Safety and efficacy of lumefantrine-artemether (Coartem) for the treatment of uncomplicated Plasmodium falciparum malaria in Zambian adults.
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.
Mulenga
Modest
M
Department Parasitology, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium. clinsciences@zamtel.zm
VangGeertruyden
Jean-Pierre
JP
Mwananyanda
Lawrence
L
Chalwe
Victor
V
Moerman
Filip
F
Chilengi
Roma
R
Van Overmeir
Chantal
C
Dujardin
Jean-Claude
JC
D'Alessandro
Umberto
U
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
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D000077549:Artemether; D000078102:Lumefantrine; D011739:Pyrimethamine