Background: Great strides have been made in combating malaria, however, the indicators in sub Saharan Africa still do not show promise for elimination in the near future as malaria infections still result in high morbidity and mortality among children. The abundance of the malaria-transmitting mosquito vectors in these regions are driven by climate suitability. In order to achieve malaria elimination by 2030, strengthening of surveillance systems have been advocated. Based on malaria surveillance and climate monitoring, forecasting models may be developed for early warnings. Therefore, in this thesis, we strived to illustrate the use malaria surveillance and climate data for policy and decision making by assessing the association between weather variability (from ground and remote sensing sources) and malaria mortality, and by building malaria admission forecasting models. We further propose an economic framework for integrating forecasts into operational surveillance system for evidence based decisionmaking and resource allocation. Methods: The studies were based in Asembo, Gem and Karemo areas of the KEMRI/CDC Health and Demographic Surveillance System in Western Kenya. Lagged association of rainfall and temperature with malaria mortality was modeled using general additive models, while distributed lag non-linear models were used to explore relationship between remote sensing variables, land surface temperature(LST), normalized difference vegetation index(NDVI) and rainfall on weekly malaria mortality. General additive models, with and without boosting, were used to develop malaria admissions forecasting models for lead times one to three months. We developed a framework for incorporating forecast output into economic evaluation of response strategies at different lead times including uncertainties. The forecast output could either be an alert based on a threshold, or absolute predicted cases. In both situations, interventions at each lead time could be evaluated by the derived net benefit function and uncertainty incorporated by simulation. Results: We found that the environmental factors correlated with malaria mortality with varying latencies. In the first paper, where we used ground weather data, the effect of mean temperature was significant from lag of 9 weeks, with risks higher for mean temperatures above 250C. The effect of cumulative precipitation was delayed and began from 5 weeks. Weekly total rainfall of more than 120 mm resulted in increased risk for mortality. In the second paper, using remotely sensed data, the effect of precipitation was consistent in the three areas, with increasing effect with weekly total rainfall of over 40 mm, and then declined at 80 mm of weekly rainfall. NDVI below 0.4 increased the risk of malaria mortality, while day LST above 350C increased the risk of malaria mortality with shorter lags for high LST weeks. The lag effect of precipitation was more delayed for precipitation values below 20 mm starting at week 5 while shorter lag effect for higher precipitation weeks. The effect of higher NDVI values above 0.4 were more delayed and protective while shorter lag effect for NDVI below 0.4. For all the lead times, in the malaria admissions forecasting modelling in the third paper, the boosted regression models provided better prediction accuracy. The economic framework in the fourth paper presented a probability function of the net benefit of response measures, where the best response at particular lead time corresponded to the one with the highest probability, and absolute value, of a net benefit surplus. Conclusion: We have shown that lagged relationship between environmental variables and malaria health outcomes follow the expected biological mechanism, where presentation of cases follow the onset of specific weather conditions and climate variability. This relationship guided the development of predictive models showcased with the malaria admissions model. Further, we developed an economic framework connecting the forecasts to response measures in situations with considerable uncertainties. Thus, the thesis work has contributed to several important components of early warning systems including risk assessment; utilizing surveillance data for prediction; and a method to identifying cost-effective response strategies. We recommend economic evaluation becomes standard in implementation of early warning system to guide long-term sustainability of such health protection programs
