Efficacy of zinc supplementation on the severity and duration of diarrhea in malnourished Turkish children. Zinc Supplementation in Malnourished Children With Persistent Diarrhea in Pakistan Micronutrients as adjunct therapy of acute illness in children: impact on the episode outcome and policy implications of current findings. Influence of Zinc Supplementation in Acute Diarrhea Differs by the Isolated Organism A randomized controlled clinical trial of zinc, vitamin A or both in undernourished children with persistent diarrhea in Bangladesh Randomized, community-based trial of the effect of zinc supplementation, with and without other micronutrients, on the duration of persistent childhood diarrhea in Lima, Peru. Cobalamin status modifies the effect of zinc supplementation on the incidence of prolonged diarrhea in 6- to 30-month-old north Indian children. Zinc supplementation and serum zinc during diarrhea Short-Course Prophylactic Zinc Supplementation for Diarrhea Morbidity in Infants of 6 to 11 Months Zinc supplementation in the management of shigellosis in malnourished children in Bangladesh Zinc and copper supplementation are not cost-effective interventions in the treatment of acute diarrhea. Supplementing iron and zinc: double blind, randomized evaluation of separate or combined delivery Effect of zinc supplementation on immune and inflammatory responses in pediatric patients with shigellosis. Impact of zinc supplementation on morbidity from diarrhea and respiratory infections among rural Guatemalan children. Zinc supplementation for four months does not affect growth in young north Indian children. Comparison of Preventive and Therapeutic Zinc Supplementation in Young Children in Burkina Faso: A Cluster-Randomized, Community-Based Trial. Village-Randomized Clinical Trial of Home Distribution of Zinc for Treatment of Childhood Diarrhea in Rural Western Kenya Substantial reduction in severe diarrheal morbidity by daily zinc supplementation in young north Indian children. Effect of Preventive Supplementation with Zinc and Other Micronutrients on Non-Malarial Morbidity in Tanzanian Pre-School Children: A Randomized Trial Zinc Supplementation for the Treatment of Diarrhea in Infants in Pakistan, India and Ethiopia Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea Effectiveness and efficacy of zinc for the treatment of acute diarrhea in young children.
BACKGROUND Intervention trials have shown that zinc may be efficacious in treating acute diarrhea in children of developing countries . A double-blind placebo-controlled study was design ed to evaluate the effects of zinc supplementation on the clinical course and duration of diarrhea in malnourished Turkish children . METHODS The study group comprised 40 subjects with low zinc levels ( Group 1a ) and 52 subjects with normal zinc levels ( Group 1b ) . The control group was also comprised of two subgroups : 36 subjects with low zinc levels ( Group 2a ) and 54 subject with normal zinc levels ( Group 2b ) . Forty-three percent of children in the study group and 40 % of controls had low serum zinc levels ( < 14 micromol/L ) , and 43 % of subjects in both groups had very low serum zinc concentrations ( < 10 micromol/L ) . The study group were given 20 mg zinc per day for 10 days and the control group were given 750 mg glucose per day as a placebo for 10 days . RESULTS The mean duration of diarrhea was shorter and the percentage of children with consistent diarrhea for more than 3 - 7 days was lower in the study subgroups than in the control subgroups . Prolonged diarrhea was present in 12 % of children in the study group , and in 44 % and 37 % of children in the hypozincemic and normozincemic control subgroups , respectively . The was no significant difference among the four subgroups of children in the number of cases with post-enrollment diarrhea of a duration of>14 days . Stool frequency over the first 4 days after enrollment was lower in children in the study group . CONCLUSION It was concluded that zinc supplementation in malnourished children with acute diarrhea may reduce the severity and duration of diarrhea , especially in children with low zinc levels Objective . To evaluate the potential benefit of dietary supplementation of a rice-lentil ( Khitchri ) and yogurt diet with 3 mg/kg/d of elemental zinc ( as zinc sulfate ) in hospitalized malnourished children ( age 6–36 months ) with persistent diarrhea for 14 days . Methodology . R and omized , double-blind placebo-controlled trial . Setting . Nutrition Research Ward at the National Institute of Child Health , Karachi , Pakistan , where children were admitted for 14 days of inpatient supervised rehabilitation . Main Outcome Measures . Primary outcome : overall weight gain by day 14 . Secondary outcomes : overall energy intake , stool output , time to diarrheal recovery and weight gain ( ≥3 days ) , plasma zinc , copper , prealbumin , and insulin-like growth factor-1 . Results . Of 87 children r and omized for supplementation with either zinc or placebo , the two groups were comparable at admission in terms of severity and duration of diarrhea , as well as nutritional and anthropometric parameters . The overall weight gain , stool volume , stool frequency , as well as the time taken for diarrheal recovery or steady weight gain , were comparable for both supplemented children and controls . Supplemented children had a significant improvement in plasma zinc levels and serum alkaline phosphatase by day 14 of therapy in comparison with controls . Plasma copper levels were low in both groups at admission and although an increase was seen in control children , levels decreased further after zinc supplementation . There was no significant difference between the two groups for hemoglobin , serum albumin , prealbumin , and plasma insulin-like growth factor-1 increments during the course of therapy . Evaluation of primary and secondary outcome criteria among the subset of children with plasma zinc levels < 60 μg/d at admission did not reveal any significant differences . Conclusions . Although there was satisfactory recovery in malnourished children with persistent diarrhea receiving the Khitchri-yogurt diet , there was no evidence of improved weight gain or acceleration of recovery from diarrhea with zinc supplementation . In contrast , the reduction in plasma copper levels in zinc-supplemented malnourished children suggests that caution should be exercised in supplementing severely malnourished children with zinc alone Role of micronutrients namely vitamin A , zinc and folate , as adjunct therapy of illness episodes in children in developing countries have been discussed in the light of health policy . Apart from a selective review , attempts have been made to statistically combine results of several studies to address policy issues . In children , vitamin A supplementation during illness has ( a ) a profound effect in reducing mortality in measles , ( b ) possibly a significant effect in reducing persistent diarrhea episodes in children with acute diarrhea , and ( c ) no benefit in pneumonia . Use of large dose vitamin A is recommended during measles episodes but not in non-measles pneumonia . Its use in acute diarrhea is debatable but recommended in persistent diarrhea and in severe malnutrition as a component of a micronutrient mixture . Large dose vitamin A supplementation should be used with caution in young infants as there are unresolved concerns about its safety particularly , bulging fontanelle observed in infants when co-administered at immunization . In children , zinc supplementation during illness , ( a ) had a marked effect in reducing prolonged episodes and a modest effect on episode duration in acute diarrhea , ( b ) result ed in reduced rate of treatment failure and death in persistent diarrhea , ( c ) had no effect in measles and non-measles pneumonia , and ( d ) probably had a detrimental effect of increasing death rate when a large dose was used in severely malnourished children . The desirability of routine zinc supplementation therapy of undernourished children with acute diarrhea should be assessed further . Concerning policy , zinc supplementation as a component of a micronutrient mixture is recommended in the rehabilitation of severely malnourished children and in persistent diarrhea . However , recommendation for its routine use in all cases of acute diarrhea in children needs additional studies on effectiveness , cost , operations and safety . In two r and omized controlled trials folate has been evaluated in acute and persistent diarrhea and found to have no beneficial effect . Folate is not recommended as adjunct therapy of diarrhea . Role of folate in preventing severe disease and /or death deserves further evaluation Zinc supplementation is recommended in all acute diarrheas in children from developing countries . We aim ed to assess whether zinc supplementation would be equally effective against all the common organisms associated with acute diarrheas . We used data on 801 children with acute diarrhea recruited in a r and omized , double blind controlled trial ( IS RCT N85071383 ) of zinc and copper supplementation .  Using prespecified subgroup analyses , multidimensionality reduction analyses , tests of heterogeneity , and stepwise logistic regression for tests of interactions , we found that the influence of zinc on the risk of diarrhea for more than 3 days depended on the isolated organism — beneficial in Klebsiella , neutral in Esherichia coli and parasitic infections , and detrimental in rotavirus coinfections . Although we found similar results for the outcome of high stool volume , the results did not reach statistical significance . Our findings suggest that the current strategy of zinc supplementation in all cases of acute diarrheas in children may need appropriate fine tuning to optimize the therapeutic benefit based on the causative organism , but further studies need to confirm and extend our findings In a double‐blind r and omized controlled clinical trial , moderately malnourished Bangladeshi children ( 61–75 % of the median weight/age ) were studied for the effect of zinc and /or vitamin A supplementation on the clinical outcome of persistent diarrhea . Children 6 mo to 2 y of age with diarrhea for more than 14 d were r and omly allocated into 4 groups of 24 receiving a multivitamin syrup and ( i ) zinc ( 20 mg elemental ) , ( ii ) vitamin A , ( iii ) both zinc and vitamin A , or ( iv ) neither , in 2 doses daily for 7 d. Clinical data on recovery and on stool output , consistency and frequency were recorded for 7 d , and weight change from day 1 to day 7 was assessed . The baseline characteristics of the four study groups were comparable . The mean daily stool outputs from days 2 to 7 of therapy were significantly less in the zinc and zinc plus vitamin A groups , but not in the vitamin A group , in comparison with the control group . In children receiving zinc , the cumulative stool weight in the 7 d was 39 % less than in the control group ( p < 0.001 ) and 32 % less than in the vitamin A group ( p= 0.006 ) . The cumulative stool weight in the zinc plus vitamin A group was 24 % less than in the control group ( p < 0.001 ) , but the 14 % lower output than in the vitamin A group was not statistically different The change in body weight over the 7d study period was significantly different between the group receiving zinc and the control group ( + 111 g vs –90 g , p = 0.045 ) . The rate of clinical recovery of children within 7 d was significantly greater in the zinc group ( 88 % ) compared with the control group ( 46 % , p= 0.002 ) or vitamin A group ( 50 % , p= 0 005 ) , but not statistically different from the zinc plus vitamin A group ( 67 % , p= 0.086 ) OBJECTIVE To determine whether supplemental zinc , with or without additional micronutrients , affects the severity and duration of persistent childhood diarrhea  and the rate of nutritional recovery . DESIGN The study was a community-based , double-blind , r and omized trial implemented in a shanty town in Lima , Peru . Children aged 6 to 36 months with persistent ( > /=14 days ) diarrhea received daily , for 2 weeks , a placebo ( group P , n = 136 ) or a supplement of 20 mg of zinc , either with ( group Z+VM , n = 137 ) or without ( group Z , n = 139 ) additional vitamins and minerals . Symptoms of illness were recorded daily , and biochemical and anthropometric assessment s were completed at baseline and on day 15 . RESULTS The treatment groups were similar at baseline with regard to the characteristics of the presenting episode , anthropometric data , and plasma zinc concentration . The children consumed , on average , 95 % ( group P ) , 94 % ( group Z ) , or 88 % ( group Z+VM ) of the supplement ( P < .001 ) . The plasma zinc concentration did not change significantly from baseline to day 15 in group P ( 4 microg/dL ) but increased by 38 microg/dL in group Z and 14 microg/dL in group Z+VM . The median duration of diarrhea after starting treatment was 1 day ; among children who continued to have diarrhea , there was a significant effect of treatment on diarrheal duration ( P = .04 , analysis of covariance ) . Specifically , the duration of illness was significantly reduced by 28 % in children in group Z ( P = .01 ) and by 33 % in girls in group Z+VM ( P = .04 ) . There were no differences in the severity of the episode by treatment group . CONCLUSION There was a significant reduction in the duration of persistent diarrhea in selected subgroups of zinc-supplemented ambulatory patients in this population The observed effect of zinc supplementation on  diarrheal morbidity  varies between trials and there is a need to identify subgroups most likely to benefit from improved zinc nutriture . In a r and omized , double-blind trial in 2296 children in New Delhi , India , we assessed whether baseline cobalamin or folate status modified the effect of zinc supplementation on the incidence of  prolonged ( ≥ 7 d duration ) and acute diarrhea . Children aged 6 - 30 mo  received zinc or placebo daily for 4 mo . We measured plasma concentrations of folate , cobalamin , total homocysteine ( tHcy ) , and methylmalonic acid ( MMA ) at enrollment and assessed the efficacy of zinc supplementation in subgroups based on these variables . The efficacy of zinc on reducing the risk of prolonged diarrhea was higher in those with plasma cobalamin concentrations below the 25th percentile and in those with tHcy and MMA concentrations above the 75th percentile . The OR ( 95 % CI ) for children below and above the 25th percentile for cobalamin were 0.53 ( 0.35 - 0.78 ) and 0.90 ( 0.73 - 1.11 ) , respectively ( P-interaction = 0.015 ) . There were similar differences for the OR when comparing efficacy in those above and below the 75th percentile for tHcy and MMA ( P-interaction = 0.045 and 0.188 , respectively ) . Baseline folate status did not modify the effect of zinc on prolonged diarrhea . Neither cobalamin nor folate status influenced the effect of zinc on acute diarrhea . Children with poor cobalamin status benefited more from zinc supplementation for the prevention of prolonged diarrhea Objective Zinc deficiency is very common in developing countries and is more pronounced during an episode of diarrhea . Supplementation with zinc improves diarrhea and might correct zinc deficiency in both the short and longer term . Method .We conducted a nested study within a cluster r and omized treatment trial . Fifty children with diarrhea living in the zinc treated clusters , 50 children with diarrhea living in control clusters , and 50 healthy children living in the control clusters were enrolled . We assessed serum zinc at the start of the diarrhea episode , which was 1–3 days after supplementation began in zinc treated children , and again one week after the diarrhea ended and supplementation ceased . Baseline characteristics and serum zinc concentration were assessed . Results .Serum zinc was low in 44 % of healthy children at the first blood draw . Compared to healthy controls , serum zinc was 3.1 mmol/L higher among children with diarrhea who were supplemented with zinc at first blood draw and 1.3mmol/L higher 3 weeks later . Conclusion .Zinc supplementation  enhances serum zinc concentration when given as a treatment for diarrhea and helps children maintain a more adequate zinc status during the convalescent period BACKGROUND : Zinc supplementation during diarrhea substantially reduces the incidence and severity of diarrhea . However , the effect of short-course zinc prophylaxis has been observed only in children > 12 months of age . Because the incidence of diarrhea is comparatively high in children aged 6 to 11 months , we assessed the prophylactic effect of zinc on incidence and duration of diarrhea in this age group . METHODS : In this r and omized , double-blind , placebo-controlled trial , we enrolled infants aged 6 to 11 months from an urban resettlement colony in Delhi , India , between January 1 , 2011 , and January 15 , 2012 . We r and omly assigned 272 infants to receive either 20 mg of zinc or a placebo suspension orally every day for 2 weeks . The primary outcome was the incidence of diarrhea per child-year . All analyses were done by intention-to-treat . RESULTS : A total of 134 infants in the zinc and 124 in the placebo groups were assessed for the incidence of diarrhea . There was a 39 % reduction ( crude incident rate ratio [ IRR ] 0.61 , 95 % confidence interval [ CI ] 0.53–0.71 ) in episodes of diarrhea , 39 % ( adjusted IRR 0.61 , 95 % CI 0.54–0.69 ) in the total number of days that a child suffered from diarrhea , and reduction of 36 % in duration per episode of diarrhea ( IRR 0.64 , 95 % CI 0.56–0.74 ) during the 5 months of follow-up . CONCLUSIONS : Short-course prophylactic zinc supplementation for 2 weeks may reduce diarrhea morbidity in infants of 6 to 11 months for up to 5 months , in population s with high prevalence of wasting and stunting Objective : To assess the impact of zinc supplementation on clinical recovery , weight gain and subsequent growth and morbidity in moderately malnourished children with shigellosis . Design : A r and omized , double-blind , controlled trial . Setting : Dhaka hospital of ICDDR , B : Centre for Health and Population Research , Dhaka , Bangladesh . Subjects : Fifty-six moderately malnourished children , aged 12–59 months with culture-proven shigellosis . Methods : Subjects were r and omly allocated to receive zinc ( 20 mg/day elemental ) in multivitamin syrup ( intervention ) or multivitamin syrup without zinc ( control ) in two equally divided doses daily for 2 weeks . All children received pivmecillinam in a dose of 15 mg/kg every 6 h for 5 days . After supplementation , children were followed in their respective homes every 2 weeks for 6 months . Results : Children receiving zinc recovered from acute illness significantly faster than the control children ( P<0.05 ) . The medians time ( days ) to recovery and disappearances of blood and mucous were significantly 50 % shorter in the zinc-supplemented group compared to the control group . The mean body weight of zinc supplemented children increased significantly from 8.8 kg on admission to 9.2 kg ( P<0.01 ) at recovery , which was not observed in the control children ( from 9.3 to 9.6 kg ; P=0.12 ) . During the 6-month follow-up period , zinc-supplemented children had significantly fewer mean episodes of diarrhoea compared to the control children ( 2.2 vs 3.3 ; P=0.03 ) . Conclusion : Zinc supplementation significantly shortens the duration of acute shigellosis , promotes better weight gain during recovery and reduces diarrhoeal morbidity during the subsequent 6 months BACKGROUND Diarrhea is one of the principal causes of morbidity and mortality among children in the developing world . Cumulative costs of treating diarrhea would be high and would further increase if zinc was used as an adjunct to treatment of acute diarrhea . OBJECTIVE To determine the impact of zinc supplementation on the mean predicted costs of treating acute diarrhea and the incremental cost-effectiveness ( CE ) as compared with placebo , from the provider 's ( government ) and patient 's perspective . STUDY DESIGN AND SETTING In a r and omized , double-blind , placebo-controlled clinical trial , 808 children aged 6 - 59 months with acute diarrhea were individually r and omized to placebo ( Pl ) , zinc ( Zn ) only , and zinc and copper ( Zn + Cu ) together with st and ard treatment of acute diarrhea . The actual re source utilization and cost data were collected for all participants . The incremental CE ratio and its 95 % confidence interval ( 95 % CI ) were assessed . RESULTS The relative CE for treating acute diarrhea was 1.5 ( 95 % CI : 1.50 , 1.52 ) times more when supplemented with zinc and 1.7 ( 95 % CI : 1.69 , 1.71 ) times more when supplemented with Zn + Cu with no additional beneficial effect . CONCLUSION This study showed that zinc or zinc with copper supplementation were not cost-effective in the treatment of acute diarrhea in this study population Background / Objectives : Many children have diets deficient in both iron and zinc , but there has been some evidence of negative interactions when they are supplemented together . The optimal delivery approach would maximize clinical benefits of both nutrients . We studied the effectiveness of different iron and zinc supplement delivery approaches to improve  diarrhea and anemia in a rural Bangladesh population . Study Design : R and omized , double blind , placebo-controlled factorial community trial . Results : Iron supplementation alone increased diarrhea , but adding zinc , separately or together , attenuated these harmful effects . Combined zinc and iron was as effective as iron alone for iron outcomes . All supplements were vomited < 1 % of the time , but combined iron and zinc were vomited significantly more than any of the other supplements . Children receiving zinc and iron ( together or separately ) had fewer hospitalizations . Separating delivery of iron and zinc may have some additional benefit in stunted children . Conclusions : Separate and combined administration of iron and zinc are equally effective for reducing diarrhea , hospitalizations and improving iron outcomes . There may be some benefit in separate administration in stunted children BACKGROUND Several studies showed benefits of long-term zinc supplementation on the incidence , severity , and duration of diarrhea and on the incidence of respiratory infections . Prolonged zinc supplementation also improves cell-mediated immunity in severely malnourished children . OBJECTIVE We studied the effect of short-term zinc supplementation on intrinsic and specific immune and inflammatory responses in moderately malnourished children with acute shigellosis . DESIGN A r and omized , double-blind , placebo-controlled trial was conducted in Shigella-infected children aged 12 - 59 mo .  Elemental zinc ( 20 mg ) and a multivitamin containing vitamins A and D , thiamine , riboflavin , nicotinamide , and calcium at twice the recommended dietary allowance were given daily for 2 wk to the zinc group ( n = 28 ) , whereas the multivitamin alone was given to the control group  ( n = 28 ) . St and ard antibiotic therapy was given to all patients . RESULTS Serum zinc concentrations increased in both groups during convalescence ; however , zinc supplementation showed a significant effect . The lymphocyte proliferation response in the zinc group increased relative to that in the control group ( P = 0.002 ) , but no significant effects were seen on concentrations of cytokines ( interleukin 2 and interferon gamma ) released from mitogen-stimulated mononuclear cells or on concentrations of cytokines ( interleukin 2 , interferon gamma , and interleukin 1beta ) in feces . Among the antigen [ lipopolysaccharide and invasion plasmid-encoded antigen (Ipa)]-specific antibodies , plasma Ipa-specific immunoglobulin G responses at day 30 were significantly higher in the zinc group than in the control group . However , the 2 groups did not differ significantly in the other antigen-specific responses in plasma and stool . CONCLUSION A 14-d course of zinc supplementation during acute shigellosis increases the lymphocyte proliferation response and the Ipa-specific immunoglobulin G response OBJECTIVE A community-based , r and omized , double-blind intervention trial was conducted to measure the impact of zinc supplementation on young Guatemalan children 's morbidity from diarrhea and respiratory infections .  METHODS Children aged 6 to 9 months were r and omly assigned to receive 4 mL of a beverage containing 10 mg of zinc ( as zinc sulfate ) daily ( 7 d/wk ) for 7 months ( n = 45 ) or a placebo ( n = 44 ) . Morbidity data were collected daily . Diagnoses of diarrhea , fever , and anorexia were based on mothers ' definitions . Respiratory infections were defined as the presence of at least two of the following symptoms : runny nose , cough , wheezing , difficulty breathing , or fever . RESULTS High rates of diarrhea and respiratory infections were reported . Children from the placebo group had a 20 % episodic prevalence of diarrhea , with 8 episodes/100 d , and a 7 % episodic prevalence of respiratory infections , with 3 episodes/100 d. The median incidence of diarrhea among children who received zinc supplementation was reduced by 22 % ( Wilcoxon rank test ) , with larger reductions among boys and among children with weight-for-length at baseline lower than the median of the sample ( 39 % reductions in both subgroups ) . Zinc supplementation also produced a 67 % reduction in the percentage of children who had one or more episodes of persistent diarrhea ( chi2 test ) . No significant effects were found on the episodic prevalence of diarrhea , the number of days per episode , or the episodic prevalence or incidence of respiratory infections . CONCLUSIONS The large impact of zinc supplementation on diarrhea incidence suggests that young , rural Guatemalan children may be zinc deficient and that zinc supplementation may be an effective intervention to improve their health and growth Our objective in this trial was to assess the impact of daily zinc supplementation on growth in young children .  A double-blind , r and omized , placebo-controlled trial was conducted in New Delhi , India . We enrolled 2482 children aged 6 - 30 mo who were supplemented daily with placebo or zinc ( 10 mg elemental zinc to infants and 20 mg to older children ) for 4 mo . At enrollment , all children also received a single dose of vitamin A ( 104.7 micromol for infants and 209.4 micromol for older children ) . Weight and length were measured at enrollment and 4 mo later . Weekly visits were conducted by field workers to ascertain morbidity in the previous 7 d. Change in length , weight , length-for-age Z-scores ( LAZ ) , and weight-for-length Z-scores ( WLZ ) after 4 mo of supplementation were assessed in the zinc and placebo groups . After 4 mo of supplementation , the weight and length gains in the 2 groups did not differ and there was no impact on LAZ , weight-for-age , and WLZ in the 2 groups . There was no substantial effect in any of the subgroups defined for age , income , gender , zinc levels in the crude analysis nor after adjusting for age , gender , income , breast-feeding status , and baseline anthropometric status . Despite successful zinc supplementation reflected in increased plasma zinc concentration and a substantially reduced incidence of diarrhea and pneumonia in zinc-supplemented children , the intervention did not have a beneficial effect on growth BACKGROUND The WHO and UNICEF recommend therapeutic zinc supplementation ( TZS ) for the treatment of diarrhea . In zinc-deficient population s , preventive zinc supplementation might provide greater benefits for reducing diarrhea and malaria incidence and increasing growth and plasma zinc ( pZn ) concentration . If effective , intermittent preventive zinc supplementation ( IPZS ) would cost less than daily preventive zinc supplementation ( DPZS ) . OBJECTIVE We assessed the effects of IPZS , DPZS , and TZS in children on the primary outcomes of diarrhea incidence , malaria incidence , growth , and pZn concentration compared with nonsupplemented control groups . METHODS Rural Burkinabe children ( n = 7641 ; 6 - 30 mo old ) in 36 clusters were r and omly assigned to 1 of 5 treatment groups for 16 , 32 , or 48 wk : 1 ) IPZS ( 10 mg Zn/d for 10 d every 16 wk ) ; 2 ) DPZS ( 7 mg Zn/d ) ; 3 ) TZS ( 20 mg Zn/d for 10 d for diarrhea ) ; 4 ) morbidity surveillance control ( MSC ) ; or 5 ) nonintervention control ( NIC ) . Supplemented groups remained masked until completion of primary analyses with mixed models . RESULTS At baseline , stunting ( 28.6 % ) and low pZn concentration ( < 65 μg/dL ; 43.5 % ) were common . After 48 wk , mean ± SE pZn increased more ( P = 0.008 ) in the DPZS group ( 3.9 ± 1.3 μg/dL ) than in the TZS ( -0.5 ± 1.2 μg/dL ) and NIC ( -1.2 ± 0.9 μg/dL ) groups . All supplemented groups had a moderately lower incidence of reported diarrhea ( 0.48 - 0.49 compared with 0.57 episodes/100 d , P = 0.001 ) and reported fever ( 1.1 - 1.2 compared with 1.5 episodes/100d , P < 0.001 ) and gained slightly less length ( 3.15 - 3.20 compared with 3.36 cm/16 wk , P < 0.001 ) than the MSC group , but did not differ from each other . Prevalence of diarrhea and incidences of confirmed fever and malaria were not different across study groups . CONCLUSIONS The preventive and TZS groups had reduced diarrhea incidence , but it is uncertain whether this result ed from a functional response to zinc or reporting bias . The comparison should be re-examined in population s known to respond to zinc supplementation . This trial was registered at www . clinical trials.gov as NCT00944359 Background Zinc treatment shortens diarrhea episodes and can prevent future episodes . In rural Africa , most children with diarrhea are not brought to health facilities . In a village-r and omized trial in rural Kenya , we assessed if zinc treatment might have a community-level preventive effect on diarrhea incidence if available at home versus only at health facilities . Methods We r and omized 16 Kenyan villages ( 1,903 eligible children ) to receive a 10-day course of zinc and two oral rehydration solution ( ORS ) sachets  every two months at home and 17 villages ( 2,241 eligible children ) to receive ORS  at home , but zinc at the health – facility only . Children ’s caretakers were educated in zinc/ORS use by village workers , both unblinded to intervention arm . We evaluated whether incidence of diarrhea and acute lower respiratory illness ( ALRI ) reported at biweekly home visits and presenting to clinic were lower in zinc villages , using poisson regression adjusting for baseline disease rates , distance to clinic , and children ’s age . Results There were no differences between village groups in diarrhea incidence either reported at the home or presenting to clinic . In zinc villages ( 1,440 children analyzed ) , 61.2 % of diarrheal episodes were treated with zinc , compared to 5.4 % in comparison villages ( 1,584 children analyzed , p<0.0001 ) . There were no differences in ORS use between zinc ( 59.6 % ) and comparison villages ( 58.8 % ) . Among children with fever or cough without diarrhea , zinc use was low ( < 0.5 % ) . There was a lower incidence of reported ALRI in zinc villages ( adjusted RR 0.68 , 95 % CI 0.46–0.99 ) , but not presenting at clinic . Conclusions In this study , home zinc use to treat diarrhea did not decrease disease rates in the community . However , with proper training , availability of zinc at home could lead to more episodes of pediatric diarrhea being treated with zinc in parts of rural Africa where healthcare utilization is low . Trial Registration Clinical Trials.gov OBJECTIVE To evaluate the impact of 4 months of daily zinc supplementation on the incidence of  severe and recurrent diarrhea in children 6 to 30 months of age . METHODS A double-blind , r and omized , placebo-controlled trial was conducted on children who were identified by a door-to-door survey to be aged 6 to 30 months and residing in the urban slum of Dakshinpuri , New Delhi . They were r and omized to receive daily zinc gluconate ( elemental zinc 10 mg to infants and 20 mg to older children  ) or placebo . A field attendant administered the syrup daily at home for 4 months except on Sundays , when the mother did so . One bottle that contained 250 mL was kept in the child 's home and replaced monthly . Field workers visited households every seventh day during the 4-month follow-up period . At each visit , information was obtained for the previous 7 days on history of fever , number and consistency of stools , and presence of cough . When the child was ill , illness characteristics and treatment seeking outside the home were determined . If the child had diarrhea or vomiting , then dehydration was assessed . At household visits , 2 packets of oral rehydration salts were given when a child had diarrhea . Children who visited the study clinic spontaneously for illness or were referred by the field workers were treated according to the st and ard national program guidelines . Antibiotics were advised only for diarrhea with bloody stools or for associated illnesses . For using generalized estimating equations for longitudinal analysis of a recurring event such as diarrhea , the follow-up data for each child was divided into 17 child-periods of 7 days each and presence or absence of an incident episode of diarrhea or severe diarrhea within each 7-day period was coded . This method of analysis does not assume independence of events and therefore prevents underestimation of variance that results because of correlation of morbidity within the same child . A logistic generalized estimating equations model with exchangeable correlation covariance-variance matrix was then used to estimate the effect size . RESULTS Zinc or placebo doses were administered on 88.8 % and 91.2 % , respectively , of study days during the 4 months of follow-up . There was a small but significant increase in the average number of days with vomiting in the zinc group ( 4.3 [ st and ard deviation ( SD ) : 5.8 ] vs 2.6 [ SD 3.9 ] days ; difference in means : 1.7 [ 95 % confidence interval ( CI ) : 1.3 - 2.1 ] days ) . At the baseline , mean plasma zinc was 62.0 microg/dL ( SD : 14.3 microg/dL ) in the zinc and 62.0 microg/dL ( SD : 11.2 microg/dL ) in the placebo group ; 45.8 % and 42 % , respectively , had low plasma zinc levels below 60 microg/dL. At the end of the study , plasma zinc levels were substantially higher in the zinc group ( ratio of geometric means : 1.94 [ 95 % CI : 1.86 - 2.03 ] ) and the proportion with low plasma zinc was lower ( difference in proportions : -46.7 % [ 95 % CI : -41.8 % to -51.4 % ] ) . The incidence of diarrhea during follow-up was lower in the zinc-supplemented as compared with the placebo group ( odds ratio [ OR ] : 0.88 ; 95 % CI : 0.82 - 0.95 ) . The beneficial impact of zinc was greater on the incidence of diarrhea with progressively increasing duration : episodes of diarrhea that lasted 1 to 6 days ( OR : 0.92 ; 95 % CI : 0.85 - 1.00 ) , 7 to 13 days ( OR : 0.79 ; 95 % CI : 0.65 - 0.95 ) , and > or = 14 days ( OR : 0.69 ; 95 % CI : 0.48 - 0.98 ) . The impact was also greater on the incidence of episodes with progressively higher stool frequency : 3 to 5 stools per day ( OR : 0.90 ; 95 % CI : 0.83 - 0.98 ) , 6 to 9 stools per day ( OR : 0.87 ; 95 % CI : 0.77 - 0.98 ) , and > or = 10 per day ( OR : 0.77 ; 95 % CI : 0.63 - 0.94 ) . In the zinc group , significantly more children experienced no diarrheal episode during the study period ( risk ratio [ RR ] : 1.22 ; 95 % CI : 1.02 - 1.44 ) . Furthermore , substantially fewer children ( RR : 0.51 ; 95 % CI : 0.36 - 0.73 ) experienced recurrent diarrhea , defined as > 6 diarrheal episodes in the follow-up period as compared with children in the placebo group . The number of children who were hospitalized for any cause tended to be lower in the zinc group , but the difference was not statistically significant ( 1.79 % vs 2.43 % ; RR : 0.74 ; 95 % CI : 0.43 - 1.27 ) . The baseline mean plasma copper ( microg/dL ) was similar in the 2 groups ( difference in means : 1.6 ; 95 % CI : -2.9 to 6.1 ) . The end study plasma copper levels were significantly lower in the zinc group ( difference in means : -15.5 ; 95 % CI : -19.9 to - 11.1 ) . CONCLUSIONS Zinc supplementation substantially reduced the incidence of severe and prolonged diarrhea , the 2 important determinants of diarrhea-related mortality and malnutrition . This intervention also substantially reduced the proportion of children who experienced recurrent diarrhea . Prompt measures to improve zinc status of deficient population s are warranted . The potential approaches to achieve this goal include food fortification , dietary diversification , cultivation of plants that are zinc dense or have a decreased concentration of zinc absorption inhibitors , and supplementation of selected groups of children . Future studies should assess the impact of increased zinc intakes on childhood  mortality in developing countries . For facilitating intervention , there is a need to obtain reliable estimates of zinc deficiency , particularly in developing countries . The functional consequences of the effect of various doses of zinc on plasma copper levels merits additional study Background The efficacy of preventive zinc supplementation against  diarrhea and respiratory illness  may depend on simultaneous supplementation with other micronutrients . We aim ed to assess the effect of supplementation with zinc and multiple micronutrients on diarrhea and other causes of  non-malarial morbidity . Methods and Findings Rural Tanzanian children ( n = 612 ) aged 6–60 months and with height-for-age z-score < –1.5 SD were r and omized to daily supplementation with zinc ( 10 mg ) alone , multi-nutrients without zinc , multi-nutrients with zinc , or placebo .  Children were followed for an average of 45 weeks . During follow-up , we recorded morbidity episodes . We found no evidence that concurrent supplementation with multi-nutrients influenced the magnitude of the effect of zinc on rates of diarrhea , respiratory illness , fever without localizing signs , or other illness ( guardian-reported illness with symptoms involving skin , ears , eyes and abscesses , but excluding trauma or burns ) . Zinc supplementation reduced the hazard rate of diarrhea by 24 % ( 4%–40 % ) . By contrast , multi-nutrients seemed to increase this rate ( HR ; 95 % CI : 1.19 ; 0.94–1.50 ) , particularly in children with asymptomatic Giardia infection at baseline ( 2.03 ; 1.24–3.32 ) . Zinc also protected against episodes of fever without localizing signs ( 0.75 ; 0.57–0.96 ) , but we found no evidence that it reduced the overall number of clinic visits . Conclusions We found no evidence that the efficacy of zinc supplements in reducing diarrhea rates is enhanced by concurrent supplementation with other micronutrients . By reducing rates of fever without localizing signs , supplementation with zinc may reduce inappropriate drug use with anti-malarial medications and antibiotics . Trial Registration Clinical Trials.gov Objective : This r and omized , placebo controlled trial was design ed to assess the safety and efficacy of 10-mg zinc supplementation for the treatment of acute diarrhea in infants . Methods : A total of 1110 infants aged 28 days to 5 months with acute diarrhea were enrolled and r and omized to receive either zinc ( n = 554 ) or placebo ( n = 556 ) for 14 days . Diarrhea history , anthropometric status , breast-feeding status and socioeconomic indicators were assessed at baseline . The homes of all infants were visited every 3 days until the diarrhea episode was over . The number of stools , presence of blood and additional illnesses were recorded daily . Results : The geometric mean duration of the diarrhea episode was 0.21 days longer among infants receiving zinc versus those receiving placebo , but this was not statistically significant and no difference was observed after controlling for sex , exclusive breast-feeding and length for age Z score . There were no differences in any subgroup ( ie , sex , baseline length for age Z score , exclusive breast-feeding or site after controlling for the remaining subgroup variables ) . There were no differences in reported stool frequency or among the proportion of episodes lasting longer than 7 days . Rates of vomiting were similar in the zinc and placebo groups . Conclusions : Young infants do not appear to benefit from zinc supplementation for the treatment of diarrhea OBJECTIVE To evaluate the impact of zinc supplementation on the clinical course , stool weight , duration of diarrhoea , changes in serum zinc , and body weight gain of children with acute diarrhoea . DESIGN R and omised double blind controlled trial . Children were assigned to receive zinc ( 20 mg elemental zinc per day ) containing multivitamins or control group ( zinc-free multivitamins ) daily in three divided doses for two weeks . SETTING A diarrhoeal disease hospital in Dhaka , Bangladesh . PATIENTS 111 children , 3 to 24 months old , below 76 % median weight for age of the National Center for Health Statistics st and ard with acute diarrhoea . Children with severe infection and /or oedema were excluded . MAIN OUTCOME MEASURES Total diarrhoeal stool output , duration of diarrhoea , rate of weight gain , and changes in serum zinc levels after supplementation . RESULTS Stool output was 28 % less and duration 14 % shorter in the zinc supplemented group than placebo ( p = 0.06 ) . There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter ( less than 95 % height for age ) , 239 v 326 g/kg ( p < 0.04 ) , and who had a lower initial serum zinc ( < 14 mmol/l ) , 279 v 329 g/kg ( p < 0.05 ) ; a shortening of mean time to recovery occurred ( 4.7v 6.2 days , p < 0.04 ) in those with lower serum zinc . There was an increase in mean serum zinc in the zinc supplemented group ( + 2.4 v −0.3 μmol/l , p < 0.001 ) during two weeks of supplementation , and better mean weight gain ( 120 v 30 g , p < 0.03 ) at the time of discharge from hospital . CONCLUSIONS Zinc supplementation is a simple , acceptable , and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished . Key messages 20 mg of daily zinc supplementation reduced diarrhoeal stool in shorter children Zinc reduced diarrhoeal stool in those with low serum zinc Zinc reduced duration of diarrhoea in children with low serum zinc Zinc increased body weight of children during acute diarrhoeal episode Malnourished children are likely to benefit more from zinc UNLABELLED Intervention trials have shown that zinc is efficacious in treating acute diarrhea in children of developing countries . In a r and omized , placebo-controlled trial , we assessed the effectiveness and efficacy of giving 3 Recommended Daily Allowances of elemental zinc to 6- to 35-month-old children with acute diarrhea . METHODS Seventeen hundred ninety-two cases of acute diarrhea in Nepalese children were r and omized to 4 study groups . Three groups were blinded and the children supplemented daily by field workers with placebo syrup , zinc syrup , or zinc syrup and a massive dose of vitamin A at enrollment . The fourth group was open and the caretaker gave the children zinc syrup daily . Day-wise information on morbidity was obtained by household visits every fifth day . RESULTS The relative hazards for termination of diarrhea were 26 % ( 95 % confidence interval [ CI ] : 8 % , 46 % ) , 21 % ( 95 % CI : 4 % , 38 % ) , and 19 % ( 95 % CI : 2 % , 40 % ) higher in the zinc , zinc-vitamin A , and zinc-caretaker groups , respectively , than in the placebo group . The relative risks of prolonged diarrhea ( duration > 7 days ) in these groups were 0.57 ( 95 % CI : 0.38 , 0.86 ) , 0.53 ( 95 % CI : 0.35 , 0.81 ) , and 0.55 ( 0.37 , 0.84 ) ; zinc accordingly reduced the risk of prolonged diarrhea with 43 % to 47 % . Five percent and 5.1 % of all syrup administrations were followed by regurgitation in the zinc and zinc-vitamin A group , respectively , whereas this occurred after only 1.3 % of placebo administrations . Vomiting during diarrhea was also more common in children receiving zinc . CONCLUSIONS Three Recommended Daily Allowances of zinc given daily by caretakers or by field workers substantially reduced the duration of diarrhea . The effect of zinc was not dependent on or enhanced by concomitant vitamin A administration
Diarrhea prevalence on days 3 , 5 , and 7 was lower in the zinc group .
The incidence of vomiting was significantly greater in the group that received zinc than in the control group .
CONCLUSIONS Oral zinc supplementation significantly decreases diarrhea duration and has a greater effect on malnourished children .
OBJECTIVE To up date the available evidence about zinc use for treating diarrhea in children and to assess its effect on the malnourished population , a subgroup that has not been fully explored in previous analyses .