Randomized Noninferiority Trial of Dihydroartemisinin-Piperaquine Compared with Sulfadoxine-Pyrimethamine plus Amodiaquine for Seasonal Malaria Chemoprevention in Burkina Faso.
The WHO recommends that children living in areas of highly seasonal malaria transmission in the Sahel subregion should receive seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ). We evaluated the use of dihydroartemisinin-piperaquine (DHAPQ) as an alternative drug that could be used if SPAQ starts to lose efficacy. A total of 1,499 children 3 to 59 months old were randomized to receive SMC with SPAQ or DHAPQ over 3 months. The primary outcome measure was the risk of clinical malaria (fever or a history of fever with a parasite density of at least 3,000/μl). A cohort of 250 children outside the trial was followed up as a control group. Molecular markers of drug resistance were assessed. The risk of a malaria attack was 0.19 in the DHAPQ group and 0.15 in the SPAQ group, an odds ratio of 1.33 (95% confidence interval [CI], 1.02 to 1.72). Efficacy of SMC compared to the control group was 77% (67% to 84%) for DHAPQ and 83% (74% to 89%) for SPAQ. pfdhfr and pfdhps mutations associated with antifolate resistance were more prevalent in parasites from children who received SPAQ than in children who received DHAPQ. Both regimens were highly efficacious and well tolerated. DHAPQ is a potential alternative drug for SMC. (This trial is registered at ClinicalTrials.gov under registration no. NCT00941785.).
Institut de Recherche en Sciences de la Santé, Direction Régionale de l'Ouest, Bobo-Dioulasso, Burkina Faso London School of Hygiene & Tropical Medicine, London, United Kingdom zongo_issaka@yahoo.fr paul.milligan@lshtm.ac.uk.
Issaka
I
Zongo
London School of Hygiene & Tropical Medicine, London, United Kingdom zongo_issaka@yahoo.fr paul.milligan@lshtm.ac.uk.
Paul
http://orcid.org/0000-0003-3430-3395
P
Milligan
Institut de Recherche en Sciences de la Santé, Direction Régionale de l'Ouest, Bobo-Dioulasso, Burkina Faso.
Yves Daniel
YD
Compaore
Institut de Recherche en Sciences de la Santé, Direction Régionale de l'Ouest, Bobo-Dioulasso, Burkina Faso.
A Fabrice
AF
Some
London School of Hygiene & Tropical Medicine, London, United Kingdom.
Brian
B
Greenwood
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
Joel
http://orcid.org/0000-0003-4566-4030
J
Tarning
Department of Medicine, University of California, San Francisco General Hospital, San Francisco, California, USA.
Philip J
PJ
Rosenthal
London School of Hygiene & Tropical Medicine, London, United Kingdom.
Colin
C
Sutherland
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sod, Thailand.
Francois
F
Nosten
Institut de Recherche en Sciences de la Santé, Direction Régionale de l'Ouest, Bobo-Dioulasso, Burkina Faso.
Jean-Bosco
JB
Ouedraogo
D000655:Amodiaquine / Q000627:therapeutic use*; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D002050:Burkina Faso; D016022:Case-Control Studies; D018890:Chemoprevention / Q000379:methods; D002675:Child, Preschool; D004338:Drug Combinations; D004351:Drug Resistance / Q000187:drug effects; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D011739:Pyrimethamine / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D012621:Seasons; D013413:Sulfadoxine / Q000627:therapeutic use*; D010879:Piperazines
D000655:Amodiaquine; D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D011739:Pyrimethamine; D011804:Quinolines; D013413:Sulfadoxine; C001205:fanasil, pyrimethamine drug combination; C039060:artenimol; C034759:piperaquine; D010879:Piperazines