Oral Rehydration Solution (ORS) and Zinc

Summary

What does this program do?

We think that free provision of ORS and zinc to caregivers (such as through a voucher system) could increase use of ORS and zinc and, in turn, decrease diarrhea-related mortality among children under five. (more)

How cost-effective is it?

We think that a program that increases ORS and zinc usage through free commodity provision could be highly cost-effective in a context with a high burden of deaths due to diarrhea. We estimate that in Nigeria, a context with a high burden, a program that increases ORS and zinc usage is 12 times as cost-effective as unconditional cash transfers (GiveWell’s benchmark for comparing different programs). (more)

A sketch of our cost-effectiveness analysis is below. This analysis requires taking a stand on several uncertain parameters that could change cost-effectiveness substantially. These key parameters are in gray.

You can see our preliminary cost-effectiveness analysis for the program here and a simple version here.

We estimate that a program to provide ORS and zinc free to caregivers is cost-effective because we think:

• Providing ORS and zinc free to caregivers is cheap. We estimate the cost per treated child is around $3 per year, including both commodity and non-commodity costs (such as staff and delivery costs). This low cost is driven partly by low estimated commodity costs ($0.30–$0.70 for a course of ORS and zinc per diarrhea episode, where we assume that children experience two to three diarrhea episodes per year on average and that costs differ depending on the age of the child). It is also driven by modest non-commodity costs and a small adjustment for leakage. (more)
• The program leads to modest increases in the uptake of ORS and zinc among children aged under five. Our best guess is that without free provision of ORS, roughly 42% of Nigerian children under five with diarrhea receive ORS and that free provision would increase this to roughly 58%. This estimate is based on the results of one RCT in Uganda, to which we apply downward adjustments to account for the internal validity and generalizability of the study. (more)
• Diarrhea is a major driver of mortality in high-burden settings. This is based on data from the Institute for Health Metrics and Evaluation, showing that 17% of under-five deaths in Nigeria are due to diarrhea, and that the diarrheal-mortality rate is around 0.4% annually from diarrhea. After making adjustments for indirect deaths, we think that the diarrhea-related mortality rate for children not using ORS is around 0.8% annually.
• There is a substantial reduction in mortality for those who start using ORS with zinc as a result of the program. A frequently cited meta-analysis estimates that ORS reduces mortality by around 93% in community settings, and there is evidence from randomized studies that ORS is roughly as effective as intravenous fluids at rehydrating children in hospital settings. We apply a downward adjustment to the effect size estimate from that meta-analysis to account for the non-randomized nature of the studies, and because we are uncertain about their generalizability. After this adjustment, we assume that the effective reduction in mortality for under-5s covered by the intervention is 60%. We assume that there is no marginal mortality benefit of providing zinc in addition to ORS. (more)

Our main uncertainties about this cost-effectiveness estimate are:

• The effect of the program on ORS and zinc usage. Our estimates rely on evidence from a single RCT and it is very possible that further RCT evidence could update our assumption. In addition, this study estimated the effect of "free provision," "convenient provision" (home delivery), and "free and convenient provision." We use the estimated effect of "free provision" in our model, but it is possible that implementation partners use a distribution method more comparable to "free and convenient provision" for which there are larger effects. We think that a 25th-75th percentile range for our assumption for the increase in the number of children treated for diarrhea is 10ppt-19ppt, which implies a cost-effectiveness range of 8x-14x cash. We may consider funding activities to generate additional evidence on this question as part of a future grant investigation. (more)
• The effect of ORS and zinc usage on mortality of children under five. We are not aware of any randomized studies of ORS in community settings, and so we rely on estimates from a meta-analysis of non-randomized studies. We think that a 25th-75th percentile range for our assumption for the effective reduction in mortality of children under five due to ORS and zinc use is 37%-75%, which implies a cost-effectiveness range of 7x-17x. We think it is unlikely that new randomized studies will be generated on this research question due to ethical concerns with running RCTs for ORS and zinc provision. (more)
• The non-commodity costs of providing free ORS and zinc. We assume that non-commodity costs are 125% of the commodity costs based on similar commodity-related interventions, but we view this figure as a rough guess. We think that a 25th-75th percentile range for the cost per child provided with ORS and zinc is $1.50-$5.00, which implies a cost-effectiveness range of 8x-28x cash. We expect to learn more about this by speaking to implementation partners, and we may consider funding activities to better estimate this parameter as part of a future grant investigation. (more)

Is there room for more funding?

We have not yet completed a full analysis of room for more funding for ORS and zinc provision programs. We believe there may be substantial room for more funding based on conversations with charities working in child health programs, including in areas with a high burden of mortality from diarrhea. (more)

Published: August 2023

What is the problem?

Diarrheal disease is the frequent passing of loose or liquid stools,1 usually caused by an infection of the intestinal tract.2 Infections are most commonly transmitted through feces-contaminated water or food.3 Diarrhea generally causes death via severe dehydration and fluid loss.4 Diarrhea is a significant cause of morbidity and mortality in low- and middle-income countries.5 The Institute for Health Metrics and Evaluation (IHME) estimated that diarrhea killed about 500,000 children under five years old in 2019.6 We have not carefully reviewed the methodology used to produce this estimate.

What is the program?

Oral rehydration solution (ORS) is a type of fluid replacement used to prevent and treat dehydration due to diarrhea.7 ORS programs typically deliver a packet of glucose, sodium, and other minerals in a powder to be dissolved in water.8

Therapeutic zinc supplementation (generally in the form of dispersible tablets) is also often provided alongside ORS, because it is understood to reduce the duration and severity of diarrhea episodes.9

The World Health Organization and UNICEF recommend that children with diarrhea take ORS, as well as 10-14 days of zinc supplements.10

Organizations aiming to increase uptake of ORS and zinc may provide these commodities to households for free through existing distribution networks (such as via community health workers). We focus on this program model in this report, but acknowledge that there may be other methods of increasing rates of ORS and zinc use for diarrhea treatment, such as through media campaigns or management of supply chains to avoid stockouts.11

Does the program have strong evidence of effectiveness?

We have moderate confidence that free ORS and zinc provision will increase usage of ORS and zinc, and that using ORS and zinc will reduce child mortality caused by diarrhea. We are highly uncertain how the program’s effectiveness (and in particular, the uptake in ORS and zinc usage) may vary by context and delivery model, and about the additive mortality benefit of zinc supplementation.

Effect of provision of commodities on ORS/zinc usage

To estimate the effect of free provision of ORS/zinc to caregivers on the usage of ORS/zinc, we rely on one randomized controlled trial (RCT) that studied the link between ORS provision and usage in Uganda. Our best guess is that free provision of ORS can decrease the share of children not using ORS when they have diarrhea by 27%. This is equivalent to a 15-16 percentage point increase in the share of children treated with ORS when they have diarrhea in settings we model. We make a simplifying assumption that this also applies to zinc usage.

Based on our review of the evidence, we have moderate confidence that ORS/zinc provision programs could increase the share of children receiving ORS/zinc when experiencing diarrhea. We identified one relevant randomized study on which we base our estimate (Wagner et al. 2019).12 We also identified three additional non-randomized studies related to ORS provision, but we did not use them to generate our estimate in favor of considering the randomized evidence.13 Wagner et al. 2019 included three treatment arms (“free only,” “convenient only,” and “free and convenient”); we focus on the difference between the control and “free only” arm because we expect that this will most closely match potential funding opportunities where commodities are made available to caregivers at no cost.14 Wagner et al. 2019 found that free provision of ORS increased the usage rates of ORS by 31%, or reduced the rate of children not receiving ORS by 40%.15

We apply an 80% adjustment to the estimate of the reduction of non-ORS usage to account for internal validity factors, including a lack of masking of data analysts and self-reporting by participants.16 We also apply an 85% adjustment to the effect size to account for external validity factors. In particular, community health workers in the study visited households and provided redeemable vouchers to parents,17 many of whom redeemed them for ORS prior to their child being sick.18 This program may have driven greater demand than a program where caregivers are unable to stock up on ORS, or are not aware of the availability of free ORS/zinc. We think it is plausible that usage rates would be lower in settings where the program does not fully replicate the study.

Effect of ORS on mortality outcomes

Our impression is that it is widely accepted that ORS is effective at reducing mortality due to diarrhea.19 Our best guess is that treating children with ORS reduces diarrhea mortality by 60%. Due to the lack of randomized controlled trials in community settings, we are uncertain about the magnitude of the effect in those contexts. Below, we discuss the evidence for the effect of ORS on mortality in community and hospital settings. Our impression is that funding opportunities we might consider recommending are likely to support ORS use through free commodity provision in community settings.

Evidence from hospital settings

The evidence that ORS succeeds at rehydrating children in hospital settings, and is comparably effective to intravenous rehydration, appears to be reasonably strong. Because of its effectiveness in rehydrating children, and because we assume that intravenous rehydration is highly effective at reducing diarrhea mortality through reducing dehydration,20 we guess that ORS is highly effective at reducing mortality due to diarrhea in hospital settings.

A 2006 Cochrane review (17 trials, 1,811 participants)21 compares oral rehydration therapy (ORT)22 with intravenous rehydration therapy in hospitals. The review included studies that treated dehydration due to gastroenteritis,23 and some of the included trials involved ORT that was administered through a nasogastric tube.24 It concludes that oral rehydration therapy is comparably effective to intravenous therapy at rehydrating children.25 ORT had a statistically significantly greater chance (4% risk difference, 95% CI 1 to 7) of failing to rehydrate26 than intravenous rehydration therapy.27 The authors conclude this difference was not clinically important.28 15 of the trials were randomized and two were quasi-randomized. The authors note that the trials varied in methodology and quality.29 We have not vetted this review or the individual studies included in the review.

Evidence from community settings

Observational case studies and non-randomized trials indicate that increased ORS coverage in the community has been associated with substantial reductions in diarrhea mortality. A frequently cited meta-analysis we have found estimates that ORS reduces mortality by around 93% in community settings.30 This analysis allowed for RCTs in its inclusion criteria, but did not find any that measured mortality.31 We are not aware of any randomized studies of ORS in community settings,32 and our understanding is that these are unlikely to exist due to ethical concerns.33

A number of case studies have also found a correlation between ORS usage and reductions in mortality.34 While we recognize the limitations of non-randomized evidence, this observational evidence, combined with the evidence of ORT’s effect on dehydration in hospital settings and the biological plausibility of the effect, leads us to think it is likely that reducing dehydration through increased ORS coverage would cause reductions in diarrhea mortality.

Due to the lack of high quality randomized evidence on the effect of ORS at reducing mortality in community settings, we are uncertain about the magnitude of the expected effect. We discount the effect size (a 93% reduction in diarrhea mortality among children who are treated with ORS) to account for this low evidence quality in the following ways:

• We apply a 20% downward adjustment for internal validity because of the non-randomized nature of the studies and the limited available evidence.
• We apply a 20% downward adjustment for external validity because we are very uncertain about how generalizable the studies’ results are (particularly because all three studies included in Munos, Walker, and Black 2010 occurred in south or southeast Asia).35 The adjustment also accounts for the possibility that children who do not receive ORS early enough into their illness may not be as protected. We are highly uncertain about the importance of this concern.

Effect of zinc on mortality outcomes

We have conducted a shallow evidence review, and have moderate confidence that zinc supplementation reduces the duration of diarrhea episodes, and may reduce the prevalence of diarrhea (although we are unsure how persistent this effect may be). We do not explicitly account for zinc-related mortality effects in our model as we are highly uncertain about the marginal mortality benefit of zinc in addition to ORS.

In the Cochrane review on zinc supplementation for treating diarrhea in children under five years old, Lazzerini and Wanzira 2016 review the results of 33 randomized, placebo-controlled trials, finding that therapeutic zinc supplementation may cause a moderate reduction in the duration of diarrhea.36 The authors were unable to determine whether zinc supplementation reduced mortality or hospitalization rates.37

We are aware of two additional studies that compared zinc supplementation alongside ORS to ORS alone:

• Baqui et al. 2002 conducted an RCT in Bangladesh.38 They found that children who received zinc in addition to ORS had a shorter duration and lower incidence of diarrhea than children who only received ORS.39 Excluding deaths related to drownings, they also found a lower mortality rate among children who received zinc,40 although we have some concerns how to interpret this given a statistically insignificant effect on all-cause mortality.41
• Bhandari et al. 2008 conducted an RCT in India.42 They found that children who received zinc in addition to ORS had a lower prevalence of diarrhea and hospitalizations than children who only received ORS at the time of the six-month survey.43 However, ORS usage rates in the intervention group also increased significantly over the trial period, so it is unclear what additional benefit zinc may have had.44

Additional benefits and negative effects

We believe that ORS and zinc provision may have additional benefits, including:

• Morbidity reductions due to zinc supplementation (including morbidity related to diarrhea and respiratory infections).45 We have not investigated these thoroughly because we believe their value is small relative to child mortality and there is a lack of high-quality evidence of these benefits. We have included a rough estimate for additional benefits in our cost-effectiveness analysis and may investigate these further in the future.46
• Medical costs savings. ORS and zinc provision may also lead to some medical cost savings if children are more likely to recover from diarrheal diseases and not need further treatment. We include a rough adjustment intended to account for this, based on GiveWell’s estimates of the average benefits per DALY averted. We make a subjective downward adjustment due to our guess that a curative intervention (where the patient still becomes ill and may require health care access) will avert fewer medical costs than a preventive one (where the patient may never become ill). We also assume that morbidity will decrease by the same share as mortality. We have not interrogated these assumptions in depth, and will likely investigate this benefit further if we investigate a specific giving opportunity. We estimate that medical costs averted account for around 7% of total benefits of the program.47

We believe there are unlikely to be substantial adverse effects associated with this intervention.48 Risks to an ORS/zinc provision program could include the following:

• Commodity expiration or market leakage. It is possible that commodities could expire before use, although we think this is unlikely given the long shelf life of ORS and zinc.49 We think it is more likely that there is “leakage” whereby commodities intended for young children don’t reach them. This could be through provided commodities being lost by caregivers, or because they are used by older age cohorts (who are at lower risk of death).50 It is also possible that children would require more ORS than initially provided to them.51 We have roughly attempted to account for this risk in the costs of the program.52
• Crowding out of private providers. Depending on the method of distribution, it is possible that distributing commodities for free could reduce their availability at private providers.53 We are highly uncertain about the likelihood of this risk.
• Timing of treatment. Wagner et al. 2019 imply that the timing of treatment for diarrhea could be important as mortality can occur quickly.54 We have not vetted this claim, but believe it is plausible. We are unsure when children participating in the trials included in Munos, Walker, and Black 2010 received treatment on average, but we think it is possible that they took ORS sooner than they would outside of a trial context and thus that the effect on mortality in the trials is larger than it might be in implementation contexts. We have attempted to account for this in our external validity adjustment (detailed above).
• Incorrect treatment. We are unsure to what extent caregivers or health workers correctly prepare and provide ORS to children. However, we are not aware of any reports indicating that ORS may become ineffective if mixed with more or less water than intended.

We will also consider potential context-specific negative effects if we consider a specific funding opportunity.

How cost-effective is the program?

We conducted a preliminary cost-effectiveness analysis. As of July 2023, we estimate that a program that increases access to ORS/zinc could be around the level of cost-effectiveness of programs we expect to direct marginal donations to.55 This cost-effectiveness analysis is for a generic program that provides free ORS and zinc targeted at children. We expect our bottom line cost-effectiveness estimate will change for specific giving opportunities and methods of delivery.

Note that our cost-effectiveness analyses are simplified models that do not take into account a number of factors. There are limitations to this kind of cost-effectiveness analysis, and we believe that cost-effectiveness estimates such as these should not be taken literally due to the significant uncertainty around them. We provide these estimates (a) for comparative purposes and (b) because working on them helps us ensure that we are thinking through as many of the relevant issues as possible.

ORS and zinc are very inexpensive commodities, and we expect that using these commodities leads to a substantial decline in mortality caused by diarrhea. If the intervention were implemented in contexts where diarrhea accounts for a large share of child deaths, this would lead to high cost-effectiveness in those settings.

A sketch of the cost-effectiveness model is below:

• We’re modeling a hypothetical program that provides ORS and zinc to households for free (either directly or through redeemable vouchers). We anticipate this will lead to an increase in use of ORS with zinc among children with diarrhea.
• We estimate ORS with zinc is around 6 times as cost-effective as unconditional cash transfers in the average low socio-demographic index (SDI) country and around 12 times as cost-effective in Nigeria, which has a higher burden of deaths due to diarrhea.
  • We consider a hypothetical cohort of 100,000 children whose households receive free ORS and zinc.
  • We guess that without this intervention around 40-45% of children would receive ORS with zinc during diarrhea episodes during the year and that providing these commodities increases this to around 55-60%, or a 15-16 percentage point increase in use of ORS with zinc.
  • Without treatment, we estimate that around 0.4% of children not receiving ORS with zinc would die over the course of the year from diarrhea in the average setting and around 0.8% would in Nigeria. This includes indirect deaths associated with diarrhea.
  • We estimate ORS with zinc lowers mortality from diarrhea by around 60%.
  • As a result, we think this program would avert around 40 deaths in the average low-SDI setting and around 70 deaths in Nigeria.56
  • We estimate that ORS with zinc costs around $3 per year for each child who uses ORS with zinc for all diarrhea episodes. This includes commodity and non-commodity costs.57
  • We estimate that this program would cost a total of around $180,000 to an implementing organization.
  • This implies $3,000-$5,000 per death averted, which is around 7 to 13 times as cost-effective as unconditional cash transfers.
  • We also incorporate additional benefits from development effects58 and medical costs averted.59 We estimate that mortality benefits account for around 90% of the total benefits of the program.60 We also incorporate an adjustment for excluded effects,61 as well as adjustments for leveraged costs incurred by the government as a result of the program and the possibility of funging other funders.62 These roughly balance out and leave our bottom line cost-effectiveness at around 6 times as cost-effective as unconditional cash transfers in average low SDI settings and around 12 times as cost-effective in Nigeria.

However, we have high uncertainty about the costs of the program, the share of in-kind costs paid by governments or other stakeholders, and the marginal benefit of zinc supplementation:

• Costs. We have moderate uncertainty about the commodity cost estimates that we use, and high uncertainty about the non-commodity cost estimates. Commodity costs seem to differ across sources, and we are unsure which source would be most applicable for a specific giving opportunity.63 We also expect that non-commodity costs will differ significantly between giving opportunities. While we have limited confidence in these estimates, we believe they are the best ones at our disposal at this stage of our investigation. We expect to be able to refine our estimates if we investigate a specific giving opportunity.
• Leverage and funging. We have high uncertainty about the magnitude of government costs that would be leveraged by a commodity provision program. If commodities are distributed through government health facilities or community health workers, then substantial government costs (in staff time) would be leveraged. We use a rough guess for this value, but expect to be able to refine this if we investigate a specific opportunity.
• Marginal benefit of zinc. We think it is plausible that zinc supplementation provides some additional mortality benefits for children with diarrhea, but we are highly uncertain about the magnitude of this. We have applied some rough adjustments to account for morbidity benefits, but have not incorporated any mortality benefits. We think that our mortality estimates are likely to be a lower bound of the plausible effect if a child takes both ORS and zinc.
• Programmatic model. We think that the uptake in usage of ORS with zinc is likely to differ by the type of promotion activity. We have modeled a general program that provides free commodities to caregivers, but we are uncertain about what any given program might look like. We expect to refine our estimates if we investigate a specific giving opportunity.
• Non-diarrheal/indirect mortality averted. We have assumed that there are 0.5 indirect deaths averted for each direct diarrhea death we estimate is averted. This estimate captures both deaths related to diarrhea but attributed to a different cause in the data,64 and the possibility that children may be less susceptible to other diseases if they are treated for diarrhea.65 We currently base our estimate of indirect deaths averted on our estimate for indirect deaths averted by seasonal malaria chemoprevention, but we assume that the effect is smaller in this case because ORS with zinc is a treatment rather than preventive intervention (and therefore children may still experience a period of vulnerability to other diseases). We think it is plausible that the number of indirect deaths related to diarrhea and those related to malaria could be substantially different, and may investigate this further in future analyses.

Room for more funding

We have not conducted a comprehensive search for charities implementing ORS/zinc provision programs. Based on some initial discussions with charities working in this area, we believe there may be opportunities to support ORS/zinc provision, although different program modalities may be more or less cost-effective.

Key questions for further investigation

If we were considering making a grant to a charity working on this program, some questions we may ask as part of further investigation include:

• What is the barrier to ORS and zinc use in a given context (e.g. commodity availability, awareness, health facility access)?
• What are the baseline treatment rates in a given context?
• What is the existing health care coverage/access in an area?
• How would the program operate in practice? For example, would ORS and zinc be distributed through community health workers, health facilities, directly to caregivers, or through private facilities?
  • Would caregivers be able to stock up on ORS and zinc (for example, if they were provided with commodities ahead of time)? Or would they only receive them on an as-needed basis?
• Is the quality of treatment likely to be lower for interventions in which caregivers administer ORS rather than community health workers?
• Does the timing, treatment frequency, and dosage of ORS treatment change its effectiveness?
• Is ORS similarly effective in homes without access to safe drinking water?
• Is there additional information that we could gather to better estimate the magnitude of the mortality effect of ORS?
• Is the underlying mortality rate lower in children not receiving treatment than in children receiving treatment (i.e., are children who are currently receiving treatment sicker than average)?

Our process

We reviewed GiveWell’s previous work on ORS and zinc supplementation. We updated this work by correcting a calculation error that caused us to underestimate the number of marginal children treated,66 and estimating general programmatic costs and commodity uptake rates (rather than using cost and uptake estimates based on a specific program). We conducted a brief literature review of more recent evidence.

Sources

• 1

  "Diarrhoea is defined as the passage of three or more loose or liquid stools per day (or more frequent passage than is normal for the individual). Frequent passing of formed stools is not diarrhoea, nor is the passing of loose, 'pasty' stools by breastfed babies." WHO, "Diarrhoeal disease," 2017

• 2

  "Diarrhoea is usually a symptom of an infection in the intestinal tract, which can be caused by a variety of bacterial, viral and parasitic organisms. Infection is spread through contaminated food or drinking-water, or from person-to-person as a result of poor hygiene." WHO, "Diarrhoeal disease," 2017

• 3
  • "Infection: Diarrhoea is a symptom of infections caused by a host of bacterial, viral and parasitic organisms, most of which are spread by faeces-contaminated water. Infection is more common when there is a shortage of adequate sanitation and hygiene and safe water for drinking, cooking and cleaning. Rotavirus and Escherichia coli, are the two most common etiological agents of moderate-to-severe diarrhoea in low-income countries. Other pathogens such as cryptosporidium and shigella species may also be important. Location-specific etiologic patterns also need to be considered." WHO, "Diarrhoeal disease," 2017
  • "Other causes: Diarrhoeal disease can also spread from person-to-person, aggravated by poor personal hygiene. Food is another major cause of diarrhoea when it is prepared or stored in unhygienic conditions. Unsafe domestic water storage and handling is also an important risk factor. Fish and seafood from polluted water may also contribute to the disease." WHO, "Diarrhoeal disease," 2017

• 4

  "Diarrhoeal disease is the second leading cause of death in children under five years old, and is responsible for killing around 525 000 children every year [estimate as of 2017]. Diarrhoea can last several days, and can leave the body without the water and salts that are necessary for survival. In the past, for most people, severe dehydration and fluid loss were the main causes of diarrhoea deaths. Now, other causes such as septic bacterial infections are likely to account for an increasing proportion of all diarrhoea-associated deaths. Children who are malnourished or have impaired immunity as well as people living with HIV are most at risk of life-threatening diarrhoea." WHO, "Diarrhoeal disease," 2017
  We have been unable to verify this claim about the increasing share of diarrhea-associated deaths that are caused by septic bacterial infection. If we learn more about this, we may update our best guess about the share of diarrhea-related mortality that using ORS and zinc will avert.

• 5

  "Diarrhoeal disease is a leading cause of child mortality and morbidity in the world, and mostly results from contaminated food and water sources. Worldwide, 780 million individuals lack access to improved drinking-water and 2.5 billion lack improved sanitation. Diarrhoea due to infection is widespread throughout developing countries." WHO, "Diarrhoeal disease," 2017
  

• 6

  See IHME data. The World Health Organization (WHO) separately estimated that diarrhea killed about 370,000 children under five years old in 2019: "Diarrhoeal disease is the second leading cause of death in children under five years old, and was responsible for the deaths of 370,000 children in 2019." WHO, "Diarrhoea"

• 7
  • "Dehydration from diarrhoea can be prevented by giving extra fluids at home, or it can be treated simply, effectively, and cheaply in all age-groups and in all but the most severe cases by giving patients by mouth an adequate glucose-electrolyte solution. This way of giving fluids to prevent or treat dehydration is called oral rehydration therapy (ORT)." WHO, Oral rehydration salts report, 2006, p. 1.
  • The WHO defines oral rehydration therapy (ORT) as "The administration of fluid by mouth to prevent or correct the dehydration that is a consequence of diarrhoea" versus oral rehydration salt solution (ORS), defined in the same report as "Specifically, the complete, new WHO/UNICEF formula." WHO, Oral rehydration salts report, 2006, p. iv.

• 8
  • "The recommended formulations of ORS can be produced in three dosage forms: powder, tablet, and liquid. In view of the overriding need to make available an essential drug through the simplest and most appropriate technology at an affordable price, this document deals only with the production of ORS in powder form, which also is the dosage form on the WHO model list of Essential Medicines." WHO, Oral rehydration salts report, 2006, pp. 6-7.
  • The WHO’s recommended ORS formulation consists of glucose (75 mmol/L), sodium (75 mmol/L), potassium (20 mmol/L), chloride (65 mmol/L), and citrate (10 mmol/L), WHO, Oral rehydration salts report, 2006, p. 3, Table 1, “Composition of the new ORS formulation.”

• 9

  “Evidence shows that zinc is beneficial in managing acute or persistent diarrhoea in children ages 6–59 months, showing clinically important reductions in illness duration and severity.” UNICEF, Pneumonia and diarrhoea: Tackling the deadliest diseases for the world's poorest children, 2012, p. 22.

• 10
  • "The number [of children who die each year as a result of acute diarrhea] can be dramatically reduced through critical therapies such as prevention and treatment of dehydration with ORS and fluids available in the home, breastfeeding, continued feeding, selective use of antibiotics and zinc supplementation for 10–14 days." WHO and UNICEF, Joint statement for clinical management of acute diarrhoea, 2004, p. 3.
  • "Mothers and other caregivers should…[p]rovide children with 20 mg per day of zinc supplementation for 10–14 days (10 mg per day for infants under six months old)." WHO and UNICEF, Joint statement for clinical management of acute diarrhoea, 2004, p. 4.
  • "The WHO-recommended treatment for acute diarrheal disease is ORS and zinc supplementation and continued feeding…This combined treatment is highly cost-effective and easily administered by caregivers in the home. WHO and UNICEF have recommended the use of ORS for the treatment of diarrhea since the 1970’s and, in 2004, the two organizations released the Joint Statement for Clinical Management of Acute Diarrhea updating their recommendations. Specifically, WHO and UNICEF encouraged the use of a new low-osmolarity ORS (Lo-ORS) formula and included zinc supplementation." Goh and Pollak 2016, p. 4.

• 11

  “Activities in diarrheal disease control programs vary widely from country to country and have included social marketing and mass media campaigns, the involvement of political figures and religious leaders, educational campaigns in schools, training of partly skilled health care workers, changes to medical school curricula, distribution schemes, as well as the establishment of outpatient oral rehydration centers.” Lenters, Das, and Bhutta 2013, p. 1.

• 12

  Wagner et al. 2019 conducted a cluster randomized controlled trial on the roles of price and convenience in ORS usage:

  • “In July of 2016, we recruited 118 community health workers (CHWs; representing 10,384 households) in Central and Eastern Uganda to participate in the study. Study villages were predominantly peri-urban, and most caretakers had no more than primary school education” (p. 1).
  • “In March of 2017, we randomized CHWs to one of four methods of ORS distribution: (1) free delivery of ORS prior to illness (free and convenient); (2) home sales of ORS prior to illness (convenient only); (3) free ORS upon retrieval using voucher (free only); and (4) status quo CHW distribution, where ORS is sold and not delivered (control). CHWs offered zinc supplements in addition to ORS in all treatment arms (free in groups 1 and 3 and for sale in group 2), following international treatment guidelines. We used household surveys to measure ORS (primary outcome) and ORS + zinc use 4 weeks after the interventions began (between April and May 2017). We assessed impact using an intention-to-treat (ITT) framework” (p. 1.)

• 13

  We identified but did not use the following studies in our analysis:

  • Das et al. 2013 conducted a meta-analysis and found that “Community based interventions led to significant rise in care seeking behaviors with 13% and 9% increase in care seeking for pneumonia and diarrhea respectively. These interventions were associated with 160% increase in the use of ORS and 80% increase in the use of zinc for diarrhea” (p. 1). Only two studies were included in the meta-analysis of free provision of ORS specifically, both of which were conducted in the 1980s in Asia: Jintaganont, Stoeckel, and Butaras 1988 (Thailand) and Kumar, Kumar, and Datta 1987 (India). These studies are both quasi-experimental:
    • “This study utilizes a quasi-experimental research design characterized by four sets of interrelated activities” Jintaganont, Stoeckel, and Butaras 1988, p. 1.
    • Kumar, Kumar, and Datta 1987 is cited as quasi-experimental by Munos, Walker, and Black 2010 (Table 1, row 1, p. i79).
  • Lam et al. 2019 conducted a (non-randomized) program that “addressed demand, supply, and policy barriers to ORS and zinc uptake through interventions in both public and private sectors. The interventions included: (1) policy revision and partner coordination; (2) market shaping to improve availability of affordable, high-quality ORS and zinc; (3) provider training and mentoring; and (4) caregiver demand generation” (p. 1). They used cross–sectional household surveys and found that “38% (95% CI = 34%-42%) received ORS at baseline and 4% (95% CI = 3%-5%) received both ORS and zinc. At endline, we found 55% (95% CI = 51%-58%) received ORS and 30% (95% CI = 27%-33%) received both ORS and zinc. Adjusting for other covariates, the odds of diarrhea being treated with ORS were 1.88 (95% CI = 1.46, 2.43) times greater at endline. The odds of diarrhea being treated with ORS and zinc combined were 15.14 (95% CI = 9.82, 23.34) times greater at endline” (p. 1).
  • Braimoh et al. 2021 implemented a (non-randomized) program in eight Nigerian states to “address critical barriers to the optimal functioning of the health care market to deliver these treatments” (p. 1). Using baseline and endline household surveys, they found that “ORS coverage increased by 21%-points (P <  0.001) for the poorest and 17%-points (P <  0.001) for the richest. Zinc coverage increased significantly for both quintiles at endline from an equally low baseline coverage level” (p. 2).

  We have not reviewed these papers in depth.

• 14

  In the “free only” arm, caretakers of a child under 5 redeemed vouchers for free ORS packets and zinc tablets at a community health worker’s home; in the “convenient only” arm, community health workers visited households with children under 5 and provided ORS and zinc at market price; in the “free and convenient arm,” community health workers visited households with children under 5 and provided ORS and zinc free of charge. Wagner et al. 2019, p. 4.

• 15
  • “The share of cases treated with ORS was 77% (448/584) in the free and convenient group, 64% (340/527) in the convenient only group, 74% (447/648) in the free only group, and 56% (335/597) in the control group.” Wagner et al. 2019, p. 1.
  • We have spoken to the authors who confirmed a typo for the free only group (the numerator should be 477 rather than 447). Zachary Wagner, email to GiveWell, December 12, 2022 (unpublished).
  • 31% increase in ORS usage = (477/648) / (335/597) - 1; 40% decrease in non-ORS usage = ((648-447)/648) / ((597-335)/597) - 1
  • Note that these simple calculations do not adjust for potential confounders, but we believe that the results are likely to broadly hold: “After adjusting for potential confounders, instructing CHWs to provide free and convenient distribution increased ORS coverage by 19 percentage points relative to the control group (95% CI 13–26; P < 0.001), 12 percentage points relative to convenient only (95% CI 6–18; P < 0.001), and 2 percentage points (not significant) relative to free only (95% CI −4 to 8; P = 0.38). Effect sizes were similar, but more pronounced, for the use of both ORS and zinc.” Wagner et al. 2019, pp. 1-2.

• 16
  • “Masking of participants was not feasible; data analysts were not masked either, but analysis followed a detailed pre-analysis plan.” Wagner et al. 2019, p. 5.
  • “This study has several other limitations. First, our measure of ORS use relies on caretaker reports. Although caretaker reports are used to monitor ORS use globally, self-reported data rely on accurate memory and could be subject to social desirability bias.” Wagner et al. 2019, p. 15.

• 17

  “We instructed CHWs to visit all of the households in their catchment area that contained a child under five years old at the beginning of the study and provide caretakers with one voucher per child under five that they could redeem at the CHW’s home for two packets of ORS and 10 tablets of zinc. We also asked CHWs to provide the standard information on ORS + zinc.” Wagner et al. 2019, p. 4.

• 18

  “Many caretakers in the free only arm redeemed their vouchers prior to a child having a diarrhea episode (33% of cases had ORS stored when the episode began, relative to only 8% in control villages; Table 4). Thus, these households already had ORS conveniently available when the child came down with diarrhea.” Wagner et al. 2019, p. 14.

• 19

  For example, see this quote from a Cochrane review: "Since the 1980s, efforts to reduce the number of deaths from diarrhoea have been based on several interventions, including the improvement of water quality and sanitation, promotion of breastfeeding, and the introduction of treatment programmes that include oral rehydration therapy (Claeson 1990). The World Health Organization (WHO) introduced the oral rehydration solution (ORS) in 1979, and it rapidly became the cornerstone of programmes for the control of diarrhoeal diseases (Claeson 1990). The osmolarity of the original formulation is 310 mOsm/L (referred to as ORS ≥ 310) and consists of glucose (111 mmol/L), sodium (90 mmol/L), potassium (20 mmol/L), chloride (80 mmol/L), and citrate (10 mmol/L) or bicarbonate (30 mmol/L). The ORS was shown to improve signs of dehydration, including thirst, sunken eyeballs, sunken fontanelles, poor skin turgor, or a decreased or absence of urine output (WHO/icddr,b 1995). It was considered to be both safe and effective (Santosham 1991), and mainly responsible for the decrease in case-fatality rates from acute dehydrating diarrhoea (Victora 2000). In 2004, the WHO recommended a different formulation in which the glucose and sodium content were each reduced to 75 mmol/L to give a total osmolarity of 245 mOsm/L (referred to as ORS ≤ 270) (WHO 2004). The ORS ≤ 270 reduces stool volume, shortens the duration of diarrhoea, and decreases the need for unscheduled intravenous therapy compared with ORS ≥ 310 (Hahn 2002)." Gregorio et al. 2016, p. 6.

• 20
  • “The most severe threat posed by diarrhoea is dehydration. During a diarrhoeal episode, water and electrolytes (sodium, chloride, potassium and bicarbonate) are lost through liquid stools, vomit, sweat, urine and breathing. Dehydration occurs when these losses are not replaced.” WHO, "Diarrhoeal disease," 2017
  • “There was a statistically significant difference in failure to rehydrate between treatment groups (RD 4%, 95% CI 1 to 7; 1811 participants, 18 trials, Analysis 1.1) . . . the failure risks were 4.9% for ORT and 1.3% for IVT [intravenous rehydration therapy].” Hartling et al. 2006, p. 6.

• 21

  "Seventeen trials (1811 participants), of poor to moderate quality, were included." Hartling et al. 2006, p. 1.

• 22
  • “Oral rehydration therapy (ORT, also referred to as ORS) is one of the most common treatments used to prevent dehydration caused by diarrhea.” Our World in Data, “Oral rehydration therapy,” 2019
  • “The term ORT is often used interchangeably with ORS (oral rehydration salts or solution), though the World Health Organisation (WHO) generally refers to the treatment itself as ORT and the exact combination of water, salt and sugar as the ORS.” Our World in Data, “Oral rehydration therapy,” 2019, endnote 2.

• 23

  “Selection criteria: Randomized and quasi‐randomized controlled trials comparing intravenous rehydration therapy (IVT) with oral rehydration therapy (ORT) in children up to 18 years of age with acute gastroenteritis.” Hartling et al. 2006, p. 1.

• 24

  “While some trials counted children taking ORS by mouth with persistent vomiting as treatment failures, others inserted nasogastric tubes in these children, thus giving ORT more chances of success in the process (Hernandez 1987; Vesikari 1987; Gonzalez 1988; Mackenzie 1991).” Hartling et al. 2006, p. 6.

• 25

  "Dehydration is when body water content is reduced causing dry skin, headaches, sunken eyes, dizziness, confusion, and sometimes death. Children with dehydration due to gastroenteritis need rehydrating either by liquids given by mouth or a tube through the nose, or intravenously. The review of 17 trials (some funded by drug companies) found that the trials were not of high quality; however the evidence suggested that there are no clinically important differences between giving fluids orally or intravenously. For every 25 children treated with fluids given orally, one child would fail and require intravenous rehydration. Further, the results for low osmolarity solutions, the currently recommended treatment by the World Health Organization, showed a lower failure rate for oral rehydration that was not significantly different from that of intravenous rehydration. Oral rehydration should be the first line of treatment in children with mild to moderate dehydration with intravenous therapy being used if the oral route fails. The evidence showed that there may be a higher risk of paralytic ileus with oral rehydration while intravenous therapy carries the risk of phlebitis (ie inflammation of the veins)." Hartling et al. 2006, p. 2.

• 26
  • We are uncertain about how failure was measured in the different trials, and to what extent this was a subjective assessment by healthcare or research staff.
  • "The definition of "failure" varied by study. We evaluated the sensitivity of a more homogeneous definition in which we limited failures to children with persistent vomiting, having some level of dehydration persisting, and experiencing shock or seizures. (We excluded children with paralytic ileus, intussusception, cerebral palsy, septicemia, urinary tract infection, and duodenal ulcer from this analysis.) This post hoc failure definition was statistically significant and favoured IVT for the fixed-effect model (RD 2%, 95% CI +0 to 4) but not for the random-effects model (RD 2%, 95% CI -0 to 4) (Analysis 2.1)." Hartling et al. 2006, p. 9.

• 27
  • "Seventeen trials (1811 participants), of poor to moderate quality, were included. There were more treatment failures with ORT (RD 4%, 95% confidence interval (CI) 1 to 7, random-effects model; 1811 participants, 18 trials; NNT = 25)." Hartling et al. 2006, p. 1.
  • This risk difference implies that if 25 children were treated with ORT, and 25 children were treated with intravenous therapy, one more child would fail to rehydrate on average with ORT than with intravenous therapy (.04x25=1).

• 28

  "Although [there were] no clinically important differences between ORT and IVT, the ORT group did have a higher risk of paralytic ileus, and the IVT group was exposed to risks of intravenous therapy. For every 25 children (95% CI 14 to 100) treated with ORT one would fail and require IVT." Hartling et al. 2006, p. 2.

• 29
  • "All trials compared an IVT arm with one or more ORT arms (oral or nasogastric). The trials varied widely in methodology and quality. They were published from 1982 to 2005 and though most were randomized, two trials were quasi-randomized (Singh 1982; Mackenzie 1991)." Hartling et al. 2006, p. 5.
  • We do not believe the inclusion of quasi-randomized trials had a substantial impact on the results as the two quasi-randomized trials (Singh 1982; Mackenzie 1991) only account for two out of the 66 incidents of failure to rehydrate for ORT, and zero for IVT. Hartling et al. 2006, Analysis 1.1.

• 30

  Munos, Walker, and Black 2010, included a meta-analysis of ORS reducing diarrhea mortality in community settings. For an example citation of this study, see Lives Saved Tool sources 2010.

  • The pooled estimate for the effectiveness of ORS interventions (from three studies reporting mortality, 68 total deaths in the studies) found an approximately 69% decrease in diarrhea mortality (95% CI 51% to 80%) with ~74% ORS coverage: "Diarrhea Mortality (n=3; 68 events). ORS reduces mortality by 69% (95% CI: 51-80%) given mean coverage of 74% (range 52-96%) (93% reduction with 100% coverage)" Munos, Walker, and Black 2010, p. i80.
  • The authors estimate that 100% coverage would cause a 93% reduction in diarrhea mortality. "The mean and median coverage levels in the intervention arms of the diarrhoea mortality studies were 74%; assuming a linear relationship between coverage and mortality reduction, at 100% coverage a 93% relative reduction in diarrhoea mortality would be expected (Figure 2)." Munos, Walker, and Black 2010, p. i78.
  • We have not vetted the individual studies included in the meta-analysis.

  We interpret their results to mean that diarrhea mortality risk when using ORS is 93% lower than mortality risk without ORS in community settings.

• 31
  • See Table 1, “Diarrhoea mortality rate: low outcome-specific quality” row, “Design” column: “Quasi experimental”. Munos, Walker, and Black 2010, p. i79.
  • The authors report the evidence was low quality due to non-randomized study designs: "We found a large body of evidence evaluating the efficacy and effectiveness of ORS, and a more limited number of studies assessing RHFs [recommended home fluids]. Based on this evidence, we estimated that ORS may reduce diarrhoea mortality by up to 93%, but were unable to estimate the effectiveness of RHFs against diarrhoea mortality because no studies were conducted outside hospital setting, which is inconsistent with the definition of ‘home fluids’ (Figures 2 and 3). Whereas the overall quality of evidence supporting the effectiveness of ORS against diarrhoea mortality was low as a result of non-randomized study designs, our conclusions are strengthened by the consistency of the effect size and direction among the studies included and those excluded from the meta-analysis. Moreover, the biological basis for ORS, co-transport of glucose and sodium across the epithelial layer in the small intestine is well established and supports a protective effect of ORS against fluid losses and electrolyte imbalances." Munos, Walker, and Black 2010, p. i81.

• 32

  We did not find any relevant studies from the first few pages of results of Google Scholar searches using the terms "ORS community mortality" or "ORS mortality RCT" (results were filtered to be since 2010).

• 33

  "At the time ORS was developed, placebo-controlled trials would have been unethical given the efficacy of IV therapy, and to our knowledge none exists. The randomized controlled trials (RCTs) of ORS conducted to confirm its efficacy instead used a comparator such as IV therapy or alternative formulations of ORS." Munos, Walker, and Black 2010, p. i75.

• 34
  • Victora et al. 2000 is a collection of four case studies which find correlations between rising ORS coverage and declining diarrhea mortality in Brazil, the Philippines, Egypt, and Mexico: “Case studies in Brazil, Egypt, Mexico, and the Philippines confirm increases in the use of ORT [Oral Rehydration Therapy] which are concomitant with marked falls in mortality. In some countries, possible alternative explanations for the observed decline in mortality have been fairly confidently ruled out.” p. 1246.
  • The scale-up of ORS in Egypt was also the subject of a Center for Global Development (CGD) case study, which found a decline in diarrhea deaths of approximately 62%-82% in the same period that ORS coverage increased considerably.
    • "During the peak of the program in the mid-1980s, the program had achieved a fourfold increase in the distribution of oral rehydration salts, compared with the 1979 baseline. . . . Between 1982 and 1987, infant mortality declined by 36 percent, and child mortality fell by 43 percent. Mortality attributed to diarrhea during this same period fell 82 percent among infants and 62 percent among children." Center for Global Development, Millions saved: Preventing diarrheal deaths in Egypt, 2007, p. 1.
  • We have not yet investigated the case studies in detail or searched for other case studies published since Victora et al. 2000.

• 35

  The three studies included in the meta-analysis were Kumar, Kumar, and Datta 1987 (India), Rahaman et al. 1979 (Bangladesh) and Thane-Toe et al. 1984 (Myanmar).

• 36
  • “Thirty‐three trials that included 10,841 children met our inclusion criteria. Most included trials were conducted in Asian countries that were at high risk of zinc deficiency.” Lazzerini and Wanzira 2016, p. 1.
  • “In children older than six months of age, zinc supplementation may shorten the average duration of diarrhoea by around half a day (MD −11.46 hours, 95% CI −19.72 to −3.19; 2581 children, 9 trials, low certainty evidence), and probably reduces the number of children whose diarrhoea persists until day seven (RR 0.73, 95% CI 0.61 to 0.88; 3865 children, 6 trials, moderate certainty evidence). In children with signs of malnutrition the effect appears greater, reducing the duration of diarrhoea by around a day (MD −26.39 hours, 95% CI −36.54 to −16.23; 419 children, 5 trials, high certainty evidence).
    Conversely, in children younger than six months of age, the available evidence suggests zinc supplementation may have no effect on the mean duration of diarrhoea (MD 5.23 hours, 95% CI −4.00 to 14.45; 1334 children, 2 trials, low certainty evidence), or the number of children who still have diarrhoea on day seven (RR 1.24, 95% CI 0.99 to 1.54; 1074 children, 1 trial, low certainty evidence)...
    Persistent diarrhoea
    In children with persistent diarrhoea, zinc supplementation probably shortens the average duration of diarrhoea by around 16 hours (MD −15.84 hours, 95% CI −25.43 to −6.24; 529 children, 5 trials, moderate certainty evidence).” Lazzerini and Wanzira 2016, p. 2.

• 37

  “There is currently not enough evidence from well‐conducted RCTs to be able to say whether zinc supplementation during acute diarrhoea reduces death or number of children hospitalized (very low certainty evidence).” Lazzerini and Wanzira 2016, p. 2.

• 38

  “Setting[:] Matlab field site of International Center for Diarrhoeal Disease Research, Bangladesh.
  Participants[:] 8070 children aged 3-59 months contributed 11 881 child years of observation during a two year period.
  Intervention[:] Children with diarrhoea in the intervention clusters were treated with zinc (20 mg per day for 14 days); all children with diarrhoea were treated with oral rehydration therapy.” Baqui et al. 2002, p. 1.

• 39
  • “Children from the intervention cluster received zinc for about seven days on average during each episode of diarrhoea. They had a shorter duration (hazard ratio 0.76, 95% confidence interval 0.65 to 0.90) and lower incidence of diarrhoea (rate ratio 0.85, 0.76 to 0.96) than children in the comparison group.” Baqui et al. 2002, p. 1.
  • “The children in the intervention and comparison clusters received oral rehydration solution, and their mothers received advice on feeding during diarrhoea and on referral to the Matlab treatment centre, if needed.” Baqui et al. 2002, p. 2.

• 40
  • “The rate of non-injury deaths in the intervention clusters was considerably lower (0.49, 0.25 to 0.94).” Baqui et al. 2002, p. 1.
  • “The lower non-injury death rate in the intervention clusters was almost entirely due to fewer deaths from diarrhoea and acute lower respiratory infection. Diarrhoea and acute lower respiratory infection together accounted for 10 deaths in the intervention clusters and 20 deaths in the comparison clusters (table 7).” Baqui et al. 2002, p. 4.

• 41

  There were a large number of deaths due to drowning in the Baqui et al. 2002 study, asymmetrically distributed across the treatment and control groups (20 in the treatment group, 10 in the control group):

  • We calculate this based on Table 4 (which shows non-injury deaths) and the statement, “a total of 70 children died—33 in the intervention clusters and 37 in the comparison clusters” (p. 4).

  If these deaths are included, Baqui et al. 2002 find no statistically significant difference between the treatment and control groups in all-cause mortality:

  • Including drowning deaths, there were 33 child deaths in the intervention group and 37 in the control group. We estimate a mortality rate of 5.63 (=33/5,866 child-years observed) per 1,000 child-years for the treatment group and a mortality rate of 6.15 (=37/6,015 child-years observed) per 1,000 child-years for the control group (see Table 6, p. 4 for child years observed).
  • The standard error for the comparison between non-injury mortality rates is around .79. We impute this from the confidence interval of the difference in mean rates shown in Table 6. Given rounding, the estimates derived from the upper and lower bounds are different ((3.7-2.2)/1.96 = 0.77); (2.2-0.6)/1.96 = 0.82), so we use the simple average.Therefore, the difference in all-cause mortality would not be statistically significant. Baqui et al. 2002, Table 6, p. 4.

  We find this concerning, as the ex-post nature of the emphasis on non-injury (rather than total) deaths makes data mining a concern and suggests that the estimate for averted non-injury mortality could be biased upwards (i.e. that zinc supplementation is actually less effective than this study suggests).

• 42

  “Six clusters of 30 000 people each in Haryana, India, were randomly assigned to intervention and control sites. Government and private providers and village health workers were trained to prescribe zinc and oral rehydration salts for use in diarrheal episodes in 1-month-old to 5-year-old children in intervention communities; in the control sites, oral rehydration salts alone was promoted.” Bhandari et al. 2008, p. e1279.

• 43

  “There was a significantly lower prevalence of diarrhea in the intervention versus the control communities (Table 4) in the 24-hour (P = .003) and 2-week (P < .0001) time intervals in survey 3. Using the local term for pneumonia or the WHO definition of ALRI, the 24-hour prevalence was lower (P < .0001) in the intervention areas compared with control areas in survey 3 (Table 4). Hospital admissions because of any cause were also significantly lower in the intervention areas than control areas in survey 3 (P < .0001), as were hospitalizations because of diarrhea (P = .023) and pneumonia (P < .0001; Table 4).” Bhandari et al. 2008, p. e1282.

• 44

  “In the 2 surveys, zinc was used in 36.5% (n = 1571) and 59.8% (n = 1649) and oral rehydration salts in 34.8% (n = 1571) and 59.2% (n = 1649) of diarrheal episodes occurring in the 4 weeks preceding interviews in the intervention areas. In control areas, oral rehydration salts were used in 7.8% (n = 2209) and 9.8% (n = 2609) of episodes.” Bhandari et al. 2008, p. e1279.

• 45

  Some studies have noted a link between zinc supplementation and respiratory infections:

  • “The 24-hour prevalences of diarrhea and acute lower respiratory infections were lower in the intervention communities (survey 3). All-cause, diarrhea, and pneumonia hospitalizations in the preceding 3 months were reduced in the intervention compared with control areas (survey 3).” Bhandari et al. 2008, p. e1279.
  • "The five studies with available information are also consistent in showing that zinc-supplemented children have a lower incidence of pneumonia than control children (Table 2). In the pooled analysis, there was a 41% (95% CI, 17–59%) lower rate of pneumonia in zinc-supplemented children (18). A study that was more recently completed shows a statistically significant 26% reduction in the incidence of pneumonia as diagnosed by clinical examination by two physicians using specific predefined clinical criteria (17)." Black 2003, p. 1486s.
  • "There are two large-scale studies among children of all ages and one smaller study among infants 1–5 months of age which demonstrated that zinc given as a treatment for diarrhoea may decrease diarrhoea prevalence by 19% and the prevalence of severe acute lower respiratory infection (ALRI)/pneumonia episodes in the months following supplementation by 23%.5,6,21 In addition, the two large-scale effectiveness studies found that the introduction of zinc led to a decrease of pneumonia hospitalizations by 50%. However, these estimates are not statistically significant and thus, at this point in time, it is not possible to conclude that there is an evidence of benefit." Walker and Black 2010, p. i67.

• 46

  See ORS/Zinc CEA, "Adjustments for excluded effects" sheet, "Diarrhea morbidity" and "Other morbidity effects (respiratory infections)" rows.

• 47

  See ORS/Zinc CEA, "Simple CEA" sheet, "Medical costs averted" row for calculations.

• 48

  We are aware that zinc supplementation has been associated with increased risk of vomiting, but do not view this as a substantive risk to our overall conclusions: “zinc supplementation increased the risk of vomiting in both age groups (children greater than six months of age: RR 1.57, 95% CI 1.32 to 1.86; 2605 children, 6 trials, moderate certainty evidence; children less than six months of age: RR 1.54, 95% CI 1.05 to 2.24; 1334 children, 2 trials, moderate certainty evidence).” Lazzerini and Wanzira 2016, p. 2.

• 49
  • “ORS is stable at room temperature and does not require cold chain storage.” USAID, Manual for procurement and supply of quality-assured MNCH commodities: Module III oral rehydration, p. 3.
  • “ORS containing citrate (as opposed to bicarbonate containing ORS) is stable at ambient temperatures/humidity and is unlikely to undergo any significant degradation as a result of heat/humidity if it is properly manufactured, packaged, and sealed. Shelf life: 2–3 years, depending on the manufacturer. It is recommended to check the product label before use.” USAID, Manual for procurement and supply of quality-assured MNCH commodities: Module III oral rehydration, p. 8.
  • Zinc’s shelf life is 36 months: “6.3 Shelf life 36 months”, WHO, Summary of product characteristics, 2013, p. 5.

• 50

  The estimated mortality rates for diarrhea and pneumonia in the 5-19 age group range from around 22 to 104 times smaller than for the under-5 age range in low SDI countries and Nigeria. See data here.

• 51

  "The amount of ORS solution consumed per day is extremely variable from child to child. Some children with high purging diarrhoea may consume very large amounts of ORS solution." WHO, Oral rehydration salts report, 2006, p. 5.

• 52

  See ORS/Zinc CEA, "CEA" sheet, "Costs" section, "Adjustment for leakage/additional doses" row.

• 53

  “Another potential concern not captured in our short follow-up period is that free distribution could reduce the number of private providers who stock ORS. This could dilute the effectiveness of our intervention. Free distribution of other health products has not been shown to effect local markets, but more evidence is needed to understand the private sector response to an increase in free ORS.” Wagner et al. 2019, p. 15.

• 54

  “In addition to increasing ORS coverage, free and convenient distribution also reduced the time between diarrhea onset and ORS initiation. Mortality from diarrhea can occur quickly, and treatment guidelines recommend immediate initiation of ORS after the first symptoms. Accelerating the start of ORS could provide meaningful health benefits.” Wagner et al. 2019, p. 14.

• 55
  • For an example of the cost-effectiveness of our recommendations, see this page. As of July 2023, we estimate that the cost-effectiveness of opportunities we direct funding to is 10 times as cost-effective as 6.1 to 12.2 times as cost-effective as unconditional cash transfers, depending on the context. See our ORS/Zinc CEA, “CEA” sheet, "Cost-effectiveness in multiples of cash transfers, after all adjustments" row.

• 56

  100,000 x 0.1518 x 0.40% x 60% (low SDI settings) and 100,000 x 0.1575 x 0.79% x 60% (Nigeria).

• 57

  We think that ORS and zinc cost $0.32 per diarrhea episode for a child aged 2 to 6 months, and $0.72 per diarrhea episode for a child aged 6 months to 5 years.

  • The WHO recommends that children receive 3 sachets of ORS, and 5 or 10 zinc tablets (for children aged under 6 months, and 6 months to 5 years respectively): “If Diarrhoea (less than 14 days AND no blood in stool)
    • Give ORS. Help caregiver give child ORS solution in front of you until child is no longer thirsty
    • Give caregiver 2 ORS packets to take home. Advise to give as much as child wants, but at least ½ cup ORS solution after each loose stool
    • Give zinc supplement. Give 1 dose daily for 10 days:
      • Age 2 months up to 6 months - ½ tablet (total 5 tablets)
      • Age 6 months up to 5 years - 1 tablet (total 10 tablets)” WHO and UNICEF, Caring for the sick child in the community: Participant's manual, 2011, p. 66.
  • We base costs on UNICEF, Oral rehydration salts and zinc: Market and supply update, 2022:
    • One packet of ORS costs around $0.07 (see Table 1, 'ORS low osm. orange flavour sachet 20.5g / 1l' row, 'Indicative Price 2021' column, p. 4).
    • An ORS-zinc co-pack (2x1L ORS sachets and 10x zinc tablets) costs around $0.57 (see Table 1, 'ORS flav. 2 x 20.5g / 1l + zinc 20mg, 10 tablets' row, 'Indicative Price 2021' column, p. 4).
    • One zinc tablet costs around $0.01 (see Table 1, 'Zinc 20mg tablets' row, 'Indicative Price 2021' column, p. 4).
  • US dollar inflation from 2021 to May 2023 was 12%. See US Inflation Calculator.

  We apply a 125% adjustment for non-commodity costs such as staff and monitoring costs. We based this estimate on the split of estimated costs of a previous commodity-related intervention we investigated. We also apply a rough 10% adjustment to account for the risk of leakage. Assuming a uniform age distribution, and an average of 2 cases of diarrhea per year in low SDI countries and in Nigeria, we therefore estimate that an ORS/zinc provision program could cost around $3.02 per year per child reached in a low SDI context, or $3.31 in Nigeria.

• 58

  See ORS/Zinc CEA, "CEA" sheet, "Units of value from development effects generated by hypothetical donation" row for calculations.

• 59

  See ORS/Zinc CEA, "CEA" sheet, "Units of values from costs averted" row for calculations.

• 60

  See ORS/Zinc CEA, "Simple CEA" sheet, "Child mortality benefits" row for calculations.

• 61

  See ORS/Zinc CEA, "CEA" sheet, "Total adjustment factor for excluded effects" row for calculations.

• 62

  See ORS/Zinc CEA, "CEA" sheet, "Leverage/Funging adjustment" section for calculations. For a full introduction to our approach to leverage and funging adjustments, see this blog post.

• 63

  See, for example, the difference between the cost of commodities procured by UNICEF in Tables 3 and 4, UNICEF, Oral rehydration salts and zinc: Market and supply update, 2016, and supplier/buyer prices indicated by MSH in sections 17.5.1 and 17.5.2 (p. T-49-50), Management Sciences for Health, International medical products price guide, 2016.

  • UNICEF indicates that the unit price of a 1 liter sachet of ORS (unflavored) was $0.07 (S1561121), while MSH indicates that the median supplier price was $0.09 (Oral Rehydration Salts (ORS) 1 PKT/1 L POWDER (PO); Supplier median price).
  • UNICEF indicates that the unit price of a co-pack with two 1 liter sachets of ORS and 10 zinc tablets was $0.58 (S1580022), while MSH indicates that the median supplier price was $0.44 (ORS+Zinc Co-Pack (2 1-lt ORS + 10 tabs Zinc) 2 ORS+20 mg EACH (PO); Supplier median price).

• 64

  Deaths are encoded as one cause in the data we use, so where there may be deaths related to two or more causes (and encoded as something other than diarrhea), these could be averted by treating children for diarrhea.
  

• 65

  Our work on water quality interventions indicates that improving water quality could reduce mortality from a wider set of infectious diseases, including some that do not cause diarrhea:

  • “These studies provide a mechanism that could contribute to explaining the surprisingly large reduction in mortality observed in the Kremer et al. 2022 (working paper) meta-analysis: water quality improvements may reduce mortality from infectious diseases that are not classified as waterborne, in addition to waterborne diseases.” GiveWell, "Water Quality Interventions," 2022. See also the modeled input to our Water Quality CEA for more information.

  ORS with zinc is a curative rather than preventive treatment for diarrhea, and so children will still experience diarrhea before treatment, which may weaken them and make them more susceptible to other diseases. Our guess is therefore that additional mortality benefits would be lower than for water quality interventions.

• 66

  Our previous CEA applied the percentage point reduction in ORS usage to the total estimated under-5 diarrhea deaths in the absence of a charity's program (see here for our previous CEA, and here for a version that shows a corrected version of our previous model). This use of the percentage point difference, and application to the estimated number of deaths, doesn’t account for the fact that there is some ORS usage already in the population.