Background: Preterm birth is a global health problem which causes significant short- and long-term morbidity and mortality. Pathophysiology is not entirely clear and due to climate change environmental risk factors, such as extreme temperatures, should be considered as emerging and modifiable risk factors. The evidence from low- and middle-income countries on their role is limited.  Objective: The goal of this study was to assess the relationship of daily mean temperature and number of preterm births in the period from March 2019 to May 2020 in Nepal.  Methods: Perinatal data from nine Nepalese hospitals, which took part in two recent quality improvement studies, was matched with climate data from 15 temperature stations. A time- series analysis using conditional Poisson regression and distributed lag non-linear models was done for the three stations with the largest study populations.  Results: Across the three analyzed regions in Nepal heterogenous results were found. Only in one area an overall increase in preterm birth risk for high temperatures within the last 2 weeks before delivery was found. One region showed a protective effect for heat, but increased risk for low temperatures. In the third region there was no overall association of ambient temperature and risk of preterm birth.  Discussion: Potential explanations for the heterogenous results are different sociodemographic and geographical background of the participants. Limitations concerning the selected study population as well as quality of climate data should be mentioned. Further studies are needed for more detailed investigation.

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.