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1. Differential yellow fever susceptibility in new world nonhuman primates, comparison with humans, and implications for surveillance

Author

Leila delC Saad, Cristina Takami Kanamura, Fernanda G. S. Vasami, Isis Paixão de Jesus, Juliana Mariotti Guerra, Silvia D'Andretta Iglezias, Josué Díaz-Delgado, Mariana Sequetin Cunha, Júlia de Carvalho, Leonardo José Tadeu de Araújo, Rodrigo Albergaria Réssio, Adriana Yurika Maeda, Cinthya dos Santos Cirqueira, Juliana Silva Nogueira, Roberta Spinola, José Luiz Catão-Dias, Renato Pereira de Souza, and Natália Coelho Couto de Azevedo Fernandes

Subjects
Primates, Microbiology (medical), Epidemiology, Differential Yellow Fever Susceptibility in New World Nonhuman Primates, Comparison with Humans, and Implications for Surveillance, 030231 tropical medicine, lcsh:Medicine, liver, Virus, lcsh:Infectious and parasitic diseases, yellow fever, 03 medical and health sciences, 0302 clinical medicine, Virus antigen, biology.animal, medicine, Animals, Humans, lcsh:RC109-216, viruses, Primate, 030212 general & internal medicine, Alouatta, outbreak, biology, Research, Mortality rate, lcsh:R, immunohistochemical analysis, Yellow fever, Outbreak, VIGILÂNCIA SANITÁRIA, medicine.disease, biology.organism_classification, new world nonhuman primates, Callithrix, Virology, zoonoses, PCR, Infectious Diseases, arboviruses, differential susceptibility, surveillance, Yellow fever virus, Viral load, Brazil
Abstract

A major outbreak of yellow fever (YF) occurred in Brazil during 2016–2018. Epizootics in New World nonhuman primates are sentinel events for YF virus circulation. However, genus-specific susceptibilities and suitability for YF surveillance remain poorly understood. We obtained and compared epidemiologic, histopathologic, immunohistochemical, and molecular results from 93 human and 1,752 primate cases submitted during the recent YF outbreak in Brazil (2017), with the support of the Brazilian National YF Surveillance Program. We detected heterogeneous YF-associated profiles among the various genera of primates we analyzed. Alouatta primates were the most reliable sentinel; Sapajus and Callicebus primates had higher viral loads but lower proportional mortality rates. Callithrix primates were the least sensitive, showing lower viral loads, lower proportional mortality rates, and no demonstrable YF virus antigen or extensive lesions in liver, despite detectable viral RNA. These differences in susceptibility, viral load, and mortality rates should be considered in strategic surveillance of epizootics and control measures for YF.

Published
2021

2. Genomic surveillance of Yellow Fever Virus Epizootic in São Paulo, Brazil, 2016 - 2018

Author

Natália Coelho Couto de Azevedo Fernandes, Maria do Carmo Sampaio Tavares Timenetsky, Paola P. Silveira, Julien Thézé, Mariana Sequetin Cunha, Louis du Plessis, Leandro Abade, Renato De Souza, Laura Nogueira da Cruz, Jaqueline Goes de Jesus, Rodrigo Albergaria Réssio, F. L. L. Macedo, Oliver G. Pybus, Juliana Telles de Deus, Josué Díaz-Delgado, Luiz Carlos Junior Alcantara, Iray Maria Rocco, Renato S. Aguiar, Fernanda G. S. Vasami, Juliana Mariotti Guerra, Simon Dellicour, Regiane Maria Tironi de Menezes, Nuno R. Faria, Flavia Cristina da Silva Salles, Ester Cerdeira Sabino, Luis Filipe Mucci, Adriana Yurika Maeda, Cinthya dos Santos Cirqueira, Rosa Maria Tubaki, André Luiz de Abreu, Marta Giovanetti, Nicholas J. Loman, Regiane de Paula, Juliana Silva Nogueira, Joshua Quick, Patrícia Locosque Ramos, Roberta Spinola, Sarah C. Hill, Fabiana Cristina Pereira dos Santos, Ingra Morales Claro, Department of Zoology [Oxford], University of Oxford [Oxford], Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques (UMR EPIA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratório de Radioecologia e Mudanças Globais (LARAMG), Universidade do Estado do Rio de Janeiro [Rio de Janeiro] (UERJ), Department of Infectious Diseases, Istituto Superiore di Sanita [Rome], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidad Nacional de San Agustín (UNSA), University of Birmingham [Birmingham], and Biotempo

Subjects
Epidemiology, [SDV]Life Sciences [q-bio], Virologie générale, Geographical locations, law.invention, Disease Outbreaks, Animal Diseases, 0302 clinical medicine, Medical Conditions, law, Zoonoses, Immunologie, Medicine and Health Sciences, Biology (General), Phylogeny, ComputingMilieux_MISCELLANEOUS, Data Management, 0303 health sciences, Parasitologie, Mammalian Genomics, Geography, Transmission (medicine), 030302 biochemistry & molecular biology, Yellow fever, Phylogenetic Analysis, Genomics, 3. Good health, Phylogenetics, Phylogeography, Transmission (mechanics), Infectious Diseases, Biogeography, Sylvatic cycle, Yellow fever virus, Biologie, Brazil, geographic locations, Research Article, Primates, Computer and Information Sciences, Infectious Disease Control, QH301-705.5, Genomic data, 030231 tropical medicine, Immunology, Zoology, Genome, Viral, Disease Surveillance, Epizootics, Microbiology, Virus, 03 medical and health sciences, Virology, Yellow Fever, parasitic diseases, Genetics, medicine, Animals, Humans, Evolutionary Systematics, Molecular Biology, Epizootic, Taxonomy, 030304 developmental biology, Evolutionary Biology, Population Biology, Ecology and Environmental Sciences, Primate Diseases, Virologie médicale, Biology and Life Sciences, Outbreak, Biologie moléculaire, South America, RC581-607, medicine.disease, Animal Genomics, Infectious Disease Surveillance, Earth Sciences, Biological dispersal, Parasitology, People and places, Immunologic diseases. Allergy, Microbiologie et protistologie [bacteriol.virolog.mycolog.], human activities, Population Genetics
Abstract

São Paulo, a densely inhabited state in southeast Brazil that contains the fourth most populated city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in decades. YFV does not normally circulate extensively in São Paulo, so most people were unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is important for determining the magnitude and geographic extent of an epizootic, thereby helping to evaluate the risk of YFV spillover to humans. Data from infected NHPs can give more accurate insights into YFV spread than when using data from human cases alone. To contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV spread in São Paulo, we generated and analysed virus genomic data and epizootic case data from NHPs in São Paulo. We report the occurrence of three spatiotemporally distinct phases of the outbreak in São Paulo prior to February 2018. We generated 51 new virus genomes from YFV positive cases identified in 23 different municipalities in São Paulo, mostly sampled from NHPs between October 2016 and January 2018. Although we observe substantial heterogeneity in lineage dispersal velocities between phylogenetic branches, continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in São Paulo at a mean rate of approximately 1km per day during all phases of the outbreak. Viral lineages from the first epizootic phase in northern São Paulo subsequently dispersed towards the south of the state to cause the second and third epizootic phases there. This alters our understanding of how YFV was introduced into the densely populated south of São Paulo state. Our results shed light on the sylvatic transmission of YFV in highly fragmented forested regions in São Paulo state and highlight the importance of continued surveillance of zoonotic pathogens in sentinel species., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2020

3. Propranolol for familial cerebral cavernous malformation (Treat_CCM): study protocol for a randomized controlled pilot trial

Author

Lanfranconi, S., Scola, E., Bertani, G. A., Zarino, B., Pallini, Roberto, D'Alessandris, Quintino Giorgio, Mazzon, E., Marino, S., Carriero, M. R., Scelzo, E., Farago, G., Castori, M., Fusco, C., Petracca, A., D'Agruma, L., Tassi, L., D'Orio, P., Lampugnani, M. G., Nicolis, E. B., Vasami, A., Novelli, D., Torri, V., Meessen, J. M. T. A., Salman, R. A. -S., Dejana, E., Latini, R., Pignotti, Fabrizio, Sturiale, Carmelo Lucio, Albanese, Alessio, Valcamonica, G., Ronchi, D., Pogliani, S., De Grazia, U., Bossi, C., Ciurleo, R., Raggi, P., Simeone, A., Balconi, G., Foresta, A., Buratti, M. G., Carrara, M., Ojeda-Fernandez, M. L., Treglia, R., Maggioni, A. P., Beghi, E., Tettamanti, M., Regna-Gladin, C., Prelle, A., Mangiavacchi, M., Poloni, M., Lazzaroni, F., Malinverno, M., Ungaro, C., and Raucci, F.

Subjects
Male, Hemangioma, Cavernous, Central Nervous System, Pediatrics, medicine.medical_treatment, Settore MED/27 - NEUROCHIRURGIA, Medicine (miscellaneous), Anxiety, Severity of Illness Index, law.invention, Study Protocol, Mice, 0302 clinical medicine, Randomized controlled trial, law, Medicine, Pharmacology (medical), Prospective Studies, Depression (differential diagnoses), 0303 health sciences, lcsh:R5-920, medicine.diagnostic_test, Depression, Propranolol, Treatment Outcome, Italy, Models, Animal, Disease Progression, Female, Epileptic seizure, Safety, medicine.symptom, lcsh:Medicine (General), Intracranial Hemorrhages, medicine.drug, Adult, medicine.medical_specialty, Adrenergic beta-Antagonists, Radiosurgery, 03 medical and health sciences, Magnetic resonance imaging, Cerebral cavernous malformation, Animals, Humans, Adverse effect, 030304 developmental biology, business.industry, Case-Control Studies, Quality of Life, Nervous System Diseases, business, 030217 neurology & neurosurgery
Abstract

Background Cerebral cavernous malformations (CCMs) are vascular malformations characterized by clusters of enlarged leaky capillaries in the central nervous system. They may result in intracranial haemorrhage, epileptic seizure(s), or focal neurological deficits, and potentially lead to severe disability. Globally, CCMs represent the second most common intracranial vascular malformation in humans, and their familial form (FCCMs) accounts for one-fifth of cases. Neurosurgical excision, and perhaps stereotactic radiosurgery, is the only available therapeutic option. Case reports suggest that propranolol might modify disease progression. Methods Treat_CCM is a prospective, randomized, open-label, blinded endpoint (PROBE), parallel-group trial involving six Italian clinical centres with central reading of brain magnetic resonance imaging (MRI) and adverse events. Patients with symptomatic FCCMs are randomized (2:1 ratio) either to propranolol (40–80 mg twice daily) in addition to standard care or to standard care alone (i.e. anti-epileptic drugs or headache treatments). The primary outcome is intracranial haemorrhage or focal neurological deficit attributable to CCMs. The secondary outcomes are MRI changes over time (i.e. de novo CCM lesions, CCM size and signal characteristics, iron deposition, and vascular leakage as assessed by quantitative susceptibility mapping and dynamic contrast enhanced permeability), disability, health-related quality of life, depression severity, and anxiety (SF-36, BDI-II, State-Trait Anxiety Inventory). Discussion Treat_CCM will evaluate the safety and efficacy of propranolol for CCMs following promising case reports in a randomized controlled trial. The direction of effect on the primary outcome and the consistency of effects on the secondary outcomes (even if none of them yield statistically significant differences) of this external pilot study may lead to a larger sample size in a definitive phase 2 trial. Trial registration ClinicalTrails.gov, NCT03589014. Retrospectively registered on 17 July 2018.

Published
2020

4. Probable transfusion-transmitted Zika virus in Brazil

Author

F S F Ilka, Addas-Carvalho, P Renato, R Mariangela, Boin, Barjas-Castro, Rocco, Stucchi, M Iray, Nogueira, Marcelo, S Juliana, Angerami, G S Fernanda, Esposito, D. I. De Souza, S B Raquel, Gizelda, L Maria, Suzuki, Resende, L A Danillo, Katz, Akemi, Cunha, N Rodrigo, Vasami, S Mariana, Y Adriana, da Fonseca, A Benedito, and Maeda

Subjects
0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, biology, Immunology, Immunology and Allergy, Hematology, 030204 cardiovascular system & hematology, biology.organism_classification, Virology, Zika virus
Published
2016

5. Epizootics due to Yellow Fever Virus in São Paulo State, Brazil: viral dissemination to new areas (2016-2017)

Author

Leandro Guariglia D’Agostino, Paloma Alana de Souza Facioli, Renato Pereira de Souza, Fernanda G. S. Vasami, Fabiana Cristina Pereira dos Santos, Adriana Yurika Maeda, Shirley Vasconcelos Komninakis, Juliana Mariotti Guerra, Élcio Leal, Natália Coelho Couto de Azevedo Fernandes, Rodrigo Albergaria Réssio, Mariana Sequetin Cunha, Juliana Silva Nogueira, F. L. L. Macedo, Lais Sampaio de Azevedo, Antonio Charlys da Costa, Steven S. Witkin, Ester Cerdeira Sabino, and Ursula Mitsue Abreu Kaigawa

Subjects
0301 basic medicine, Veterinary medicine, Espirito santo, lcsh:Medicine, Biology, Disease cluster, Virus, Molecular taxonomy, Article, Cell Line, Disease Outbreaks, 03 medical and health sciences, 0302 clinical medicine, Zoonoses, parasitic diseases, Yellow Fever, medicine, Animals, Humans, lcsh:Science, Antigens, Viral, Phylogeny, Multidisciplinary, Indirect immunofluorescence, Whole Genome Sequencing, lcsh:R, Yellow fever, Outbreak, Bayes Theorem, Haplorhini, biology.organism_classification, medicine.disease, Callithrix, Phylogeography, 030104 developmental biology, Culicidae, lcsh:Q, Yellow fever virus, 030217 neurology & neurosurgery, Brazil
Abstract

Beginning in late 2016 Brazil faced the worst outbreak of Yellow Fever in recent decades, mainly located in southeastern rural regions of the country. In the present study we characterize the Yellow Fever Virus (YFV) associated with this outbreak in São Paulo State, Brazil. Blood or tissues collected from 430 dead monkeys and 1030 pools containing a total of 5,518 mosquitoes were tested for YFV by quantitative RT-PCR, immunohistochemistry (IHC) and indirect immunofluorescence. A total of 67 monkeys were YFV-positive and 3 pools yielded YFV following culture in a C6/36 cell line. Analysis of five nearly full length genomes of YFV from collected samples was consistent with evidence that the virus associated with the São Paulo outbreak originated in Minas Gerais. The phylogenetic analysis also showed that strains involved in the 2016–2017 outbreak in distinct Brazilian states (i.e., Minas Gerais, Rio de Janeiro, Espirito Santo) intermingled in maximum-likelihood and Bayesian trees. Conversely, the strains detected in São Paulo formed a monophyletic cluster, suggesting that they were local-adapted. The finding of YFV by RT-PCR in five Callithrix monkeys who were all YFV-negative by histopathology or immunohistochemistry suggests that this YFV lineage circulating in Sao Paulo is associated with different outcomes in Callithrix when compared to other monkeys.

Published
2018

6. Zika virus in the Americas: Early epidemiological and genetic findings

Author

Raimunda do Socorro da Silva Azevedo, Moritz U. G. Kraemer, Luiz Carlos Junior Alcantara, Elisabeth Salbe Travassos da Rosa, Iray Maria Rocco, Edson Delatorre, Eliana Vieira Pinto da Silva, Lívia Carício Martins, Sueli Guerreiro Rodrigues, Daniele Barbosa de Almeida Medeiros, Robert B. Tesh, Mariana Sequetin Cunha, Helena Baldez Vasconcelos, Poliana da Silva Lemos, Kamran Khan, Gonzalo Bello, Alice Louize Nunes Queiroz, Thomas A. Bowden, Livia Medeiros Neves Casseb, José Lourenço, Leandro Abade, Juliana Silva Nogueira, Daniela Sueli Guerreiro Rodrigues, Giovanini E. Coelho, João Lídio Silva Gonçalves Vianez-Júnior, Pedro Fernando da Costa Vasconcelos, Márcio Roberto Teixeira Nunes, Sarah C. Hill, Fernanda Giseli da Silva Vasami, Marisa I Creatore, Ilona Rissanen, Renato Pereira de Souza, Maricélia Maia de Lima, Jedson Ferreira Cardoso, Layanna Freitas de Oliveira, L. C Franco, Daniele Freitas Henriques, Sandro Patroca da Silva, Wanderson Kleber de Oliveira, Michael B. Bonsall, Darlene B. Simith, F. L. L. Macedo, Akemi Suzuki, Ana Cecília Ribeiro Cruz, Bruno Tardeli Nunes, Rodrigo Santos de Oliveira, Janaina Mota de Vasconcelos, Simon I. Hay, Jane P. Messina, Marta Giovanetti, Consuelo Silva de Oliveira, Daiana Mir, Adriana Yurika Maeda, Nuno R. Faria, Oliver G. Pybus, Julien Thézé, Clayton Pereira Silva de Lima, and University of Oxford [Oxford]

Subjects
0301 basic medicine, Microcephaly, Microcefalia / embriologia, [SDV]Life Sciences [q-bio], Brasil / epidemiologia, Zika virus, Disease Outbreaks, 0302 clinical medicine, Aedes, Pregnancy, Molecular clock, Phylogeny, Molecular Epidemiology, Travel, Multidisciplinary, biology, Zika Virus Infection, Incidence (epidemiology), Incidence, 3. Good health, RNA, Viral, Female, Zika V?rus, Malforma??es cong?nitas, 030231 tropical medicine, Molecular Sequence Data, Context (language use), Genome, Viral, Pacific Islands, Article, Evolu??o Molecular, 03 medical and health sciences, Microcefalia, Genoma Viral, medicine, Animals, Humans, Epidemiologia, Molecular epidemiology, Infec??o pelo Zika virus / transmiss?o, Sequence Analysis, RNA, Outbreak, Zika Virus, biology.organism_classification, medicine.disease, Zika virus / gen?tica, Virology, Insect Vectors, 030104 developmental biology, Gen?tica, Mutation, Americas
Abstract

Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro de Inova??es Tecnol?gicas. Ananindeua, PA, Brazil / University of Oxford. Department of Zoology. Oxford, UK. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. University of Oxford. Department of Zoology. Oxford, UK. Universidade de S?o Paulo. Instituto Adolfo Lutz. S?o Paulo, SP, Brasil. Universidade de S?o Paulo. Instituto Adolfo Lutz. S?o Paulo, SP, Brasil. University of Oxford. Department of Zoology. Oxford, UK. University of Oxford. Department of Zoology. Oxford, UK. University of Oxford. Wellcome Trust Centre for Human Genetics. Oxford, UK. University of Oxford. Wellcome Trust Centre for Human Genetics. Oxford, UK. Universidade de S?o Paulo. Instituto Adolfo Lutz. S?o Paulo, SP, Brasil. Universidade de S?o Paulo. Instituto Adolfo Lutz. S?o Paulo, SP, Brasil. Universidade de S?o Paulo. Instituto Adolfo Lutz. S?o Paulo, SP, Brasil. Universidade de S?o Paulo. Instituto Adolfo Lutz. S?o Paulo, SP, Brasil. Universidade de S?o Paulo. Instituto Adolfo Lutz. S?o Paulo, SP, Brasil. Universidade de S?o Paulo. Instituto Adolfo Lutz. S?o Paulo, SP, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. University of Oxford. Department of Zoology. Oxford, UK / Metabiota. San Francisco, CA 94104, USA. University of Oxford. Department of Zoology. Oxford, UK. University of Oxford. Department of Zoology. Oxford, UK. Funda??o Oswaldo Cruz. Salvador, BA, Brasil. Universidade Estadual de Feira de Santana, Feira de Santana. Departamento de Sa?de. Centro de P?s-Gradua??o em Sa?de Coletiva. Feira de Santana, BA, Brasil. Funda??o Oswaldo Cruz. Salvador, BA, Brasil. University of Washington. Institute for Health Metrics and Evaluation,. Seattle, WA, USA / University of Oxford. Wellcome Trust Centre for Human Genetics. Oxford, UK. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro de Inova??es Tecnol?gicas. Ananindeua, PA, Brasil Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro de Inova??es Tecnol?gicas. Ananindeua, PA, Brasil Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro de Inova??es Tecnol?gicas. Ananindeua, PA, Brasil Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro de Inova??es Tecnol?gicas. Ananindeua, PA, Brasil Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro de Inova??es Tecnol?gicas. Ananindeua, PA, Brasil Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro de Inova??es Tecnol?gicas. Ananindeua, PA, Brasil Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro de Inova??es Tecnol?gicas. Ananindeua, PA, Brasil Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro de Inova??es Tecnol?gicas. Ananindeua, PA, Brasil Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro de Inova??es Tecnol?gicas. Ananindeua, PA, Brasil Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil. Li Ka Shing Knowledge Institute. St. Michael?s Hospital. Toronto, Canada / University of Toronto. Department of Medicine. Division of Infectious Diseases. Toronto, Canada. University of Toronto.Dalla Lana School of Public Health. Toronto, Canada; Brasil. Minist?rio da Sa?de. Bras?lia, DF, Brasil. Brasil. Minist?rio da Sa?de. Bras?lia, DF, Brasil. University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA. University of Oxford. Department of Zoology. Oxford, UK / Metabiota. San Francisco, CA 94104, USA. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas, Centro de Inova??o tecnol?gica. Ananindeua, PA, Brasil / University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil 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. Using next generation sequencing we generated 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. Phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, estimated to have occurred between May-Dec 2013, more than 12 months prior to the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV endemic areas, and with reported outbreaks in 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 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 in the Americas of this emerging virus.

Published
2016

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