Efficacy of sulphadoxine-pyrimethamine with or without artesunate for the treatment of uncomplicated Plasmodium falciparum malaria in southern Mozambique: a randomized controlled trial.
BACKGROUND
An artemisinin-based combination therapy, artesunate (AS) plus sulphadoxine-pyrimethamine (SP), was compared to SP monotherapy to provide evidence of further treatment options in southern Mozambique.


METHODS
Between 2003 and 2005, 411 patients over one year and 10 kg with uncomplicated Plasmodium falciparum malaria were randomly allocated SP (25/1.25 mg per kg day 0) or AS/SP (as above plus 4 mg/kg artesunate days 0, 1 and 2). Allocation was concealed, but treatment was open-label except to microscopists. The primary objective was the relative risk of treatment failure, which was assessed using World Health Organization response definitions modified to a 42-day follow-up.


RESULTS
Of the 411 subjects enrolled, 359 (87.3%) completed the follow up period (SP n = 175, AS/SP n = 184). A survival analysis including 408 subjects showed that the polymerase chain reaction-adjusted cure rates were 90.4% (95% confidence interval [CI] 84.9%-93.9%) and 98.0% (95% CI 94.8%-99.3%) for SP and AS/SP respectively. Multivariable analysis showed that treatment with AS/SP decreased the relative hazard of treatment failure by 80% compared to SP (hazard ratio [HR] 0.2; 95% CI 0.1-0.6) and age over seven years decreased the relative hazard of failure by 70% (HR 0.3; 95% CI 0.1-0.9), when compared to younger age. However, having a quintuple dhfr/dhps mutation increased the relative hazard of failure compared to fewer mutations (HR 3.2; 95% CI 1.3-7.5) and baseline axillary temperature increased the relative hazard of failure by 50% for each degree C increase (HR 1.5; 95% CI 1.1-2.2).


CONCLUSIONS
While both treatments were efficacious, AS plus SP significantly decreased the relative hazard of treatment failure compared to SP monotherapy Artesunate plus sulphadoxine-pyrimethamine, but not sulphadoxine-pyrimethamine monotherapy, met the current WHO criteria of >95% efficacy for policy implementation.


BACKGROUND
NCT00203736 and NCT00203814.
Allen
Elizabeth N
EN
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa. elizabeth.allen@uct.ac.za
Little
Francesca
F
Camba
Tunisio
T
Cassam
Yasmin
Y
Raman
Jaishree
J
Boulle
Andrew
A
Barnes
Karen I
KI
D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000235:genetics / Q000469:parasitology; D008297:Male; D009073:Mozambique; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011739:Pyrimethamine