Effect of micronutrient supplementation on diarrhoeal disease among stunted children in rural South Africa.
ABSTRACT: The efficacy of zinc combined with vitamin A or multiple micronutrients in preventing diarrhoea is unclear in African countries with high prevalence of human immunodeficiency virus (HIV)-exposed children. Potential modifying factors, such as stunting, need to be addressed. The objective of this study was to determine whether adding zinc or zinc plus multiple micronutrients to vitamin A reduces diarrhoea incidence, and whether this differs between the strata of stunted or HIV-infected children.We analyzed data from a randomized, controlled, double-blinded trial (ClinicalTrials.gov NCT00156832) of prophylactic micronutrient supplementation to children aged 6-24 months. Three cohorts of children: 32 HIV-infected children, 154 HIV-uninfected children born to HIV-infected mothers and 187 uninfected children born to HIV-uninfected mothers, received vitamin A, vitamin A plus zinc or multiple micronutrients, which included vitamin A and zinc. The main outcome was incidence of diarrhoea. Poisson regression was used in intent-to-treat analyses. Stratified analyses followed testing for statistical interaction between intervention and stunting.We observed no significant differences in overall diarrhoea incidence among treatment arms. Stunting modified this effect with stunted HIV-uninfected children having significantly lower diarrhoea incidence when supplemented with zinc or multiple micronutrients compared with vitamin A alone (2.04 and 2.23 vs 3.92 episodes/year, respectively, P=0.024). No meaningful subgroup analyses could be done in the cohort of HIV-infected children.Compared with vitamin A alone, supplementation with zinc and with zinc and multiple micronutrients, reduced diarrhoea morbidity in stunted rural South African children. Efficacy of zinc supplementation in HIV-infected children needs confirmation in studies that represent the spectrum of disease severity and age groups.
Project description:Prophylactic zinc supplementation has been shown to reduce diarrhea and respiratory illness in children in many developing countries, but its efficacy in children in Africa is uncertain.To determine if zinc, or zinc plus multiple micronutrients, reduces diarrhea and respiratory disease prevalence.Randomized, double-blind, controlled trial.Rural community in South Africa.THREE COHORTS: 32 HIV-infected children; 154 HIV-uninfected children born to HIV-infected mothers; and 187 HIV-uninfected children born to HIV-uninfected mothers.Children received either 1250 IU of vitamin A; vitamin A and 10 mg of zinc; or vitamin A, zinc, vitamins B1, B2, B6, B12, C, D, E, and K and copper, iodine, iron, and niacin starting at 6 months and continuing to 24 months of age. Homes were visited weekly.Primary outcome was percentage of days of diarrhea per child by study arm within each of the three cohorts. Secondary outcomes were prevalence of upper respiratory symptoms and percentage of children who ever had pneumonia by maternal report, or confirmed by the field worker.Among HIV-uninfected children born to HIV-infected mothers, median percentage of days with diarrhea was 2.3% for 49 children allocated to vitamin A; 2.5% in 47 children allocated to receive vitamin A and zinc; and 2.2% for 46 children allocated to multiple micronutrients (P = 0.852). Among HIV-uninfected children born to HIV-uninfected mothers, median percentage of days of diarrhea was 2.4% in 56 children in the vitamin A group; 1.8% in 57 children in the vitamin A and zinc group; and 2.7% in 52 children in the multiple micronutrient group (P = 0.857). Only 32 HIV-infected children were enrolled, and there were no differences between treatment arms in the prevalence of diarrhea. The prevalence of upper respiratory symptoms or incidence of pneumonia did not differ by treatment arms in any of the cohorts.When compared with vitamin A alone, supplementation with zinc, or with zinc and multiple micronutrients, did not reduce diarrhea and respiratory morbidity in rural South African children.ClinicalTrials.gov NCT00156832.
Project description:The benefits of zinc or multiple micronutrient supplementations in African children are uncertain. African children may differ from other populations of children in developing countries because of differences in the prevalence of zinc deficiency, low birth weight and preterm delivery, recurrent or chronic infections such as HIV, or the quality of complementary diets and genetic polymorphisms affecting iron metabolism.The aim of this study was to ascertain whether adding zinc or multiple micronutrients to vitamin A supplementation improves longitudinal growth or reduces prevalence of anemia in children aged 6-24 months.Randomized, controlled double-blinded trial of prophylactic micronutrient supplementation to children aged 6-24 months. Children in three cohorts - 32 HIV-infected children, 154 HIV-uninfected children born to HIV-infected mothers, and 187 uninfected children born to HIV-uninfected mothers - were separately randomly assigned to receive daily vitamin A (VA) [n = 124], vitamin A plus zinc (VAZ) [n = 123], or multiple micronutrients that included vitamin A and zinc (MM) [n = 126].Among all children there were no significant differences between intervention arms in length-for-age Z scores (LAZ) changes over 18 months. Among stunted children (LAZ below -2) [n = 62], those receiving MM had a 0.7 Z-score improvement in LAZ versus declines of 0.3 in VAZ and 0.2 in VA (P = 0.029 when comparing effects of treatment over time). In the 154 HIV-uninfected children, MM ameliorated the effect of repeated diarrhea on growth. Among those experiencing more than six episodes, those receiving MM had no decline in LAZ compared to 0.5 and 0.6 Z-score declines in children receiving VAZ and VA respectively (P = 0.06 for treatment by time interaction). After 12 months, there was 24% reduction in proportion of children with anemia (hemoglobin below 11 g/dL) in MM arm (P = 0.001), 11% in VAZ (P = 0.131) and 18% in VA (P = 0.019). Although the within arm changes were significant; the between-group differences were not significant.Daily multiple micronutrient supplementation combined with vitamin A was beneficial in improving growth among children with stunting, compared to vitamin A alone or to vitamin A plus zinc. Effects on anemia require further study.This study is registered with ClinicalTrials.gov, number. NCT00156832.
Project description:To evaluate the efficacy of milk fortified with specific multiple micronutrients on morbidity in children compared with the same milk without fortification.Community based, double masked, individually randomised trial.Peri-urban settlement in north India.Children (n=633) aged 1-3 randomly allocated to receive fortified milk (n=316) or control milk (n=317).One year of fortified milk providing additional 7.8 mg zinc, 9.6 mg iron, 4.2 microg selenium, 0.27 mg copper, 156 microg vitamin A, 40.2 mg vitamin C, 7.5 mg vitamin E per day (three feeds).Days with severe illnesses, incidence and prevalence of diarrhoea, and acute lower respiratory illness.Study groups were comparable at baseline; compliance in the groups was similar. Mean number of episodes of diarrhoea per child was 4.46 (SD 3.8) in the intervention (fortified milk) group and 5.36 (SD 4.1) in the control group. Mean number of episodes of acute lower respiratory illness was 0.62 (SD 1.1) and 0.83 (SD 1.4), respectively. The fortified milk reduced the odds for days with severe illnesses by 15% (95% confidence interval 5% to 24%), the incidence of diarrhoea by 18% (7% to 27%), and the incidence of acute lower respiratory illness by 26% (3% to 43%). Consistently greater beneficial effects were observed in children aged < or =24 months than in older children.Milk is well accepted as a means of delivery of micronutrients. Consumption of milk fortified with specific micronutrients can significantly reduce the burden of common morbidities among preschool children, especially in the first two years of life.NCT00255385 [ClinicalTrials.gov].
Project description:OBJECTIVES:The World Health Organization recommends that human immunodeficiency virus (HIV)-infected children increase energy intake and maintain a balanced macronutrient distribution for optimal growth and nutrition. Few studies have evaluated dietary intake of HIV-infected children in resource-limited settings. METHODS:We conducted a cross-sectional analysis of the dietary intake of 220 perinatally HIV-infected children and 220 HIV-uninfected controls ages 5 to 9 years in Johannesburg, South Africa. A standardized 24-hour recall questionnaire and software developed specifically for the South African population were used to estimate intake of energy, macronutrients, and micronutrients. Intake was categorized based on recommendations by the World Health Organization and Acceptable Macronutrient Distribution Ranges established by the IOM. RESULTS:The overall mean age was 6.7 years and 51.8% were boys. Total energy intake was higher in HIV-infected than HIV-uninfected children (1341 vs 1196?kcal/day, P?=?0.002), but proportions below the recommended energy requirement were similar in the 2 groups (82.5% vs 85.2%, P?=?0.45). Overall, 51.8% of the macronutrient energy intake was from carbohydrates, 13.2% from protein, and 30.8% from fat. The HIV-infected group had a higher percentage of their energy intake from carbohydrates and lower percentage from protein compared with the HIV-uninfected group. Intakes of folate, vitamin A, vitamin D, calcium, iodine, and selenium were suboptimal for both groups. CONCLUSIONS:Our findings suggest that the typical diet of HIV-infected children and uninfected children in Johannesburg, South Africa, does not meet energy or micronutrient requirements. There appear to be opportunities for interventions to improve dietary intake for both groups.
Project description:AIMS: To examine the effect of the daily use of micronutrients (including zinc) or the same micronutrients plus heat inactivated lactic acid bacteria (LAB), on diarrhoea in children compared to placebo. METHODS: A triple blind randomised clinical trial in an urban slum of Karachi, Pakistan. Micronutrients (including zinc), micronutrients (including zinc and LAB), or placebo, were provided daily for two months to 75 young children (aged 6-12 months) identified at high risk for diarrhoea related mortality on the basis of history of at least one episode of diarrhoea in the preceding two weeks. The longitudinal prevalence of diarrhoea was defined as the percentage of days a child had diarrhoea out of the days the child was observed. RESULTS: Mean longitudinal prevalence of diarrhoea in the micronutrient-zinc group was 15% (SD = 10%) child-days compared to 26% (SD = 20%) child-days in the placebo group and 26% (SD = 19%) child-days in the micronutrient-zinc-LAB group. The difference between the micronutrient-zinc-LAB and placebo groups was not significant. CONCLUSION: The daily provision of micronutrients (including zinc) reduces the longitudinal prevalence of diarrhoea and thus may also reduce diarrhoea related mortality in young children; heat inactivated LAB has negative effects in these children.
Project description:To evaluate the protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children (uninfected children born to HIV infected mothers) in Africa.Non-blinded randomised control trialTororo district, rural Uganda, an area of high malaria transmission intensity203 breastfeeding HIV exposed infants enrolled between 6 weeks and 9 months of ageCo-trimoxazole prophylaxis from enrollment until cessation of breast feeding and confirmation of negative HIV status. All children who remained HIV uninfected (n = 185) were then randomised to stop co-trimoxazole prophylaxis immediately or continue co-trimoxazole until 2 years old.Incidence of malaria, calculated as the number of antimalarial treatments per person year.The incidence of malaria and prevalence of genotypic mutations associated with antifolate resistance were high throughout the study. Among the 98 infants randomised to continue co-trimoxazole, 299 malaria cases occurred in 92.28 person years (incidence 3.24 cases/person year). Among the 87 infants randomised to stop co-trimoxazole, 400 malaria cases occurred in 71.81 person years (5.57 cases/person year). Co-trimoxazole prophylaxis yielded a 39% reduction in malaria incidence, after adjustment for age at randomisation (incidence rate ratio 0.61 (95% CI 0.46 to 0.81), P = 0.001). There were no significant differences in the incidence of complicated malaria, diarrhoea, pneumonia, hospitalisations, or deaths between the two treatment arms.Co-trimoxazole prophylaxis was moderately protective against malaria in HIV exposed infants when continued beyond the period of HIV exposure despite the high prevalence of Plasmodium genotypes associated with antifolate resistance. Trial registration Clinical Trials NCT00527800.
Project description:OBJECTIVE:Preventive zinc supplementation in the form of tablets or syrup reduces the incidence of diarrhoea and acute lower respiratory tract infections (RTI), but its effect on malaria is inconsistent. When zinc is administered with other micronutrients or foods, its effect is also uncertain. We assessed the effects of different amounts and sources of zinc on the frequency of diarrhoea, malaria, fever and RTI in young children. DESIGN, SETTING AND POPULATIONS:This community-based, double-blind, placebo-controlled, cluster-randomised trial of 2435 children 9 months of age was carried out between April 2010 and July 2012 in rural southwestern Burkina Faso. INTERVENTIONS:Participants were randomly assigned at the concession level to receive daily 1 of 4 interventions for 9 months: (1) 20 g small-quantity lipid-based nutrient supplement (SQ-LNS) without zinc and placebo tablet, (2) 20 g SQ-LNS with 5 mg zinc and placebo tablet, (3) 20 g SQ-LNS with 10 mg zinc and placebo tablet or (4) 20 g SQ-LNS without zinc and 5 mg zinc tablet. Participants were visited weekly in their homes for morbidity surveillance for 9 months, and those with uncomplicated diarrhoea and malaria received treatment from the study field workers in the community. MAIN OUTCOMES:Incidence and longitudinal prevalence of diarrhoea, malaria, fever, and lower and upper RTI by intervention group. RESULTS:The incidence of diarrhoea, malaria and fever was 1.10 (±1.03 SD), 0.61 (±0.66 SD) and 1.49 (±1.12 SD) episodes per 100 child-days at risk, respectively, and did not differ by intervention group (p=0.589, p=0.856 and p=0.830, respectively). The longitudinal prevalence of acute lower RTI (0.1%; 95% IC 0.1-0.2%) and of upper RTI (7.8%; 95% IC 7.1-8.4%) did not differ among groups (p=0.234 and p=0.501, respectively). CONCLUSIONS:Inclusion of 5 or 10 mg zinc in SQ-LNS and provision of 5 mg zinc dispersible tablet along with SQ-LNS had no impact on the incidence of diarrhoea, malaria and fever or the longitudinal prevalence of RTI compared with SQ-LNS without zinc in this population. TRIAL REGISTRATION NUMBER:NCT00944281.
Project description:The aim of this study was to determine whether maternal vitamin supplementation affects long-term mortality and morbidity of children born to HIV-infected mothers.In total, 1078 HIV-infected pregnant woman were enrolled in a double-blind, 2×2 factorial, randomised, placebo-controlled trial in Tanzania. Data were collected for 874 children at monthly clinic visits through a median age of 51 months.Maternal receipt of multivitamins (HR=0.93; 95% CI: 0.70-1.22) or vitamin A (HR=1.00; 95% CI: 0.76-1.32) did not affect all-cause child mortality through age 5 years. Among HIV-negative children, maternal multivitamin supplementation was associated with a lower mortality rate up to 5 years (HR=0.60; 95% CI: 0.38-0.95), primarily in children <2 years of age. Maternal vitamin A supplementation did not significantly affect child mortality up to 5 years (HR=0.76; 95% CI: 0.48-1.20). Children born to mothers who received multivitamins had a lower risk of all types of diarrhoea (RR=0.86; 95% CI: 0.75-0.98) through 5 years of age. The reduced risk of watery diarrhoea persisted in children from 2-5 years of age (RR=0.71; 95% CI: 0.54-0.95).Maternal vitamin supplementation during pregnancy and lactation may be associated with long-lasting affects in HIV-exposed children [ClinicalTrials.gov Identifier: NCT00197743].
Project description:In sub-Saharan Africa, malnutrition and malaria remain major causes of morbidity and mortality in young children. There are conflicting data as to whether malnutrition is associated with an increased or decreased risk of malaria. In addition, data are limited on the potential interaction between HIV infection and the association between malnutrition and the risk of malaria.A cohort of 100 HIV-unexposed, 203 HIV-exposed (HIV negative children born to HIV-infected mothers) and 48 HIV-infected children aged 6 weeks to 1 year were recruited from an area of high malaria transmission intensity in rural Uganda and followed until the age of 2.5 years. All children were provided with insecticide-treated bed nets at enrolment and daily trimethoprim-sulphamethoxazole prophylaxis (TS) was prescribed for HIV-exposed breastfeeding and HIV-infected children. Monthly routine assessments, including measurement of height and weight, were conducted at the study clinic. Nutritional outcomes including stunting (low height-for-age) and underweight (low weight-for-age), classified as mild (mean z-scores between -1 and -2 during follow-up) and moderate-severe (mean z-scores < -2 during follow-up) were considered. Malaria was diagnosed when a child presented with fever and a positive blood smear. The incidence of malaria was compared using negative binomial regression controlling for potential confounders with measures of association expressed as an incidence rate ratio (IRR).The overall incidence of malaria was 3.64 cases per person year. Mild stunting (IRR = 1.24, 95% CI 1.06-1.46, p = 0.008) and moderate-severe stunting (IRR = 1.24, 95% CI 1.03-1.48, p = 0.02) were associated with a similarly increased incidence of malaria compared to non-stunted children. Being mildly underweight (IRR = 1.09, 95% CI 0.95-1.25, p = 0.24) and moderate-severe underweight (IRR = 1.12, 95% CI 0.86-1.46, p = 0.39) were not associated with a significant difference in the incidence of malaria compared to children who were not underweight. There were no significant interactions between HIV-infected, HIV-exposed children taking TS and the associations between malnutrition and the incidence of malaria.Stunting, indicative of chronic malnutrition, was associated with an increased incidence of malaria among a cohort of HIV-infected and -uninfected young children living in an area of high malaria transmission intensity. However, caution should be made when making causal inferences given the observational study design and inability to disentangle the temporal relationship between malnutrition and the incidence of malaria.ClinicalTrials.gov: NCT00527800.
Project description:Malaria is a leading cause of morbidity and mortality among young children and is estimated to cause at least 1 million deaths each year especially among pregnant women and young children under the age of five years. Vitamin A supplementation is known to reduce morbidity and mortality in young children. Zinc is required for growth and immunity and we sought to replicate the study by Zeba et al. which showed 30% lower cases of clinical malaria in children on a combination of zinc and a large dose of vitamin A compared with children on vitamin A alone based on the hypothesis that combined vitamin A and zinc reduced symptomatic malaria compared to vitamin A alone.The primary objective was to determine the effect of vitamin A alone vs. vitamin A and zinc supplements on the incidence of clinical malaria and other anthropometric indices. It also sought to assess the effects on the incidence of anaemia, diarrhoea and pneumonia.The study was community-based and 200 children between the ages of 6-24 months were randomised to receive either vitamin A (100,000 IU for infants less than 12 months & 200,000 IU for children greater than 12 months and 10 mg daily zinc in the intervention group or vitamin A and zinc placebo for 6 months in the control group.The number of children who were diagnosed with uncomplicated malaria in the intervention group was 27% significantly lower compared with the children in the control group (p = 0.03). There were, however, no effects on severe malaria, pneumonia, anaemia and diarrhea.Our study confirms a significant role of vitamin A and zinc in reducing malaria morbidity.