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Genome analysis of yellow fever virus of the ongoing outbreak in Brazil reveals polymorphisms.

ABSTRACT: The current yellow fever outbreak in Brazil is the most severe one in the country in recent times. It has rapidly spread to areas where YF virus (YFV) activity has not been observed for more than 70 years and vaccine coverage is almost null. Here, we sequenced the whole YFV genome of two naturally infected howler-monkeys (Alouatta clamitans) obtained from the Municipality of Domingos Martins, state of Espírito Santo, Brazil. These two ongoing-outbreak genome sequences are identical. They clustered in the 1E sub-clade (South America genotype I) along with the Brazilian and Venezuelan strains recently characterised from infections in humans and non-human primates that have been described in the last 20 years. However, we detected eight unique amino acid changes in the viral proteins, including the structural capsid protein (one change), and the components of the viral replicase complex, the NS3 (two changes) and NS5 (five changes) proteins, that could impact the capacity of viral infection in vertebrate and/or invertebrate hosts and spreading of the ongoing outbreak.

SUBMITTER: Bonaldo MC

PROVIDER: S-EPMC5446234 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Genome analysis of yellow fever virus of the ongoing outbreak in Brazil reveals polymorphisms.

Bonaldo Myrna C MC Gómez Mariela Martínez MM Dos Santos Alexandre Ac AA Abreu Filipe Vieira Santos de FVS Ferreira-de-Brito Anielly A Miranda Rafaella Moraes de RM Castro Marcia Gonçalves de MG Lourenço-de-Oliveira Ricardo R

Memorias do Instituto Oswaldo Cruz 20170601 6

The current yellow fever outbreak in Brazil is the most severe one in the country in recent times. It has rapidly spread to areas where YF virus (YFV) activity has not been observed for more than 70 years and vaccine coverage is almost null. Here, we sequenced the whole YFV genome of two naturally infected howler-monkeys (Alouatta clamitans) obtained from the Municipality of Domingos Martins, state of Espírito Santo, Brazil. These two ongoing-outbreak genome sequences are identical. They cluster ...[more]

PMID: 28591405

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Project description: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.

Project description: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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Genome analysis of yellow fever virus of the ongoing outbreak in Brazil reveals polymorphisms.

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Genome analysis of yellow fever virus of the ongoing outbreak in Brazil reveals polymorphisms.

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