Spatio-temporal dynamics of dengue-related deaths and associated factors

Since the reintroduction of dengue viruses in 1987, Sao Paulo State (SP), Brazil, has experienced recurrent epidemics in a growing number of municipalities, each time with more cases and deaths. In the present study, we investigated the spatio-temporal dynamics of dengue-related deaths and associated factors in SP. This was an ecological study with spatial and temporal components, based on notified dengue-related deaths in the municipalities of SP between 2007 and 2017. A latent Gaussian Bayesian model with Poisson probability distribution was used to estimate the standardized mortality ratios (SMR) for dengue and relative risks (RR) for the socioeconomic, demographic, healthcare-related, and epidemiological factors considered. Epidemiological factors included the annual information on the number of circulating serotypes. A total of 1,019 dengue-related deaths (0.22 per 100,000 inhabitant-years) between 2007 and 2017 were confirmed in SP by laboratory testing. Mortality increased with age, peaking at 70 years or older (1.41 deaths per 100,000 inhabitant-years). Mortality was highest in 2015, and the highest SMR values were found in the North, Northwest, West, and coastal regions of SP. An increase of one circulating serotype, one standard deviation in the number of years with cases, and one standard deviation in the degree of urbanization were associated with increases of 75, 35, and 45% in the risk of death from dengue, respectively. The risk of death from dengue increased with age, and the distribution of deaths was heterogeneous in space and time. The positive relationship found between the number of dengue serotypes circulating and years with cases at the municipality/micro-region level indicates that this information can be used to identify risk areas, intensify surveillance and control measures, and organize healthcare to better respond to this disease

Deaths from dengue in the state of São Paulo: spatio-temporal analysis

Introdução - Considerada um grave problema de saúde pública mundial em regiões de clima tropical e subtropical, a dengue foi a única dentre as doenças tropicais negligenciadas a apresentar tendência de aumento na mortalidade nos últimos anos. Fatores relacionados ao ciclo de vida do principal vetor, fêmeas do mosquito Aedes aegypti, influenciam a distribuição espacial e o caráter sazonal da doença. A incidência de casos de dengue é dependente de uma complexa rede de relações entre vetor, vírus e hospedeiro, assim como a ocorrência de casos graves e de óbito. Desde a introdução do vírus, o estado de São Paulo vem apresentado epidemias envolvendo número cada vez maior de municípios, de incidência de casos e de óbitos por dengue. Objetivo - Avaliar a distribuição espacial, temporal e espaço-temporal dos óbitos por dengue no estado de São Paulo. Métodos - Trata-se de estudo ecológico, com componentes espacial e temporal, a partir da notificação de óbitos por dengue no SINAN, tendo como unidades de análise os municípios e as microrregiões do estado de São Paulo, no período de 1998 a 2017. Os óbitos por dengue no estado de São Paulo foram descritos segundo sexo e idade. As taxas de mortalidade bruta, padronizada por sexo e idade e suavizada pelo método bayesiano empírico local foram estimadas e mapeadas segundo município de residência. Os sorotipos detectados pelo Instituto Adolfo Lutz foram mapeados segundo microrregião. Estimou-se as tendências temporais da mortalidade. Aglomerados de alto risco espacial e espaço-temporal e de variação espacial na tendência temporal foram detectados e mapeados. O risco relativo espacial da mortalidade por dengue ajustado pelo tempo e covariáveis consideradas foi estimado por modelos Bayesianos Gaussianos Latentes com abordagem INLA (2007 - 2016). Foi aprovado pelo Comitê de Ética em Pesquisa da Faculdade de Saúde Pública da Universidade de São Paulo sob parecer de número 1.687.650. Resultados - Foram identificados 1.121 óbitos por dengue com confirmação laboratorial e residentes no estado de São Paulo entre 1998 e 2017. A mediana de idade foi de 57 anos. A média anual da mortalidade bruta por dengue no estado de São Paulo na série histórica foi de 0,14 óbitos por 100.000 habitantes. Houve tendência de elevação da mortalidade para todos os sexos e idades no período, sendo o crescimento mais proeminente nos adultos com >= 50 anos, e de aumento do percentual de municípios com casos e óbitos ao longo dos anos estudados. Houve associação positiva entre as regiões com maior quantidade de sorotipos e taxas de mortalidade mais elevadas. Aglomerados de alto risco foram identificados nas áreas com alta taxa de mortalidade. O grau de urbanização, número de anos com casos e a introdução de novo sorotipo associaram-se a um maior risco relativo para a mortalidade por dengue. Tanto as taxas de mortalidade mais elevadas, quanto os maiores riscos relativos para o óbito foram observados nas regiões norte, noroeste, oeste, sudeste e litoral do estado de São Paulo. Conclusão - a mortalidade por dengue no estado de São Paulo apresentou padrão cíclico e sazonal, com tendência de elevação principalmente nas faixas etárias mais avançadas. Houve identificação de agregados de área de alto risco, com associação do grau de urbanização, do número de anos com casos e da introdução de novo sorotipo a maior risco de mortalidade por dengue.Introduction - Considered a major global public health problem in tropical and subtropical regions, dengue was the only one among neglected tropical diseases to show an increase in mortality in recent years. Factors related to the life cycle of the main vector, females of Aedes aegypti mosquito, influence the spatial distribution and the seasonal nature of the disease. The incidence of dengue cases is dependent on a complex network of relationships between vector, virus and host, as well as the occurrence of severe cases and death. Since the introduction of the virus, the state of São Paulo has been presenting epidemics involving an increasing number of municipalities, incidence of cases and deaths due to dengue. Objective - To evaluate the spatial, temporal and spatial-temporal distribution of dengue deaths in the state of São Paulo. Methods - This is an ecological study, with spatial and temporal components, based on the notification of dengue deaths at SINAN, with the municipalities and microregions of the state of São Paulo as analysis units from 1998 to 2017. Deaths from dengue in the State of São Paulo were described according to sex and age. The crude mortality rates standardized by sex and age and smoothed by the local empirical Bayesian method were estimated and mapped according to the municipality of residence. The serotypes detected by the Adolfo Lutz Institute were mapped according to microregion. The temporal trends of mortality were estimated. High-risk space and space-time clusters and spatial variation in time trend were detected and mapped. The spatial relative risk of dengue mortality adjusted by time and covariables considered was estimated by Latent Gaussian Bayesian models with INLA approach (2007 - 2016). It was approved by the Research Ethics Committee of the School of Public Health of the University of São Paulo under opinion number 1,687,650. Results - A total of 1,121 dengue deaths with laboratory confirmation were identified and residents of the State of São Paulo between 1998 and 2017. The median age was 57 years. The annual average of the gross mortality from dengue in State of São Paulo in the historical series was 0.14 deaths per 100,000 inhabitants. There was a trend of increased mortality for all sexes and ages in the period, with the most prominent growth in adults aged >= 50 years, and an increase in the percentage of municipalities with cases and deaths over the years studied. There was positive association between the regions with the highest number of serotypes and the highest mortality rates. High-risk clusters were identified in areas with high mortality rates. The degree of urbanization, number of years with cases and the introduction of a new serotype were associated with a higher relative risk for dengue mortality. Both the highest mortality rates and the highest relative risks for death were observed in the north, northwest, west, southeast and coastal regions of the State of São Paulo. Conclusion - dengue mortality in the state of São Paulo presented a cyclical and seasonal pattern, with a tendency to increase mainly in the more advanced age groups. There was identification of high risk area clusters, with association of the degree of urbanization, number of years with cases and the introduction of a new serotype at greater risk of dengue mortality

Deaths from dengue in the state of São Paulo: spatio-temporal analysis

Introdução - Considerada um grave problema de saúde pública mundial em regiões de clima tropical e subtropical, a dengue foi a única dentre as doenças tropicais negligenciadas a apresentar tendência de aumento na mortalidade nos últimos anos. Fatores relacionados ao ciclo de vida do principal vetor, fêmeas do mosquito Aedes aegypti, influenciam a distribuição espacial e o caráter sazonal da doença. A incidência de casos de dengue é dependente de uma complexa rede de relações entre vetor, vírus e hospedeiro, assim como a ocorrência de casos graves e de óbito. Desde a introdução do vírus, o estado de São Paulo vem apresentado epidemias envolvendo número cada vez maior de municípios, de incidência de casos e de óbitos por dengue. Objetivo - Avaliar a distribuição espacial, temporal e espaço-temporal dos óbitos por dengue no estado de São Paulo. Métodos - Trata-se de estudo ecológico, com componentes espacial e temporal, a partir da notificação de óbitos por dengue no SINAN, tendo como unidades de análise os municípios e as microrregiões do estado de São Paulo, no período de 1998 a 2017. Os óbitos por dengue no estado de São Paulo foram descritos segundo sexo e idade. As taxas de mortalidade bruta, padronizada por sexo e idade e suavizada pelo método bayesiano empírico local foram estimadas e mapeadas segundo município de residência. Os sorotipos detectados pelo Instituto Adolfo Lutz foram mapeados segundo microrregião. Estimou-se as tendências temporais da mortalidade. Aglomerados de alto risco espacial e espaço-temporal e de variação espacial na tendência temporal foram detectados e mapeados. O risco relativo espacial da mortalidade por dengue ajustado pelo tempo e covariáveis consideradas foi estimado por modelos Bayesianos Gaussianos Latentes com abordagem INLA (2007 - 2016). Foi aprovado pelo Comitê de Ética em Pesquisa da Faculdade de Saúde Pública da Universidade de São Paulo sob parecer de número 1.687.650. Resultados - Foram identificados 1.121 óbitos por dengue com confirmação laboratorial e residentes no estado de São Paulo entre 1998 e 2017. A mediana de idade foi de 57 anos. A média anual da mortalidade bruta por dengue no estado de São Paulo na série histórica foi de 0,14 óbitos por 100.000 habitantes. Houve tendência de elevação da mortalidade para todos os sexos e idades no período, sendo o crescimento mais proeminente nos adultos com >= 50 anos, e de aumento do percentual de municípios com casos e óbitos ao longo dos anos estudados. Houve associação positiva entre as regiões com maior quantidade de sorotipos e taxas de mortalidade mais elevadas. Aglomerados de alto risco foram identificados nas áreas com alta taxa de mortalidade. O grau de urbanização, número de anos com casos e a introdução de novo sorotipo associaram-se a um maior risco relativo para a mortalidade por dengue. Tanto as taxas de mortalidade mais elevadas, quanto os maiores riscos relativos para o óbito foram observados nas regiões norte, noroeste, oeste, sudeste e litoral do estado de São Paulo. Conclusão - a mortalidade por dengue no estado de São Paulo apresentou padrão cíclico e sazonal, com tendência de elevação principalmente nas faixas etárias mais avançadas. Houve identificação de agregados de área de alto risco, com associação do grau de urbanização, do número de anos com casos e da introdução de novo sorotipo a maior risco de mortalidade por dengue.Introduction - Considered a major global public health problem in tropical and subtropical regions, dengue was the only one among neglected tropical diseases to show an increase in mortality in recent years. Factors related to the life cycle of the main vector, females of Aedes aegypti mosquito, influence the spatial distribution and the seasonal nature of the disease. The incidence of dengue cases is dependent on a complex network of relationships between vector, virus and host, as well as the occurrence of severe cases and death. Since the introduction of the virus, the state of São Paulo has been presenting epidemics involving an increasing number of municipalities, incidence of cases and deaths due to dengue. Objective - To evaluate the spatial, temporal and spatial-temporal distribution of dengue deaths in the state of São Paulo. Methods - This is an ecological study, with spatial and temporal components, based on the notification of dengue deaths at SINAN, with the municipalities and microregions of the state of São Paulo as analysis units from 1998 to 2017. Deaths from dengue in the State of São Paulo were described according to sex and age. The crude mortality rates standardized by sex and age and smoothed by the local empirical Bayesian method were estimated and mapped according to the municipality of residence. The serotypes detected by the Adolfo Lutz Institute were mapped according to microregion. The temporal trends of mortality were estimated. High-risk space and space-time clusters and spatial variation in time trend were detected and mapped. The spatial relative risk of dengue mortality adjusted by time and covariables considered was estimated by Latent Gaussian Bayesian models with INLA approach (2007 - 2016). It was approved by the Research Ethics Committee of the School of Public Health of the University of São Paulo under opinion number 1,687,650. Results - A total of 1,121 dengue deaths with laboratory confirmation were identified and residents of the State of São Paulo between 1998 and 2017. The median age was 57 years. The annual average of the gross mortality from dengue in State of São Paulo in the historical series was 0.14 deaths per 100,000 inhabitants. There was a trend of increased mortality for all sexes and ages in the period, with the most prominent growth in adults aged >= 50 years, and an increase in the percentage of municipalities with cases and deaths over the years studied. There was positive association between the regions with the highest number of serotypes and the highest mortality rates. High-risk clusters were identified in areas with high mortality rates. The degree of urbanization, number of years with cases and the introduction of a new serotype were associated with a higher relative risk for dengue mortality. Both the highest mortality rates and the highest relative risks for death were observed in the north, northwest, west, southeast and coastal regions of the State of São Paulo. Conclusion - dengue mortality in the state of São Paulo presented a cyclical and seasonal pattern, with a tendency to increase mainly in the more advanced age groups. There was identification of high risk area clusters, with association of the degree of urbanization, number of years with cases and the introduction of a new serotype at greater risk of dengue mortality

Dengue forecasting in São Paulo city with generalized additive models, artificial neural networks and seasonal autoregressive integrated moving average models

<div><p>Globally, the number of dengue cases has been on the increase since 1990 and this trend has also been found in Brazil and its most populated city—São Paulo. Surveillance systems based on predictions allow for timely decision making processes, and in turn, timely and efficient interventions to reduce the burden of the disease. We conducted a comparative study of dengue predictions in São Paulo city to test the performance of trained seasonal autoregressive integrated moving average models, generalized additive models and artificial neural networks. We also used a naïve model as a benchmark. A generalized additive model with lags of the number of cases and meteorological variables had the best performance, predicted epidemics of unprecedented magnitude and its performance was 3.16 times higher than the benchmark and 1.47 higher that the next best performing model. The predictive models captured the seasonal patterns but differed in their capacity to anticipate large epidemics and all outperformed the benchmark. In addition to be able to predict epidemics of unprecedented magnitude, the best model had computational advantages, since its training and tuning was straightforward and required seconds or at most few minutes. These are desired characteristics to provide timely results for decision makers. However, it should be noted that predictions are made just one month ahead and this is a limitation that future studies could try to reduce.</p></div

Observed and predicted number of dengue cases in training and test data from São Paulo, Brazil, 2000–2016.

<p>Predictions were made by the generalized additive model presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0195065#pone.0195065.t004" target="_blank">Table 4</a>.</p

Observed and predicted number of dengue cases in training and test data from São Paulo, Brazil, 2000–2016.

<p>Predictions were made by models presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0195065#pone.0195065.t004" target="_blank">Table 4</a>.</p

Topology and tuned parameters of trained artificial neural networks.

<p>Topology and tuned parameters of trained artificial neural networks.</p

Correlation between the number of cases and lags 1–3 of six predictors.

<p>Correlation between the number of cases and lags 1–3 of six predictors.</p

Root mean squared errors (RMSE) of predictive models of dengue cases.

<p>Root mean squared errors (RMSE) of predictive models of dengue cases.</p

Configuration of artificial neural networks.

<p>Configuration of artificial neural networks.</p