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Rio de Janeiro, Brazil

Lana R.M.,Federal University of Ouro Preto | Carneiro T.G.S.,Federal University of Ouro Preto | Honorio N.A.,Instituto Oswaldo Cruz Fiocruz | Codeco C.T.,Programa de Computacao Cientifica
Acta Tropica

Mathematical models suggest that seasonal transmission and temporary cross-immunity between serotypes can determine the characteristic multi-year dynamics of dengue fever. Seasonal transmission is attributed to the effect of climate on mosquito abundance and within host virus dynamics. In this study, we validate a set of temperature and density dependent entomological models that are built-in components of most dengue models by fitting them to time series of ovitrap data from three distinct neighborhoods in Rio de Janeiro, Brazil. The results indicate that neighborhoods differ in the strength of the seasonal component and that commonly used models tend to assume more seasonal structure than found in data. Future dengue models should investigate the impact of heterogeneous levels of seasonality on dengue dynamics as it may affect virus maintenance from year to year, as well as the risk of disease outbreaks. © 2013 The Authors. Source

Schechtman H.,Programa de Computacao Cientifica | Souza M.O.,Federal University of Fluminense

Global emergence of arboviruses is a growing public health concern, since most of these diseases have no vaccine or prevention treatment available. In this scenario, vector control through the use of chemical insecticides is one of the most important prevention tools. Nevertheless, their effectiveness has been increasingly compromised by the development of strong resistance observed in field populations, even in spite of fitness costs usually associated to resistance. Using a stage-structured deterministic model parametrised for the Aedes aegypti - the main vector for dengue - we investigated the persistence of resistance by studying the time for a population which displays resistance to insecticide to revert to a susceptible population. By means of a comprehensive series of in-silico experiments, we studied this reversal time as a function of fitness costs and the initial presence of the resistance allele in the population. The resulting map provides both a guiding and a surveillance tool for public health officers to address the resistance situation of field populations. Application to field data from Brazil indicates that reversal can take, in some cases, decades even if fitness costs are not small. As by-products of this investigation, we were able to fit very simple formulas to the reversal times as a function of either cost or initial presence of the resistance allele. In addition, the in-silico experiments also showed that density dependent regulation plays an important role in the dynamics, slowing down the reversal process. © 2015 Schechtman, Souza. Source

Suarez-Kurtz G.,Instituto Nacional Of Cancer | Pena S.D.J.,Federal University of Minas Gerais | Struchiner C.J.,Programa de Computacao Cientifica | Hutz M.H.,Federal University of Rio Grande do Sul
Frontiers in Pharmacology

By virtue of being the product of the genetic admixture of three ancestral roots: Europeans, Africans, and Amerindians, the present-day Brazilian population displays very high levels of genomic diversity, which have important pharmacogenetic/-genomic (PGx) implications. Recognition of this fact has prompted the creation of the Brazilian Pharmacogenomics Network (Refargen), a nationwide consortium of research groups, with the mission to provide leadership in PGx research and education in Brazil, with a population heath impact. Here, we present original data and review published results from a Refargen comprehensive study of the distribution of PGx polymorphisms in a representative cohort of the Brazilian people, comprising 1,034 healthy, unrelated adults, self-identified as white, brown, or black, according to the Color categories adopted by the Brazilian Census. Multinomial log-linear regression analysis was applied to infer the statistical association between allele, genotype, and haplotype distributions among Brazilians (response variables) and self-reported Color, geographical region, and biogeographical ancestry (explanatory variables), whereas Wright's FST statistics was used to assess the extent of PGx divergence among different strata of the Brazilian population. Major PGx implications of these findings are: first, extrapolation of data from relatively well-defined ethnic groups is clearly not applicable to the majority of Brazilians; second, the frequency distribution of polymorphisms in several pharmacogenes of clinical relevance (e.g., ABCB1, CYP3A5, CYP2C9, VKORC) varies continuously among Brazilians and is not captured by race/Color self-identification; third, the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of PGx studies in order to avoid spurious conclusions based on improper matching of study cohorts. © 2012 Suarez-Kurtz, Pena, Struchiner and Hutz. Source

Suarez-Kurtz G.,Instituto Nacional do Cancer | Paula D.P.,Federal Rural University of Rio de Janeiro | Struchiner C.J.,Programa de Computacao Cientifica

The heterogeneous Brazilian population, with European, African and Amerindian ancestral roots is a model case for exploring the impact of population admixture on the frequency distribution of polymorphisms in pharmacogenes, and the design and interpretation of pharmacogenomics trials. Examples drawn from studies carried out by researchers of the Brazilian pharmacogenomics network, support the following conclusions: the distribution of polymorphisms varies across geographical regions and self-reported 'race/color categories, and is best modeled as continuous functions of individual proportions of European and African ancestry; the differential frequency of polymorphisms impacts the calculations of sample sizes required for adequate statistical power in clinical trials performed in different segments of the Brazilian population; and extrapolation of pharmacogenomics data from well-defined ethnic groups to Brazilians is plagued with uncertainty. Data for warfarin and tacrolimus are reviewed to highlight the advantages and challenges of performing pharmacogenomic trials in Brazilians. © 2014 Future Medicine Ltd. Source

Perini J.A.,Instituto Nacional Of Cancer | Struchiner C.J.,Programa de Computacao Cientifica | Silva-Assuncao E.,Ambulatorio de Anticoagulacao | Suarez-Kurtz G.,Instituto Nacional Of Cancer
Clinical Pharmacology and Therapeutics

There is controversy regarding the association between the CYP4F2 rs2108622 (V33M) polymorphism and warfarin dose requirement in white patients, and there are no data for nonwhite populations. We observed no association in self-identified white, black, or intermediate Brazilian patients (n = 370). The addition of the rs2108622 genotype as a variable has only a marginal effect on the predictive power of a warfarin dosing algorithm derived from this patient cohort. We conclude that prospective CYP4F2 genotyping is not justified in Brazilians who are potential candidates for warfarin therapy. © 2010 American Society2010 American Society for Clinical Pharmacology and Therapeutics. Source

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