Sulphadoxine/pyrimethamine versus amodiaquine for treating uncomplicated childhood malaria in Gabon: a randomized trial to guide national policy.
BACKGROUND
In Gabon, following the adoption of amodiaquine/artesunate combination (AQ/AS) as first-line treatment of malaria and of sulphadoxine/pyrimethamine (SP) for preventive intermittent treatment of pregnant women, a clinical trial of SP versus AQ was conducted in a sub-urban area. This is the first study carried out in Gabon following the WHO guidelines.


METHODS
A random comparison of the efficacy of AQ (10 mg/kg/day x 3 d) and a single dose of SP (25 mg/kg of sulphadoxine/1.25 mg/kg of pyrimethamine) was performed in children under five years of age, with uncomplicated falciparum malaria, using the 28-day WHO therapeutic efficacy test. In addition, molecular genotyping was performed to distinguish recrudescence from reinfection and to determine the frequency of the dhps K540E mutation, as a molecular marker to predict SP-treatment failure.


RESULTS
The day-28 PCR-adjusted treatment failures for SP and AQ were 11.6% (8/69; 95% IC: 5.5-22.1) and 28.2% (20/71; 95% CI: 17.7-38.7), respectively This indicated that SP was significantly superior to AQ (P = 0.019) in the treatment of uncomplicated childhood malaria and for preventing recurrent infections. Both treatments were safe and well-tolerated, with no serious adverse reactions recorded. The dhps K540E mutation was not found among the 76 parasite isolates tested.


CONCLUSIONS
The level of AQ-resistance observed in the present study may compromise efficacy and duration of use of the AQ/AS combination, the new first-line malaria treatment. Gabonese policy-makers need to plan country-wide and close surveillance of AQ/AS efficacy to determine whether, and for how long, these new recommendations for the treatment of uncomplicated malaria remain valid.
Nsimba
Basile
B
National Malaria Control Programme - Division for Disease Control, Ministry of Health, Brazzaville, Congo. basilensimba@aol.com
Guiyedi
Vincent
V
Mabika-Mamfoumbi
Modeste
M
Mourou-Mbina
Jean Romain
JR
Ngoungou
Edgard
E
Bouyou-Akotet
Marielle
M
Loembet
Romaric
R
Durand
Rémy
R
Le Bras
Jacques
J
Kombila
Maryvonne
M
D000655:Amodiaquine / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use; D000077332:Artesunate; D002675:Child, Preschool; D004094:Dihydropteroate Synthase / Q000235:genetics; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005681:Gabon; D006291:Health Policy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D009154:Mutation; D010963:Plasmodium falciparum / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011739:Pyrimethamine / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use*; D016896:Treatment Outcome
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000655:Amodiaquine; D000077332:Artesunate; D013413:Sulfadoxine; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine