Oral iron supplements for children in malaria-endemic areas.

BACKGROUND: Iron-deficiency anaemia is common during childhood. Iron supplementation has been claimed to increase the risk of malaria. OBJECTIVES: To assess the effect of iron on malaria and deaths. SEARCH STRATEGY: We searched The Cochrane Library, PUBMED, MEDLINE, LILACS; and trial registry databases, all up to June 2011. We scanned references of included trials. SELECTION CRITERIA: Individually and cluster randomized controlled trials conducted in hypoendemic to holoendemic malaria regions and including children below 18 years of age. We included trials comparing orally administered iron, iron with antimalarial treatment, or iron with folic acid versus placebo or no treatment. Iron fortification was excluded. Antihelminthics could be administered to either group. Additional micronutrients had to be administered equally to both groups. DATA COLLECTION AND ANALYSIS: The primary outcomes were clinical (symptomatic) malaria, severe malaria, and death. Two authors independently selected the studies and extracted the data. We assessed heterogeneity and conducted subgroup analyses by the presence of anaemia at baseline, age, and malaria endemicity. We assessed risk of bias using domain-based evaluation. We performed a fixed-effect meta-analysis for all outcomes and random-effects meta-analysis for hematological outcomes. We adjusted analyses for cluster randomized trials. MAIN RESULTS: Seventy-one trials (45,353 children) were included. For clinical malaria, no significant difference between iron alone and placebo was detected, (risk ratio (RR) 0.99, 95% confidence intervals (CI) 0.90 to 1.09, 13 trials). The results were similar in the subgroups of non-anaemic children and children below 2 years of age. There was no significant difference in deaths in hyper- and holoendemic areas, risk difference +1.93 per 1000 children (95% CI -1.78 to 5.64, 13 trials, 17,898 children). Iron administered for treatment of anaemia resulted in a larger increase in haemoglobin than iron given for prevention, and the benefit was similar in hyper- or holoendemic and lower endemicity settings. Iron and folic acid supplementation resulted in mixed results for severe malaria. Overall, the risk for clinical malaria was higher with iron or with iron plus folic acid in trials where services did not provide for malaria surveillance and treatment. Iron with antimalarial treatment significantly reduced malaria. Iron supplementation during an acute attack of malaria did not increase the risk for parasitological failure, (RR 0.96, 95% CI 0.74 to 1.24, three trials) or deaths. AUTHORS' CONCLUSIONS: Iron alone or with antimalaria treatment does not increase the risk of clinical malaria or death when regular malaria surveillance and treatment services are provided. There is no need to screen for anaemia prior to iron supplementation.

Therapeutic interventions for Burkitt lymphoma in children.

BACKGROUND: Burkitt lymphoma (BL) is an important cancer found mostly in children but uncertainty remains as to the most effective form of management. In endemic areas, late-stage presentation as a result of delayed access to treatment compounds the situation. OBJECTIVES: To assess the evidence for chemotherapy, surgery, radiotherapy and immunotherapy in the treatment of children with endemic BL. SEARCH STRATEGY: We updated and re-ran the searches in the following electronic databases from the time of the first publication; the Cochrane Controlled Trials Register (CENTRAL) (Issue 1, 2011); MEDLINE (January 2011); EMBASE (January 2011); and the clinical trials registry (up to January 2011) to identify relevant trials. In addition, we also updated the search of the US clinical trials register for on-going and completed trials up to January 2011. We also updated the search terms and used the Cochrane filter for identifying randomised trials in MEDLINE. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of any duration. We included studies conducted in children with a confirmed diagnosis of BL. We did not restrict studies by geographical location or by language of publication. We considered any therapeutic intervention. The primary outcome was overall survival. DATA COLLECTION AND ANALYSIS: Two review authors assessed studies for relevance. We assessed studies that met the entry criteria for study quality. We independently extracted data and entered the data into Review Manager (RevMan). In this update, two review authors independently assessed citations from the updated search and reviewed abstracts for relevance. MAIN RESULTS: We included one new study in this update. In total, 13 trials involving 1824 participants met the inclusion criteria for this review however, data in usable format were only available in 10 trials (732 participants). Inadequate reporting of study methodology was a common feature of the trials preventing thorough assessment of study quality. We were unable to pool data for any of the outcomes due to the differences between the interventions assessed in the studies. Eight studies aimed to induce remission; overall survival did not differ significantly between treatment groups. Five studies aimed to maintain remission. In two out of three studies reporting survival, this was substantial but the difference was not statistically significant between treatment groups. Less aggressive treatment schedules appear to produce similar effects with less adverse event profiles. AUTHORS' CONCLUSIONS: This review notes a preference in more recent studies for less aggressive care options for treatment of BL. However, the evidence for the relative effectiveness of interventions to treat BL is not strong as studies were small, underpowered and prone to both systematic and random error. We included one additional trial without change of conclusions.

Oral iron supplementation for preventing or treating anaemia among children in malaria-endemic areas.

BACKGROUND: Iron-deficiency anaemia is common during childhood. Iron supplementation has been claimed to increase the risk of malaria. OBJECTIVES: To assess the effect of iron on malaria and deaths. SEARCH STRATEGY: We searched The Cochrane Library (2009, issue 1); MEDLINE; EMBASE; LILACS and metaRegister of Controlled Trials, all up to March 2009. We scanned references of included trials. SELECTION CRITERIA: Individually and cluster-randomized controlled trials conducted in hypoendemic to holoendemic malaria regions and including children < 18 years. We included trials comparing orally administered iron with or without folic acid vs. placebo or no treatment. Iron fortification was excluded. Antimalarials and/or antiparasitics could be administered to either group. Additional micronutrients could only be administered equally to both groups. DATA COLLECTION AND ANALYSIS: The primary outcomes were malaria-related events and deaths. Secondary outcomes included haemoglobin, anaemia, other infections, growth, hospitalizations, and clinic visits. We assessed risk of bias using domain-based evaluation. Two authors independently selected studies and extracted data. We contacted authors for missing data. We assessed heterogeneity. We performed fixed-effect meta-analysis and presented random-effects results when heterogeneity was present. We present pooled risk ratios (RR) with 95% confidence intervals (CIs). We used adjusted analyses for cluster-randomized trials. MAIN RESULTS: Sixty-eight trials (42,981 children) fulfilled the inclusion criteria. Iron supplementation did not increase the risk of clinical malaria (RR 1.00, 95% CI 0.88 to 1.13; 22,724 children, 14 trials, random-effects model). The risk was similar among children who were non-anaemic at baseline (RR 0.96, 95% CI 0.85 to 1.09). An increased risk of malaria with iron was observed in trials that did not provide malaria surveillance and treatment. The risk of malaria parasitaemia was higher with iron (RR 1.13, 95% CI 1.01 to 1.26), but there was no difference in adequately concealed trials. Iron + antimalarial was protective for malaria (four trials). Iron did not increase the risk of parasitological failure when given during malaria (three trials). There was no increased risk of death across all trials comparing iron versus placebo (RR 1.11, 95% CI 0.91 to 1.36; 21,272 children, 12 trials). Iron supplementation increased haemoglobin, with significant heterogeneity, and malaria endemicity did not affect this effect. Growth and other infections were mostly not affected by iron supplementation. AUTHORS' CONCLUSIONS: Iron does not increase the risk of clinical malaria or death, when regular malaria surveillance and treatment services are provided. There is no need to screen for anaemia prior to iron supplementation.