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Journal ArticleDOI

Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study

TL;DR: This is the first study providing evidence for Zika virus infection causing Guillain-Barré syndrome, and because Zika virus is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity to manage patients with Guillay-B Barré syndrome.
About: This article is published in The Lancet.The article was published on 2016-04-09 and is currently open access. It has received 1925 citations till now. The article focuses on the topics: Zika virus & Zika virus disease.
Citations
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Journal ArticleDOI
TL;DR: The in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases were investigated and changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells.
Abstract: Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.

3,514 citations

Journal Article
TL;DR: High-dose of intravenous immunoglobulin (0.4 g/kg daily for 5 days) and PE are equally effective in intermediate and severe forms and the choice between the two treatments depends on their respective contra-indications and local availability.
Abstract: L'incidence annuelle du syndrome de Guillain-Barre est de 1,5/100000 habitants La mortalite actuelle est estimee a environ 5 % d'apres des essais therapeutiques recents, bien conduits Dix pour cent des malades gardent des sequelles motrices tres invalidantes un an apres le debut des premiers signes neurologiques La prise en charge de ces malades necessite des equipes entrainees, multidisciplinaires, pouvant pratiquer l'ensemble des therapeutiques specifiques La corticotherapie per os'ou par voie intraveineuse est inefficace Les echanges plasmatiques sont le premier traitement dont l'efficacite a ete demontree par rapport a un groupe controle Les indications sont maintenant mieux connues Les formes benignes (marche possible) beneficient de 2 echanges plasmatiques; 2 echanges supplementaires sont realises en cas d'aggravation Dans les formes intermediaires (marche impossible) et les formes severes (recours a la ventilation mecanique), 4 echanges plasmatiques sont conseilles Il n'est pas utile d'augmenter leur nombre dans les formes severes ou en cas d'absence d'amelioration De fortes doses d'immunoglobulines donnees par voie intraveineuse (lq IV) [0,4 g/kg/j pendant 5 jours] sont aussi efficaces que les echanges plasmatiques dans les formes intermediaires et severes Dans ces formes, le choix entre Ig IV et echanges plasmatiques depend des contre-indications respectives de ces traitements et de leur faisabilite Les travaux en cours ont comme objectif de mieux preciser les indications respectives des echanges plasmatiques et des lq IV dans des formes de gravite differente, leur morbidite comparee, la dose optimale des lq IV

1,842 citations

Journal ArticleDOI
11 May 2016-Nature
TL;DR: It is demonstrated that the ZIKVBR infects fetuses, causing intra-uterine growth restriction (IUGR), and crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, impairing neurodevelopment.
Abstract: Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barre syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment.

1,095 citations

Journal ArticleDOI
TL;DR: The data for GBS suggests that the immunologic mechanism can involve molecular mimicry, at least in some GBS variants, and it is likely that multiple mechanisms render the axon vulnerable.

925 citations

Journal ArticleDOI
Nuno R. Faria1, Nuno R. Faria2, Raimunda do Socorro da Silva Azevedo2, Moritz U. G. Kraemer1, Renato Pereira de Souza3, Mariana Sequetin Cunha3, Sarah C. Hill1, Julien Thézé1, Michael B. Bonsall1, Thomas A. Bowden4, Ilona Rissanen4, Iray Maria Rocco3, Juliana Silva Nogueira3, Adriana Yurika Maeda3, Fernanda Giseli da Silva Vasami3, F. L. L. Macedo3, Akemi Suzuki3, Sueli Guerreiro Rodrigues2, Ana Cecília Ribeiro Cruz2, Bruno Tardeli Nunes2, Daniele Barbosa de Almeida Medeiros2, Daniela Sueli Guerreiro Rodrigues2, Alice Louize Nunes Queiroz2, Eliana Vieira Pinto da Silva2, Daniele Freitas Henriques2, Elisabeth Salbe Travassos da Rosa2, Consuelo Silva de Oliveira2, Lívia Carício Martins2, Helena Baldez Vasconcelos2, Livia Medeiros Neves Casseb2, Darlene B. Simith2, Jane P. Messina1, Leandro Abade1, José Lourenço1, Luiz Carlos Junior Alcantara5, Maricélia Maia de Lima6, Marta Giovanetti5, Simon I. Hay4, Simon I. Hay7, Rodrigo Santos de Oliveira2, Poliana da Silva Lemos2, Layanna Freitas de Oliveira2, Clayton Pereira Silva de Lima2, Sandro Patroca da Silva2, Janaina Mota de Vasconcelos2, L. C Franco2, Jedson Ferreira Cardoso2, João Lídio Silva Gonçalves Vianez-Júnior2, Daiana Mir5, Gonzalo Bello5, Edson Delatorre5, Kamran Khan8, Kamran Khan9, Marisa I Creatore8, Giovanini E. Coelho, Wanderson Kleber de Oliveira, Robert B. Tesh10, Oliver G. Pybus1, Márcio Roberto Teixeira Nunes2, Márcio Roberto Teixeira Nunes10, Pedro Fernando da Costa Vasconcelos2 
15 Apr 2016-Science
TL;DR: Results of phylogenetic and molecular clock analyses show a single introduction of ZikV into the Americas, which is estimated to have occurred between May and December 2013, more than 12 months before the detection of ZIKV in Brazil.
Abstract: Brazil has experienced an unprecedented epidemic of Zika virus (ZIKV), with ~30,000 cases reported to date. ZIKV was first detected in Brazil in May 2015, and cases of microcephaly potentially associated with ZIKV infection were identified in November 2015. We performed next-generation sequencing to generate seven Brazilian ZIKV genomes sampled from four self-limited cases, one blood donor, one fatal adult case, and one newborn with microcephaly and congenital malformations. Results of phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, which we estimated to have occurred between May and December 2013, more than 12 months before the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV-endemic areas, as well as with reported outbreaks in the Pacific Islands. ZIKV genomes from Brazil are phylogenetically interspersed with those from other South American and Caribbean countries. Mapping mutations onto existing structural models revealed the context of viral amino acid changes present in the outbreak lineage; however, no shared amino acid changes were found among the three currently available virus genomes from microcephaly cases. Municipality-level incidence data indicate that reports of suspected microcephaly in Brazil best correlate with ZIKV incidence around week 17 of pregnancy, although this correlation does not demonstrate causation. Our genetic description and analysis of ZIKV isolates in Brazil provide a baseline for future studies of the evolution and molecular epidemiology of this emerging virus in the Americas.

921 citations

References
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Journal ArticleDOI
TL;DR: This outbreak of Zika virus illness in Micronesia represents transmission of Zikairus outside Africa and Asia and clinicians and public health officials should be aware of the risk of further expansion of Zika viruses transmission.
Abstract: BACKGROUND In 2007, physicians on Yap Island reported an outbreak of illness characterized by rash, conjunctivitis, and arthralgia. Although serum from some patients had IgM antibody against dengue virus, the illness seemed clinically distinct from previously detected dengue. Subsequent testing with the use of consensus primers detected Zika virus RNA in the serum of the patients but no dengue virus or other arboviral RNA. No previous outbreaks and only 14 cases of Zika virus disease have been previously documented. METHODS We obtained serum samples from patients and interviewed patients for information on clinical signs and symptoms. Zika virus disease was confirmed by a finding of Zika virus RNA or a specific neutralizing antibody response to Zika virus in the serum. Patients with IgM antibody against Zika virus who had a potentially cross-reactive neutralizing-antibody response were classified as having probable Zika virus disease. We conducted a household survey to estimate the proportion of Yap residents with IgM antibody against Zika virus and to identify possible mosquito vectors of Zika virus. RESULTS We identified 49 confirmed and 59 probable cases of Zika virus disease. The patients resided in 9 of the 10 municipalities on Yap. Rash, fever, arthralgia, and conjunctivitis were common symptoms. No hospitalizations, hemorrhagic manifestations, or deaths due to Zika virus were reported. We estimated that 73% (95% confidence interval, 68 to 77) of Yap residents 3 years of age or older had been recently infected with Zika virus. Aedes hensilli was the predominant mosquito species identified. CONCLUSIONS This outbreak of Zika virus illness in Micronesia represents transmission of Zika virus outside Africa and Asia. Although most patients had mild illness, clinicians and public health officials should be aware of the risk of further expansion of Zika virus transmission.

2,717 citations

Journal ArticleDOI
TL;DR: Cross neutralization tests indicate that Zika virus is not related to yellow fever, Hawaii dengue nor to the FA and GD VII strains of Theiler's mouse encephalomyelitis virus.
Abstract: 1. (1) The isolation of what is believed to be a hitherto unrecorded virus is described. The first isolation was made in April 1947 from the serum of a pyrexial rhesus monkey caged in the canopy of Zika Forest. The second isolation was made from a lot of A. africanus taken in January, 1948, in the same forest. The virus has been called Zika virus after the locality from where the isolations were made. 2. (2) Cross neutralization tests indicate that Zika virus is not related to yellow fever, Hawaii dengue nor to the FA and GD VII strains of Theiler's mouse encephalomyelitis virus. Neutralization tests with Zika virus and the antisera of some other viruses which are neurotropic in mice gave no evidence of any identity of these with Zika virus.

2,338 citations

Journal ArticleDOI
TL;DR: The full coding region nucleic acid sequence and serologic properties of the virus were identified and the virus was identified as Crimean-Congo-Wales coronavirus.
Abstract: Zika virus (ZIKV) is a mosquito-borne flavivirus first isolated in Uganda from a sentinel monkey in 1947. Mosquito and sentinel animal surveillance studies have demonstrated that ZIKV is endemic to Africa and Southeast Asia, yet reported human cases are rare, with <10 cases reported in the literature. In June 2007, an epidemic of fever and rash associated with ZIKV was detected in Yap State, Federated States of Micronesia. We report the genetic and serologic properties of the ZIKV associated with this epidemic.

1,944 citations

Journal Article
TL;DR: High-dose of intravenous immunoglobulin (0.4 g/kg daily for 5 days) and PE are equally effective in intermediate and severe forms and the choice between the two treatments depends on their respective contra-indications and local availability.
Abstract: L'incidence annuelle du syndrome de Guillain-Barre est de 1,5/100000 habitants La mortalite actuelle est estimee a environ 5 % d'apres des essais therapeutiques recents, bien conduits Dix pour cent des malades gardent des sequelles motrices tres invalidantes un an apres le debut des premiers signes neurologiques La prise en charge de ces malades necessite des equipes entrainees, multidisciplinaires, pouvant pratiquer l'ensemble des therapeutiques specifiques La corticotherapie per os'ou par voie intraveineuse est inefficace Les echanges plasmatiques sont le premier traitement dont l'efficacite a ete demontree par rapport a un groupe controle Les indications sont maintenant mieux connues Les formes benignes (marche possible) beneficient de 2 echanges plasmatiques; 2 echanges supplementaires sont realises en cas d'aggravation Dans les formes intermediaires (marche impossible) et les formes severes (recours a la ventilation mecanique), 4 echanges plasmatiques sont conseilles Il n'est pas utile d'augmenter leur nombre dans les formes severes ou en cas d'absence d'amelioration De fortes doses d'immunoglobulines donnees par voie intraveineuse (lq IV) [0,4 g/kg/j pendant 5 jours] sont aussi efficaces que les echanges plasmatiques dans les formes intermediaires et severes Dans ces formes, le choix entre Ig IV et echanges plasmatiques depend des contre-indications respectives de ces traitements et de leur faisabilite Les travaux en cours ont comme objectif de mieux preciser les indications respectives des echanges plasmatiques et des lq IV dans des formes de gravite differente, leur morbidite comparee, la dose optimale des lq IV

1,842 citations

Journal ArticleDOI
TL;DR: Phylogenetic analysis suggests that the ZikV identified belongs to the Asian clade, the first report of ZIKV infection in Brazil, and the result was confirmed by DNA sequencing.
Abstract: In the early 2015, several cases of patients presenting symptoms of mild fever, rash, conjunctivitis and arthralgia were reported in the northeastern Brazil. Although all patients lived in a dengue endemic area, molecular and serological diagnosis for dengue resulted negative. Chikungunya virus infection was also discarded. Subsequently, Zika virus (ZIKV) was detected by reverse transcription-polymerase chain reaction from the sera of eight patients and the result was confirmed by DNA sequencing. Phylogenetic analysis suggests that the ZIKV identified belongs to the Asian clade. This is the first report of ZIKV infection in Brazil.

1,047 citations

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