title: Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for treatment of uncomplicated malaria in children in Zaire and Uíge Provinces, angola.
abstract: The development of resistance to antimalarials is a major challenge for global malaria control. Artemisinin-based combination therapies, the newest class of antimalarials, are used worldwide but there have been reports of artemisinin resistance in Southeast Asia. In February through May 2013, we conducted open-label, nonrandomized therapeutic efficacy studies of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) in Zaire and Uíge Provinces in northern Angola. The parasitological and clinical responses to treatment in children with uncomplicated Plasmodium falciparum monoinfection were measured over 28 days, and the main outcome was a PCR-corrected adequate clinical and parasitological response (ACPR) proportion on day 28. Parasites from treatment failures were analyzed for the presence of putative molecular markers of resistance to lumefantrine and artemisinins, including the recently identified mutations in the K13 propeller gene. In the 320 children finishing the study, 25 treatment failures were observed: 24 in the AL arms and 1 in the DP arm. The PCR-corrected ACPR proportions on day 28 for AL were 88% (95% confidence interval [CI], 78 to 95%) in Zaire and 97% (91 to 100%) in Uíge. For DP, the proportions were 100% (95 to 100%) in Zaire, and 100% (96 to 100%) in Uíge. None of the treatment failures had molecular evidence of artemisinin resistance. In contrast, 91% of AL late-treatment failures had markers associated with lumefantrine resistance on the day of failure. The absence of molecular markers for artemisinin resistance and the observed efficacies of both drug combinations suggest no evidence of artemisinin resistance in northern Angola. There is evidence of increased lumefantrine resistance in Zaire, which should continue to be monitored.
authors.affiliation: Malaria Branch and President's Malaria Initiative, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia, USA mplucinski@cdc.gov.
authors.forename: Mateusz M
authors.initials: MM
authors.lastname: Plucinski
authors.affiliation: Malaria Branch and President's Malaria Initiative, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Eldin
authors.initials: E
authors.lastname: Talundzic
authors.affiliation: Malaria Branch and President's Malaria Initiative, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Morton
authors.affiliation: National Malaria Control Program, Ministry of Health, Luanda, Angola.
authors.forename: Pedro Rafael
authors.initials: PR
authors.lastname: Dimbu
authors.affiliation: Field Epidemiology and Laboratory Training Program, Ministry of Health, Luanda, Angola.
authors.forename: Aleixo Panzo
authors.initials: AP
authors.lastname: Macaia
authors.affiliation: National Malaria Control Program, Ministry of Health, Luanda, Angola.
authors.forename: Filomeno
authors.initials: F
authors.lastname: Fortes
authors.affiliation: Malaria Branch and President's Malaria Initiative, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Goldman
authors.affiliation: Malaria Branch and President's Malaria Initiative, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Lucchi
authors.affiliation: Malaria Branch and President's Malaria Initiative, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Gail
authors.initials: G
authors.lastname: Stennies
authors.affiliation: Malaria Branch and President's Malaria Initiative, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: MacArthur
authors.affiliation: Malaria Branch and President's Malaria Initiative, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Udhayakumar
mesh_terms: D000810:Angola; D000962:Antimalarials / Q000627:therapeutic use; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use*; D002648:Child; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D011804:Quinolines / Q000627:therapeutic use*; D017211:Treatment Failure; D010879:Piperazines
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines