Spatio-temporal modelling of climate-sensitive disease risk : towards an early warning system for dengue in Brazil

The transmission of many infectious diseases is affected by climate variations, particularly for diseases spread by arthropod vectors such as malaria and dengue. Previous epidemiological studies have demonstrated statistically significant associations between infectious disease incidence and climate variations. Such research has highlighted the potential for developing climate-based epidemic early warning systems. To establish how much variation in disease risk can be attributed to climatic conditions, non-climatic confounding factors should also be considered in the model parameterisation to avoid reporting misleading climate-disease associations. This issue is sometimes overlooked in climate related disease studies. Due to the lack of spatial resolution and/or the capability to predict future disease risk (e.g. several months ahead), some previous models are of limited value for public health decision making. This thesis proposes a framework to model spatio-temporal variation in disease risk using both climate and non-climate information. The framework is developed in the context of dengue fever in Brazil. Dengue is currently one of the most important emerging tropical diseases and dengue epidemics impact heavily on Brazilian public health services. A negative binomial generalised linear mixed model (GLMM) is adopted which makes allowances for unobserved confounding factors by including spatially structured and unstructured random effects. The model successfully accounts for the large amount of overdispersion found in disease counts. The parameters in this spatio-temporal Bayesian hierarchical model are estimated using Markov Chain Monte Carlo (MCMC). This allows posterior predictive distributions for disease risk to be derived for each spatial location and time period (month/season). Given decision and epidemic thresholds, probabilistic forecasts can be issued, which are useful for developing epidemic early warning systems. The potential to provide useful early warnings of future increased and geographically specific dengue risk is investigated. The predictive validity of the model is evaluated by fitting the GLMM to data from 2001-2007 and comparing probabilistic predictions to the most recent out-of-sample data in 2008-2009. For a probability decision threshold of 30% and the pre-defined epidemic threshold of 300 cases per 100,000 inhabitants, successful epidemic alerts would have been issued for 94% of the 54 microregions that experienced high dengue incidence rates in South East Brazil, during February - April 2008.EThOS - Electronic Theses Online ServiceLeverhulme TrustGBUnited Kingdo