Abstract

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.

Highlights

  • Yellow 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

  • Unlike other mosquito-borne diseases in Brazil, such as malaria and dengue, Yellow fever virus (YFV) circulates in a sylvatic transmission cycle among non-human primate (NHP) reservoirs maintained by Haemagogus and Sabethes mosquitoes, with spillover occurring when mosquitoes transmit outside

  • The area under the receiver-operator curve (AUC) values for models evaluated on the training dataset were 0.81, 0.79 and 0.88 for the national dataset, low reservoir richness (LRR) and high reservoir richness (HRR) regions, respectively

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Summary

Introduction

Yellow 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. Predictive maps of disease risk use statistical methods to account for disease transmission dynamics via their relationship with environmental and socio-demographic covariates. This approach has been applied to a range of infectious diseases, including Ebola [7, 8], malaria [9, 10] and dengue [11, 12]. We used a balanced spatial and temporal sampling design via the BalancedSampling package in R to split the data into training (70%) and testing (30%) sets, preserving the proportion of municipality-months with a spillover event (positive observations) in each [36]. The final bagged logistic regression model is the average of the logistic regressions

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