A theoretical model is proposed that relates the level of ingestion of diarrhoea-causing pathogens to the frequency of diarrhoea in the community. The implications of this model are that, in poor communities with inadequate water supply and excreta disposal, reducing the level of enteric pathogen ingestion by a given amount will have a greater impact on diarrhoea mortality rates than on morbidity rates, a greater impact on the incidence rate of severe diarrhoea than on that of mild diarrhoea, and a greater impact on diarrhoea caused by pathogens having high infectious doses than on diarrhoea caused by pathogens of a low infectious dose. The impact of water supply and sanitation on diarrhoea, related infections, nutritional status, and mortality is analysed by reviewing 67 studies from 28 countries. The median reductions in diarrhoea morbidity rates are 22% from all studies and 27% from a few better-designed studies. All studies of the impact on total mortality rates show a median reduction of 21%, while the few better-designed studies give a median reduction of 30%. Improvements in water quality have less of an impact than improvements in water availability or excreta disposal.

Interventions for the control of diarrhoeal diseases among young children: improving water supplies and excreta disposal facilities.

This brief summarizes the results of a gender impact evaluation study, entitled The illusion of sustainability, conducted during the time period 1998 to 2001 in Kenya. The study observed that deworming is a public good since much of its social benefit comes through reduced disease transmission. People were less likely to take deworming if their direct first-order or indirect second-order social contacts were exposed to deworming. The introduction of a small fee for deworming drugs led to an 80 percent reduction in treatment rates. Take-up was not sensitive to the exact price level, suggesting that it is particularly counter-productive to charge small positive prices for the treatment of infectious diseases. An intensive school health education had no impact on worm prevention. Funding for the study derived from World Bank, NIH Fogarty International Center, Berkeley Center for Health Research.

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The Illusion of Sustainability

Background
Vitamin A deficiency (VAD) is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to many adverse health consequences, including death. Based on prior evidence and a previous version of this review, the World Health Organization has continued to recommend vitamin A supplementation for children aged 6 to 59 months. There are new data available from recently published randomised trials since the previous publication of this review in 2010, and this update incorporates this information and reviews the evidence.

Objectives
To assess the effects of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged six months to five years.

Search methods
In March 2016 we searched CENTRAL, Ovid MEDLINE, Embase, six other databases, and two trials registers. We also checked reference lists and contacted relevant organisations and researchers to identify additional studies.

Selection criteria
Randomised controlled trials (RCTs) and cluster-RCTs evaluating the effect of synthetic VAS in children aged six months to five years living in the community. We excluded studies involving children in hospital and children with disease or infection. We also excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods, or beta-carotene supplementation.

Data collection and analysis
For this update, two reviewers independently assessed studies for inclusion and abstracted data, resolving discrepancies by discussion. We performed meta-analyses for outcomes, including all-cause and cause-specific mortality, disease, vision, and side effects. We used the GRADE approach to assess the quality of the evidence.

Main results
We identified 47 studies (4 of which are new to this review), involving approximately 1,223,856 children. Studies took place in 19 countries: 30 (63%) in Asia, 16 of these in India; 8 (17%) in Africa; 7 (15%) in Latin America, and 2 (4%) in Australia. About one-third of the studies were in urban/periurban settings, and half were in rural settings; the remaining studies did not clearly report settings. Most of the studies included equal numbers of girls and boys and lasted about a year. The included studies were at variable overall risk of bias; however, evidence for the primary outcome was at low risk of bias. A meta-analysis for all-cause mortality included 19 trials (1,202,382 children). At longest follow-up, there was a 12% observed reduction in the risk of all-cause mortality for vitamin A compared with control using a fixed-effect model (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.93; high-quality evidence). This result was sensitive to choice of model, and a random-effects meta-analysis showed a different summary estimate (24% reduction: RR 0.76, 95% CI 0.66 to 0.88); however, the confidence intervals overlapped with that of the fixed-effect model. Nine trials reported mortality due to diarrhoea and showed a 12% overall reduction for VAS (RR 0.88, 95% CI 0.79 to 0.98; 1,098,538 participants; high-quality evidence). There was no significant effect for VAS on mortality due to measles, respiratory disease, and meningitis. VAS reduced incidence of diarrhoea (RR 0.85, 95% CI 0.82 to 0.87; 15 studies; 77,946 participants; low-quality evidence) and measles (RR 0.50, 95% CI 0.37 to 0.67; 6 studies; 19,566 participants; moderate-quality evidence). However, there was no significant effect on incidence of respiratory disease or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR 1.97, 95% CI 1.44 to 2.69; 4 studies; 10,541 participants; moderate-quality evidence).

Authors' conclusions
Vitamin A supplementation is associated with a clinically meaningful reduction in morbidity and mortality in children. Therefore, we suggest maintaining the policy of universal supplementation for children under five years of age in populations at risk of VAD. Further placebo-controlled trials of VAS in children between six months and five years of age would not change the conclusions of this review, although studies that compare different doses and delivery mechanisms are needed. In populations with documented vitamin A deficiency, it would be unethical to conduct placebo-controlled trials.

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Vitamin A supplementation for preventing morbidity and mortality in children from 6 months to 5 years of age.

Objective To determine if vitamin A supplementation is associated with reductions in mortality and morbidity in children aged 6 months to 5 years. Design Systematic review and meta-analysis. Two reviewers independently assessed studies for inclusion. Data were double extracted; discrepancies were resolved by discussion. Meta-analyses were performed for mortality, illness, vision, and side effects. Data sources Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, Embase, Global Health, Latin American and Caribbean Health Sciences, metaRegister of Controlled Trials, and African Index Medicus. Databases were searched to April 2010 without restriction by language or publication status. Eligibility criteria for selecting studies Randomised trials of synthetic oral vitamin A supplements in children aged 6 months to 5 years. Studies of children with current illness (such as diarrhoea, measles, and HIV), studies of children in hospital, and studies of food fortification or β carotene were excluded. Results 43 trials with about 215 633 children were included. Seventeen trials including 194 483 participants reported a 24% reduction in all cause mortality (rate ratio=0.76, 95% confidence interval 0.69 to 0.83). Seven trials reported a 28% reduction in mortality associated with diarrhoea (0.72, 0.57 to 0.91). Vitamin A supplementation was associated with a reduced incidence of diarrhoea (0.85, 0.82 to 0.87) and measles (0.50, 0.37 to 0.67) and a reduced prevalence of vision problems, including night blindness (0.32, 0.21 to 0.50) and xerophthalmia (0.31, 0.22 to 0.45). Three trials reported an increased risk of vomiting within the first 48 hours of supplementation (2.75, 1.81 to 4.19). Conclusions Vitamin A supplementation is associated with large reductions in mortality, morbidity, and vision problems in a range of settings, and these results cannot be explained by bias. Further placebo controlled trials of vitamin A supplementation in children between 6 and 59 months of age are not required. However, there is a need for further studies comparing different doses and delivery mechanisms (for example, fortification). Until other sources are available, vitamin A supplements should be given to all children at risk of deficiency, particularly in low and middle income countries.

https://www.bmj.com/content/bmj/343/bmj.d5094.full.pdf

Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis

Physical height is an important economic variable reflecting health and human capital. Puzzingly, however, differences in average height across developing countries are not well explained by differences in wealth. In particular, children in India are shorter, on average, than children in Africa who are poorer, on average, a paradox which is often called the Asian enigma. The primary contribution of this paper is to document that cross-country variation in sanitation statistically explains a large and important fraction of international height differences. Over a billion people worldwide and more than half of Indian households defecate openly without using a toilet or latrine, introducing germs into the environment that cause disease and stunt children's growth. I apply three complementary empirical strategies to Demographic and Health Survey data to identify the fraction due to sanitation: country-level regressions using collapsed DHS surveys; within-country analysis of differences between India's first and second DHS surveys; and econometric decomposition of the India-Africa height difference in child-level data. Open defecation, which is exceptionally widespread in India, accounts for much of the excess stunting in India.

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How much international variation in child height can sanitation explain

A general theory on the relationship between water supply and sanitation investments and health, the threshold-saturation theory, is proposed. The theory takes into consideration three variables: health status, socioeconomic status, and sanitation level, and attempts to encompass, for the first time in one general theoretical framework, numerous conflicting empirical findings. The two-tiered S-shaped logistic form of the relationship that is proposed assumes that at the lower end of the socioeconomic spectrum there is a threshold below which investments in community water supplies and/or excreta disposal facilities alone result in little detectable improvement in health status. Similarly, at the higher end of the socioeconomic scale, it is suggested that a point of saturation is reached beyond which further significant health benefits cannot be obtained by investments in conventional community sanitation facilities.

A preliminary attempt to validate this model using published data on sanitation level (defined as access to water supply), life expectancy, and adult literacy rates, for 65 developing countries, appears to provide preliminary support for the threshold saturation theory but further empirical validation is required before a quantitative predictive model can be developed.

Effect of investments in water supply and sanitation on health status: a threshold-saturation theory.

The impact on vitamin A deficiency (VAD), wasting malnutrition, and excessive childhood mortality of two alternative approaches-nutrition education and mega-dose capsule distribution (6-12-month-olds: 100,000 IU; 1-5-year-olds: 200,000 IU)-in communities in Nepal are compared. Approximately 40,000 children from 75 locations in seven districts in two ecological settings (lowland and hills) took part in the study and were randomly allocated to intervention cohorts or a control group. At 24 months after the implementation of the project the reduction of risk for xerophthalmia was greater among children whose mothers were able to identify vitamin-A-rich foods (relative risk (RR) = 0.25; 95% confidence interval (CI) = 0.10-0.62) than among the children who received mega-dose capsules (RR = 0.59; 95% CI = 0.41-0.84). The risk of mortality at 2 years was reduced for both the nutrition education (RR = 0.64; 95% Cl = 0.48-0.86) and capsule distribution (RR = 0.57; 95% CI = 0.42-0.77) cohorts. The nutrition education programme was, however, more expensive to deliver than the capsule distribution programme. High rates of participation for children in the supplementation programme were achieved quickly. The nutrition education messages also spread rapidly throughout the study population (regardless of intervention cohort assignment). Practices, however, were slower to change. In communities where maternal literacy was low and channels of communication were limited the capsule distribution programme appeared to be more economical. However, there are economies of scale for nationwide education programmes that do not exist for capsule distribution programmes. Although nutrition education provides economies of scale and the promise of long-term sustainability, a comprehensive national programme requires both dietary supplementation and nutrition education components.

Impact of nutrition education and mega-dose vitamin A supplementation on the health of children in Nepal.

A major constraint to obtaining reliable information about blindness and its causes in developing countries is the limited availability of ophthalmologists for diagnosis in population-based surveys. This study in rural south India assessed the feasibility of using non-ophthalmologists to make diagnoses in a population-based survey. Ten men in their early twenties with 12 years of schooling were recruited and trained as ophthalmic assistants through a six week course in basic ophthalmology. All people aged 40 and older in households in 24 villages were enumerated and invited to have an eye examination. At a central site, 1309 subjects were independently examined by an ophthalmologist and two different ophthalmic assistants. Ophthalmic assistant cataract diagnosis is both sensitive and specific relative to the ophthalmologist's diagnosis. Sensitivity and specificity estimates were used to adjust prevalence estimates obtained from ophthalmic assistant examinations conducted at the central site as well as at the doorstep of sample households. The findings indicate that epidemiologic assessment of cataract blindness can be completed using non-ophthalmologists to diagnose cataract.

Rapid Epidemiologic Assessment of Cataract Blindness

Two approaches to improve vitamin A nutriture are compared: nutrition education and mega-dose capsule distribution. The impact of these programmes on vitamin A deficiency (VAD), wasting malnutrition, and excessive childhood mortality are compared for approximately 40,000 children who were assigned to either intervention cohorts or a control group from 75 sites within seven districts in two ecological settings (Terai, or lowland, and hills) of Nepal. Twenty-four months after the implementation of the project, the reduction of risk of xerophthalmia was greater among children of mothers who were able to identify vitamin A-rich foods [relative risk (RR) = 0.25; 95% Cl = 0.10−0.62] than among children who received mega-dose capsules (RR = 0.59; 95% Cl = 0.41−0.84). The risk of mortality at two years was reduced for both the nutrition education cohort (RR = 0.64; 95% Cl = 0.48-0.86) and capsule distribution cohort (RR = 0.57; 95% Cl = 0.42−0.77). The nutrition education program, however, was more expensive to deliver than the capsule distribution programme. High rates of participation in the supplementation programme were achieved within a short period. The nutrition education message spread rapidly throughout the study population, although practice was slower to change. Where maternal literacy was low and channels of communication were limited, the capsule programme appeared to be more cost-effective. However, economies of scale for nationwide programmes exist for nutrition education programmes that do not exist for capsule distribution programmes. A comprehensive national programme requires both dietary supplementation and nutrition education.

Robert L. Tilden

Papers

Effect of investments in water supply and sanitation on health status: a threshold-saturation theory.

Impact of nutrition education and mega-dose vitamin A supplementation on the health of children in Nepal.

Rapid Epidemiologic Assessment of Cataract Blindness

Nutrition education and mega-dose vitamin A supplementation in Nepal

Vitamin a cost‐effectiveness model