Artesunate-clindamycin versus quinine-clindamycin in the treatment of Plasmodium falciparum malaria: a randomized controlled trial.
BACKGROUND
Artemisinin-based drug combinations are the mainstay in the fight against drug-resistant malaria in Africa. Currently available antimalarial drug combinations that include artemisinins are pharmacokinetically unmatched and are therefore potentially increasing the risk of selection of resistant mutants in areas in which the rate of transmission of malaria is high. We tested the potential value of artemisinin-based combination therapy with a short elimination half-life for the treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa.


METHODS
We conducted an open-label, randomized, controlled clinical trial to evaluate the efficacy and tolerability of oral artesunate-clindamycin therapy given twice daily for 3 days (artesunate, 2 mg/kg, and clindamycin, 7 mg/kg, per dose), compared with a standard quinine-clindamycin regimen given twice daily for 3 days (quinine, 15 mg/kg, and clindamycin, 7 mg/kg, per dose), for the treatment of uncomplicated falciparum malaria in 100 Gabonese children aged 3-12 years. The primary end point of the study was the polymerase chain reaction-corrected cure rate for the per-protocol population.


RESULTS
The activity of artesunate-clindamycin was comparable to that of quinine-clindamycin in the per-protocol analysis of cure rates at day 28 of follow-up (87% versus 94%). No serious adverse events were reported, and tolerability was good and was similar in both groups. Times to clearance of fever and clearance of parasites were significantly shorter in the artesunate-clindamycin group.


CONCLUSIONS
Artesunate-clindamycin and other matching artemisinin-based combinations with a short plasma half-life merit further attention for use in regions in which the rate of transmission of malaria is high.
Ramharter
Michael
M
Albert Schweitzer Hospital, Lambaréné, Gabon, Germany.
Oyakhirome
Sunny
S
Klein Klouwenberg
Peter
P
Adégnika
Ayola A
AA
Agnandji
Sélidji T
ST
Missinou
Michel A
MA
Matsiégui
Pierre-Blaise
PB
Mordmüller
Benjamin
B
Borrmann
Steffen
S
Kun
Jürgen F
JF
Lell
Bertrand
B
Krishna
Sanjeev
S
Graninger
Wolfgang
W
Issifou
Saadou
S
Kremsner
Peter G
PG
D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D002981:Clindamycin / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005681:Gabon; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D011803:Quinine / Q000009:adverse effects / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000009:adverse effects / Q000627:therapeutic use*
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D002981:Clindamycin; D000077332:Artesunate; D011803:Quinine