Reemergence of yellow fever virus in southeastern Brazil, 2017-2018: what sparked the spread?

AbstractBackgroundThe 2017-2018 yellow fever virus (YFV) outbreak in southeastern Brazil marked a reemergence of YFV in urban states that had been YFV free for nearly a century. Unlike earlier urban YFV transmission, this epidemic was also driven by forest mosquitos. The objective of this study was to evaluate environmental drivers of this outbreak.Methodology/Principal FindingsUsing surveillance data from the Brazilian Ministry of Health of human and non-human primate (NHP) cases of yellow fever, we traced the spatiotemporal progression of the outbreak. We then assessed the epidemic timing in relation to drought using a monthly Standardized Precipitation Evapotranspiration Index (SPEI). Lastly, we evaluated demographic risk factors for rural or outdoor exposure amongst YFV cases. Both human and NHP cases were first identified in a hot, dry, rural area in northern Minas Gerais before spreading southeast into the more cool, wet urban states of Espírito Santo, São Paulo, and Rio de Janeiro. Outbreaks also coincided with drought in all four southeastern states of Brazil. Confirmed YFV cases had an increased odds of being male (OR 2.58; 95% CI 2.28-2.92), working age (OR: 2.03; 95% CI: 1.76-2.35), and reporting recent travel from an urban to a rural area (OR: 5.02; 95% CI: 3.76-6.69).Conclusions/SignificanceThe 2017-2018 YFV epidemic in Brazil originated in hot, dry rural areas of Minas Gerais before expanding south into urban centers. An unusually severe drought in this region may have created environmental pressures that sparked the reemergence of YFV in Brazil’s southeastern cities.Author SummaryIn 2017-2018, cities in southeastern Brazil experienced an unusual outbreak of yellow fever virus. In the early 20th century, these cities had large outbreaks of yellow fever, spread by Aedes mosquitos. But until this recent outbreak, they had been free of yellow fever for nearly a century. While this outbreak was spread by Haemagogous forest mosquitos, the reemergence of yellow fever in densely populated urban areas raises serious concerns about it reestablishing ongoing transmission in cities, spread by urban Aedes mosquitos. Our study sought to understand how and why yellow fever virus remerged in this area. We traced the outbreak, finding that it started in hot, dry, rural areas and spread south into cool, wet urban areas. Additionally, the outbreak coincided with a severe drought; this extreme weather may have promoted the spread of yellow fever. Infection was also associated with rural and outdoor exposure, further suggesting this epidemic originated in rural areas.

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Yellow Fever Virus Reemergence and Spread in Southeast Brazil, 2016–2019

Journal of Virology ◽

10.1128/jvi.01623-19 ◽

2019 ◽

Vol 94 (1) ◽

Cited By ~ 8

Author(s):

Marta Giovanetti ◽

Marcos Cesar Lima de Mendonça ◽

Vagner Fonseca ◽

Maria Angélica Mares-Guia ◽

Allison Fabri ◽

...

Keyword(s):

Genetic Diversity ◽

Yellow Fever ◽

Rio De Janeiro ◽

Nonhuman Primates ◽

Yellow Fever Virus ◽

Genomic Data ◽

Fever Virus ◽

Southeastern Brazil ◽

Espirito Santo ◽

Southeastern Region

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.

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Genomic evidence of yellow fever virus in Aedes scapularis, southeastern Brazil, 2016

Acta Tropica ◽

10.1016/j.actatropica.2020.105390 ◽

2020 ◽

Vol 205 ◽

pp. 105390 ◽

Cited By ~ 1

Author(s):

Mariana Sequetin Cunha ◽

Nuno Rodrigues Faria ◽

Giovana Santos Caleiro ◽

Darlan Silva Candido ◽

Sarah C. Hill ◽

...

Keyword(s):

Yellow Fever ◽

Yellow Fever Virus ◽

Fever Virus ◽

Southeastern Brazil

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Flight Height Preference for Oviposition of Mosquito (Diptera: Culicidae) Vectors of Sylvatic Yellow Fever Virus Near the Hydroelectric Reservoir of Simplício, Minas Gerais, Brazil

Journal of Medical Entomology ◽

10.1603/me12120 ◽

2013 ◽

Vol 50 (4) ◽

pp. 791-795 ◽

Cited By ~ 11

Author(s):

Jeronimo Alencar ◽

Fernanda Morone ◽

Cecília Ferreira De Mello ◽

Nicolas Dégallier ◽

Paulo Sérgio Lucio ◽

...

Keyword(s):

Yellow Fever ◽

Yellow Fever Virus ◽

Minas Gerais ◽

Fever Virus ◽

Hydroelectric Reservoir ◽

Flight Height

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Potential of Aedes albopictus and Aedes aegypti (Diptera: Culicidae) to transmit yellow fever virus in urban areas in Central Africa

Emerging Microbes & Infections ◽

10.1080/22221751.2019.1688097 ◽

2019 ◽

Vol 8 (1) ◽

pp. 1636-1641 ◽

Cited By ~ 6

Author(s):

Basile Kamgang ◽

Marie Vazeille ◽

Aurélie P. Yougang ◽

Armel N. Tedjou ◽

Theodel A. Wilson-Bahun ◽

...

Keyword(s):

Aedes Aegypti ◽

Yellow Fever ◽

Aedes Albopictus ◽

Urban Areas ◽

Yellow Fever Virus ◽

Central Africa ◽

Fever Virus

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Fast surveillance response and genome sequencing reveals the circulation of a new Yellow Fever Virus sublineage in 2021, in Minas Gerais, Brazil

10.1101/2021.11.24.469129 ◽

2021 ◽

Author(s):

Miguel Souza Andrade ◽

Fabricio Souza Campos ◽

Cirilo Henrique Oliveira ◽

Ramon Silva Oliveira ◽

Aline Alves Scarpellini Campos ◽

...

Keyword(s):

Genome Sequencing ◽

Yellow Fever ◽

Yellow Fever Virus ◽

Minas Gerais ◽

Amazon Region ◽

The State ◽

Fever Virus ◽

Sylvatic Cycle ◽

Viral Genomes ◽

A Genome

Yellow fever virus (YFV) exhibits a sylvatic cycle of transmission involving wild mosquitoes and non-human primates (NHP). In Brazil, YFV is endemic in the Amazon region, from where waves of epidemic expansion towards other Brazilian states eventually occur. During such waves, the virus usually follows the route from North to the Central-West and Southeast Brazilian regions. Amidst these journeys, outbreaks of Yellow Fever (YF) in NHPs, with spillovers to humans have been observed. In the present work, we describe a surveillance effort encompassing the technology of smartphone applications and the coordinated action of several research institutions and health services that succeeded in the first confirmation of YFV in NHPs in the state of Minas Gerais (MG), Southeast region, in 2021, followed by genome sequencing in an interval of only ten days. Samples from two NHPs (one of the species Alouatta caraya in the municipality of Icarai de Minas and other of the species Callithrix penicillata in the municipality of Ubai) were collected and the presence of YFV was confirmed by RT-qPCR. We generated three near-complete and one partial-genome by Nanopore sequencer MinION. Phylogenetic analysis revealed that all viral genomes recovered are equal and related to lineage South America 1, clustering with a genome detected in the Amazon region (Para state) in 2017. These findings reveal the occurrence of a new wave of viral expansion in MG, six years after detection in the state of Para in 2015, with no human outbreaks to date reported. Coordinated work between local surveillance and support laboratories has been of major importance to ensure a quick response and implementation of contingency measures towards avoiding the occurrence of YF cases in humans.

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Yellow fever virus spread in Rio de Janeiro and Espírito Santo, 2016-2019: Phylodynamic assessment to improve intervention strategies

10.1101/711994 ◽

2019 ◽

Cited By ~ 1

Author(s):

Marta Giovanetti ◽

Marcos Cesar Lima de Mendonça ◽

Vagner Fonseca ◽

Maria Angélica Mares-Guia ◽

Allison Fabri ◽

...

Keyword(s):

Public Health ◽

Real Time ◽

Yellow Fever ◽

Rio De Janeiro ◽

Yellow Fever Virus ◽

Fever Virus ◽

Southeastern Brazil ◽

Espírito Santo ◽

Espirito Santo ◽

Southeastern Region

ABSTRACTThe recent re-emergence of yellow fever virus (YFV) in Brazil has raised serious concerns due to the virus’ rapid dissemination in the southeastern region. To better understand YFV genetic diversity and dynamics during the recent outbreak in southeastern Brazil we generated 18 complete and near-complete genomes from the peak of the epidemic curve from non-human primates (NHPs) and human infected cases across Espírito Santo and Rio de Janeiro states. Genomic sequencing of 18 YFV genomes revealed the timing, source and likely routes of yellow fever virus transmission and dispersion during the one of the largest outbreaks ever registered in Brazil. We showed that the recent YFV epidemic spillover southwards several times from Minas Gerais to Espírito Santo and Rio de Janeiro states in 2016 to 2019. The quick production and analysis of data from portable sequencing could identify the corridor of spread of YFV. These findings reinforce that real-time and continued genomic surveillance strategies can assist in the monitoring and public health responses of arbovirus epidemics.IMPORTANCEArbovirus 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 limited availability of real time genomic data. In this study, we investigated the genetic diversity and spatial distribution of YFV during the current outbreak in southeastern Brazil. To gain insights into the routes of YFV introduction and dispersion, we tracked the virus by sequencing YFV genomes sampled from non-human 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 near-real time genomics in the field can augment traditional approaches to infectious disease surveillance and control.

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Detection of Yellow Fever Virus in Sylvatic Mosquitoes during Disease Outbreaks of 2017–2018 in Minas Gerais State, Brazil

Insects ◽

10.3390/insects10050136 ◽

2019 ◽

Vol 10 (5) ◽

pp. 136 ◽

Cited By ~ 5

Author(s):

Guilherme Garcia Pinheiro ◽

Marcele Neves Rocha ◽

Maria Angélica de Oliveira ◽

Luciano Andrade Moreira ◽

José Dilermando Andrade Filho

Keyword(s):

Yellow Fever ◽

Yellow Fever Virus ◽

Disease Outbreaks ◽

Minas Gerais ◽

Fever Virus ◽

Metropolitan Region ◽

Pcr Analysis ◽

Urban Centers ◽

Conservation Units ◽

Belo Horizonte

Brazil has experienced several arbovirus outbreaks in recent years, among which yellow fever stands out. The state of Minas Gerais faced outbreaks of sylvatic yellow fever in 2017 and 2018, with 1002 confirmed cases and 340 deaths. This work presents the results of survey efforts to detect the yellow fever virus in mosquitoes from two conservation areas in the metropolitan region of Belo Horizonte, Brazil. A total of 867 mosquitoes of 20 species were collected between September 2017 and May 2018, the most abundant being Psorophora (Janthinosoma) ferox (von Humboldt, 1819) (31.3%), Limatus durhamii Theobald, 1901 (19.1%) and Haemagogus (Haemagogus) janthinomys Dyar, 1921 (18.2%). Total RNA was extracted from the mosquitoes for real-time PCR analysis for yellow fever, chikungunya, mayaro, Zika and dengue viruses. The yellow fever infection rate was 8.2% for Hg. janthinomys (13 mosquitoes), which is the main vector of sylvatic yellow fever in Brazil. In addition to surveying the mosquito fauna of these conservation units, this work demonstrates the importance of monitoring the circulation of viruses near large urban centers.

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Neighbor danger: Yellow fever virus epizootics in urban and urban-rural transition areas of Minas Gerais state, during 2017-2018 yellow fever outbreaks in Brazil

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0008658 ◽

2020 ◽

Vol 14 (10) ◽

pp. e0008658

Author(s):

Lívia Sacchetto ◽

Natalia Ingrid Oliveira Silva ◽

Izabela Maurício de Rezende ◽

Matheus Soares Arruda ◽

Thais Alkifeles Costa ◽

...

Keyword(s):

Yellow Fever ◽

Yellow Fever Virus ◽

Minas Gerais ◽

Fever Virus ◽

Minas Gerais State ◽

Urban Rural ◽

Rural Transition ◽

Transition Areas

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Machine learning models exploring characteristic single-nucleotide signatures in Yellow Fever Virus

10.1101/2021.03.23.436688 ◽

2021 ◽

Author(s):

Álvaro Salgado ◽

Raquel Minardi ◽

Marta Giovanetti ◽

Adriano Veloso ◽

Francielly Morais-Rodrigues ◽

...

Keyword(s):

Machine Learning ◽

Yellow Fever ◽

Protein Function ◽

Urban Areas ◽

Yellow Fever Virus ◽

Fever Virus ◽

Single Nucleotide ◽

Host Interactions ◽

Human Infections ◽

The Tropics

Yellow fever virus (YFV) is the agent of the most severe mosquito-borne disease in the tropics. Recently, Brazil suffered major YFV outbreaks with a high fatality rate affecting areas where the virus has not been reported for decades, consisting of urban areas where a large number of unvaccinated people live. We developed a machine learning framework combining three different algorithms (XGBoost, random forest and regularized logistic regression). This method was applied to 56 YFV sequences from human infections and 27 from non-human primate (NHPs) infections to investigate the presence of genetic signatures possibly related to disease severity (in human related sequences) and differences in the PCR cycle threshold (Ct) values (in NHP related sequences). Our analyses reveal four non-synonymous single nucleotide variations (SNVs) on sequences from human infections, in proteins NS3 (E614D), NS4a (I69V), NS5 (R727G, V643A) and six non-synonymous SNVs on NHP sequences, in proteins E (L385F), NS1 (A171V), NS3 (I184V) and NS5 (N11S, I374V, E641D). We performed comparative protein structural analysis on these SNVs, describing possible impacts on protein function. Despite the fact that the dataset is limited in size and that this study does not consider virus-host interactions, our work highlights the use of machine learning as a versatile and fast initial approach to genomic data exploration.

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