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1. Risk factors associated with in-hospital mortality during yellow fever outbreak in Brazil

Author

Max McClure, Izabela Maurício de Rezende, Leonardo Soares Pereira, Maria Rita Teixeira Dutra, Jordana Rodrigues Barbosa Fradico, Rodrigo Macedo, Marcelle Cardoso Marçal, Lívia Soares Coelho Fonte Boa, Alexandre Maurício Castro Bragato, Flávio Augusto de Almeida Faria, Livia Pamplona, Rodrigo Fabiano do Carmo Said, Carlos Eduardo Calzavara-Silva, Dario Brock Ramalho, Cintia Lopes de Brito Magalhães, Pedro Augusto Alves, Thaysa Drummond Palmeira Gama, Gláucia Fernandes Cota, Thomas P. Monath, Olindo Assis Martins-Filho, Marcelo Antônio Pascoal-Xavier, Andrea Teixeira-Carvalho, Betânia Paiva Drumond, A. Desiree LaBeaud, Yellow Fever Collaborative Group, Argus Leão Araújo, Barbara Lenoir, Bruno Dala Vedova Gomes Beato, Carolina Lins Rodrigues Vieira, Daniel Vitor de Vasconcelos Santos, Flavia Mansur Starling, Gabriela Miana de Mattos Paixão, Indiara Penido, Izabela Aparecida Coelho, Leandro Henrique Malta Cunha, Letícia Menezes, Livia Frota Rabelo, Letícia Lemos Jardim, Lívia Fulgêncio da Cunha Melo, Lívia Zignago Moreira dos Santos, Ludmila de Paula, Luísa Lages de Abre Paladino, Natalia Soares Albuquerque, Simone Lopes Oliveira Lemos, and Tayrine Araújo

Subjects
yellow fever, yellow fever virus, mortality, clinical management, Brazil, Medicine (General), R5-920
Abstract

ObjectiveTo characterize the clinical manifestations of yellow fever disease and identify risk factors for mortality.MethodsA retrospective study was conducted in the referral center for infectious diseases (Hospital Eduardo de Menezes-HEM) in Belo Horizonte, Minas Gerais, Brazil. Analysis included data from 283 patients with confirmed YF infection older than 13 years old who presented to HEM between January 2017 and June 2018. In-hospital mortality (hypothesis formulated after data collection), demographic factors and clinical and laboratory assessments were used.ResultsStudy patients were mainly men (87.6%), with a median age of 46.0 (IQR 36.5, 57.0). 131 (46.3%) patients were admitted to the ICU, and 62 (22.0%) used invasive mechanical ventilation for a median of 2 days (IQR 1, 3). The median (IQR) total length of stay (LOS) in the ICU was 6 days (IQR 4, 8). The in-hospital mortality rate was 24.0%. Age was significantly higher in fatal (median 49.5, IQR 41.0, 61.0]) than in non-fatal cases [46 (36, 55)] (p < 0.01). Male sex was associated with an increased risk of death (RR 4.66, 95% CI 1.19, 18.2; p < 0.01). Most common symptoms and signs on admission to HEM were fever (31.9%), myalgia (27.8%), jaundice (24.3%), headache (23.9%), abdominal pain (16.1%), vomiting (12.2%), weakness (10.4%), and arthralgias (10.0%). Initial viral load above the cutoff of 4.45 log10 copies/mL was significantly associated with death prior to discharge (OR 12.2; CI 2.83, 92.3). Five factors were significantly related to increased odds of death prior to discharge: log-transformed AST (OR 3.65; CI 2.02, 7.81; p < 0.001), log-transformed INR (OR 7.40; CI 1.31, 33.0; p = 0.010), log-transformed lactate (OR 4.57; CI 1.48, 17.1; p = 0.013), log-transformed WBC (OR 4.33; CI 1.19, 18.5; p = 0.034), and age (OR 1.06; CI 1.01, 1.12; p = 0.026).Conclusions and relevanceAST, INR, lactate, WBC, and age are statistically associated with death prior to discharge in YF patients. These clinical markers should be applied to improve patient screening and management during future YF epidemics.

Published
2025
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2. Haemagogus leucocelaenus and Haemagogus janthinomys are the primary vectors in the major yellow fever outbreak in Brazil, 2016–2018

Author

Filipe Vieira Santos de Abreu, Ieda Pereira Ribeiro, Anielly Ferreira-de-Brito, Alexandre Araujo Cunha dos Santos, Rafaella Moraes de Miranda, Iule de Souza Bonelly, Maycon Sebastião Alberto Santos Neves, Maria Ignez Bersot, Taissa Pereira dos Santos, Marcelo Quintela Gomes, José Luis da Silva, Alessandro Pecego Martins Romano, Roberta Gomes Carvalho, Rodrigo Fabiano do Carmo Said, Mario Sergio Ribeiro, Roberto da Costa Laperrière, Eduardo Oyama Lins Fonseca, Aloísio Falqueto, Christophe Paupy, Anna-Bella Failloux, Sara Moutailler, Marcia Gonçalves de Castro, Mariela Martínez Gómez, Monique de Albuquerque Motta, Myrna Cristina Bonaldo, and Ricardo Lourenço-de-Oliveira

Subjects
Yellow fever, Atlantic forest, Haemagogus, Aedes, Sabethes, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

ABSTRACTThe yellow fever virus (YFV) caused a severe outbreak in Brazil in 2016–2018 that rapidly spread across the Atlantic Forest in its most populated region without viral circulation for almost 80 years. A comprehensive entomological survey combining analysis of distribution, abundance and YFV natural infection in mosquitoes captured before and during the outbreak was conducted in 44 municipalities of five Brazilian states. In total, 17,662 mosquitoes of 89 species were collected. Before evidence of virus circulation, mosquitoes were tested negative but traditional vectors were alarmingly detected in 82% of municipalities, revealing high receptivity to sylvatic transmission. During the outbreak, five species were found positive in 42% of municipalities. Haemagogus janthinomys and Hg. leucocelaenus are considered the primary vectors due to their large distribution combined with high abundance and natural infection rates, concurring together for the rapid spread and severity of this outbreak. Aedes taeniorhynchus was found infected for the first time, but like Sabethes chloropterus and Aedes scapularis, it appears to have a potential local or secondary role because of their low abundance, distribution and infection rates. There was no evidence of YFV transmission by Aedes albopictus and Aedes aegypti, although the former was the most widespread species across affected municipalities, presenting an important overlap between the niches of the sylvatic vectors and the anthropic ones. The definition of receptive areas, expansion of vaccination in the most affected age group and exposed populations and the adoption of universal vaccination to the entire Brazilian population need to be urgently implemented.

Published
2019
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3. CCL3, CCL5, IL-15, IL-1Ra and VEGF compose a reliable algorithm to discriminate classes of adverse events following 17DD-YF primary vaccination according to cause-specific definitions

Author

Marília Lima Cruz Rocha, Eva Lídia Arcoverde Medeiros, Izabela Maurício de Rezende, Valeria Valim, Maira Alves Pereira, Matheus de Souza Gomes, Ana Carolina Campi-Azevedo, Daniel Garkauskas Ramos, Josiane Dias Gusmão, Maria Auxiliadora-Martins, Talita Émile Ribeiro Adelino, Regina Coeli Magalhães Rodrigues, Marcos Vieira Silva, Andréa Teixeira-Carvalho, Francieli Fontana Sutile Tardetti Fantinato, Alessandro Pecego Martins Romano, Laurence Rodrigues do Amaral, Rodrigo Fabiano do Carmo Said, Glauco de Carvalho Pereira, Sandra Carvalho, Eder Gatti Fernandes, Jordana Rodrigues Barbosa Fradico, Jordana Grazziela Alves Coelho-dos-Reis, Elaine Spezialli Faria, Betânia Paiva Drumond, Vanessa Peruhype-Magalhães, Janaina Fonseca Almeida, Felipe Campos de Melo Iani, José Geraldo Leite Ribeiro, Roberta Barros da Silva, and Olindo Assis Martins-Filho

Subjects
Vascular Endothelial Growth Factor A, VEGF receptors, 030231 tropical medicine, CCL3, Reference range, CCL5, BIOMARCADORES, 03 medical and health sciences, 0302 clinical medicine, Serum biomarkers, Yellow Fever, Humans, Medicine, 030212 general & internal medicine, Adverse effect, Chemokine CCL5, Interleukin-15, General Veterinary, General Immunology and Microbiology, biology, business.industry, Vaccination, Yellow Fever Vaccine, Public Health, Environmental and Occupational Health, Interleukin 1 Receptor Antagonist Protein, Infectious Diseases, Interleukin 15, biology.protein, Molecular Medicine, Differential diagnosis, business, Algorithm, Algorithms
Abstract

In the present study, a range of serum biomarkers were quantified in suspected cases of adverse events following YF immunization (YEL-AEFI) to propose a reliable laboratorial algorithm to discriminate confirmed YEL-AEFI (“A1” class) from cases with other illnesses (“C” class). Our findings demonstrated that increased levels of CXCL8, CCL2, CXCL10, IL-1β, IL-6 and TNF-α were observed in YEL-AEFI (“A1” and “C” classes) as compared to primary vaccines without YEL-AEFI [PV(day 3–28)] and reference range (RR) controls. Notably, increased levels of CCL3, CCL4, CCL2, CCL5, IL-1β, IL-15, IL-1Ra and G-CSF were found in “A1” as compared to “C” class. Venn diagrams analysis allowed the pre-selection of biomarkers for further analysis of performance indices. Data demonstrated that CCL3, CCL5, IL-15 and IL-1Ra presented high global accuracy (AUC = 1.00) to discriminate “A1” from “C”. Decision tree was proposed with a reliable algorithm to discriminate YEL-AEFI cases according to cause-specific definitions with outstanding overall accuracy (91%). CCL3, CCL5, IL-15 and IL-1Ra appears as root attributes to identify “A1” followed by VEGF as branch nodes to discriminate Wild Type YFV infection (“C(WT-YFV)”) from cases with other illnesses (“C*”). Together, these results demonstrated the applicability of serum biomarker measurements as putative parameters towards the establishment of accurate laboratorial tools for complementary differential diagnosis of YEL-AEFI cases.

Published
2021
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4. Yellow fever transmission in non-human primates, Bahia, Northeastern Brazil

Author

Leandro Ferraz Oliveira Santos, Alessandro Pecego Martins Romano, Jaqueline Goes de Jesus, Allison Fabri, Vagner Fonseca, Joilson Xavier, Mirza de Carvalho Santana Cordeiro, Roberto Fonseca dos Santos, Adeilde do Socorro Guedes, Neuza Santos de Jesus Silva, Arabela Leal e Silva de Mello, Sintia Sacramento Cerqueira Torquato, Jeane Magnavita da Fonseca Cerqueira, Pedro Macedo da Silva Filho, André Luiz de Abreu, Ademilson Brás Alves, Rosemary Sarmento Oitiçica Dourado, Julien Thézé, Maricelia Lima Maia, Felicidade Mota Pereira, Marta Giovanetti, Nuno R. Faria, Maria Angélica Mares-Guia, Ana Maria Bispo de Filippis, Luciana Reboredo de Oliveira da Silva, Tiago Gräf, Leandro Abade, Zuinara Pereira Gusmão Maia, Carlos F. Campelo de Albuquerque, Julio Croda, Rodrigo Fabiano do Carmo Said, Eloisa Bahia Santana, Gabriel Muricy Cunha, Jananci Xavier Gomes Cerqueira, Luiz Carlos Junior Alcantara, Instituto Gonçalo Moniz, Partenaires INRAE, Department of Infectious Diseases, Istituto Superiore di Sanita [Rome], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Universidade Federal de Minas Gerais, Department of Zoology, 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), Coordenação Geral de Vigilância de Arboviroses (CGARB), Wellcome Trust, and Medical Research Council-São Paulo Research Foundation (FAPESP)

Subjects
0301 basic medicine, Epidemiology, [SDV]Life Sciences [q-bio], RC955-962, Disease Vectors, Mosquitoes, Geographical locations, Animal Diseases, 0302 clinical medicine, Medical Conditions, Arctic medicine. Tropical medicine, Genotype, Medicine and Health Sciences, Alouatta, 11 Medical and Health Sciences, Phylogeny, Data Management, Mammals, Mammalian Genomics, Phylogenetic tree, Transmission (medicine), Yellow fever, Eukaryota, Callithrix, Phylogenetic Analysis, Genomics, 3. Good health, Phylogenetics, Insects, Infectious Diseases, Vertebrates, Public aspects of medicine, RA1-1270, Yellow fever virus, Brazil, Research Article, Primates, medicine.medical_specialty, Computer and Information Sciences, Infectious Disease Control, Arthropoda, 030231 tropical medicine, Genome, Viral, Biology, Disease Surveillance, Epizootics, 03 medical and health sciences, Tropical Medicine, Yellow Fever, medicine, Genetics, Animals, Humans, Evolutionary Systematics, Epizootic, Ecosystem, Taxonomy, Evolutionary Biology, Molecular epidemiology, Public Health, Environmental and Occupational Health, Primate Diseases, Organisms, Outbreak, Biology and Life Sciences, 06 Biological Sciences, South America, medicine.disease, Virology, Invertebrates, Insect Vectors, Species Interactions, 030104 developmental biology, Animal Genomics, Infectious Disease Surveillance, Amniotes, People and places, Zoology, Entomology
Abstract

Yellow fever virus (YFV) causes a clinical syndrome of acute hemorrhagic hepatitis. YFV transmission involves non-human primates (NHP), mosquitoes and humans. By late 2016, Brazil experienced the largest YFV outbreak of the last 100 years, with 2050 human confirmed cases, with 681 cases ending in death and 764 confirmed epizootic cases in NHP. Among affected areas, Bahia state in Northeastern was the only region with no autochthonous human cases. By using next generation sequence approach, we investigated the molecular epidemiology of YFV in NHP in Bahia and discuss what factors might have prevented human cases. We investigated 47 YFV positive tissue samples from NHP cases to generate 8 novel YFV genomes. ML phylogenetic tree reconstructions and automated subtyping tools placed the newly generated genomes within the South American genotype I (SA I). Our analysis revealed that the YFV genomes from Bahia formed two distinct well-supported phylogenetic clusters that emerged most likely of an introduction from Minas Gerais and Espírito Santo states. Vegetation coverage analysis performed shows predominantly low to medium vegetation coverage in Bahia state. Together, our findings support the hypothesis of two independent YFV SA-I introductions. We also highlighted the effectiveness of the actions taken by epidemiological surveillance team of the state to prevented human cases., Author summary Between 2016 and 2018, Brazil witnessed the largest YFV outbreak since years, with 2.154 cases and 745 deaths. Here we report the introduction of the virus in the state of Bahia suggesting two independent introductions from Minas Gerais and Espirito Santo. We also highlight the actions taken by epidemiological surveillance division that may have prevent human infections.

Published
2020
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5. Correction for Giovanetti et al., 'Yellow Fever Virus Reemergence and Spread in Southeast Brazil, 2016-2019'

Author

Marta Giovanetti, Tulio de Oliveira, Rivaldo Venâncio da Cunha, Wanderson Kleber de Oliveira, Carlos Fernandes, Vagner Fonseca, Simone Alves Sampaio, Daniel Garkauskas Ramos, Marcos Cesar Lima de Mendonça, Carlos F. Campelo de Alburque, Jaqueline Goes de Jesus, Ana Maria Bispo de Filippis, Alexandre Otavio Chieppe, Shirlei Ferreira Aguiar, Tiago Gräf, Alessandro Pecego Martins Romano, Carolina Cardoso dos Santos, Nuno R. Faria, Maria Angélica Mares-Guia, Luiz Carlos Junior Alcantara, Cintia Damasceno dos Santos Rodrigues, Rodrigo Fabiano do Carmo Said, Patrícia Carvalho de Sequeira, Allison Fabri, Flávia Löwen Levy Chalhoub, Julien Thézé, Joilson Xavier, Fernanda de Bruycker Nogueira, and André Luiz de Abreu

Subjects
Genetic Diversity and Evolution, Virology, Insect Science, Immunology, Yellow fever, medicine, Biology, medicine.disease, Microbiology, Virus
Abstract

The recent reemergence of yellow fever virus (YFV) in Brazil has raised serious concerns due to the rapid dissemination of the virus in the southeastern region. To better understand YFV genetic diversity and dynamics during the recent outbreak in southeastern Brazil, we generated 18 complete and nearly complete genomes from the peak of the epidemic curve from nonhuman primates (NHPs) and human infected cases across the Espírito Santo and Rio de Janeiro states. Genomic sequencing of 18 YFV genomes revealed the estimated timing, source, and likely routes of yellow fever virus transmission and dispersion during one of the largest outbreaks ever registered in Brazil. We showed that during the recent epidemic, YFV was reintroduced from Minas Gerais to the Espírito Santo and Rio de Janeiro states multiple times between 2016 and 2019. The analysis of data from portable sequencing could identify the corridor of spread of YFV. These findings reinforce the idea that continued genomic surveillance strategies can provide information on virus genetic diversity and transmission dynamics that might assist in understanding arbovirus epidemics. IMPORTANCE Arbovirus infections in Brazil, including yellow fever, dengue, zika, and chikungunya, result in considerable morbidity and mortality and are pressing public health concerns. However, our understanding of these outbreaks is hampered by the limited availability of genomic data. In this study, we investigated the genetic diversity and spatial distribution of YFV during the current outbreak by analyzing genomic data from areas in southeastern Brazil not covered by other previous studies. To gain insights into the routes of YFV introduction and dispersion, we tracked the virus by sequencing YFV genomes sampled from nonhuman primates and infected patients from the southeastern region. Our study provides an understanding of how YFV initiates transmission in new Brazilian regions and illustrates that genomics in the field can augment traditional approaches to infectious disease surveillance and control.

Published
2020

6. Yellow Fever Virus Genotyping Tool and Investigation of Suspected Adverse Events Following Yellow Fever Vaccination

Author

Carlos Eduardo Calzavara, Betânia Paiva Drumond, Rodrigo Fabiano do Carmo Said, Gabriela Fernanda Garcia Oliveira, Olindo Assis Martins-Filho, Andréa Teixeira-Carvalho, Ana Carolina Campi-Azevedo, Renata Santos Tourinho, Erna Geessien Kroon, Izabela Maurício de Rezende, Valeria Valim, Andreza Parreiras Gonçalves, Leonardo Soares Pereira, Pedro Augusto Alves, Maria Rita Teixeira Dutra, Matheus Soares Arruda, and Jaquelline Germano de Oliveira

Subjects
0301 basic medicine, 030106 microbiology, Immunology, adverse event, Arbovirus, Virus, Article, yellow fever, 03 medical and health sciences, vaccine, Drug Discovery, Medicine, wild-type virus, Pharmacology (medical), Adverse effect, Genotyping, yellow fever virus, Pharmacology, Attenuated vaccine, business.industry, Yellow fever, immunisation, Outbreak, medicine.disease, YFV-17DD, vaccination, Virology, Vaccination, 030104 developmental biology, Infectious Diseases, arbovirus, genotyping, business
Abstract

The yellow fever (YF) vaccine consists of an attenuated virus, and despite its relative safety, some adverse events following YF vaccination have been described. At the end of 2016, Brazil experienced the most massive sylvatic yellow fever outbreak over the last 70 years and an intense campaign of YF vaccination occurred in Minas Gerais state in Southeast Brazil from 2016 to 2018. The present study aimed to develop a genotyping tool and investigate 21 cases of suspected adverse events following YF vaccination. Initial in silico analyses were performed using partial NS5 nucleotide sequences to verify the discriminatory potential between wild-type and vaccine viruses. Samples from patients were screened for the presence of the YFV RNA, using 5&prime, UTR as the target, and then used for amplification of partial NS5 gene amplification, sequencing, and phylogenetic analysis. Genotyping indicated that 17 suspected cases were infected by the wild-type yellow fever virus, but four cases remained inconclusive. The genotyping tool was efficient in distinguishing the vaccine from wild-type virus, and it has the potential to be used for the differentiation of all yellow fever virus genotypes.

Published
2019

7. Yellow Fever Virus Reemergence and Spread in Southeast Brazil, 2016-2019

Author

Marta Giovanetti, Ana Maria Bispo de Filippis, Tulio de Oliveira, Patrícia Carvalho de Sequeira, Jaqueline Goes de Jesus, Luiz Carlos Junior Alcantara, Tiago Gräf, Cintia Damasceno dos Santos Rodrigues, Joilson Xavier, Vagner Fonseca, Nuno R. Faria, Carlos Fernandes, André Luiz de Abreu, Rodrigo Fabiano do Carmo Said, Shirlei Ferreira Aguiar, Alexandre Otavio Chieppe, Alessandro Pecego Martins Romano, Rivaldo Venâncio da Cunha, Marcos Cesar Lima de Mendonça, Fernanda de Bruycker Nogueira, Wanderson Kleber de Oliveira, Carlos F. Campelo de Alburque, Simone Alves Sampaio, Maria Angélica Mares-Guia, Allison Fabri, Flávia Löwen Levy Chalhoub, Julien Thézé, Daniel Garkauskas Ramos, Carolina Cardoso dos Santos, Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Universidade Federal de Minas Gerais, University of KwaZulu-Natal (UKZN), Department of Zoology, University of Cambridge [UK] (CAM), Instituto Gonçalo Moniz, Partenaires INRAE, Coordenação Geral de Vigilância de Arboviroses (CGARB), Coordenação Geral dos Laboratórios de Saúde Pública/Secretaria de Vigilância em Saúde, Ministério da Saúde, (CGLAB/SVS-MS) Brasília, Distrito Federal, Secretaria de em Saúde, Ministério da Saúde (SVS-MS), Brasília, Distrito Federal, Organização Pan-Americana da Saúde/Organização Mundial da Saúde, Brasília, Distrito Federal, Brazil, Laboratório Central de Saúde Pública Noel Nutels (LACEN-RJ), Superintendência de Vigilância do Estado, and Universidade Federal de Mato Grosso do Sul (UFMS)

Subjects
Male, Leontopithecus, Arbovirus Infections, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Immunology, Genomics, Genome, Viral, Mosquito Vectors, Biology, medicine.disease_cause, Microbiology, Arbovirus, Dengue fever, Disease Outbreaks, 03 medical and health sciences, 0302 clinical medicine, Aedes, Virology, Yellow Fever, medicine, Animals, Cebus, Humans, Chikungunya, Author Correction, Alouatta, ComputingMilieux_MISCELLANEOUS, Phylogeny, 030304 developmental biology, 0303 health sciences, Whole Genome Sequencing, Incidence, Yellow fever, Outbreak, Genetic Variation, Callithrix, medicine.disease, 3. Good health, Phylogeography, Infectious disease (medical specialty), Insect Science, Female, Yellow fever virus, Brazil
Abstract

The recent reemergence of yellow fever virus (YFV) in Brazil has raised serious concerns due to the rapid dissemination of the virus in the southeastern region. To better understand YFV genetic diversity and dynamics during the recent outbreak in southeastern Brazil, we generated 18 complete and nearly complete genomes from the peak of the epidemic curve from nonhuman primates (NHPs) and human infected cases across the Espirito Santo and Rio de Janeiro states. Genomic sequencing of 18 YFV genomes revealed the estimated timing, source, and likely routes of yellow fever virus transmission and dispersion during one of the largest outbreaks ever registered in Brazil. We showed that during the recent epidemic, YFV was reintroduced from Minas Gerais to the Espirito Santo and Rio de Janeiro states multiple times between 2016 and 2019. The analysis of data from portable sequencing could identify the corridor of spread of YFV. These findings reinforce the idea that continued genomic surveillance strategies can provide information on virus genetic diversity and transmission dynamics that might assist in understanding arbovirus epidemics.IMPORTANCE Arbovirus infections in Brazil, including yellow fever, dengue, zika, and chikungunya, result in considerable morbidity and mortality and are pressing public health concerns. However, our understanding of these outbreaks is hampered by the limited availability of genomic data. In this study, we investigated the genetic diversity and spatial distribution of YFV during the current outbreak by analyzing genomic data from areas in southeastern Brazil not covered by other previous studies. To gain insights into the routes of YFV introduction and dispersion, we tracked the virus by sequencing YFV genomes sampled from nonhuman primates and infected patients from the southeastern region. Our study provides an understanding of how YFV initiates transmission in new Brazilian regions and illustrates that genomics in the field can augment traditional approaches to infectious disease surveillance and control.

Published
2019
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8. Haemagogus leucocelaenus and Haemagogus janthinomys are the primary vectors in the major yellow fever outbreak in Brazil, 2016-2018

Author

Aloísio Falqueto, Maria Ignez Lima Bersot, Monique de Albuquerque Motta, Anna-Bella Failloux, Ieda Pereira Ribeiro, Mario Sergio Ribeiro, Eduardo Oyama Lins Fonseca, Alessandro Pecego Martins Romano, Iule de Souza Bonelly, Mariela Martínez Gómez, Ricardo Lourenço-de-Oliveira, José Luis da Silva, Taissa Pereira dos Santos, Myrna C. Bonaldo, Rafaella Moraes de Miranda, Roberto da Costa Laperrière, Rodrigo Fabiano do Carmo Said, Christophe Paupy, Márcia Gonçalves de Castro, Anielly Ferreira-de-Brito, Sara Moutailler, Marcelo Quintela Gomes, Alexandre Dos Santos, Roberta Gomes Carvalho, Filipe Vieira Santos de Abreu, Maycon Sebastião Alberto Santos Neves, Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Instituto Federal do Norte de Minas Gerais (IFNMG), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Ministério da Saúde [Brasília, Brazil], Diversity, ecology, evolution & Adaptation of arthropod vectors (MIVEGEC-DEEVA), Evolution des Systèmes Vectoriels (ESV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors, Institut Pasteur [Paris] (IP), Biologie moléculaire et immunologie parasitaires et fongiques (BIPAR), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Acknowledgments to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and the Institut Pasteur - Transversal Research Program for funding this work., Fundação Oswaldo Cruz (FIOCRUZ), Institut Pasteur [Paris], Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Lourenco-de-Oliveira, Ricardo, Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Arbovirus et Insectes Vecteurs, École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, and École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé

Subjects
0301 basic medicine, Male, Aedes albopictus, Epidemiology, [SDV]Life Sciences [q-bio], 030106 microbiology, Immunology, Population Dynamics, education, Zoology, Aedes aegypti, Mosquito Vectors, Biology, Microbiology, sabethes, aedes, haemagogus, atlantic forest, yellow fever, Article, law.invention, Disease Outbreaks, 03 medical and health sciences, Abundance (ecology), law, Aedes, Virology, Drug Discovery, medicine, Animals, Haemagogus, Cities, ComputingMilieux_MISCELLANEOUS, Yellow fever, Outbreak, General Medicine, medicine.disease, biology.organism_classification, 3. Good health, Phylogeography, 030104 developmental biology, Infectious Diseases, Transmission (mechanics), Sabethes, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Parasitology, Female, Atlantic forest, Yellow fever virus, Brazil
Abstract

International audience; The yellow fever virus (YFV) caused a severe outbreak in Brazil in 2016-2018 that rapidly spread across the Atlantic Forest in its most populated region without viral circulation for almost 80 years. A comprehensive entomological survey combining analysis of distribution, abundance and YFV natural infection in mosquitoes captured before and during the outbreak was conducted in 44 municipalities of five Brazilian states. In total, 17,662 mosquitoes of 89 species were collected. Before evidence of virus circulation, mosquitoes were tested negative but traditional vectors were alarmingly detected in 82% of municipalities, revealing high receptivity to sylvatic transmission. During the outbreak, five species were found positive in 42% of municipalities. Haemagogus janthinomys and Hg. leucocelaenus are considered the primary vectors due to their large distribution combined with high abundance and natural infection rates, concurring together for the rapid spread and severity of this outbreak. Aedes taeniorhynchus was found infected for the first time, but like Sabethes chloropterus and Aedes scapularis, it appears to have a potential local or secondary role because of their low abundance, distribution and infection rates. There was no evidence of YFV transmission by Aedes albopictus and Aedes aegypti, although the former was the most widespread species across affected municipalities, presenting an important overlap between the niches of the sylvatic vectors and the anthropic ones. The definition of receptive areas, expansion of vaccination in the most affected age group and exposed populations and the adoption of universal vaccination to the entire Brazilian population need to be urgently implemented.

Published
2019
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9. Genomic and epidemiological monitoring of yellow fever virus transmission potential

Author

Marcos Cesar Lima de Mendonça, Maira Alves Pereira, Mariana Sequetin Cunha, Mariane Talon de Menezes, Ester Cerdeira Sabino, Deise Aparecida dos Santos, Giliane de Souza Trindade, Juliana Silva Nogueira, Felipe Campos de Melo Iani, Rodrigo Dias de Oliveira Carvalho, Guy Baele, Erna Geessien Kroon, Talita Émile Ribeiro Adelino, Alexandre Otavio Chieppe, Betânia Paiva Drumond, Simon Dellicour, Maria Angelica Mares Guia, Nuno R. Faria, Kuiama Lewandowski, Izabela Maurício de Rezende, Ludmila Ferraz de Santana, William Wint, Ricardo Gadelha de Abreu, Julien Thézé, André Luis de Abreu, Jaqueline Goes de Jesus, Tetyana I. Vasylyeva, Vagner Fonseca, Shirley Vasconcelos Komninakis, Marcos Vieira Silva, Carlos Frederico Campelo de Albuquerque, Renato S. Aguiar, Miles W. Carroll, Sarah C. Hill, Freya M Shearer, Paola P. Silveira, D. Yi, Moritz U. G. Kraemer, Luiz Carlos Junior Alcantara, Joshua Quick, Vasco Azevedo, L. du Plessis, Érica Munhoz de Mello, T. de Oliveira, Philippe Lemey, Carolina Cardoso dos Santos, Daniel J. Weiss, José Lourenço, Leandro Abade, Patrícia Carvalho de Sequeira, Oliver G. Pybus, Lívia Sacchetto, Rita Maria Ribeiro Nogueira, Osnei Okumoto, Rodrigo Fabiano do Carmo Said, Monica B. Arruda, Ana Maria Bispo de Filippis, Poliana de Oliveira Figueiredo, Uri Obolski, Iray Maria Rocco, Chieh-Hsi Wu, Eliane Saraiva Machado de Araújo, Rodrigo Brindeiro, Renato Pereira de Souza, Birgit Nikolay, Marta Giovanetti, Simon Cauchemez, Nicholas J. Loman, Mariana Gontijo de Brito, Sebastian Funk, Steven T. Pullan, Cintia Damasceno dos Santos Rodrigues, Joilson Xavier, Gavin Pereira, A. C. da Costa, Marcio Henrique de Oliveira Garcia, Amilcar Tanuri, Marc A. Suchard, Fabiana Cristina Pereira dos Santos, Marcela Lencine Ferraz, Marluce Aparecida Assunção Oliveira, University of Oxford, Laboratório de Biologia Molecular de Flavivírus [Rio de Janeiro], Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Universidade Federal do Rio de Janeiro (UFRJ), Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), London School of Hygiene and Tropical Medicine (LSHTM), Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Universidade Federal de Minas Gerais [Belo Horizonte] (UFMG), University of Oxford [Oxford], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz (FIOCRUZ), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Virus transmission, Spatial expansion, [SDV]Life Sciences [q-bio], Polymerase Chain Reaction, law.invention, Disease Outbreaks, 0302 clinical medicine, law, Aedes, 2.2 Factors relating to the physical environment, Aetiology, Phylogeny, Multidisciplinary, Yellow fever, Age Factors, Genomics, Sciences bio-médicales et agricoles, 3. Good health, Transmission (mechanics), Infectious Diseases, Epidemiological Monitoring, Yellow fever virus, Early phase, Infection, Brazil, Risk, Evolution, General Science & Technology, 030231 tropical medicine, Biology, Age and sex, Vaccine Related, Evolution, Molecular, 03 medical and health sciences, Rare Diseases, Sex Factors, Spatio-Temporal Analysis, Biodefense, Yellow Fever, medicine, Genetics, Animals, Humans, Prevention, Molecular, biology.organism_classification, medicine.disease, Virology, 030104 developmental biology, Emerging Infectious Diseases, BRASIL
Abstract

The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics., info:eu-repo/semantics/published

Published
2018
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