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2.
Elife ; 72018 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-29336306

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus from camels causing significant mortality and morbidity in humans in the Arabian Peninsula. The epidemiology of the virus remains poorly understood, and while case-based and seroepidemiological studies have been employed extensively throughout the epidemic, viral sequence data have not been utilised to their full potential. Here, we use existing MERS-CoV sequence data to explore its phylodynamics in two of its known major hosts, humans and camels. We employ structured coalescent models to show that long-term MERS-CoV evolution occurs exclusively in camels, whereas humans act as a transient, and ultimately terminal host. By analysing the distribution of human outbreak cluster sizes and zoonotic introduction times, we show that human outbreaks in the Arabian peninsula are driven by seasonally varying zoonotic transfer of viruses from camels. Without heretofore unseen evolution of host tropism, MERS-CoV is unlikely to become endemic in humans.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , Transmissão de Doença Infecciosa , Variação Genética , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Zoonoses/epidemiologia , Zoonoses/transmissão , Animais , Camelus , Análise por Conglomerados , Infecções por Coronavirus/transmissão , Surtos de Doenças , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/classificação , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Epidemiologia Molecular , Filogenia , Análise de Sequência de DNA
3.
Nature ; 544(7650): 309-315, 2017 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-28405027

RESUMO

The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics.


Assuntos
Ebolavirus/genética , Ebolavirus/fisiologia , Genoma Viral/genética , Doença pelo Vírus Ebola/transmissão , Doença pelo Vírus Ebola/virologia , Clima , Surtos de Doenças/estatística & dados numéricos , Ebolavirus/isolamento & purificação , Geografia , Doença pelo Vírus Ebola/epidemiologia , Humanos , Internacionalidade , Modelos Lineares , Epidemiologia Molecular , Filogenia , Viagem/legislação & jurisprudência , Viagem/estatística & dados numéricos
4.
Cell ; 167(4): 1088-1098.e6, 2016 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-27814506

RESUMO

The magnitude of the 2013-2016 Ebola virus disease (EVD) epidemic enabled an unprecedented number of viral mutations to occur over successive human-to-human transmission events, increasing the probability that adaptation to the human host occurred during the outbreak. We investigated one nonsynonymous mutation, Ebola virus (EBOV) glycoprotein (GP) mutant A82V, for its effect on viral infectivity. This mutation, located at the NPC1-binding site on EBOV GP, occurred early in the 2013-2016 outbreak and rose to high frequency. We found that GP-A82V had heightened ability to infect primate cells, including human dendritic cells. The increased infectivity was restricted to cells that have primate-specific NPC1 sequences at the EBOV interface, suggesting that this mutation was indeed an adaptation to the human host. GP-A82V was associated with increased mortality, consistent with the hypothesis that the heightened intrinsic infectivity of GP-A82V contributed to disease severity during the EVD epidemic.


Assuntos
Ebolavirus/genética , Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/virologia , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , África Ocidental/epidemiologia , Substituição de Aminoácidos , Animais , Callithrix , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Cheirogaleidae , Citoplasma/virologia , Ebolavirus/fisiologia , Doença pelo Vírus Ebola/epidemiologia , Humanos , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/metabolismo , Conformação Proteica em alfa-Hélice , Proteínas do Envelope Viral/metabolismo , Vírion/química , Vírion/patogenicidade , Virulência
5.
Int J Infect Dis ; 51: 128-132, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27664930

RESUMO

OBJECTIVES: The recent emergence of Zika in Brazil and its association with an increased rate of congenital malformations has raised concerns over its impact on the birth rate in the country. Using data on the incidence of Zika in 2015-2016 and dengue in 2013 and 2015-2016 for the city of Rio de Janeiro (population 6.4 million), a massive increase of Zika in women compared to men was documented. METHODS: The age-adjusted incidence was compared between men and women. A negative binomial Poisson generalized linear model was fitted to the Zika incidence data to determine the significance of sexual transmission statistically. RESULTS: Even after correcting for the bias due to the systematic testing of pregnant women for Zika, there were found to be 90% more registered cases per 100000 women than men in the sexually active age group (15-65 years); this was not the case for age groups <15 years and >65 years. Assuming that infected men transmit the disease to women in their semen, but that the converse is not true, some extra incidence in women is to be expected. An alternate hypothesis would be that women visit doctors more often than men. To test this, the incidence of dengue fever was compared in men and women in 2015 and in 2013 (before Zika reached Rio de Janeiro): in both years, women were 30% more likely to be reported with dengue. CONCLUSION: Women in the sexually active age group are far more likely to get Zika than men (+90% increase); sexual transmission is the most probable cause. Women in the 15-65 years age group are also 30% more likely to be reported with dengue than men, which is probably due to women being more careful with their health.


Assuntos
Doenças Virais Sexualmente Transmissíveis/epidemiologia , Infecção por Zika virus/epidemiologia , Zika virus/isolamento & purificação , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Gravidez , Fatores Sexuais , Doenças Virais Sexualmente Transmissíveis/transmissão , Doenças Virais Sexualmente Transmissíveis/virologia , Adulto Jovem , Zika virus/fisiologia , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
6.
Science ; 353(6300): 658, 2016 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-27516592

RESUMO

Hoenen et al (Reports, 3 April 2015, p. 117; published online 26 March) suggested that the Ebola virus Makona responsible for the West African epidemic evolved more slowly than previously reported. We show that this was based on corrupted data. An erratum provided a rate compatible with the initial and later, more precise, estimates but did not correctly state the nature of the error.


Assuntos
Ebolavirus/genética , Doença pelo Vírus Ebola/epidemiologia , Genótipo , Humanos , Mali/epidemiologia , Taxa de Mutação
7.
Sci Rep ; 5: 18455, 2015 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-26675824

RESUMO

Quantifying the attack ratio of disease is key to epidemiological inference and public health planning. For multi-serotype pathogens, however, different levels of serotype-specific immunity make it difficult to assess the population at risk. In this paper we propose a Bayesian method for estimation of the attack ratio of an epidemic and the initial fraction of susceptibles using aggregated incidence data. We derive the probability distribution of the effective reproductive number, Rt, and use MCMC to obtain posterior distributions of the parameters of a single-strain SIR transmission model with time-varying force of infection. Our method is showcased in a data set consisting of 18 years of dengue incidence in the city of Rio de Janeiro, Brazil. We demonstrate that it is possible to learn about the initial fraction of susceptibles and the attack ratio even in the absence of serotype specific data. On the other hand, the information provided by this approach is limited, stressing the need for detailed serological surveys to characterise the distribution of serotype-specific immunity in the population.


Assuntos
Teorema de Bayes , Coleta de Dados/estatística & dados numéricos , Vírus da Dengue/crescimento & desenvolvimento , Dengue/epidemiologia , Epidemias , Algoritmos , Brasil/epidemiologia , Simulação por Computador , Coleta de Dados/métodos , Dengue/transmissão , Dengue/virologia , Vírus da Dengue/classificação , Vírus da Dengue/fisiologia , Humanos , Incidência , Modelos Teóricos , Densidade Demográfica , Sorotipagem , Fatores de Tempo
8.
BMC Bioinformatics ; 15: 133, 2014 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-24885610

RESUMO

BACKGROUND: Simulated nucleotide or amino acid sequences are frequently used to assess the performance of phylogenetic reconstruction methods. BEAST, a Bayesian statistical framework that focuses on reconstructing time-calibrated molecular evolutionary processes, supports a wide array of evolutionary models, but lacked matching machinery for simulation of character evolution along phylogenies. RESULTS: We present a flexible Monte Carlo simulation tool, called πBUSS, that employs the BEAGLE high performance library for phylogenetic computations to rapidly generate large sequence alignments under complex evolutionary models. πBUSS sports a user-friendly graphical user interface (GUI) that allows combining a rich array of models across an arbitrary number of partitions. A command-line interface mirrors the options available through the GUI and facilitates scripting in large-scale simulation studies. πBUSS may serve as an easy-to-use, standard sequence simulation tool, but the available models and data types are particularly useful to assess the performance of complex BEAST inferences. The connection with BEAST is further strengthened through the use of a common extensible markup language (XML), allowing to specify also more advanced evolutionary models. To support simulation under the latter, as well as to support simulation and analysis in a single run, we also add the πBUSS core simulation routine to the list of BEAST XML parsers. CONCLUSIONS: πBUSS offers a unique combination of flexibility and ease-of-use for sequence simulation under realistic evolutionary scenarios. Through different interfaces, πBUSS supports simulation studies ranging from modest endeavors for illustrative purposes to complex and large-scale assessments of evolutionary inference procedures. Applications are not restricted to the BEAST framework, or even time-measured evolutionary histories, and πBUSS can be connected to various other programs using standard input and output format.


Assuntos
Evolução Molecular , Análise de Sequência/métodos , Software , Teorema de Bayes , Simulação por Computador , Método de Monte Carlo , Filogenia , Alinhamento de Sequência
9.
PLoS One ; 9(6): e98519, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24897118

RESUMO

The Asian/American (AS/AM) genotype of dengue virus type 2 (DENV-2) has been evolving in the Americas over the last 30 years, leading to several waves of dengue epidemics and to the emergence of different viral lineages in the region. In this study, we investigate the spatiotemporal dissemination pattern of the DENV-2 lineages at a regional level. We applied phylogenetic and phylogeographic analytical methods to a comprehensive data set of 582 DENV-2 E gene sequences of the AS/AM genotype isolated from 29 different American countries over a period of 30 years (1983 to 2012). Our study reveals that genetic diversity of DENV-2 AS/AM genotype circulating in the Americas mainly resulted from one single founder event and can be organized in at least four major lineages (I to IV), which emerged in the Caribbean region at the early 1980s and then spread and die out with different dynamics. Lineages I and II dominate the epidemics in the Caribbean region during the 1980s and early 1990 s, lineage III becomes the prevalent DENV-2 one in the Caribbean and South America during the 1990 s, whereas lineage IV dominates the epidemics in South and Central America during the 2000s. Suriname and Guyana seem to represent important entry points for DENV-2 from the Lesser Antilles to South America, whereas Venezuela, Brazil and Nicaragua were pointed as the main secondary hubs of dissemination to other mainland countries. Our study also indicates that DENV-2 AS/AM genotype was disseminated within South America following two main routes. The first route hits Venezuela and the western side of the Andes, while the second route mainly hits Brazil and the eastern side of the Andes. The phenomenon of DENV-2 lineage replacement across successive epidemic outbreaks was a common characteristic in all American countries, although the timing of lineage replacements greatly vary across locations.


Assuntos
Americanos Asiáticos/genética , Vírus da Dengue/genética , Dengue/virologia , Variação Genética , Américas , Bases de Dados Genéticas , Genótipo , Humanos , Epidemiologia Molecular , Filogeografia
10.
Trans R Soc Trop Med Hyg ; 107(5): 324-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23442573

RESUMO

BACKGROUND: Yellow fever is an acute, frequently fatal, febrile arbovirosis that in Brazil occurs only in the sylvatic form. Sylvatic yellow fever (SYF) appears in sporadic outbreaks over a large area of Brazil. In this paper, we analyze the demographic profile of 831 SYF cases that occurred between 1973 and 2008, to determine which segments of the exposed population are at greater risk. METHODS: Data were statistically analyzed and were also geo-referenced in order to observe their spatial pattern. The basic reproductive number of infections, R0, was estimated by the ratio between average life expectancy and the average age of the cases. RESULTS: SYF cases showed a modal profile of young male adults, approximately 30 years of age, living in rural areas of the states of Pará, Goiás, Maranhão and Minas Gerais, who were unvaccinated or whose vaccination was out of date. The disease showed a high mortality rate (51%, 421/831) among the notified cases, with death occurring on around the seventh day of illness for most patients. The R0 for SYF was estimated at approximately 2.4. CONCLUSION: The results of this study suggest that lack of vaccination coverage is a major risk factor for SYF, and that the groups most at risk are migrant laborers, farm workers and tourists.


Assuntos
Demografia , Febre Amarela/epidemiologia , Febre Amarela/prevenção & controle , Febre Amarela/transmissão , Doença Aguda , Adolescente , Adulto , Brasil/epidemiologia , Feminino , Humanos , Masculino , Periodicidade , Fatores de Risco , Febre Amarela/mortalidade , Vacina contra Febre Amarela , Adulto Jovem
11.
Infect Genet Evol ; 13: 76-88, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22985683

RESUMO

Foot-and-mouth disease virus (FMDV) is the causative agent of the most important disease of domestic cattle, foot-and-mouth disease. In Ecuador, FMDV is maintained at an endemic state, with sporadic outbreaks. To unravel the tempo and mode of FMDV spread within the country we conducted a Bayesian phylogeographic analysis using a continuous time Markov chain (CTMC) to model the diffusion of FMDV between Ecuadorian provinces. We implement this framework through Markov chain Monte Carlo available in the BEAST package to study 90 FMDV serotype O isolates from 17 provinces in the period 2002-2010. The Bayesian approach also allowed us to test hypotheses on the mechanisms of viral spread by incorporating environmental and epidemiological data in our prior distributions and perform Bayesian model selection. Our analyses suggest an intense flow of viral strains throughout the country that is possibly coupled to animal movements and ecological factors, since most of inferred viral spread routes were in Coast and Highland regions. Moreover, our results suggest that both short- and long-range spread occur within Ecuador. The province of Esmeraldas, in the border with Colombia and where most animal commerce is done, was found to be the most probable origin of the circulating strains, pointing to a transboundary behavior of FMDV in South America. These findings suggest that uncontrolled animal movements can create a favorable environment for FMDV maintenance and pose a serious threat to control programmes. Also, we show that phylogeographic modeling can be a powerful tool in unraveling the spatial dynamics of viruses and potentially in controlling the spread of these pathogens.


Assuntos
Vírus da Febre Aftosa/classificação , Vírus da Febre Aftosa/genética , Animais , Teorema de Bayes , Bovinos , Equador , Febre Aftosa/epidemiologia , Febre Aftosa/virologia , Geografia , Filogenia , Filogeografia
12.
Braz J Infect Dis ; 16(1): 34-7, 2012 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22358353

RESUMO

OBJECTIVES: To compare epidemiological aspects of young (15 to 49 years old) and older (more than 50 years old) AIDS patients. METHODS: We analyzed 511,633 AIDS cases notified to the Brazilian Ministry of Health in the period of 1980-2008 looking at sex, age ranges, educational level and exposure category. Patients were divided into three age groups: under 15, from 15 to 49 and over 50 years old. Using a comparative approach, we analyzed data with regard to category of exposure, education (expressed in years of schooling), and sex ratio among younger (15-49) and older adults (over 50 years old). Time series data were log-transformed and normalized, and the temporal trend was evaluated. RESULTS: AIDS incidence is increasing among people over 50 years old in Brazil, with those older than 50 being responsible for 9.64 % of AIDS cases. There was no significant difference between educational level and gender (p = 0.468), but there was a significant difference in exposure category with a lower proportion of injecting drug users amongst the older group. CONCLUSION: Based on this analysis over the last 10 years, the percentage of AIDS cases has increased almost three times among people over 50 years old when compared with the 15-49 year-old group. Our findings suggest that public campaigns have to be specially targeted to the older segment of the population, aiming at heterosexual transmission.


Assuntos
Síndrome de Imunodeficiência Adquirida/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Brasil/epidemiologia , Escolaridade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Distribuição por Sexo , Adulto Jovem
13.
Braz. j. infect. dis ; 16(1): 34-37, Jan.-Feb. 2012. ilus, tab
Artigo em Inglês | LILACS | ID: lil-614547

RESUMO

OBJECTIVES: To compare epidemiological aspects of young (15 to 49 years old) and older (more than 50 years old) AIDS patients. METHODS: We analyzed 511,633 AIDS cases notified to the Brazilian Ministry of Health in the period of 1980-2008 looking at sex, age ranges, educational level and exposure category. Patients were divided into three age groups: under 15, from 15 to 49 and over 50 years old. Using a comparative approach, we analyzed data with regard to category of exposure, education (expressed in years of schooling), and sex ratio among younger (15-49) and older adults (over 50 years old). Time series data were log-transformed and normalized, and the temporal trend was evaluated. RESULTS: AIDS incidence is increasing among people over 50 years old in Brazil, with those older than 50 being responsible for 9.64 percent of AIDS cases. There was no significant difference between educational level and gender (p = 0.468), but there was a significant difference in exposure category with a lower proportion of injecting drug users amongst the older group. CONCLUSION: Based on this analysis over the last 10 years, the percentage of AIDS cases has increased almost three times among people over 50 years old when compared with the 15-49 year-old group. Our findings suggest that public campaigns have to be specially targeted to the older segment of the population, aiming at heterosexual transmission.


Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Síndrome de Imunodeficiência Adquirida/epidemiologia , Distribuição por Idade , Brasil/epidemiologia , Escolaridade , Incidência , Distribuição por Sexo
14.
Rev. Soc. Bras. Med. Trop ; 44(3): 297-299, May-June 2011. graf
Artigo em Inglês | LILACS | ID: lil-593347

RESUMO

INTRODUCTION: Sylvatic yellow fever (SYF) is enzootic in Brazil, causing periodic outbreaks in humans living near forest borders or in rural areas. In this study, the cycling patterns of this arbovirosis were analyzed. METHODS: Spectral Fourier analysis was used to capture the periodicity patterns of SYF in time series. RESULTS: SYF outbreaks have not increased in frequency, only in the number of cases. There are two dominant cycles in SYF outbreaks, a seven year cycle for the central-western region and a 14 year cycle for the northern region. Most of the variance was concentrated in the central-western region and dominated the entire endemic region. CONCLUSIONS: The seven year cycle is predominant in the endemic region of the disease due the greater contribution of variance in the central-western region; however, it was possible identify a 14 cycle that governs SYF outbreaks in the northern region. No periodicities were identified for the remaining geographical regions.


INTRODUÇÃO: A febre amarela silvestre (FAS) é enzoótica no Brasil, causando surtos periódicos em humanos que vivem próximos às áreas florestais ou em áreas rurais. Neste estudo, foram analisados os padrões de periodicidade desta arbovirose. MÉTODOS: Utilizamos a análise espectral de Fourier para capturar os padrões de periodicidades da FAS em séries temporais. RESULTADOS: Os surtos de FAS aparentemente não aumentaram em frequência, mas em número de casos. Há dois ciclos dominantes na FAS, um de sete anos predominando na região centro-oeste, e um de 14 anos predominando na região norte. A maior parte da variância concentrou-se na região centro-oeste e dominava toda região endêmica. CONCLUSÕES: O ciclo de sete anos é predominante para a região endêmica da doença devido a maior contribuição da variância do centro-oeste. No entanto, foi possível identificar um ciclo de 14 que rege a FAS na região norte. Não foram detectadas periodicidades nas demais regiões geográficas.


Assuntos
Humanos , Surtos de Doenças , Periodicidade , Febre Amarela/epidemiologia , Brasil/epidemiologia
15.
Rev Soc Bras Med Trop ; 44(3): 297-9, 2011 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21537794

RESUMO

INTRODUCTION: Sylvatic yellow fever (SYF) is enzootic in Brazil, causing periodic outbreaks in humans living near forest borders or in rural areas. In this study, the cycling patterns of this arbovirosis were analyzed. METHODS: Spectral Fourier analysis was used to capture the periodicity patterns of SYF in time series. RESULTS: SYF outbreaks have not increased in frequency, only in the number of cases. There are two dominant cycles in SYF outbreaks, a seven year cycle for the central-western region and a 14 year cycle for the northern region. Most of the variance was concentrated in the central-western region and dominated the entire endemic region. CONCLUSIONS: The seven year cycle is predominant in the endemic region of the disease due the greater contribution of variance in the central-western region; however, it was possible identify a 14 cycle that governs SYF outbreaks in the northern region. No periodicities were identified for the remaining geographical regions.


Assuntos
Surtos de Doenças , Periodicidade , Febre Amarela/epidemiologia , Brasil/epidemiologia , Humanos
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