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Climate change can affect water supply in Nepal by its impact on precipitation, glacier melting and increase in temperature. This study identifies the vulnerability of the water supply system in Kathmandu Valley to the impact of the worst case scenario of climate change and suggests adaptation strategies to deal with the situation. It finds that existing strategies are insufficient and more than five million people would be deprived of the minimum needed water by 2050 under the driest scenario. Similarly, the reduction in low flow under the driest scenario or frequent extreme rainfall events under the wettest scenario could further degrade the water quality and increase the vulnerability of water supply infrastructures. The study suggests a combination of strategies to help manage the situation until 2050. The situation, however, would become worse after 2050 due to the projected sharp reduction in precipitation, making all precipitation-dependent water supply strategies ineffective.