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Ali AA, Naqvi SK, Hasnain Z, Zubairi MBA, Sharif A, Salam RA, Soofi S, Ariff S, Nisar YB, Das JK. Zinc supplementation for acute and persistent watery diarrhoea in children: A systematic review and meta-analysis. J Glob Health 2024; 14:04212. [PMID: 39641338 PMCID: PMC11622351 DOI: 10.7189/jogh.14.04212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2024] Open
Abstract
Background Zinc is a micronutrient that plays a role in immune system strengthening and regulation of intestinal epithelial cells, and can reduce the duration and severity of diarrhoea. We conducted a systematic review of randomised controlled trials (RCTs) to assess the effectiveness of zinc compared to no zinc for the management of acute and persistent diarrhoea in children. Methods We searched PubMed, the Cochrane Library, Scopus, CINAHL, ClinicalTrials.gov, and World Health Organization (WHO) International Clinical Trials Registry Platform from inception until 31 July 2023 for studies published from year 2000 onwards that assessed the use of zinc in the management of acute and persistent diarrhoea in children aged less than 10 years. We conducted the meta-analysis in Cochrane's RevMan software, determined risk of bias in individual studies using the Risk of Bias 2 (RoB 2) tool, and assessed the quality of evidence through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. This review was commissioned by the WHO for revision of their guidelines for childhood diarrhoea management. Results We included 38 RCTs in this systematic review. Our findings suggest that, in children with acute diarrhoea, zinc supplementation resulted in a greater proportion of children who recovered from diarrhoea at last follow-up (risk ratio (RR) = 1.07; 95% confidence interval (CI) = 1.03, 1.1; moderate certainty of evidence) and a reduction in the duration of diarrhoea (mean difference (MD) = -13.27 hours; 95% CI = -17.66, -8.89; moderate certainty of evidence) when compared to placebo. A significant number of children in the zinc group compared to placebo experienced vomiting (RR = 1.46; 95% CI = 1.22, 1.76; moderate certainty of evidence), however, there were few vomiting episodes in low-dose zinc group compared to high-dose (RR = 0.80; 95% CI = 0.72, 0.89; moderate certainty of evidence). In children with persistent diarrhoea, zinc supplementation led to a greater proportion of children who recovered from diarrhoea (RR = 1.75; 95% CI = 1.34, 2.30; low certainty of evidence). The low certainty of evidence ratings were mostly due to high heterogeneity among the studies. Conclusions Zinc should continue to be recommended in children under the age of 10 years with acute or persistent diarrhoea, but moderate certainty of evidence concludes that the dose of zinc should be reduced. However, further multi-country randomised clinical trials are required with a direct comparison to assess the appropriate dosage, duration and adverse effects. Registration PROSPERO: CRD42023439028.
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Affiliation(s)
- Ayesha Arshad Ali
- Institute for Global Health and Development, Aga Khan University, Karachi, Pakistan
| | - Syeda Kanza Naqvi
- Institute for Global Health and Development, Aga Khan University, Karachi, Pakistan
| | - Zain Hasnain
- Institute for Global Health and Development, Aga Khan University, Karachi, Pakistan
| | | | - Ashraf Sharif
- University Library, Aga Khan University, Karachi, Pakistan
| | - Rehana Abdus Salam
- The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, New South Wales, Australia
| | - Sajid Soofi
- Centre of Excellence in Women and Child Health, Aga Khan University, Karachi, Pakistan
- Department of Pediatrics & Child Health, Aga Khan University, Karachi, Pakistan
| | - Shabina Ariff
- Department of Pediatrics & Child Health, Aga Khan University, Karachi, Pakistan
| | - Yasir Bin Nisar
- Department of Maternal, Newborn, Child, and Adolescent Health and Ageing, World Health Organization, Geneva, Switzerland
| | - Jai K Das
- Institute for Global Health and Development, Aga Khan University, Karachi, Pakistan
- Division of Women and Child Health, Aga Khan University, Karachi, Pakistan
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Barffour MA, Hinnouho GM, Wessells KR, Kounnavong S, Ratsavong K, Sitthideth D, Bounheuang B, Sengnam K, Chanhthavong B, Arnold CD, Brown KH, Larson CP, Hess SY. Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial. J Glob Health 2021; 10:010424. [PMID: 32612816 PMCID: PMC7321011 DOI: 10.7189/jogh.10.010424] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. Methods Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. Results Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL). Overall diarrhea incidence (0.61 ± 0.01 episodes/100 days at risk) and duration (2.12 ± 0.03 days/episode) did not differ by study group. Age modified the impact of the interventions on diarrhea incidence (P = 0.06) and duration (P = 0.01). In children >18 months, TZ reduced diarrhea incidence by 24% vs MNP (P = 0.035), and 36% vs Control (P = 0.004), but there was no difference with PZ. This patterned remained when analyses were restricted to diarrhea episode occurring after the first treatment with TZ. Also, in children >18 months, TZ reduced diarrhea duration by 15% vs PZ (P = 0.03), and 16% vs Control (P = 0.03), but there was no difference with MNP. There were no overall effects of study group on incidence of ALRI (overall mean 0.005 ± 0.001 episodes/100 days, P = 0.14) or AURI (overall mean 0.09 ± 0.01 episodes/100 days, P = 0.72). Conclusions There was no overall impact of TZ, PZ or MNP on diarrhea, ALRI and AURI. However, in children >18 months, TZ significantly reduced both the duration of diarrhea episodes and the incidence of future diarrhea episodes compared with placebo. Trial registration ClinicalTrials.gov: NCT02428647.
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Affiliation(s)
- Maxwell A Barffour
- Institute for Global Nutrition, University of California, Davis, California, USA.,College of Health and Human Services, Public Health Program, Missouri State University, Springfield, Missouri, USA
| | - Guy-Marino Hinnouho
- Institute for Global Nutrition, University of California, Davis, California, USA
| | - K Ryan Wessells
- Institute for Global Nutrition, University of California, Davis, California, USA
| | - Sengchanh Kounnavong
- Lao Tropical and Public Health Institute, Vientiane, Lao People's Democratic Republic
| | - Kethmany Ratsavong
- Lao Tropical and Public Health Institute, Vientiane, Lao People's Democratic Republic
| | - Dalaphone Sitthideth
- Lao Tropical and Public Health Institute, Vientiane, Lao People's Democratic Republic
| | - Bangone Bounheuang
- Lao Tropical and Public Health Institute, Vientiane, Lao People's Democratic Republic
| | - Khanpaseuth Sengnam
- Lao Tropical and Public Health Institute, Vientiane, Lao People's Democratic Republic
| | - Bigphone Chanhthavong
- Lao Tropical and Public Health Institute, Vientiane, Lao People's Democratic Republic
| | - Charles D Arnold
- Institute for Global Nutrition, University of California, Davis, California, USA
| | - Kenneth H Brown
- Institute for Global Nutrition, University of California, Davis, California, USA
| | - Charles P Larson
- School of Population and Global Health, McGill University, Montreal, Canada
| | - Sonja Y Hess
- Institute for Global Nutrition, University of California, Davis, California, USA
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Abstract
The global impact of childhood malnutrition is staggering. The synergism between malnutrition and infection contributes substantially to childhood morbidity and mortality. Anthropometric indicators of malnutrition are associated with the increased risk and severity of infections caused by many pathogens, including viruses, bacteria, protozoa, and helminths. Since childhood malnutrition commonly involves the inadequate intake of protein and calories, with superimposed micronutrient deficiencies, the causal factors involved in impaired host defense are usually not defined. This review focuses on literature related to impaired host defense and the risk of infection in primary childhood malnutrition. Particular attention is given to longitudinal and prospective cohort human studies and studies of experimental animal models that address causal, mechanistic relationships between malnutrition and host defense. Protein and micronutrient deficiencies impact the hematopoietic and lymphoid organs and compromise both innate and adaptive immune functions. Malnutrition-related changes in intestinal microbiota contribute to growth faltering and dysregulated inflammation and immune function. Although substantial progress has been made in understanding the malnutrition-infection synergism, critical gaps in our understanding remain. We highlight the need for mechanistic studies that can lead to targeted interventions to improve host defense and reduce the morbidity and mortality of infectious diseases in this vulnerable population.
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Echevarría MA, Eva ML. Cryptosporidium and Cyclospora Diarrheal Infection in Malnourished Children: a Nutritional Approach. CURRENT TROPICAL MEDICINE REPORTS 2017. [DOI: 10.1007/s40475-017-0122-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Gammoh NZ, Rink L. Zinc in Infection and Inflammation. Nutrients 2017; 9:E624. [PMID: 28629136 PMCID: PMC5490603 DOI: 10.3390/nu9060624] [Citation(s) in RCA: 447] [Impact Index Per Article: 55.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Revised: 06/09/2017] [Accepted: 06/11/2017] [Indexed: 12/26/2022] Open
Abstract
Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.
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Affiliation(s)
- Nour Zahi Gammoh
- Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Pauwelstrasse 30, 52074 Aachen, Germany.
| | - Lothar Rink
- Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Pauwelstrasse 30, 52074 Aachen, Germany.
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Abstract
BACKGROUND In developing countries, diarrhoea causes around 500,000 child deaths annually. Zinc supplementation during acute diarrhoea is currently recommended by the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF). OBJECTIVES To evaluate oral zinc supplementation for treating children with acute or persistent diarrhoea. SEARCH METHODS We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library 2016, Issue 5), MEDLINE, Embase, LILACS, CINAHL, mRCT, and reference lists up to 30 September 2016. We also contacted researchers. SELECTION CRITERIA Randomized controlled trials (RCTs) that compared oral zinc supplementation with placebo in children aged one month to five years with acute or persistent diarrhoea, including dysentery. DATA COLLECTION AND ANALYSIS Both review authors assessed trial eligibility and risk of bias, extracted and analysed data, and drafted the review. The primary outcomes were diarrhoea duration and severity. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD) with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses (using either a fixed-effect or random-effects model) and assessed heterogeneity.We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS 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. Acute diarrhoeaThere 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).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, moderate 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, moderate certainty evidence).None of the included trials reported serious adverse events. However, 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). Persistent diarrhoeaIn 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). AUTHORS' CONCLUSIONS In areas where the prevalence of zinc deficiency or the prevalence of malnutrition is high, zinc may be of benefit in children aged six months or more. The current evidence does not support the use of zinc supplementation in children less six months of age, in well-nourished children, and in settings where children are at low risk of zinc deficiency.
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Affiliation(s)
- Marzia Lazzerini
- Institute for Maternal and Child Health IRCCS Burlo GarofoloWHO Collaborating Centre for Maternal and Child HealthVia dell'Istria 65/1, 34137TriesteItaly
| | - Humphrey Wanzira
- Institute for Maternal and Child Health IRCCS Burlo GarofoloWHO Collaborating Centre for Maternal and Child HealthVia dell'Istria 65/1, 34137TriesteItaly
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Shillcutt SD, LeFevre AE, Walker CLF, Black RE, Mazumder S. Protocol for the economic evaluation of the diarrhea alleviation through zinc and oral rehydration salt therapy at scale through private and public providers in rural Gujarat and Uttar Pradesh, India. Implement Sci 2014; 9:164. [PMID: 25407053 PMCID: PMC4335371 DOI: 10.1186/s13012-014-0164-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2014] [Accepted: 10/22/2014] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Child diarrhea persists as a leading public health problem in India despite evidence supporting zinc and low osmolarity oral rehydration salts as effective treatments. Across 2 years in 2010-2013, the Diarrhea Alleviation using Zinc and Oral Rehydration Salts Therapy (DAZT) program was implemented to operationalize delivery of these interventions at scale through private and public sector providers in rural Gujarat and Uttar Pradesh, India. METHODS/DESIGN This study evaluates the cost-effectiveness of DAZT program activities relative to status quo conditions existing before the study, comparing a Monte Carlo simulation method with net-benefit regression, discussing the strengths and weaknesses of each approach. A control group was not included in the 'before and after' study design as zinc has proven effectiveness for diarrhea treatment. Costs will be calculated using a societal perspective including program implementation and household out-of-pocket payments for care seeking, as well as estimates of wages lost. Outcomes will be measured in terms of episodes averted in net-benefit regression and in terms of the years of life lost component of disability-adjusted life years in the method based on Monte Carlo simulation. The Lives Saved Tool will be used to model anticipated changes in mortality over time and deaths averted based on incremental changes in coverage of oral rehydration salts and zinc. Data will derive from cross-sectional surveys at the start, midpoint, and endpoint of the program. In addition, Lives Saved Tool (LiST) projections will be used to define the reference case value for the ceiling ratio in terms of natural units. DISCUSSION This study will be useful both in its application to an economic evaluation of a public health program in its implementation phase but also in its comparison of two methodological approaches to cost-effectiveness analysis. Both policy recommendations and methodological lessons learned will be discussed, recognizing the limitations in drawing strong policy conclusions due to the uncontrolled study design. It is expected that this protocol will be useful to researchers planning what method to use for the evaluation of similar before and after studies.
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Affiliation(s)
- Samuel D Shillcutt
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205, USA.
| | - Amnesty E LeFevre
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205, USA.
| | - Christa L Fischer Walker
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205, USA.
| | - Robert E Black
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205, USA.
| | - Sarmila Mazumder
- Centre for Health Research and Development, Society for Applied Studies, 45 KaluSarai, New, Delhi, 110016, India.
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Skrovanek S, DiGuilio K, Bailey R, Huntington W, Urbas R, Mayilvaganan B, Mercogliano G, Mullin JM. Zinc and gastrointestinal disease. World J Gastrointest Pathophysiol 2014; 5:496-513. [PMID: 25400994 PMCID: PMC4231515 DOI: 10.4291/wjgp.v5.i4.496] [Citation(s) in RCA: 91] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Revised: 09/18/2014] [Accepted: 10/01/2014] [Indexed: 02/06/2023] Open
Abstract
This review is a current summary of the role that both zinc deficiency and zinc supplementation can play in the etiology and therapy of a wide range of gastrointestinal diseases. The recent literature describing zinc action on gastrointestinal epithelial tight junctions and epithelial barrier function is described. Zinc enhancement of gastrointestinal epithelial barrier function may figure prominently in its potential therapeutic action in several gastrointestinal diseases.
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MacIntyre J, McTaggart J, Guerrant RL, Goldfarb DM. Early childhood diarrhoeal diseases and cognition: are we missing the rest of the iceberg? Paediatr Int Child Health 2014; 34:295-307. [PMID: 25146836 DOI: 10.1179/2046905514y.0000000141] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Risk factors which interfere with cognitive function are especially important during the first 2 years of life - a period referred to as early child development and a time during which rapid growth and essential development occur. Malnutrition, a condition whose effect on cognitive function is well known, has been shown to be part of a vicious cycle with diarrhoeal diseases, and the two pathologies together continue to be the leading cause of illness and death in young children in developing countries. This paper reviews the burden of early childhood diarrhoeal diseases globally and the emerging evidence of their relationship with global disparities in neurocognitive development. The strength of evidence which indicates that the severe childhood diarrhoeal burden may be implicated in cognitive impairment of children from low- and middle-income counties is discussed. Findings suggest that greater investment in multi-site, longitudinal enteric infection studies that assess long-term repercussions are warranted. Furthermore, economic analyses using the concept of human capital should play a key role in advancing our understanding of the breadth and complexities of the health, social and economic ramifications of early childhood diarrhoeal diseases and enteric infections. This broadened awareness can serve to help advocate for more effective interventions, particularly in developing economies.
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Unger CC, Salam SS, Sarker MSA, Black R, Cravioto A, El Arifeen S. Treating diarrhoeal disease in children under five: the global picture. Arch Dis Child 2014; 99:273-8. [PMID: 24197873 DOI: 10.1136/archdischild-2013-304765] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Rates of childhood mortality due to diarrhoea remain unacceptably high and call for renewed global focus and commitment. Affordable, simple and effective diarrhoeal treatments have already been available for many years, yet a shift in international health priorities has seen coverage of recommended treatments slow to a near-standstill since 1995. This article reviews coverage of recommended childhood diarrhoeal treatments (low-osmolarity oral rehydration solution (ORS) and zinc), globally and regionally, and provides an overview of the major barriers to wide-scale coverage. It is argued that to ensure smooth supply and equitable distribution of ORS and zinc, adequate financing, relevant policy changes, strong public, private and non-government organisation (NGO) collaboration, local manufacturing of pharmaceuticals, mass media awareness and campaigning, in conjunction with strong government support, are necessary for successful treatment scale-up.
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Affiliation(s)
- Carla Chan Unger
- Centre for Child and Adolescent Health, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), , Dhaka, Bangladesh
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Lamberti LM, Fischer Walker CL, Chan KY, Jian WY, Black RE. Oral zinc supplementation for the treatment of acute diarrhea in children: a systematic review and meta-analysis. Nutrients 2013; 5:4715-40. [PMID: 24284615 PMCID: PMC3847757 DOI: 10.3390/nu5114715] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Revised: 10/09/2013] [Accepted: 11/04/2013] [Indexed: 12/11/2022] Open
Abstract
Evidence supporting the impact of therapeutic zinc supplementation on the duration and severity of diarrhea among children under five is largely derived from studies conducted in South Asia. China experiences a substantial portion of the global burden of diarrhea, but the impact of zinc treatment among children under five has not been well documented by previously published systematic reviews on the topic. We therefore conducted a systematic literature review, which included an exhaustive search of the Chinese literature, in an effort to update previously published estimates of the effect of therapeutic zinc. We conducted systematic literature searches in various databases, including the China National Knowledge Infrastructure (CNKI), and abstracted relevant data from studies meeting our inclusion and exclusion criteria. We used STATA 12.0 to pool select outcomes and to generate estimates of percentage difference and relative risk comparing outcomes between zinc and control groups. We identified 89 Chinese and 15 non-Chinese studies for the review, including studies in 10 countries from all WHO geographic regions, and analyzed a total of 18,822 diarrhea cases (9469 zinc and 9353 control). None of the included Chinese studies had previously been included in published pooled effect estimates. Chinese and non-Chinese studies reported the effect of therapeutic zinc supplementation on decreased episode duration, stool output, stool frequency, hospitalization duration and proportion of episodes lasting beyond three and seven days. Pooling Chinese and non-Chinese studies yielded an overall 26% (95% CI: 20%−32%) reduction in the estimated relative risk of diarrhea lasting beyond three days among zinc-treated children. Studies conducted in and outside China report reductions in morbidity as a result of oral therapeutic zinc supplementation for acute diarrhea among children under five years of age. The WHO recommendation for zinc treatment of diarrhea episodes should be supported in all low- and middle-income countries.
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Affiliation(s)
- Laura M. Lamberti
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD 21205, USA; E-Mails: (L.M.L.); (R.E.B.)
| | - Christa L. Fischer Walker
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD 21205, USA; E-Mails: (L.M.L.); (R.E.B.)
- Author to whom correspondence should be addressed; E-Mail: ; Tel.: +1-410-502-3478; Fax: +1-410-955-7159
| | - Kit Y. Chan
- Department of Health Policy and Management, School of Public Health, Peking University Health Science Centre, 38 Xueyuan Rd. in Haidian District, Beijing 10083, China; E-Mails: (K.Y.C.); (W.-Y.J.)
- Centre for Population Health Sciences, University of Edinburgh Medical School, Teviot Place, Edinburgh, Scotland EH8 9AG, UK
| | - Wei-Yan Jian
- Department of Health Policy and Management, School of Public Health, Peking University Health Science Centre, 38 Xueyuan Rd. in Haidian District, Beijing 10083, China; E-Mails: (K.Y.C.); (W.-Y.J.)
| | - Robert E. Black
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD 21205, USA; E-Mails: (L.M.L.); (R.E.B.)
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Qadir MI, Arshad A, Ahmad B. Zinc: Role in the management of diarrhea and cholera. World J Clin Cases 2013; 1:140-142. [PMID: 24303485 PMCID: PMC3845954 DOI: 10.12998/wjcc.v1.i4.140] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2013] [Revised: 05/30/2013] [Accepted: 06/08/2013] [Indexed: 02/05/2023] Open
Abstract
Diarrhea and cholera are major health problems. Vibrio cholera, the causative agent of cholera, infects the small intestine, resulting in vomiting, massive watery diarrhea and dehydration. Reduced water and electrolyte absorption is also due to zinc deficiency. Zinc has an important role in recovery from the disease. The combination of zinc with cholera vaccine and oral rehydration solutions has a positive impact on cholera and diarrhea. It has led to a decrease in the mortality and morbidity associated with diarrhea.
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Abstract
Diarrhea continues to stand among the most important causes of global morbidity and mortality in children under 5 years of age. Although the introduction of oral rehydration and other case-management strategies have reduced acute diarrhea fatalities, many of the survivors develop persistent diarrhea and/or deficiencies of growth and cognition. Thus understanding the true global burden of diarrhea requires attention to acute diarrhea as well is its sequelae. To understand the etiology of moderate to severe diarrhea among children in high mortality areas of sub-Saharan Africa and south Asia we performed a comprehensive case-control study of children under 5 years of age at seven sites. Each site employed an identical case-control study design and each utilized a uniform comprehensive set of microbiological assays to identify the likely bacterial, viral and protozoal etiologies. Results of the studies will inform diarrhea prevention and management efforts worldwide.
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Abstract
BACKGROUND In developing countries, diarrhoea causes around two million child deaths annually. Zinc supplementation during acute diarrhoea is currently recommended by the World Health Organization and UNICEF. OBJECTIVES To evaluate oral zinc supplementation for treating children with acute or persistent diarrhoea. SEARCH METHODS In February 2012, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2011, Issue 11), MEDLINE, EMBASE, LILACS, CINAHL, mRCT, and reference lists. We also contacted researchers. SELECTION CRITERIA Randomized controlled trials comparing oral zinc supplementation with placebo in children aged one month to five years with acute or persistent diarrhoea, including dysentery. DATA COLLECTION AND ANALYSIS Both authors assessed trial eligibility and risk of bias, extracted and analysed data, and drafted the review. Diarrhoea duration and severity were the primary outcomes. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD) with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses (using the fixed- or random-effects model) and assessed heterogeneity.The quality of evidence has been assessed using the GRADE methods MAIN RESULTS Twenty-four trials, enrolling 9128 children, met our inclusion criteria. The majority of the data is from Asia, from countries at high risk of zinc deficiency, and may not be applicable elsewhere. Acute diarrhoea. There is currently not enough evidence from well conducted randomized controlled trials to be able to say whether zinc supplementation during acute diarrhoea reduces death or hospitalization (very low quality evidence).In children aged greater than six months with acute diarrhoea, zinc supplementation may shorten the duration of diarrhoea by around 10 hours (MD -10.44 hours, 95% CI -21.13 to 0.25; 2175 children, six trials, low quality 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, six trials, moderate quality evidence). In children with signs of moderate malnutrition the effect appears greater, reducing the duration of diarrhoea by around 27 hours (MD -26.98 hours, 95% CI -14.62 to -39.34; 336 children, three trials, high quality evidence).Conversely, In children aged less than six months, the available evidence suggests zinc supplementation may have no effect on mean diarrhoea duration (MD 5.23 hours, 95% CI -4.00 to 14.45; 1334 children, two trials, low quality evidence), and may even increase the proportion of children whose diarrhoea persists until day seven (RR 1.24, 95% CI 0.99 to 1.54; 1074 children, one trial, moderate quality evidence).No trials reported serious adverse events, but zinc supplementation during acute diarrhoea causes vomiting in both age groups (RR 1.59, 95% 1.27 to 1.99; 5189 children, 10 trials, high quality evidence). Persistent diarrhoea. In children with persistent diarrhoea, zinc supplementation probably shortens the duration of diarrhoea by around 16 hours (MD -15.84 hours, 95% CI -25.43 to -6.24; 529 children, five trials, moderate quality evidence). AUTHORS' CONCLUSIONS In areas where the prevalence of zinc deficiency or the prevalence of moderate malnutrition is high, zinc may be of benefit in children aged six months or more.The current evidence does not support the use of zinc supplementation in children below six months of age.
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Affiliation(s)
- Marzia Lazzerini
- Unit for Health Services Research and International Health,WHO Collaborating Centre forMaternal and ChildHealth, Institute forMaternal and Child Health, Trieste, Italy.
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Penny ME. Zinc Supplementation in Public Health. ANNALS OF NUTRITION AND METABOLISM 2013; 62 Suppl 1:31-42. [DOI: 10.1159/000348263] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Abstract
BACKGROUND In developing countries, diarrhoea causes around two million child deaths annually. Zinc supplementation during acute diarrhoea is currently recommended by the World Health Organization and UNICEF. OBJECTIVES To evaluate oral zinc supplementation for treating children with acute or persistent diarrhoea. SEARCH METHODS In February 2012, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2011, Issue 11), MEDLINE, EMBASE, LILACS, CINAHL, mRCT, and reference lists. We also contacted researchers. SELECTION CRITERIA Randomized controlled trials comparing oral zinc supplementation with placebo in children aged one month to five years with acute or persistent diarrhoea, including dysentery. DATA COLLECTION AND ANALYSIS Both authors assessed trial eligibility and risk of bias, extracted and analysed data, and drafted the review. Diarrhoea duration and severity were the primary outcomes. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD) with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses (using the fixed- or random-effects model) and assessed heterogeneity.The quality of evidence has been assessed using the GRADE methods MAIN RESULTS Twenty-four trials, enrolling 9128 children, met our inclusion criteria. The majority of the data is from Asia, from countries at high risk of zinc deficiency, and may not be applicable elsewhere.Acute diarrhoeaThere is currently not enough evidence from well conducted randomized controlled trials to be able to say whether zinc supplementation during acute diarrhoea reduces death or hospitalization (very low quality evidence).In children aged greater than six months with acute diarrhoea, zinc supplementation may shorten the duration of diarrhoea by around 10 hours (MD -10.44 hours, 95% CI -21.13 to 0.25; 2091 children, five trials, low quality 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, six trials, moderate quality evidence). In children with signs of moderate malnutrition the effect appears greater, reducing the duration of diarrhoea by around 27 hours (MD -26.98 hours, 95% CI -14.62 to -39.34; 336 children, three trials, high quality evidence).Conversely, In children aged less than six months, the available evidence suggests zinc supplementation may have no effect on mean diarrhoea duration (MD 5.23 hours, 95% CI -4.00 to 14.45; 1334 children, two trials, low quality evidence), and may even increase the proportion of children whose diarrhoea persists until day seven (RR 1.24, 95% CI 0.99 to 1.54; 1074 children, one trial, moderate quality evidence).No trials reported serious adverse events, but zinc supplementation during acute diarrhoea causes vomiting in both age groups (RR 1.59, 95% 1.27 to 1.99; 5189 children, 10 trials, high quality evidence).Persistent diarrhoeaIn children with persistent diarrhoea, zinc supplementation probably shortens the duration of diarrhoea by around 16 hours (MD -15.84 hours, 95% CI -25.43 to -6.24; 529 children, five trials, moderate quality evidence). AUTHORS' CONCLUSIONS In areas where the prevalence of zinc deficiency or the prevalence of moderate malnutrition is high, zinc may be of benefit in children aged six months or more.The current evidence does not support the use of zinc supplementation in children below six months of age.
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Affiliation(s)
- Marzia Lazzerini
- Unit for Health Services Research and International Health,WHO Collaborating Centre forMaternal and ChildHealth, Institute forMaternal and Child Health, Trieste, Italy.
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