Childhood illness in households using biomass fuels in India: secondary data analysis of nationally representative national family health surveys.

BACKGROUND: Half of the world's population uses solid fuels for energy and cooking, resulting in 1.5 million deaths annually, approximately one-third of which occur in India. Most deaths are linked to childhood pneumonia or acute lower respiratory tract infection (ALRI), conditions that are difficult to diagnose. The overall effect of biomass combustion on childhood illness is unclear. OBJECTIVES: To evaluate whether type of household fuel is associated with symptoms of ALRI (cough and difficulty breathing), diarrhea or fever in children aged 0-36 months. METHODS: We analyzed nationally representative samples of households with children aged 0-36 months from three national family health surveys conducted between 1992 and 2006 in India. Households were categorized as using low (liquid petroleum gas/electricity), medium (coal/kerosene) or high polluting fuel (predominantly wood/agricultural waste). Odds ratios adjusted for confounders for exposure to high and medium polluting fuel were compared with low polluting fuel (LPF). RESULTS: Use of high polluting fuel (HPF) in India changed minimally (82 to 78 %), although LPF use increased from 8% to 18%. HPF was consistently associated with ALRI [adjusted odds ratio (95% confidence interval) 1.48 (1.08-2.03) in 1992-3; 1.54 (1.33-1.77) in 1998-9; and 1.53 (1.21-1.93) in 2005-6). Fever was associated with HPF in the first two surveys but not in the third survey. Diarrhea was not consistently associated with HPF. CONCLUSIONS: There is an urgent need to increase the use of LPF or equivalent clean household fuel to reduce the burden of childhood illness associated with IAP in India.

Therapeutic zinc and copper supplementation in acute diarrhea does not influence short-term morbidity and growth: double-blind randomized controlled trial.

Our objective was to evaluate the effect of zinc and copper supplementation in acute diarrhea on morbidity and growth during 12 weeks of follow-up. In a double-blind randomized controlled clinical trial of 724 children aged 6-59 months, none of the 11 evaluated outcomes showed significant association with zinc or zinc and copper supplementation. Thus, therapeutic zinc supplementation may not always yield short-term -benefits.

Zinc and copper supplementation are not cost-effective interventions in the treatment of acute diarrhea.

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 randomized, double-blind, placebo-controlled clinical trial, 808 children aged 6-59 months with acute diarrhea were individually randomized to placebo (Pl), zinc (Zn) only, and zinc and copper (Zn + Cu) together with standard treatment of acute diarrhea. The actual resource 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.

What zinc supplementation does and does not achieve in diarrhea prevention: a systematic review and meta-analysis.

BACKGROUND: Prevention of diarrhea has presented indomitable challenges. A preventive strategy that has received significant interest is zinc supplementation. Existing literature including quantitative meta-analyses and systematic reviews tend to show that zinc supplementation is beneficial however evidence to the contrary is augmenting. We therefore conducted an updated and comprehensive meta-analytical synthesis of the existing literature on the effect of zinc supplementation in prevention of diarrhea. METHODS: EMBASE®, MEDLINE ® and CINAHL® databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. Effect of zinc supplementation on the following five outcomes was studied: incidence of diarrhea, prevalence of diarrhea, incidence of persistent diarrhea, incidence of dysentery and incidence of mortality. The published RCTs were combined using random-effects meta-analyses, subgroup meta-analyses, meta-regression, cumulative meta-analyses and restricted meta-analyses to quantify and characterize the role of zinc supplementation with the afore stated outcomes. RESULTS: We found that zinc supplementation has a modest beneficial association (9% reduction) with incidence of diarrhea, a stronger beneficial association (19% reduction) with prevalence of diarrhea and occurrence of multiple diarrheal episodes (28% reduction) but there was significant unexplained heterogeneity across the studies for these associations. Age, continent of study origin, zinc salt and risk of bias contributed significantly to between studies heterogeneity. Zinc supplementation did not show statistically significant benefit in reducing the incidence of persistent diarrhea, dysentery or mortality. In most instances, the 95% prediction intervals for summary relative risk estimates straddled unity. CONCLUSIONS: Demonstrable benefit of preventive zinc supplementation was observed against two of the five diarrhea-related outcomes but the prediction intervals straddled unity. Thus the evidence for a preventive benefit of zinc against diarrhea is inconclusive. Continued efforts are needed to better understand the sources of heterogeneity. The outcomes of zinc supplementation may be improved by identifying subgroups that need zinc supplementation.

Influence of zinc supplementation in acute diarrhea differs by the isolated organism.

Zinc supplementation is recommended in all acute diarrheas in children from developing countries. We aimed 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 randomized, double blind controlled trial (ISRCTN85071383) 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.

Therapeutic evaluation of zinc and copper supplementation in acute diarrhea in children: double blind randomized trial.

OBJECTIVE: To test the hypothesis that daily supplementation of zinc and copper mixed with the oral rehydration solution (ORS) reduces the duration and the severity of acute diarrhea in children. METHODS: In a randomized, double blind, placebo controlled trial children aged 6 months to 59 months in an urban hospital with acute diarrhea, were assigned to receive the intervention of once daily 40 mg of zinc sulfate and 5 mg of copper sulfate dissolved in a liter of standard ORS (n = 102) or placebo (50 mg of standard ORS powder) dissolved in a liter of ORS (n = 98). RESULT: The baseline characteristics in the two groups were similar. The mean survival time (days) (SE) with diarrhea was not significantly different in the treatment (4.34 (0.2)) as compared to the placebo group (4.48 (0.2)), nor was there any difference in the median time to cure. Cure was less likely with longer duration of diarrhea prior to enrollment (P < 0.001), if the time taken for rehydration was more (P = 0.001) and if intravenous fluids were used (P = 0.03) regardless of the micronutrient supplementation. The proportion of children with diarrhea > 4 days was 46% in the placebo group with an adjusted odds ratio (OR) (95% CI) of 1.19 (1.58, 0.9; P = 0.2) as compared to 39% in the supplemented group. The most important risk factor for diarrhea > 4 days was diarrheal duration prior to enrollment with OR = 6.25 (3.7, 11.1). The supplemented group however had less severity of diarrhea with a lower proportion of children requiring unscheduled intravenous fluids (OR = 0.4; 95% CI 0.05, 2.2), with weight loss (OR = 0.7; 95% CI; 0.4, 1.3), with complications (OR = 0.15; 0.01, 1.3) and had no deaths as compared to two in the placebo group. CONCLUSIONS: This study showed that the most important predictor for duration of diarrhea in children was the severity of the disease at enrollment, and, not the supplementation. There were clinical beneficial effects of supplementation on rate of any complications and mortality. A larger trial is warranted before supplementation of micronutrients mixed with ORS are recommended for management of acute diarrhea.

Economic evaluation of zinc and copper use in treating acute diarrhea in children: A randomized controlled trial.

BACKGROUND: The therapeutic effects of zinc and copper in reducing diarrheal morbidity have important cost implications. This health services research study evaluated the cost of treating a child with acute diarrhea in the hospital, the impact of micronutrient supplementation on the mean predicted costs and its cost-effectiveness as compared to using only standard oral rehydration solution (ORS), from the patient's and government's (providers) perspective. METHODS: Children aged 6 months to 59 months with acute diarrhea were randomly assigned to receive either the intervention or control. The intervention was a daily dose of 40 mg of zinc sulfate and 5 mg of copper sulfate powder dissolved in a liter of standard ORS (n = 102). The control was 50 mg of standard ORS powder dissolved in a liter of standard ORS (n = 98). The cost measures were the total mean cost of treating acute diarrhea, which included the direct medical, the direct non-medical and the indirect costs. The effectiveness measures were the probability of diarrhea lasting leq; 4 days, the disability adjusted life years (DALYs) and mortality. RESULTS: The mean total cost of treating a child with acute diarrhea was US $14 of which the government incurred an expenditure of 66%. The factors that increased the total were the number of stools before admission (p = 0.01), fever (p = 0.01), increasing grade of dehydration (p = 0.00), use of antibiotics (p = 0.00), use of intra-venous fluids (p = 0.00), hours taken to rehydrate a child (p = 0.00), the amount of oral rehydration fluid used (p = 0.00), presence of any complications (p = 0.00) and the hospital stay (p = 0.00). The supplemented group had a 8% lower cost of treating acute diarrhea, their cost per unit health (diarrhea lasting leq; 4 days) was 24% less and the incremental cost-effectiveness ratio indicated cost savings (in Rupees) with the intervention [-452; 95%CI (-11306, 3410)]. However these differences failed to reach conventional levels of significance. CONCLUSION: An emphasis on the costs and economic benefits of an alternative therapy is an important aspect of health services research. The cost savings and the attractive cost-effectiveness indicates the need to further assess the role of micronutrients such as zinc and copper in the treatment of acute diarrhea in a larger and more varied population.