Return of chloroquine antimalarial efficacy in Malawi.
BACKGROUND
In 1993, Malawi became the first country in Africa to replace chloroquine with the combination of sulfadoxine and pyrimethamine for the treatment of malaria. At that time, the clinical efficacy of chloroquine was less than 50%. The molecular marker of chloroquine-resistant falciparum malaria subsequently declined in prevalence and was undetectable by 2001, suggesting that chloroquine might once again be effective in Malawi.


METHODS
We conducted a randomized clinical trial involving 210 children with uncomplicated Plasmodium falciparum malaria in Blantyre, Malawi. The children were treated with either chloroquine or sulfadoxine\#8211;pyrimethamine and followed for 28 days to assess the antimalarial efficacy of the drug.


RESULTS
In analyses conducted according to the study protocol, treatment failure occurred in 1 of 80 participants assigned to chloroquine, as compared with 71 of 87 participants assigned to sulfadoxine\#8211;pyrimethamine. The cumulative efficacy of chloroquine was 99% (95% confidence interval [CI], 93 to 100), and the efficacy of sulfadoxine\#8211;pyrimethamine was 21% (95% CI, 13 to 30). Among children treated with chloroquine, the mean time to parasite clearance was 2.6 days (95% CI, 2.5 to 2.8) and the mean time to the resolution of fever was 10.3 hours (95% CI, 8.1 to 12.6). No unexpected adverse events related to the study drugs occurred.


CONCLUSIONS
Chloroquine is again an efficacious treatment for malaria, 12 years after it was withdrawn from use in Malawi. (ClinicalTrials.gov number, NCT00125489 [ClinicalTrials.gov].).
Laufer
Miriam K
MK
University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Thesing
Phillip C
PC
Eddington
Nicole D
ND
Masonga
Rhoda
R
Dzinjalamala
Fraction K
FK
Takala
Shannon L
SL
Taylor
Terrie E
TE
Plowe
Christopher V
CV
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use*; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D019353:Endemic Diseases; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008295:Malawi; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use; D016896:Treatment Outcome
D000962:Antimalarials; D004338:Drug Combinations; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine