title: Artemether for severe malaria.
abstract: BACKGROUND
  In 2011 the World Health Organization (WHO) recommended parenteral artesunate in preference to quinine as first-line treatment for people with severe malaria. Prior to this recommendation, many countries, particularly in Africa, had begun to use artemether, an alternative artemisinin derivative. This review evaluates intramuscular artemether compared with both quinine and artesunate.
  
  
  OBJECTIVE
  To assess the efficacy and safety of intramuscular artemether versus any other parenteral medication in treating severe malaria in adults and children.
  
  
  METHODS
  We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE and LILACS, ISI Web of Science, conference proceedings and reference lists of articles. We also searched the WHO clinical trial registry platform, ClinicalTrials.gov and the metaRegister of Controlled Trials (mRCT) for ongoing trials up to 9 April 2014.
  
  
  METHODS
  Randomized controlled trials (RCTs) comparing intramuscular artemether with intravenous or intramuscular antimalarial for treating severe malaria.
  
  
  METHODS
  The primary outcome was all-cause death.Two authors independently assessed trial eligibility, risk of bias and extracted data. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD), and presented both measures with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses and assessed the quality of the evidence using the GRADE approach.
  
  
  RESULTS
  We included 18 RCTs, enrolling 2662 adults and children with severe malaria, carried out in Africa (11) and in Asia (7). Artemether versus quinine For children in Africa, there is probably little or no difference in the risk of death between intramuscular artemether and quinine (RR 0.96, 95% CI 0.76 to 1.20; 12 trials, 1447 participants, moderate quality evidence). Coma recovery may be about five hours shorter with artemether (MD -5.45, 95% CI -7.90 to -3.00; six trials, 358 participants, low quality evidence), and artemether may result in fewer neurological sequelae, but larger trials would be needed to confirm this (RR 0.84, 95% CI 0.66 to 1.07; seven trials, 968 participants, low quality evidence). Artemether probably shortens the parasite clearance time by about nine hours (MD -9.03, 95% CI -11.43 to -6.63; seven trials, 420 participants, moderate quality evidence), and may shorten the fever clearance time by about three hours (MD -3.73, 95% CI -6.55 to -0.92; eight trials, 457 participants, low quality evidence).For adults in Asia, treatment with intramuscular artemether probably results in fewer deaths than treatment with quinine (RR 0.59, 95% CI 0.42 to 0.83; four trials, 716 participants, moderate quality evidence). Artemether versus artesunate Artemether and artesunate have not been directly compared in randomized trials in African children.For adults in Asia, mortality is probably higher with intramuscular artemether (RR 1.80, 95% CI 1.09 to 2.97, two trials,494 participants, moderate quality evidence).
  
  
  CONCLUSIONS
  Although there is a lack of direct evidence comparing artemether with artesunate, artemether is probably less effective than artesunate at preventing deaths from severe malaria. In circumstances where artesunate is not available, artemether is an alternative to quinine.
authors.affiliation: Department of Public Health, University of Calabar, Calabar, Nigeria, 540271.
authors.forename: Ekpereonne
authors.initials: E
authors.lastname: Esu
authors.forename: Emmanuel E
authors.initials: EE
authors.lastname: Effa
authors.forename: Oko N
authors.initials: ON
authors.lastname: Opie
authors.forename: Amirahobu
authors.initials: A
authors.lastname: Uwaoma
authors.forename: Martin M
authors.initials: MM
authors.lastname: Meremikwu
mesh_terms: D000293:Adolescent; D000328:Adult; D000349:Africa; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects; D000077332:Artesunate; D001208:Asia; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007273:Injections, Intramuscular; D016779:Malaria, Cerebral / Q000188:drug therapy / Q000401:mortality; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000401:mortality; D044349:Oceania; D011803:Quinine / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D011803:Quinine; D000077549:Artemether