jääskeläinen, T. Smura,
A. Rosenberg, D.A. Hill, R.L. DeBiasi, G. Vezina, J. Timofeev, F.J. Rodriguez,
a n d j o u r na l o f m e dic i n e
DOI: 10.1056/NEJMoa1601824
sion of the virus as and
A. du Plessis, well as the marked in- Copyright © 2016 Massachusetts Medical Society.
L. Levanov, J. Razak, P. Iyengar, A. Hennenfent, R. Kennedy, R. Lanciotti,
O. Vapalahti
h microcephaly reported Sum m a r y

in Brazil. 8-17
A recent Severe fetal brain High ZIKV RNA loads in fetal
onographic
The current outbreak abnormalities
of Zika virus (ZIKV) infectioninhas12 of 42withwomen
been associated an
abnormalities on brain, placenta, membranes,
ultrasonography and and umbilical cord;
apparent increased risk of congenital microcephaly. We describe a case of a preg-
egnancy;
nant woman and 7 of
her the
fetus 42
infected withfetuses
ZIKV during the(17%)
Normal fetal head size
on ultrasonography that
11th gestational
The fetal head circumference decreased from the 47th percentile to the 24th per-
week. were
Normal fetal head size
on ultrasonography
MRI; ZIKV RNA virus isolated from brain
in amniotic fluid in SK-N-SH and Vero E6 cells
trophy, or
centile between 16brain
and 20 weekscalcifications. 11
of gestation. ZIKV RNA was identifiedBecause
nal serum at 16 and 21 weeks of gestation. At 19 and 20 weeks of gestation,
in mater- of
ionsubstantial
and
Gestational
microcephaly
Week
brain abnormalities
resonance imaging (MRI) without the 12 and
presence13 other
14
of microcephaly neurologic
were detected on ultrasonography and magnetic
or 15
intracranial16 17 18 19 20
Termination of Pregnancy
tionthinning,
hashighdeclared
ZIKV RNA loads,the ZIKV
and viral epidemic
particles were detected, and ZIKV a waspublic
calcifications. On postmortem analysis of the fetal brain, diffuse cerebral cortical
subsequently isolated.
ncern.13
Z
investigations into the viral pathogenesis,
ika virus (ZIKV), a mosquito-borne flavivirus and member of the The authors’ full names, academic de-
Flaviviridae family, was originally isolated from a sentinel primate in Ugan- grees, and affiliations are listed in the Ap-
virallar rash
cofactors, and sensitivity andSerum specificity
pendix. Address reprint requests to Dr.
da in 1947. ZIKV was associated with mild febrile disease and maculopapu-
1
Driggers at rdrigge1@jhmi.edu, to Dr. du
in tropical Africa and some areas of Southeast Asia. Since 2007, ZIKV has
sampledPlessis at adupless@childrensnational
more questions than answers. Nevertheless,

caused several outbreaks outside its former distribution area in islands of(Finland)
the Pa-.org, or to Dr. Vapalahti at olli.vapalahti@
Serum sampled
helsinki.fi. Patient
cific: in 2007 on Yap island inOnset
Micronesia, in 2013 and
of acute disease 2014 in French Polynesia,
DENV IgM−IgG+ (United States) informed Blood, serum, saliva,
and in 2015 in South America, where ZIKV had not been identified previously. 2-5
(>1000)
Drs. Driggers and Ho, Ms. Korhonen,
DENV IgM−and Drs. du of positive Serum urine, plasma, PBMC
(mild fever, eye pain, and Ms. Kuivanen Plessis
There are separate African and Asian lineages of the virus,6 and the latter strains ZIKV IgM+
ZIKV IgM+IgG+and Vapalahti result
this for positive for sampled (Finland);
myalgia, rash) contributed equally to
have caused the outbreaks in the Pacific and the Americas.7 As inZIKV
the transmission article.
RNA positive PRNT ZIKV>DENV ZIKV RNA ZIKV RNA negative for ZIKV RNA
of dengue and chikungunya
Trip to: viruses, the main transmission cycle of ZIKV occurs This article was published on March 30,
between urban aedes mosquitoes and humans. 2016, at NEJM.org.
Central America
One strikingGuatemala
n engl j med
feature of the current ZIKV outbreak is the apparent increased risk DOI: 10.1056/NEJMoa1601824
nejm.org
of intrauterine or perinatal transmission of the virus as well as the marked in- Copyright © 2016 Massachusetts Medical Society. 1
crease in the number of newborns with microcephaly reported in Brazil.8-17 A recent
5
.5
10
15
20
25
.5
5
.2
.1
.1
.2
.2
.1
.1
prospective study showed fetal ultrasonographic abnormalities in 12 of 42 women
n.
ec
b
n.
n.
n.
n.
ec
ec
b
ov
ec
ec
The New England Journal of Medicine

Fe
Ja
D
Fe
Fe
Ja
Ja
Ja
Ja
(29%) with ZIKV infection during pregnancy; 7 of the 42 fetuses (17%) that were
D
D
N
studied had microcephaly, cerebral atrophy, or brain calcifications.11 Because of

CHADO on April 14, 2016. For personal use only. No other uses without permission.
the association between ZIKV infection and microcephaly2015 and other neurologic 2016
Ljubljana — all in Ljubljana, Slovenia. Ad-
timates of 440,000 to 1.3 million cases of autochthonous ZIKV dress reprint requests to Dr. Avšič Županc
ted through December 2015. Brief
5 Report at the Institute of Microbiology and Im-
clinical picture of ZIKV infection resembles that of dengue fever and munology, Faculty of Medicine, Univer-
sity of Ljubljana, Zaloška 4, Ljubljana 1000,
nd is manifested by fever, headache, arthralgia, myalgia, and macu- Slovenia, or at tatjana.avsic@mf.uni-lj.si.
Zika Virus
, a complex Associated
of symptoms that hamperswithdifferential
Microcephaly diagnosis.
This article was published on February 10,
disease is self-limiting, cases of neurologic manifestations and the 2016, at NEJM.org.
Jernej Mlakar, M.D., Misa Korva, Ph.D., Nataša Tul, M.D., Ph.D.,
syndrome
Mara
were M.D.,
Popović,
described
Ph.D.,
in French
Mateja
PolynesiaPh.D.,
Poljšak-Prijatelj,
and in Brazil
Jerica
during
Mraz, M.Sc., N Engl J Med 2016;374:951-8.
s. Marko
5,6
Recent reports
Kolenc, from the
M.Sc., Katarina Ministry
Resman of Health
Rus, M.Sc., of Brazil
Tina Vesnaver suggest
Vipotnik, M.D., DOI: 10.1056/NEJMoa1600651
microcephaly have
Vesna Fabjan increased
Vodušek, M.D.,by a factor
Alenka Vizjak,of approximately
Ph.D., 20 among
Jože Pižem, M.D., Ph.D., Copyright © 2016 Massachusetts Medical Society.
he northeast region
Miroslav of theM.D.,
Petrovec, country, which
Ph.D., and indicates
Tatjana a possible
Avšič Županc,
1 µm
Ph.D. asso-
100 nm
n ZIKV infection in pregnancy and fetal malformations.5
a case
C of vertical transmissionSum of ZIKV
m a r yin a woman who D was prob-
A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in
South and Central America and the Caribbean. A major concern associated with
this infection is nthe apparent
engl increased
j med 374;10 incidenceMarch
nejm.org of microcephaly
10, 2016 in fetuses born 951
to mothers infected with ZIKV. In this report, we describe the case of an expectant
The New England Journal of Medicine
mother who had a febrile illness with rash at the end of the first trimester of
rom nejm.org by LUIZ MACHADO on April 14, 2016. For personal use only. No other uses without permission.
pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks
of gestationCopyright © 2016 Massachusetts
revealed microcephaly Medical Society.
with calcifications in the All rights
fetal reserved.
brain and pla-
centa. After the mother requested termination of the pregnancy, a fetal autopsy
was performed. Micrencephaly (an abnormally small brain) was observed, with
almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in
the cortex and subcortical white matter, with associated cortical displacement and
mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-
transcriptase–polymerase-chain-reaction (RT-PCR) assay, with consistent findings
on electron microscopy. The complete genome of100 ZIKV
nmwas recovered from the 100 nm
fetal brain.
Figure 3. Electron Microscopy of Ultrathin Sections of Fetal Brain and Staining of a Flavivirus-like Particle.
Panel A shows a damaged brain cell with a cluster of dense virions located in the disrupted endoplasmic reticulum.
IKV, an emerging mosquito-borne flavivirus, was initially iso- From the Institute of Pathology, Faculty
ed from September 2015 through February 2016; of at knielsen@mednet.ucla.edu.
PatZika
positive hways tofor neuroVirus nalZIKV injury and Infection in blood, urine, or both. Women
in Pregnant The timing
om 5inapopt o si
to Rio s i n HI V -associ
38 weeks a t e d
de Janeirodement ia of gestation. Predominant
— Preliminary
T h e n e w e ng lclinical
Report
This article was published on March 4,
a n d j o u r2016,
na lato fNEJM.org.m e dic i n e
ndingPatrícia macular
or maculopapular rash, arthralgias,
Brasil, M.D., Jose P. Pereira, Jr., M.D., Claudia Raja Gabaglia, M.D.,
*Center for Neuroscience and Aging Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jol a, California 92037, USA DOI: 10.1056/NEJMoa1602412
ache; 28% had fever (short-term and low-grade). Copyright © 2016 Massachusetts Medical Society.
(e-mail: mkaul@burnham.org and slipton@burnham.org) Luana Damasceno, M.S.,
Mayumi Wakimoto, Ph.D.,
Rita M. Ribeiro Nogueira, M.D., Patrícia Carvalho de Sequeira, Ph.D.,
Human immunodeficiency virus-1 (HIV-1) can induce dementiA B
V were André more Machado likely
a with alarming occurrence worldwide. The
mechanism remains poorly understood, but discovery in brain of HIV-1-binding sites (chemokine receptors) than
Siqueira, M.D.,those
Liege M.who
Abreu were
de negative
Carvalho, M.D., for
provides new insights. HIV-1 infects macrophages
Denise and microglia, but not neurons,
Cotrim although neurons are da Cunha, M.D., Guilherme A. Calvet, M.D.,
ashElizabeth
(44%e toxins, altNeves, vs. 12%,
macrophage, microglial and astrocytS. hough direct injury by viral proteinsM.D.,
P = 0.02), conjunctival involvement
might also contribute. Maria E. Moreira, M.D., Ana E. Rodrigues Baião, M.D.,
mphadenopathy
other neurodegenerative diseases. Recent advancesPauloin understanding the signalR.
these events offer hope for therapeutic interventStephanie
ion.
(40%
ling pathwaysNassar
mediating devs. 7%,
Carvalho, P
M.D.,= 0.02).
Carla Fetal
Janzen,
G. Valderramos, M.D., James D. Cherry, M.D.,
M.D., ultraso-
IKV-positive women (58%) and inNielsen-Saines,

all ZIKV-negative
T
Ana M. Bispo de Filippis, Ph.D., and Karin M.D.
detected by Doppler ultrasonography in 12 of the 42

human HIV-1 has been designated HIV- complete protection from the development of HAD. A BS T R AC T
n none of the 16 ZIKV-negative women. Adverse find-
ndBACKGROUND
38 weeks of gestation (2 fetuses), in utero growth
Zika virus (ZIKV) has been linked to neonatal microcephaly. To characterize the spec- From Fundação Oswaldo Cruz, Rio de Ja-
cephaly (5 disease fetuses), ventricular calcifications orto other
trum of ZIKV in pregnancy, we followed patients
Currently there is no specific treatment for HAD, mainly wil be long lasting is open to question4,12. In fact, distinct in Rio de Janeiro describe neiro (P.B., J.P.P.J., L.D., M.W., R.M.R.N.,
clinical manifestations in mothers and repercussions of acute ZIKV infection in fetuses. P.C.S., A.M.S., L.M.A.C., D.C.C., G.A.C.,
onsMETHODS
(7 fetuses), and
abnormal
amniotic fluid volume E.S.N., M.E.M., A.E.R.B., P.R.N.C., A.M.B.F.);
Biomedical Research Institute of South-
wWe(7enrolled fetuses). pregnant women To date, in whom8a of

rash the 42 women
had developed in whom
within the previous 5 days ern California, Oceanside (C.R.G.); and
David Geffen UCLA School of Medicine,
and tested blood and urine specimens for ZIKV by reverse-transcriptase–polymerase- Los Angeles (C.J., S.G.V., J.D.C., K.N.-S.).
medchain-reactionhave delivered
C We followed
assays. their babies,
the women
microglia can be activated by HIV infection itself, by ing of the pathogenesis of HAD wil help identify therapeutic andandthe
prospectively ultrasono-
collected D reprint requests to Dr. Nielsen-
clinical and Address
Saines at the Division of Pediatric Infec-
ultrasonographic data.
rmed.
RESULTS
tious Diseases, David Geffen School of
Medicine at UCLA, MDCC 22-442, 10833
contribute to neurodegeneration, although neurons HIV enters the CNS early in the course of infection, and the LeConte Ave., Los Angeles, CA 90095, or
A total
themselves are not infectof ed by HIV-1.88 Here we reviewwomenthe virus resides primarily in microglwere ia and macrophages. enrolled from September 2015 through February 2016; of
at knielsen@mednet.ucla.edu.
these
to macrophage88 or microglialwomen, 72ion12(82%)
activation, as well as those tiate neurodegenerat . It has been proposed that factotested
rs positive for ZIKV in blood, urine, or both. The timing
IKV infection during pregnancy appears to be associ-
of acute ZIKV infection ranged from 5 to 38 weeks of gestation. Predominant clinical
features
prevention or treatment of HAD.included dementia. One suchpruritic
factor could be the increased number descending macular or maculopapular rash, arthralgias,
2016, at NEJM.org.
ing fetal death, placental insufficiency, fetal growth

conjunctival
be as high as 20–30% of those patients with advancedinjection, HIV These activated cells adhere to the normal endot and helium of headache; 28% had fever (short-term and low-grade).
DOI: 10.1056/NEJMoa1602412
Copyright © 2016 Massachusetts Medical Society.
Women who were positiveen triggerfor ZIKV were more likely than those who were negative for
8
di sease and lo w CD4 count s . Many expert s believe th at HAD t h e brain mi c rovascul at ure, t r ansmi g rate , and t h
theamongvirus
people aged 40 or less, andto it is a significhave
ant indepen- The blmaculopapular
ood–brain barrier (BBB) is crucial in HIV infec- rash (44% vs. 12%, P = 0.02), conjunctival involvement
(58%
HAART, the incivs. 13%,
dence of HAD decreased to as low as 10.5% (celPl mi= gration 0.002),
(chemotaxis)-inducing cytokines), suchand as lymphadenopathy (40% vs. 7%, P = 0.02). Fetal ultraso-
nography
(ref. 10), but in recent years its incidencewas as an AIDS-defining performed
monocyte chemoattractant protein (MCP)-1, seemin to 42 ZIKV-positive women (58%) and in all ZIKV-negative
women.
HAD demonstrating a CD4 Fetal
n engl j med
count greater than 200 !l"1abnormalities
nejm.org
is through the BBB14. Histological studies in specimens from were detected by Doppler ultrasonography in 12 of the 42
1
10
ZIKV-positive women (29%) and in none of the 16 ZIKV-negative women. Adverse find-
also increasing . Moreover, a less fulminant form of HIV-1-infected humans and simian immunodeficiency
ings The New England Journal of Medicine
included
disorder (MCMD), may be more prevalent than frankfetal cytes and monocytdeaths
es migrate into the brain15,16. Howeverat , 36 and 38 weeks of gestation (2 fetuses), in utero growth
restriction with or on
Z MACHADO without microcephaly (5 fetuses), ventricular use
calcifications or other
988 | | March
| 7, 2016. For personal only. No other uses without permission.
NATURE VOL 410 19 APRIL 2001 www.nature.com
central nervous system (CNS) lesions (7 fetuses), and abnormal amniotic fluid volume
ed from September 2015 through February 2016; of
PatZika
positive hways tofor neuroVirus nalZIKV injury and Infection in blood, urine, or both. Women
in Pregnant The timing
om apopt oto sis inRio HI38 V-associweeks atde ed dementJaneiro ia of gestation. This article was published on March 4,
5in Predominant
— Preliminary Report clinical 2016, at NEJM.org.
ndingPatrícia macular
or maculopapular rash, arthralgias,
Brasil, M.D., Jose P. Pereira, Jr., M.D., Claudia Raja Gabaglia, M.D.,
*Center for Neuroscience and Aging Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jol a, California 92037, USA DOI: 10.1056/NEJMoa1602412
ache; 28%Luana(e-mail: mkaul@burnham.org and slipton@burnham.org)
hadDamasceno, fever M.S.,
†Department of Neurology, University of Washington, Seattle, Washington 98195, USA (email: gagarden@u.washington.edu) (short-term
Mayumi Wakimoto, andPh.D.,low-grade). Copyright © 2016 Massachusetts Medical Society.
Rita M. Ribeiro Nogueira, M.D., Patrícia Carvalho de Sequeira, Ph.D.,
Human immunodeficiency virus-1 (HIV-1) can induce dementia with alE F
V were y understmore
mechanism remains poorlAndré in brain of HIV-1-bindinlikely
ood, but discovery Machado
arming occurrence worldwide. The
g sites (chemokine receptSiqueira,
ors) thanM.D.,those
Liege M.who
Abreuwere negative
de Carvalho, M.D., for
provides new insights. HIV-1 infects macrophages and mi c rogl ia, but not neurons, al t hough
Denise Cotrim da Cunha, M.D., Guilherme A. Calvet, M.D., neurons are
ashElizabeth
(44% vs. 12%,
macrophage, microglial and astrocytS.e toxins, altNeves,
hough direct injury by viral proteinsM.D.,
P = 0.02), conjunctival involvement
might also contribute. Maria E. Moreira, M.D., Ana E. Rodrigues Baião, M.D.,
mphadenopathy
other neurodegenerative diseases. Recent advancesPaulo in understanding the signalR.
these events offer hope for therapeutic interventStephanie
ion.
(40%
ling pathwaysNassar
mediating devs. 7%,
Carvalho, P
M.D.,= 0.02).
Carla Fetal
Janzen,
G. Valderramos, M.D., James D. Cherry, M.D.,
M.D., ultraso-
IKV-positive women (58%) and inNielsen-Saines,

all ZIKV-negative
T
Ana M. Bispo de Filippis, Ph.D., and Karin M.D.
detected by Doppler ultrasonography in 12 of the 42

human HIV-1 has been designated HIV- complete protection from the development of HAD. A BS T R AC T
n none of the 16 ZIKV-negative women. Adverse find-
ndBACKGROUND
38 weeks of gestation (2 fetuses), in utero growth
Zika virus (ZIKV) has been linked to neonatal microcephaly. To characterize the spec- From Fundação Oswaldo Cruz, Rio de Ja-
cephaly (5 disease fetuses), ventricular calcifications orto other
trum of ZIKV in pregnancy,
Currently there is no specific treatment for HAD, mainly wil be long lasting is open to question4,12. In fact, distinct we followed patients in Rio de Janeiro describe neiro (P.B., J.P.P.J., L.D., M.W., R.M.R.N.,
because of an incomplete understanding of how HIV antiviral drug-resistance patterns in the plasma and P.C.S., A.M.S., L.M.A.C., D.C.C., G.A.C.,
clinical manifestations in mothers and repercussions of acute ZIKV infection in fetuses.
onsMETHODS
(7 fetuses), and abnormal amniotic fluid volume
E.S.N., M.E.M., A.E.R.B., P.R.N.C., A.M.B.F.);
Biomedical Research Institute of South-
wWe(7enrolled fetuses). pregnant women To date,

in whom8a of
rash the 42 women
had developed in whom
within the previous 5 days ern California, Oceanside (C.R.G.); and
David Geffen UCLA School of Medicine,
and tested blood and urine specimens for ZIKV by reverse-transcriptase–polymerase-
microglia) and their subsequent release of toxins that lead continue to extend life expectancy, resulting in an increase in Los Angeles (C.J., S.G.V., J.D.C., K.N.-S.).
medchain-reactionhave delivered
assays. G We followed
microglia can be activated by HIV infection itself, by ing of the pathogenesis of HAD wil help identify therapeutictheir babies,
the women andandthe
prospectively ultrasono-
collected clinical and H
Address reprint requests to Dr. Nielsen-
Saines at the Division of Pediatric Infec-
ultrasonographic data.
rmed.
RESULTS
tious Diseases, David Geffen School of
Medicine at UCLA, MDCC 22-442, 10833
contribute to neurodegeneration, although neurons HIV enters the CNS early in the course of infection, and the LeConte Ave., Los Angeles, CA 90095, or
A total
themselves are not infectof ed by HIV-1.88 Here we reviewwomenthe virus resides primarily in microglwere ia and macrophages. enrolled from September 2015 through February 2016; of
these
to macrophage88 or microglialwomen, 72ion12(82%)
activation, as well as those tiate neurodegenerat . It has been proposed that factotested
rs positive for ZIKV in blood, urine, or both. The timing
IKV infection during pregnancy appears to be associ-
of acute ZIKV infection ranged from 5 to 38 weeks of gestation. Predominant clinical
features
prevention or treatment of HAD.included dementia. One suchpruritic
factor could be the increased number descending macular or maculopapular rash, arthralgias,
2016, at NEJM.org.
ing fetal death, placental insufficiency, fetal growth

conjunctival
be as high as 20–30% of those patients with advancedinjection, HIV These activated cells adhere to the normal endot and helium of headache; 28% had fever (short-term and low-grade).
DOI: 10.1056/NEJMoa1602412
Copyright © 2016 Massachusetts Medical Society.
Women who were positiveen triggerfor ZIKV were more likely than those who were negative for
8
di sease and lo w CD4 count s . Many expert s believe th at HAD t h e brain mi c rovascul at ure, t r ansmi g rate , and t h
theamongvirus
people aged 40 or less, andto it is a significhave
ant indepen- The blmaculopapular
ood–brain barrier (BBB) is crucial in HIV infec- rash (44% vs. 12%, P = 0.02), conjunctival involvement
(58%
HAART, the incivs. 13%,
dence of HAD decreased to as low as 10.5% (celPl mi= gration 0.002),
(chemotaxis)-inducing cytokines), suchand as lymphadenopathy (40% vs. 7%, P = 0.02). Fetal ultraso-
nography
(ref. 10), but in recent years its incidencewas as an AIDS-defining performed
monocyte chemoattractant protein (MCP)-1, seemin to 42 ZIKV-positive women (58%) and in all ZIKV-negative
women.
HAD demonstrating a CD4 Fetal
n engl j med
count greater than 200 !l"1abnormalities
nejm.org
is through the BBB14. Histological studies in specimens from were detected by Doppler ultrasonography in 12 of the 42
1
10
ZIKV-positive women (29%) and in none of the 16 ZIKV-negative women. Adverse find-
ings The New England Journal of Medicine
included
disorder (MCMD), may be more prevalent than frankfetal cytes and monocytdeaths
es migrate into the brain15,16. Howeverat , 36 and 38 weeks of gestation (2 fetuses), in utero growth
restriction with or on
Z MACHADO without microcephaly (5 fetuses), ventricular use
calcifications or other
988 | | March
| 7, 2016. For personal only. No other uses without permission.
NATURE VOL 410 19 APRIL 2001 www.nature.com
central nervous system (CNS) lesions (7 fetuses), and abnormal amniotic fluid volume
ated
Pathwaysfor
to neuronalainjursubgroup
y andT h e n e w e ng lof pregnant women. Con- quests to Dr. Honein at the National Cen-
microcephaly
apoptosis in HIV-associated dementia for evidence of congenital ZVD.
a n d j o u r na l o f m e dic i n e ter on Birth Defects and Developmental
Disabilities, Centers for Disease Control
*Center for Neuroscience and Aging Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jol a, California 92037, USA Original Article and Prevention, 1600 Clifton Rd. NE, At-
lanta, GA 30333, or at mhonein@cdc.gov.
cases of ZVD reported in Colombia, of which
ns of reverse-transcriptase–polymerase-chain- This article was published on June 15,

Zika Virus Disease in Colombia —
2016, at NEJM.org.
reported incidence of ZVD among Report female pa-

Preliminary
s. A total of 11,944 pregnant women with ZVD DOI: 10.1056/NEJMoa1604037
T
Oscar Pacheco, M.D., Mauricio Beltrán, M.S., Christina A. Nelson, M.D., Copyright © 2016 Massachusetts Medical Society.
84 (12%) Dianaof these

Valencia, cases
M.S., confirmed
Natalia Tolosa, M.D., Sherryon
dysfunction observed after infection with
human HIV-1 has been designated HIV-
associated dementia (HAD). Although highly
RT-PCR
L. Farr,
support the hypothesis that HAART does not provide
Ph.D.,
complete protection from the development of HAD.
Unfortunately, HIV protease inhibitors and several of the
Ana V. Padilla, M.D., Van T. Tong, M.P.H., Esther L. Cuevas, M.S.,
nant women, moreM.D., than 90% Pardo,of
B.S.,women who
Andrés Espinosa-Bode, Lissethe
not seem to provide complete protection from or reversalAngélica Rico, B.S.,
JennitaAté
Reefhuis,2/4/2016 - 65.726
of HAD3,4, and the prevalence of the dementia may
Ph.D., Maritza González, M.D., Marcelacasos notificados de ZIKV
improved systemic control of viral replication is associated
Mercado, M.S.,
thirdPablo
trimester had given birth,
Duran, and
Chaparro, M.D., Mancel Martínez
no Y.infants
M.D., Carol
Rao, Sc.D.,
ing microcephaly,
María M. Muñoz, M.D.,haveAnn M.been identified. A ma-
Powers, Ph.D., Claudia Cuéllar,
principal pathway for HIV entry into the central nervous M.D.,
Rita Helfand, M.D., Claudia Huguett, M.S., Denise J. Jamieson, M.D.,
or2.485 (4%) casos confirmados

ZVD inMargaret
the first
A. Honein, second
Ph.D., trimester
and Martha
L. Ospina wereM.D.
Martínez,
to neuronal and astrocytic dysfunction. Macrophages and
still
theoverallprevalenceofHAD.Amorecompleteunderstand-
Among the cases of microcephaly investigated

interaction with viral proteins, or by immune stimulation
ing of the pathogenesis of HAD wil help identify therapeutic
targets for its prevention and treatment.
A BS T R AC T HIV entry into the brain and initiation of HAD

016, four patients had laboratory evidence of
11.944 grávidas 1.484 (12%) confirmados

ymptomatic
BACKGROUND
mothers who were not included in
Colombia began official surveillance for Zika virus disease (ZVD) in August 2015. From Instituto Nacional de Salud (O.P.,
prevention or treatment of HAD. dementia. One such factor could be the increased number M.B., N.T., A.V.P., E.L.C., L.P., A.R., M.G.,
In October 2015, an outbreak of ZVD was declared after laboratory-confirmed dis-
be as high as 20–30% of those patients with advanced HIV These activated cells adhere to the normal endothelium of M.M., P.C., M.M.D., C.H., M.L.O.M.) and
ease was identified in nine patients.
disease and low CD4 counts8. Many experts believe that HAD the brain microvasculature, transmigrate, and then trigger Ministerio de Salud y Protección Social
among people aged 40 or less, and it is a significant indepen- The blood–brain barrier (BBB) is crucial in HIV infec- (M.M.M., C.C.) — both in Bogota, Co-
METHODS
dent risk factor for death due to AIDS9. With the advent of tion of the CNS12,14. Microglial and astrocytic chemokines lombia; and the Centers for Disease Con-
Using the national population-based surveillance system, we assessed patients with
(ref. 10), but in recent years its incidence as an AIDS-defining monocyte chemoattractant protein (MCP)-1, seem to Nenhum caso de microcefalia
trol and Prevention, Atlanta (C.A.N., D.V.,
ombia suggest that maternal infection with the

HAD demonstrating a CD4 count greater than 200 !l"1 is
clinical symptoms of ZVD from August 9, 2015, to April 2, 2016. Laboratory test results
through the BBB14. Histological studies in specimens from
S.L.F., V.T.T., A.E.-B., J.R., C.Y.R., A.M.P.,
R.H., D.J.J., M.A.H.). Address reprint re-
and pregnancy outcomes were evaluated for a subgroup of pregnant women. Con- quests to Dr. Honein at the National Cen-
r of pregnancy is not linked to structural ab-
currently, we investigated reports of microcephaly for evidence of congenital ZVD.
dementia in the HAART era, and remains a significant the pathophysiological relevance of CNS-invading ter on Birth Defects and Developmental
Disabilities, Centers for Disease Control
and Prevention, 1600 Clifton Rd. NE, At-
ither
Pathwaysoral
to neuronal injor vaginal)
ury and Santos AAC, Menezes of LSR,
ZIKV da Cruzfrom
SOD, et al.
T h e n e w e ng l a n d Background
(2016) Isolation of Infective Zika Virus from Urine andIsabelle Leparc-Goffart, Ph.D.
j o u r na l o f m e dic i n e
ientapopt1.
osis in HIWe
V-associatecannot
d dementSaliva rulein Brazil.
ia of Patients outPLoS the pos-
Negl Trop Dis 10(6): Zika virus (ZIKV) is an emergent threat provoking a worldwide exp
French Armed Forces Biomedical Research Institute
ansmission occurred not through
e0004816. doi:10.1371/journal.pntd.0004816
Marcus Kaul*, Gwenn A. Garden† & Stuart A. Lipton* January 2015, 41 countries reported autochthonous cases. In Braz
Marseille, France
ough other biologic fluids, such C oas r r e slain-Barré
p o n dsyndrome e n c eand microcephaly cases was linked to ZIKV i
Editor: Alan L Rothman,
(e-mail: mkaul@burnham.org and slipton@burnham.org) University of Rhode Island,
UNITED STATES
Drs. D’Ortenzio
describing and Matheron
low experimental contributed
transmission equally
efficiency of itsto thisput
main le
secretions or saliva
Received: March 19, 2016
exchanged
Supported
in conjunction
inwith
partapparent
by the European Virus Archive
sexual transmission Goespro
notifications, Gl
kissing. TheAccepted: saliva of Patient 2 project,
which sources
other potential
May 24, 2016
receivedof viral a grant (653316)Urine
dissemination. from andthe Europ
saliva hav
e on day 10 after Published: the June 24,onset
2016 of his Union lished Horizon
as useful2020 tools inFramework
ZIKV diagnosis. Program
Here, wefordescribed
Researchtheand pr
T
novation.
infectious ZIKV particles from saliva and urine of acute phase patie
t it was notCopyright: tested earlier. ZIKV
© 2016 Bonaldo et al. This is an open
Disclosure
state, Brazil. forms provided by the authors are available
cted in saliva,Creativebut, toAttribution

our License,knowl-
5 article distributed under the terms of the
access
Evidence of which
Sexual Transmission
permitsthe full text of this letter
Commons
of Zika Virus
at NEJM.org.
of transmission through
unrestricted saliva
use, distribution, havein anyThisMethodology/Principal
and reproduction
letter was published on Findings
eventually increase as people live longer with AIDS5,6. with a decrease in the incidence of HAD, whether this effect April 13, 2016, at NEJM.org.
medium, provided the original author and source are
ted.
To the credited.Editor: Zika virus (ZIKV), an emerging
1. Nine ary
McCarthy
urine
23and
(details
M.five are
Zika provided
virus
saliva was
samples in transmitted
the
fromSupplementary by sexual
nine patients from Rioconta
de J
flavivirus, generally causes mild infection in Appendix, available with the full text of this let-
t outbreaks Dataof ZIKV infection

All relevant data are Texas,
humans
Availability
but is
Statement:
associated
health
and other
with severe neurologic ter at NEJM.org).
officials
typical report.
Zika acute phaseBMJ 2016;352:
symptoms i720.
were inoculated in V
Hill SL,
within the paper and its Supporting Information files. 2. mitted Russell
toPopulations
specific K,
ZIKV Hennessey
RNA detection M,andet al. Transmission
quantification through,of r
opportunity to
complications conduct and studies
adverse fetal to
outcomes. ZIKV
RESEARCH ARTICLE
Additionally, the genome sequences reported in this
of Aedes aegypti and A. albopictus
is transmitted to humans primarily by aedes virusRT-PCR
mos- through and sexual
mosquitoes
are notcontact
RT-qPCR. Two ZIKV
established with travelers
inisolates
the city were toachieved,
of Paris. areas ofone ongfro
e natural history ofareZIKV. We need
manuscript (Acession numbers: KU926309 and
Isolation of Infective Zika Virus
evidence transmission
from Urine
—incontinental United States, 2016. MMWR
methodsM
quitoes. However, there is some of sex-
salivaMoreover,
KU926310) available in the NIH genetic specimens. France, the diapause
ZIKV nucleic acid wasperiod of aedes
identified by all
ne recommendations ual sequence

transmission.
to prevent
Two studies have shown the species extends from65:December to May.
1,2
Mortal
ever bothWklyurine
database (GenBank). Rep 2016;
and saliva 215-6. were
samples available from the same p
andvirus. Saliva ofauthors
Patients ZIKVin Brazil
presence of infectious ZIKV in semen. A recent Three days after the onset of her symptoms, 3
Mansuy JM, Dutertre M, the Mengelle C, et
thatal.it isZika virus:
3. were higher, corroborating general sense a better sour
of the article Indescribed
Funding: particular,
The received noof
detection guide-
specific funding
RNA in se- on February 23, samples of urine and saliva were
menfor62 work. after the onset of illness, butinfectious
thisdays diagnostic. viral
infec- obtained loadof
In spite
from inthis,
semen,
Patient from
1. aurine
Thethe new sexually
twosample
isolated transmitted
strains,
tested each frompa
g how long men who P.are returning
gen? Lancet Infect Dis 2016; 16:

1
405. 1☯ 4 1☯ 1☯
Myrna C. Bonaldotious *,
virus Ieda
was not Ribeiro
The authors, have
cultured. Noemia S. Lima , Alexandre
derived from
positive
Competing Interests: declared forA.ZIKV
urine,C. dos
suggesting
RNA Santos
by that , other factors, like the acidic nat
reverse-transcriptase
is now the most common cause of dementia worldwide a number of deleterious processes12. 1☯ 1☯ 1☯
where active
Lidiane S. R. Menezes
D. Furtado ously
ZIKV
We
, Elaine
report transmission
a, Stephanie
no competing
E. de
case of ZIKV
interests
O. D. da Cruz
exist. infection
dent risk factor for death due to AIDS9. With the advent of tion of the CNS1☯
Moura , Luana
is
12,14
Damasceno
in a4.,previ-
Iasmim
Atkinson
interfere
, Kely
S. de
polymerase
withMello
that B,virion
. Microglial and astrocytic chemokines
A. B. da
,infectivity.
Hearn
chain
Silva
Nathália
P, Afrough
reaction
, Marcia
The B, etatal.
(RT-PCR)
complete1☯
a Detection
viral of bothofZIKV
genome 2☯
Zik 3‡
healthy 24-year-old woman (Patient 1) rus whoin count ofEmerg
semen.
3.5×10 Infect
copiesDis per 2016
milliliter,
(in and the
press) (http://dx.doi.
3
uld G.continue
de Castro , to use
Alexandra condoms
L. Gerber , dur-
(ref. 10), but in recent years its incidence as an AIDS-defining monocyte chemoattractant3‡
Luiz G. P. de
protein (MCP)-1, seem to
Almeida , Ricardo
was living in Paris and in whom acute fever, saliva tested positive at a viral count of 2.1×10
il ness has actually increased3. The proportion of new cases of regulate migration of peripheral blood mononuclear cells Lourenço-de- 4‡ 4‡
4
HAD demonstrating a CD4 count greater than 200 !l"13‡
Oliveira , Ana myalgia, Tereza R. Vasconcelos
arthralgia, and pruritic , Patrícia 10.3201/copies
Brasil
rash developed
eid2205 .160107).
is through the BBB14. Histological studies in specimens from
per milliliter. A plasma sample tested nega-
4‡ 2☯
act with pregnant women and those

10
on February 20, 2016. She was not receiving 5. any Barzon

1 Laboratório de PLOS Biologia MolecularTropical
Neglected de Flavivírus,
Diseases Instituto Oswaldo Cruz,
L,ZIKV
tiveFiocruz,
for
| DOI:10.1371/journal.pntd.0004816
Pacenti
RioRNA
M,RT-PCR,
by
de Janeiro,
June
Berto A, et al. Isolation of infect
2016but serum IgM an-
Brazil,
24,
g age are lacking.
2 Laboratório
988 medication,
de Doenças Febris In not
had addition,
received
Agudas, anyrec-
Instituto Nacional Zika
blood transfu-
de virus from
tibodies
Infectologia saliva
to ZIKV
Evandro wereand
Chagas, prolonged
detected
Fiocruz,
NATURE | VOL 410 | 19 APRIL 2001 | www.nature.com
Rio viral RNA shedding
(see the Supplemen-
opheles
mosquitoes
Journal of General Virology (2009), 90, 2183–2190 1 DOI 10.1099/vir.0.010165-0
2,3
eição de Maria Almeida Vieira, Marcio Roberto Teixeira Nunes,
2 2
a Vieira Pinto da Silva, Valéria Lima Carvalho,
Full-length
2 sequencing
uim Pinto Nunes Neto, Ana Cecı́lia Ribeiro Cruz, and genetic
2,3
characterization of Breu Branco virus (Reoviridae,
2 2
r Mansour Moraes Casseb, Helena Baldez Vasconcelos,
Orbivirus) 3and two related strains isolated from

ez Antônio Simões Quaresma

T
Anopheles mosquitoes
2,3
Pedro Fernando da Conceição
Costa Vasconcelos
de Maria Almeida Vieira,1 Marcio Roberto Teixeira Nunes,2,3

Eliana Vieira Pinto da Silva,2 Valéria Lima Carvalho,2
onian Rural Federal University, Belém,
Joaquim PintoBrazil
Nunes Neto,2 Ana Cecı́lia Ribeiro Cruz,2,3
Samir Mansour Moraes Casseb,2 Helena Baldez Vasconcelos,2

rtment of Arbovirology and Hemorrhagic Fevers, Evandro3 Chagas Institute, Ananindeua,

Juarez Antônio Simões Quaresma
State, Brazil
and Pedro Fernando da Costa Vasconcelos2,3

ute of Biological Sciences Federal

1
that directCorrespondence
University of Pará State, Belém, Brazil
Amazonian Rural Federal University, Belém, Brazil
effects of viral proteins on neurons may also HIV entry into the brain and initiation of HAD
themselvesMarcio
are not infected by HIV-1. Here we reviRoberto
ew the virus resides primarily in microgliTeixeira
a and macrophages. Nunes 2
extracellular and intracellular signalling pathways leading However, infection of these cells may not be sufficient to ini- Department of Arbovirology and Hemorrhagic Fevers, Evandro Tucuruí,
Isolado Chagas Institute,
em Ananindeua,
1988
marcionunes@iec.pa.gov.br
induced in neurons and astrocytes. These pathways are of associated with advanced HIV infection in the periphery Pará State, Brazil
Branco virus (BE AR 492347) was isolated fromFederal University of(Nyssorhynchus)
Anopheles Pará State, Belém, Brazil triannulatus
3
Institute of Biological Sciences dementia. One such factor could be the increased number
itoes captured in Tucuruı́, Pará State, northern Brazil, in 1988. No cross-reactivity by
Breu Branco virus (BE AR 492347) was isolated from Anopheles (Nyssorhynchus) triannulatus
ement-fixation tests was observed between Breu Branco virus and other known arboviruses.
mosquitoes captured in Tucuruı́, Pará State, northern Brazil, in 1988. No cross-reactivity by
s of electron microscopy and physicochemical

complement-fixation tests suggested
tests was observed that virus
between Breu Branco Breu andBranco
other knownvirus may
arboviruses.
Results of electron microscopy and physicochemical tests suggested that Breu Branco virus may
ember of the family Reoviridae. In order to elucidate its taxonomic status, a comprehensive
be a member of the family Reoviridae. In order to elucidate its taxonomic status, a comprehensive

Arbovírus PDF

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Arbovírus PDF

Uploaded by

Copyright:

Available Formats

Arbovírus

Prof. Dr. Luiz Fernando Almeida Machado

• Vírus → transmissão biológica → vertebrados

susceptíveis e artrópodes hematófagos (ou pela via

• Multiplicam-se e produzem viremia em vertebrados

• Multiplicam-se em artrópodes → transmitidos pela

picada de artrópodes → período de incubação

extrínseco (WHO, 1985).

Single-stranded Single-stranded Double-stranded

Family: Togaviridae Family: Bunyaviridae Family: Reoviridae

Família Flaviviridae Togaviridae

545 arbovírus já identificados

150 causam doenças em humanos

Arbovírus isolados na Amazônia Brasileira

• 1954 – 2015: >10.000 isolamentos virais

• 186 tipos: 157 novos para o Brasil

• 84 novos para o mundo

• A maioria tem patogenicidade indeterminada para o homem

• Zoonoses com ampla distribuição geográfica

• Homem como hospedeiro acidental

• Hospedeiros de manutenção: aves, roedores,

morcegos, répteis, etc

• Persistência de um arbovírus = verteb.

susceptíveis + vet. competentes

• Vírus - linfonodos satélites – replicação

(fagócitos) – viremia – órgão alvo

• Período de incubação: 1-15 dias (3-7 dias)

• - IFA, imunohistoquímica, RT-PCR

Tratamento, Prevenção e Controle

HIV entry into the brain and initiation of HAD

Endêmica na América do Sul e África

Mantidos em natureza entre primatas não

Ciclo urbano e silvestre

Tabela 2 - Apresentações clínicas da febre amarela no homem 57.

Revista da Sociedade Brasileira de Medicina Tropical 36:275-293, mar-abr, 2003

São Paulo (2008)

São Paulo (2009)

• Sorologia (ELISA - IgM e IgG)

• Biologia molecular (PCR)

RNAfs (+)active antiretroviral therapy (HAART) has

Genoma dos Togavírus

Genoma dos Flavivírus e Togavírus

Secretaria de Vigilância em Saúde − Ministério da Saúde

Epidemiológica 13, 2016 2015 a

Graus de gravidade da Febre hemorrágica do dengue/

Síndrome do choque do dengue (DHF/DSS)

Grau I: Trombocitopenia + hemoconcentração. Ausência de sangramento

Grau II: Trombocitopenia + hemoconcentração. Presença de sangramento

Grau III: Trombocitopenia + hemoconcentração. Insuficiência circulatória

Grau IV: Trombocitopenia + hemoconcentração. Choque profundo

Secretaria de Vigilância em Saúde − Ministério da Saúde

Monitoramento dos casos de

Secretaria de Vigilância em Saúde − Ministério da Saúde

Monitoramento dos casos de que as regiões Centro-Oeste e Sudeste apresentam

Semana Epidemiológica de Início de Sintomas

Fonte: Sinan Online (atualizado em a13/07/2015; b04/01/2016; c04/04/2016).

Fonte: Sinan (atualizado em 07/04/2016).

poliartrite/artralgia simétrica (principalmente punhos,

não são comuns choque ou hemorragias importantes como

na dengue, mas podem surgir sintomas neurológicos

Secretaria de Vigilância em Saúde − Ministério da Saúde

Zika que as regiões Centro-Oeste e Sudeste apresentam

Boletim 501,0 --| 1.001,0