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Using heterogeneous data to identify signatures of dengue outbreaks at fine spatio-temporal scales across Brazil.

ABSTRACT: Dengue virus remains a significant public health challenge in Brazil, and seasonal preparation efforts are hindered by variable intra- and interseasonal dynamics. Here, we present a framework for characterizing weekly dengue activity at the Brazilian mesoregion level from 2010-2016 as time series properties that are relevant to forecasting efforts, focusing on outbreak shape, seasonal timing, and pairwise correlations in magnitude and onset. In addition, we use a combination of 18 satellite remote sensing imagery, weather, clinical, mobility, and census data streams and regression methods to identify a parsimonious set of covariates that explain each time series property. The models explained 54% of the variation in outbreak shape, 38% of seasonal onset, 34% of pairwise correlation in outbreak timing, and 11% of pairwise correlation in outbreak magnitude. Regions that have experienced longer periods of drought sensitivity, as captured by the "normalized burn ratio," experienced less intense outbreaks, while regions with regular fluctuations in relative humidity had less regular seasonal outbreaks. Both the pairwise correlations in outbreak timing and outbreak trend between mesoresgions were best predicted by distance. Our analysis also revealed the presence of distinct geographic clusters where dengue properties tend to be spatially correlated. Forecasting models aimed at predicting the dynamics of dengue activity need to identify the most salient variables capable of contributing to accurate predictions. Our findings show that successful models may need to leverage distinct variables in different locations and be catered to a specific task, such as predicting outbreak magnitude or timing characteristics, to be useful. This advocates in favor of "adaptive models" rather than "one-size-fits-all" models. The results of this study can be applied to improving spatial hierarchical or target-focused forecasting models of dengue activity across Brazil.

SUBMITTER: Castro LA

PROVIDER: S-EPMC8174735 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The dengue virus has a single-stranded positive-sense RNA genome of approximately 10.700 nucleotides with a single open reading frame that encodes three structural (C, prM, and E) and seven nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins. It possesses four antigenically distinct serotypes (DENV 1-4). Many phylogenetic studies address particularities of the different serotypes using convenience samples that are not conducive to a spatio-temporal analysis in a single urban setting. We describe the pattern of spread of distinct lineages of DENV-3 circulating in São José do Rio Preto, Brazil, during 2006. Blood samples from patients presenting dengue-like symptoms were collected for DENV testing. We performed M-N-PCR using primers based on NS5 for virus detection and identification. The fragments were purified from PCR mixtures and sequenced. The positive dengue cases were geo-coded. To type the sequenced samples, 52 reference sequences were aligned. The dataset generated was used for iterative phylogenetic reconstruction with the maximum likelihood criterion. The best demographic model, the rate of growth, rate of evolutionary change, and Time to Most Recent Common Ancestor (TMRCA) were estimated. The basic reproductive rate during the epidemics was estimated. We obtained sequences from 82 patients among 174 blood samples. We were able to geo-code 46 sequences. The alignment generated a 399-nucleotide-long dataset with 134 taxa. The phylogenetic analysis indicated that all samples were of DENV-3 and related to strains circulating on the isle of Martinique in 2000-2001. Sixty DENV-3 from São José do Rio Preto formed a monophyletic group (lineage 1), closely related to the remaining 22 isolates (lineage 2). We assumed that these lineages appeared before 2006 in different occasions. By transforming the inferred exponential growth rates into the basic reproductive rate, we obtained values for lineage 1 of R(0) = 1.53 and values for lineage 2 of R(0) = 1.13. Under the exponential model, TMRCA of lineage 1 dated 1 year and lineage 2 dated 3.4 years before the last sampling. The possibility of inferring the spatio-temporal dynamics from genetic data has been generally little explored, and it may shed light on DENV circulation. The use of both geographic and temporally structured phylogenetic data provided a detailed view on the spread of at least two dengue viral strains in a populated urban area.

Project description:BackgroundAt present, dengue control focuses on reducing the density of the primary vector for the disease, Aedes aegypti, which is the only vulnerable link in the chain of transmission. The use of new approaches for dengue entomological surveillance is extremely important, since present methods are inefficient. With this in mind, the present study seeks to analyze the spatio-temporal dynamics of A. aegypti infestation with oviposition traps, using efficient computational methods. These methods will allow for the implementation of the proposed model and methodology into surveillance and monitoring systems.MethodsThe study area includes a region in the municipality of Rio de Janeiro, characterized by high population density, precarious domicile construction, and a general lack of infrastructure around it. Two hundred and forty traps were distributed in eight different sentinel areas, in order to continually monitor immature Aedes aegypti and Aedes albopictus mosquitoes. Collections were done weekly between November 2010 and August 2012. The relationship between egg number and climate and environmental variables was considered and evaluated through Bayesian zero-inflated spatio-temporal models. Parametric inference was performed using the Integrated Nested Laplace Approximation (INLA) method.ResultsInfestation indexes indicated that ovipositing occurred during the entirety of the study period. The distance between each trap and the nearest boundary of the study area, minimum temperature and accumulated rainfall were all significantly related to the number of eggs present in the traps. Adjusting for the interaction between temperature and rainfall led to a more informative surveillance model, as such thresholds offer empirical information about the favorable climatic conditions for vector reproduction. Data were characterized by moderate time (0.29 - 0.43) and spatial (21.23 - 34.19 m) dependencies. The models also identified spatial patterns consistent with human population density in all sentinel areas. The results suggest the need for weekly surveillance in the study area, using traps allocated between 18 and 24 m, in order to understand the dengue vector dynamics.ConclusionsAedes aegypti, due to it short generation time and strong response to climate triggers, tend to show an eruptive dynamics that is difficult to predict and understand through just temporal or spatial models. The proposed methodology allowed for the rapid and efficient implementation of spatio-temporal models that considered zero-inflation and the interaction between climate variables and patterns in oviposition, in such a way that the final model parameters contribute to the identification of priority areas for entomological surveillance.

Project description:BackgroundYellow fever virus is a mosquito-borne flavivirus that persists in an enzoonotic cycle in non-human primates (NHPs) in Brazil, causing disease in humans through spillover events. Yellow fever (YF) re-emerged in the early 2000s, spreading from the Amazon River basin towards the previously considered low-risk, southeastern region of the country. Previous methods mapping YF spillover risk do not incorporate the temporal dynamics and ecological context of the disease, and are therefore unable to predict seasonality in spatial risk across Brazil. We present the results of a bagged logistic regression predicting the propensity for YF spillover per municipality (administrative sub-district) in Brazil from environmental and demographic covariates aggregated by month. Ecological context was incorporated by creating National and Regional models of spillover dynamics, where the Regional model consisted of two separate models determined by the regions' NHP reservoir species richness (high vs low).ResultsOf the 5560 municipalities, 82 reported YF cases from 2001 to 2013. Model accuracy was high for the National and low reservoir richness (LRR) models (AUC = 0.80), while the high reservoir richness (HRR) model accuracy was lower (AUC = 0.63). The National model predicted consistently high spillover risk in the Amazon, while the Regional model predicted strong seasonality in spillover risk. Within the Regional model, seasonality of spillover risk in the HRR region was asynchronous to the LRR region. However, the observed seasonality of spillover risk in the LRR Regional model mirrored the national model predictions.ConclusionsThe predicted risk of YF spillover varies with space and time. Seasonal trends differ between regions indicating, at times, spillover risk can be higher in the urban coastal regions than the Amazon River basin which is counterintuitive based on current YF risk maps. Understanding the spatio-temporal patterns of YF spillover risk could better inform allocation of public health services.

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Using heterogeneous data to identify signatures of dengue outbreaks at fine spatio-temporal scales across Brazil.

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