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      Preventive zinc supplementation in developing countries: impact on mortality and morbidity due to diarrhea, pneumonia and malaria

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          Abstract

          Background

          Zinc deficiency is commonly prevalent in children in developing countries and plays a role in decreased immunity and increased risk of infection. Preventive zinc supplementation in healthy children can reduce mortality due to common causes like diarrhea, pneumonia and malaria. The main objective was to determine all-cause mortality and cause-specific mortality and morbidity in children under five in developing countries for preventive zinc supplementation.

          Data sources/ review methods

          A literature search was carried out on PubMed, the Cochrane Library and the WHO regional databases to identify RCTs on zinc supplementation for greater than 3 months in children less than 5 years of age in developing countries and its effect on mortality was analyzed.

          Results

          The effect of preventive zinc supplementation on mortality was given in eight trials, while cause specific mortality data was given in five of these eight trials. Zinc supplementation alone was associated with a statistically insignificant 9% (RR = 0.91; 95% CI: 0.82, 1.01) reduction in all cause mortality in the intervention group as compared to controls using a random effect model. The impact on diarrhea-specific mortality of zinc alone was a non-significant 18% reduction (RR = 0.82; 95% CI: 0.64, 1.05) and 15% for pneumonia-specific mortality (RR = 0.85; 95% CI: 0.65, 1.11). The incidence of diarrhea showed a 13% reduction with preventive zinc supplementation (RR = 0.87; 95% CI: 0.81, 0.94) and a 19% reduction in pneumonia morbidity (RR = 0.81; 95% CI: 0.73, 0.90). Keeping in mind the direction of effect of zinc supplementation in reducing diarrhea and pneumonia related morbidity and mortality; we considered all the outcomes for selection of effectiveness estimate for inclusion in the LiST model. After application of the CHERG rules with consideration to quality of evidence and rule # 6, we used the most conservative estimates as a surrogate for mortality. We, therefore, conclude that zinc supplementation in children is associated with a reduction in diarrhea mortality of 13% and pneumonia mortality of 15% for inclusion in the LiST tool. Preventive zinc supplementation had no effect on malaria specific mortality (RR = 0.90; 95% CI: 0.77, 1.06) or incidence of malaria (RR=0.92; 95 % CI 0.82-1.04)

          Conclusion

          Zinc supplementation results in reductions in diarrhea and pneumonia mortality.

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          Most cited references34

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          Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial.

          Anaemia caused by iron deficiency is common in children younger than age 5 years in eastern Africa. However, there is concern that universal supplementation of children with iron and folic acid in areas of high malaria transmission might be harmful. We did a randomised, placebo-controlled trial, of children aged 1-35 months and living in Pemba, Zanzibar. We assigned children to daily oral supplementation with: iron (12.5 mg) and folic acid (50 mug; n=7950), iron, folic acid, and zinc (n=8120), or placebo (n=8006); children aged 1-11 months received half the dose. Our primary endpoints were all-cause mortality and admission to hospital. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59549825. The iron and folic acid-containing groups of the trial were stopped early on Aug 19, 2003, on the recommendation of the data and safety monitoring board. To this date, 24 076 children contributed a follow-up of 25,524 child-years. Those who received iron and folic acid with or without zinc were 12% (95% CI 2-23, p=0.02) more likely to die or need treatment in hospital for an adverse event and 11% (1-23%, p=0.03) more likely to be admitted to hospital; there were also 15% (-7 to 41, p=0.19) more deaths in these groups. Routine supplementation with iron and folic acid in preschool children in a population with high rates of malaria can result in an increased risk of severe illness and death. In the presence of an active programme to detect and treat malaria and other infections, iron-deficient and anaemic children can benefit from supplementation. However, supplementation of those who are not iron deficient might be harmful. As such, current guidelines for universal supplementation with iron and folic acid should be revised.
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            Zinc and immune function: the biological basis of altered resistance to infection.

            Zinc is known to play a central role in the immune system, and zinc-deficient persons experience increased susceptibility to a variety of pathogens. The immunologic mechanisms whereby zinc modulates increased susceptibility to infection have been studied for several decades. It is clear that zinc affects multiple aspects of the immune system, from the barrier of the skin to gene regulation within lymphocytes. Zinc is crucial for normal development and function of cells mediating nonspecific immunity such as neutrophils and natural killer cells. Zinc deficiency also affects development of acquired immunity by preventing both the outgrowth and certain functions of T lymphocytes such as activation, Th1 cytokine production, and B lymphocyte help. Likewise, B lymphocyte development and antibody production, particularly immunoglobulin G, is compromised. The macrophage, a pivotal cell in many immunologic functions, is adversely affected by zinc deficiency, which can dysregulate intracellular killing, cytokine production, and phagocytosis. The effects of zinc on these key immunologic mediators is rooted in the myriad roles for zinc in basic cellular functions such as DNA replication, RNA transcription, cell division, and cell activation. Apoptosis is potentiated by zinc deficiency. Zinc also functions as an antioxidant and can stabilize membranes. This review explores these aspects of zinc biology of the immune system and attempts to provide a biological basis for the altered host resistance to infections observed during zinc deficiency and supplementation.
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              Standards for CHERG reviews of intervention effects on child survival

              Background The Lives Saved Tool (LiST) uses estimates of the effects of interventions on cause-specific child mortality as a basis for generating projections of child lives that could be saved by increasing coverage of effective interventions. Estimates of intervention effects are an essential element of LiST, and need to reflect the best available scientific evidence. This article describes the guidelines developed by the Child Health Epidemiology Reference Group (CHERG) that are applied by scientists conducting reviews of intervention effects for use in LiST. Methods The guidelines build on and extend those developed by the Cochrane Collaboration and the Working Group for Grading of Recommendations Assessment, Development and Evaluation (GRADE). They reflect the experience gained by the CHERG intervention review groups in conducting the reviews published in this volume, and will continue to be refined through future reviews. Presentation of the guidelines Expected products and guidelines are described for six steps in the CHERG intervention review process: (i) defining the scope of the review; (ii) conducting the literature search; (iii) extracting information from individual studies; (iv) assessing and summarizing the evidence; (v) translating the evidence into estimates of intervention effects and (vi) presenting the results. Conclusions The CHERG intervention reviews represent an ambitious effort to summarize existing evidence and use it as the basis for supporting sound public health decision making through LiST. These efforts will continue, and a similar process is now under way to assess intervention effects for reducing maternal mortality.
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                Author and article information

                Journal
                BMC Public Health
                BMC Public Health
                BioMed Central
                1471-2458
                2011
                13 April 2011
                : 11
                : Suppl 3
                : S23
                Affiliations
                [1 ]Division of Women & Child Health, The Aga Khan University, Karachi, Pakistan
                [2 ]Centre for Population Health Sciences, University of Edinburgh, UK
                [3 ]Department of International Health and Development, Tulane University School of Public Health and Tropical Medicine, USA
                [4 ]Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA
                Article
                1471-2458-11-S3-S23
                10.1186/1471-2458-11-S3-S23
                3231897
                21501441
                1595d29f-c27a-4870-bf83-52cf730382b3
                Copyright ©2011 Yakoob et al; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Public health
                Public health

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