Chemoprophylaxis and intermittent treatment for preventing malaria in children (Review) Meremikwu MM, Donegan S, Esu E This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2009, Issue 1 http://www.thecochranelibrary.com Chemoprophylaxis and intermittent treatment for preventing malaria in children (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 BACKGROUND .................................... 2 OBJECTIVES ..................................... 3 METHODS ...................................... 3 RESULTS....................................... 5 DISCUSSION ..................................... 13 AUTHORS’CONCLUSIONS . 14 ACKNOWLEDGEMENTS . 14 REFERENCES ..................................... 14 CHARACTERISTICSOFSTUDIES . 20 DATAANDANALYSES. 42 Analysis 1.1. Comparison 1 Antimalarial vs placebo: individually randomized trials [main analysis], Outcome 1 Clinical malaria..................................... 45 Analysis 1.2. Comparison 1 Antimalarial vs placebo: individually randomized trials [main analysis], Outcome 2 Severe anaemia. ................................... 47 Analysis 1.3. Comparison 1 Antimalarial vs placebo: individually randomized trials [main analysis], Outcome 3 Death from anycause.................................... 48 Analysis 1.4. Comparison 1 Antimalarial vs placebo: individually randomized trials [main analysis], Outcome 4 Hospital admissionforanycause. 49 Analysis 1.5. Comparison 1 Antimalarial vs placebo: individually randomized trials [main analysis], Outcome 5 Parasitaemia. .................................. 50 Analysis 1.6. Comparison 1 Antimalarial vs placebo: individually randomized trials [main analysis], Outcome 6 Enlarged spleen. .................................... 51 Analysis 1.7. Comparison 1 Antimalarial vs placebo: individually randomized trials [main analysis], Outcome 7 Impact on routine immunization: adequate protective antibodies. ................. 51 Analysis 2.1. Comparison 2 Antimalarial vs placebo: cluster-randomized trials, Outcome 1 Clinical malaria. 53 Analysis 2.2. Comparison 2 Antimalarial vs placebo: cluster-randomized trials, Outcome 2 Severe anaemia. 53 Analysis 2.3. Comparison 2 Antimalarial vs placebo: cluster-randomized trials, Outcome 3 Death from any cause. 54 Analysis 2.4. Comparison 2 Antimalarial vs placebo: cluster-randomized trials, Outcome 4 Hospital admission for any cause. .................................... 54 Analysis 3.1. Comparison 3 Antimalarial vs placebo: by drug group, Outcome 1 Clinical malaria. 55 Analysis 3.2. Comparison 3 Antimalarial vs placebo: by drug group, Outcome 2 Severe anaemia. 56 Analysis 4.1. Comparison 4 Antimalarial vs placebo: by seasonality, Outcome 1 Clinical malaria. 57 Analysis 4.2. Comparison 4 Antimalarial vs placebo: by seasonality, Outcome 2 Severe anaemia. 58 Analysis 5.1. Comparison 5 Intermittent treatment vs placebo: by presence of anaemia, Outcome 1 Severe anaemia. 60 Analysis 6.1. Comparison 6 Antimalarial vs placebo: adverse events, Outcome 1 Prophylaxis. 61 Analysis 6.2. Comparison 6 Antimalarial vs placebo: adverse events, Outcome 2 Intermittent treatment. 61 Analysis 7.1. Comparison 7 Antimalarial vs placebo: adequately concealed trials, Outcome 1 Clinical malaria. 62 Analysis 7.2. Comparison 7 Antimalarial vs placebo: adequately concealed trials, Outcome 2 Severe anaemia. 63 Analysis 7.3. Comparison 7 Antimalarial vs placebo: adequately concealed trials, Outcome 3 Death from any cause. 64 Analysis 8.1. Comparison 8 Antimalarial vs placebo: impact after stopping intervention, Outcome 1 Clinical malaria (relativerisk)................................... 65 Analysis 8.2. Comparison 8 Antimalarial vs placebo: impact after stopping intervention, Outcome 2 Clinical malaria (incidencerateratio). 65 Analysis 8.3. Comparison 8 Antimalarial vs placebo: impact after stopping intervention, Outcome 3 Severe anaemia (relativerisk)................................... 66 Analysis 8.4. Comparison 8 Antimalarial vs placebo: impact after stopping intervention, Outcome 4 Severe anaemia (incidencerateratio). 66 Chemoprophylaxis and intermittent treatment for preventing malaria in children (Review) i Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Analysis 8.5. Comparison 8 Antimalarial vs placebo: impact after stopping intervention, Outcome 5 Death from any cause (relativerisk)................................... 67 Analysis 8.6. Comparison 8 Antimalarial vs placebo: impact after stopping intervention, Outcome 6 Death from any cause (incidencerateratio). 67 Analysis 8.7. Comparison 8 Antimalarial vs placebo: impact after stopping intervention, Outcome 7 Impact on routine immunization: adequate protective antibody. ........... 68 APPENDICES ..................................... 68 WHAT’SNEW..................................... 75 HISTORY....................................... 75 CONTRIBUTIONSOFAUTHORS . 76 DECLARATIONSOFINTEREST . 76 SOURCESOFSUPPORT . 76 DIFFERENCES BETWEEN PROTOCOL AND REVIEW . .... 76 INDEXTERMS .................................... 76 Chemoprophylaxis and intermittent treatment for preventing malaria in children (Review) ii Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. [Intervention Review] Chemoprophylaxis and intermittent treatment for preventing malaria in children Martin M Meremikwu1, Sarah Donegan2, Ekpereonne Esu3 1Department of Paediatrics, University of Calabar Teaching Hospital, Calabar, Nigeria. 2International Health Group, Liverpool School of Tropical Medicine, Liverpool, UK. 3Effective Health Care Research Programme - Nigeria, University of Calabar Teaching Hospital, Calabar, Nigeria Contact address: Martin M Meremikwu, Department of Paediatrics, University of Calabar Teaching Hospital, PMB 1115, Calabar, Cross River State, Nigeria. [email protected]. Editorial group: Cochrane Infectious Diseases Group. Publication status and date: Edited (no change to conclusions), published in Issue 1, 2009. Review content assessed as up-to-date: 14 November 2007. Citation: Meremikwu MM, Donegan S, Esu E. Chemoprophylaxis and intermittent treatment for preventing malaria in children. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD003756. DOI: 10.1002/14651858.CD003756.pub3. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ABSTRACT Background Malaria causes repeated illness in children living in endemic areas. Policies of giving antimalarial drugs at regular intervals (prophylaxis or intermittent treatment) are being considered for preschool children. Objectives To evaluate prophylaxis and intermittent treatment with antimalarial drugs to prevent malaria in young children living in malaria- endemic areas. Search strategy We searched the Cochrane Infectious Diseases Group Specialized Register (August 2007), CENTRAL (The Cochrane Library 2007, Issue 3), MEDLINE (1966 to August 2007), EMBASE (1974 to August 2007), LILACS (1982 to August 2007), mRCT (February 2007), and reference lists of identified trials. We also contacted researchers. Selection criteria Individually randomized and cluster-randomized controlled trials comparing antimalarial drugs given at regular intervals (prophylaxis or intermittent treatment) with placebo or no drug in children aged one month to six years or less living in a malaria-endemic area. Data collection and analysis Two authors independently extracted data and assessed the risk of bias in the trials. We used risk ratio (RR) or mean difference with 95% confidence intervals (CI) for meta-analyses. Where we detected heterogeneity and considered it appropriate to combine the trials, we used the random-effects model (REM). Main results Twenty-one trials (19,394 participants), including six cluster-randomized trials, met the inclusion criteria. Prophylaxis or intermittent treatment with antimalarial drugs resulted in fewer clinical malaria episodes (RR 0.53, 95% CI 0.38 to 0.74, REM; 7037 participants, 10 trials), less severe anaemia (RR 0.70, 95% CI 0.52 to 0.94, REM; 5445 participants, 9 trials), and fewer hospital admissions for Chemoprophylaxis and intermittent treatment for preventing malaria in children (Review) 1 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. any cause (RR 0.64, 95% CI 0.49 to 0.82; 3722 participants, 5 trials). We did not detect a difference in the number of deaths from any cause (RR 0.90, 95% CI 0.65 to 1.23; 7369 participants, 10 trials), but the CI do not exclude a potentially important difference. One trial reported three serious adverse events with no statistically significant difference between study groups (1070 participants). Eight trials measured morbidity and mortality six months to two years after stopping regular antimalarial drugs; overall, there was no statistically significant difference, but participant numbers were small. Authors’ conclusions Prophylaxis and intermittent treatment with antimalarial drugs reduce clinical malaria and severe anaemia in preschool children. PLAIN LANGUAGE SUMMARY Preschool children taking antimalarial drugs regularly are less likely to get malaria or severe anaemia, but more trials are needed to show whether survival is improved Most children in areas where malaria is endemic are semi-immune against serious malaria by the