Using the Lives Saved Tool (LiST) Christa Fischer-Walker and colleagues estimate that scale-up of diarrhea prevention and treatment interventions over 5 years in 68 high child mortality countries could avert nearly 5 million deaths., Background Diarrhea remains a leading cause of mortality among young children in low- and middle-income countries. Although the evidence for individual diarrhea prevention and treatment interventions is solid, the effect a comprehensive scale-up effort would have on diarrhea mortality has not been estimated. Methods and Findings We use the Lives Saved Tool (LiST) to estimate the potential lives saved if two scale-up scenarios for key diarrhea interventions (oral rehydration salts [ORS], zinc, antibiotics for dysentery, rotavirus vaccine, vitamin A supplementation, basic water, sanitation, hygiene, and breastfeeding) were implemented in the 68 high child mortality countries. We also conduct a simple costing exercise to estimate cost per capita and total costs for each scale-up scenario. Under the ambitious (feasible improvement in coverage of all interventions) and universal (assumes near 100% coverage of all interventions) scale-up scenarios, we demonstrate that diarrhea mortality can be reduced by 78% and 92%, respectively. With universal coverage nearly 5 million diarrheal deaths could be averted during the 5-year scale-up period for an additional cost of US$12.5 billion invested across 68 priority countries for individual-level prevention and treatment interventions, and an additional US$84.8 billion would be required for the addition of all water and sanitation interventions. Conclusion Using currently available interventions, we demonstrate that with improved coverage, diarrheal deaths can be drastically reduced. If delivery strategy bottlenecks can be overcome and the international community can collectively deliver on the key strategies outlined in these scenarios, we will be one step closer to achieving success for the United Nations' Millennium Development Goal 4 (MDG4) by 2015. Please see later in the article for the Editors' Summary, Editors' Summary Background Diarrhea—passing three or more loose or liquid stools per day—kills about 1.5 million young children every year, mainly in low- and middle-income countries. It is the second leading cause of death in under-5-year olds and causes nearly one in five child deaths. Diarrhea, which can lead to life-threatening dehydration, is a common symptom of gastrointestinal infections. The viruses, bacteria and parasites that cause diarrhea spread through contaminated food or drinking water, and from person-to-person through poor hygiene and inadequate sanitation (unsafe disposal of human excreta). Interventions that prevent diarrhea include improvements in water supplies, sanitation and hygiene, the promotion of breastfeeding, vitamin A supplementation, and vaccination against rotavirus (a major cause of diarrhea). Treatments for diarrhea include oral rehydration salts (ORS), which prevent and treat dehydration, and zinc supplementation, which decreases the severity and duration of diarrhea, and antibiotics for dysentery. Why Was This Study Done? Deaths from diarrhea in young children have declined markedly over the past 30 years. However, if diarrhea deaths are not reduced further, it is unlikely that Millennium Development Goal 4 (MDG4; one of the goals agreed by world leaders in 2000 to reduce poverty)—the reduction of child mortality by two-thirds of the 1990 level by 2015—will be reached. In 2009, UNICEF and the World Health Organization (WHO) proposed a new diarrhea reduction plan. Although the effect of individual interventions in this plan is established, the likely effect of the whole package on diarrhea mortality has not been estimated. Such information would be useful for health policy planning. In this study, the researchers use the Lives Saved Tool (LiST) to estimate the potential lives saved by scale-up of diarrhea prevention and treatment interventions in 68 high child mortality countries that together account for 95% of child deaths. LiST is a child survival modeling tool that uses country-level under-5 death rates and cause of death profiles to model the effects of changes in health intervention package coverage on deaths among children. What Did the Researchers Do and Find? The researchers calculated 2010 (baseline) coverage values for seven prevention interventions (breastfeeding, vitamin A supplementation, hand washing with soap, improved sanitation, improved water source, better household water treatment, and rotavirus vaccination) and for three treatment interventions (ORS, zinc supplementation, and antibiotics for dysentery) from published data. They then used LiST to estimate the effect on diarrhea deaths of scaling up intervention coverage according to two scenarios. The “ambitious” scenario assumed a feasible increase in the coverage of all interventions from the baseline year to 2015 in 68 countries with high child mortality. The “universal” scenario assumed an increase to near 100% coverage for all the interventions. Diarrhea mortality was reduced by 78% and 92% by 2015 under the ambitious and universal scenarios, respectively. Over the 5 years of the scale-up, the universal scenario averted nearly 5 million deaths. The researchers also estimated that the additional costs in 2015 of personal prevention and treatment interventions would be US$0.80 per capita with universal coverage; the additional costs for these interventions and all sanitation and water interventions would be US$3.24 per capita. What Do These Findings Mean? These findings suggest that, with currently available interventions, it should be possible to reduce diarrhea deaths substantially at a reasonable cost. As with all computer models, the accuracy of these findings depends on the data and assumptions fed into the model, which does not, for example, account for the difficulties that may be encountered in scaling up intervention coverage in hard to reach populations. Similarly, the estimated costs associated with the two scenarios do not include the resources required to strengthen health systems in developing countries so that they are able to sustain high coverage levels of diarrhea prevention and treatment interventions. Nevertheless, these findings suggest that child mortality due to diarrhea could be significantly reduced by 2015 provided the international community acts collectively to deliver these interventions. Most importantly, the potential 1.4 million lives saved in that year would bring MDG4 a step closer simply by implementing existing low cost and effective interventions. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000428. The World Health Organization provides information on diarrhea (in several languages); its 2009 report with UNICEF Diarrhea: why children are still dying and what can be done, which includes the WHO/UNICEF treatment and prevention plan, can be downloaded from the Internet The children's charity UNICEF, which protects the rights of children and young people around the world, provides information on water, sanitation, and hygiene, and on diarrhea (in several languages) The United Nations Millennium Development Goals provides information on ongoing world efforts to reduce child mortality More details on LiST are available