title: Safety and efficacy of lumefantrine-artemether (Coartem) for the treatment of uncomplicated Plasmodium falciparum malaria in Zambian adults.
abstract: BACKGROUND
  In Zambia, unacceptably high resistance to commonly used antimalarial drugs prompted the choice of artemether-lumefantrine (AL) as first line treatment for uncomplicated Plasmodium falciparum malaria. Although the safety and efficacy of AL have been extensively documented, no clinical trials had been carried out in Zambia.
  
  
  METHODS
  Nine hundred seventy one adult patients with uncomplicated malaria were randomized to either sulfadoxine-pyrimethamine (SP)(486) or AL (485) and followed up for 45 days. Outcome of treatment was defined according to the standard WHO classification. Recurrent parasitaemia were genotyped to distinguish between recrudescence and new infection.
  
  
  RESULTS
  Fever at day 3 was significantly lower (AL: 0.9%; 4/455; SP: 3,5%; 15/433; p = 0.007) and the mean haemoglobin at day 45 significantly higher (AL: 134 g/l; SP 130 g/l; p = 0.02) in the AL group. Almost all clinical symptoms cleared faster with AL. Early treatment failure was significantly higher in the SP (25/464) than in the AL (2/463) (OR: 13.1 95% CI: 3.08-55.50; P < 0.001). The rate of new infections was similar in both groups (18 with SP and 19 with AL). Late clinical failure (OR: 2.55; 95% CI: 1.34-4.84; P = 0.004) and late parasitological failure (OR:3.18; 95% CI: 1.25-8.09; P = 0.02) were significantly higher in the SP group. Total treatment failure was significantly higher in the SP group (96/393; 19.3%) as compared to the AL (22/403; 5.4%) group (OR: 4.15; 95% CI: 2.52-6.83; P < 0.001).
  
  
  CONCLUSIONS
  In Zambia, the new first line regimen AL is far more efficacious than SP in treating uncomplicated P. falciparum malaria in adults. Data on safety and efficacy of AL in pregnant women are urgently needed.
authors.affiliation: Department Parasitology, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium. clinsciences@zamtel.zm
authors.forename: Modest
authors.initials: M
authors.lastname: Mulenga
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: VangGeertruyden
authors.forename: Lawrence
authors.initials: L
authors.lastname: Mwananyanda
authors.forename: Victor
authors.initials: V
authors.lastname: Chalwe
authors.forename: Filip
authors.initials: F
authors.lastname: Moerman
authors.forename: Roma
authors.initials: R
authors.lastname: Chilengi
authors.forename: Chantal
authors.initials: C
authors.lastname: Van Overmeir
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dujardin
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
mesh_terms: D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D005449:Fluorenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy*; D016017:Odds Ratio; D010963:Plasmodium falciparum; D011739:Pyrimethamine / Q000009:adverse effects / Q000627:therapeutic use; D013413:Sulfadoxine / Q000009:adverse effects / Q000627:therapeutic use; D015024:Zambia
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D000077549:Artemether; D000078102:Lumefantrine; D011739:Pyrimethamine