How Can We Accelerate the Use of Zinc for the Treatment of Diarrhea in Low- and Middle-Income Countries?

There has been considerable global progress in reducing diarrhea-related mortality in children; from an estimated 1.2 million global deaths from diarrhea in 2000, deaths were reduced to 440 000 deaths among children <5 years of age in 2021.1 Oral rehydration, along with zinc supplementation, remains the mainstay of treatment since it was recommended by the World Health Organization (WHO) and the United Nations Children’s Fund 2 decades ago, but overall progress in achieving high coverage rates at the population level has remained extremely slow.2In this issue, Karlsson et al3 present their analysis of sequential household survey data from 33 countries (studied between 2005 and 2023) and show that, after 2015, the overall change in zinc treatment reflected a median of 3.2% annual increment in utilization (interquartile range 2.7%). In addition, the overall median zinc coverage in the period of 2015 to 2023 was a meager 27.8% (95% confidence interval: 27.0–28.6) among children in need.The analysis of the pooled sample studied did not provide corresponding figures for diarrhea severity, nor was it adjusted for seasonality and care-seeking patterns. The lack of corresponding information in the analysis on the concurrent use of oral rehydration solution (ORS) therapy among children with reported diarrhea also makes it difficult to interpret the isolated findings on zinc usage in such children. The current surveys also do not provide information on the non-usage of zinc preparations based on taste and tolerance, which is often reported in children.Notwithstanding these limitations, these data reveal promising trends against a backdrop of limited success and progress. A different study of diarrhea treatment strategies in 35 countries in sub-Saharan Africa4 from 2016 to 2021 revealed that of the 44 341 children <5 years of age studied with reported diarrhea in the last 2 weeks, 39.6% reported using ORS, with only 18.4% reporting the concurrent use of zinc. Authors of other studies have documented more substantive progress, in comparison. Seifu et al5 analyzed the coverage of diarrhea management strategies across 4 countries (India, Kenya, Nigeria, and Uganda) between 2012 and 2016 and showed that improvements were possible through a comprehensive approach targeting both demand and supply barriers, including pricing, optimal product qualities, provider dispensing practices, stocking rates, and consumer demand. Variations in subnational and regional trends for zinc and ORS use also reflect variations in health system performance. An evaluation of a diarrhea treatment program using zinc and ORS among young children (aged 2–59 months) in 2 states of India (Gujarat and Uttar Pradesh) between 2010 and 2014 revealed that despite little change in overall care seeking, the usage of ORS and zinc significantly increased in Gujarat, compared with no change in Uttar Pradesh.6 The limited change in Uttar Pradesh was attributed to inadequate engagement of the private sector and barriers related to ethnicity, sex, and socioeconomic disadvantages.These studies of poor coverage and barriers to the effective use of zinc and ORS in childhood diarrhea underscore the need for better targeting and social marketing to achieve meaningful coverage globally.Several strategies have been proposed for achieving these goals, the most promising of which appears to be co-bundling zinc and ORS together as diarrhea treatment packages. These bundles have been shown to be effective in humanitarian settings,7 as well as other circumstances,8 and are now part of the WHO’s essential drug list for country use.9 There is also the considered need for revisiting the WHO/United Nations Children’s Fund recommendation for using zinc supplements for 10 to 14 days in each diarrhea episode, which is a strategy that was devised initially to offer some repletion of zinc and reduction in the risk of prolonged and persistent diarrhea. These latter categories of diarrhea have significantly diminished in magnitude and severity globally,10 and it is quite possible that a shorter duration of zinc treatment, alongside ORS use, may be much more feasible in terms of compliance and cost-effectiveness. The metallic taste of zinc formulations (lesser so with dispersible tablets) has been recognized, and there are promising results from strategies to improve flavor and taste.11Consistent findings reveal that despite large reductions in childhood mortality, diarrhea burden and morbidity in many low- and middle-income countries remains high, a finding that is underscored by the diarrhea prevalence estimates in the analysis by Karlsson et al.3 These findings underscore the need for scaling up preventive strategies, as well as optimizing case management. The latter also requires community education and building effective quality care within health systems. In an analysis of health care utilization for childhood diarrhea in the 5 highest under-5 mortality countries, Tiruneh et al12 found that the overall health care utilization for childhood diarrhea was 58.4% (95% confidence interval: 57.3%–59.5%), with close to 1 of 2 children with diarrhea not receiving appropriate care. Bridging this gap could make a huge difference and should be the focus of current diarrheal disease management strategies. Black et al13 modeled how to scale up preventive or therapeutic interventions and reductions in risk factors in 50 low- and middle-income countries. Their analysis revealed that scaling up diarrhea treatment strategies and rotavirus vaccine to 90% coverage could reduce global child diarrhea mortality by 74.1% from 2015 levels by 2030. These translate into at least 1.9 million lives saved over the next 5 to 6 years, a lofty yet worthwhile goal for global child health. Targeting an annual increase in zinc usage of at least 6%, double the currently observed 3.2% increase,3 would be an important and achievable goal.

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