Efficacy of artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum malaria in Angola, 2015.
Recent anti-malarial resistance monitoring in Angola has shown efficacy of artemether-lumefantrine (AL) in certain sites approaching the key 90% lower limit of efficacy recommended for artemisinin-based combination therapy. In addition, a controversial case of malaria unresponsive to artemisinins was reported in a patient infected in Lunda Sul Province in 2013.



During January-June 2015, investigators monitored the clinical and parasitological response of children with uncomplicated Plasmodium falciparum infection treated with AL, artesunate-amodiaquine (ASAQ), or dihydroartemisinin-piperaquine (DP). The study comprised two treatment arms in each of three provinces: Benguela (AL, ASAQ), Zaire (AL, DP), and Lunda Sul (ASAQ, DP). Samples from treatment failures were analysed for molecular markers of resistance for artemisinin (K13) and lumefantrine (pfmdr1).



A total of 467 children reached a study endpoint. Fifty-four treatment failures were observed: four early treatment failures, 40 re-infections and ten recrudescences. Excluding re-infections, the 28-day microsatellite-corrected efficacy was 96.3% (95% CI 91-100) for AL in Benguela, 99.9% (95-100) for ASAQ in Benguela, 88.1% (81-95) for AL in Zaire, and 100% for ASAQ in Lunda Sul. For DP, the 42-day corrected efficacy was 98.8% (96-100) in Zaire and 100% in Lunda Sul. All treatment failures were wild type for K13, but all AL treatment failures had pfmdr1 haplotypes associated with decreased lumefantrine susceptibility.



No evidence was found to corroborate the specific allegation of artemisinin resistance in Lunda Sul. The efficacy below 90% of AL in Zaire matches findings from 2013 from the same site. Further monitoring, particularly including measurement of lumefantrine blood levels, is recommended.
Malaria Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30329, USA. mplucinski@cdc.gov.|President's Malaria Initiative, Centers for Disease Control and Prevention, Atlanta, GA, USA. mplucinski@cdc.gov.
Mateusz M
MM
Plucinski
National Malaria Control Program, Ministry of Health, Luanda, Angola.
Pedro Rafael
PR
Dimbu
Faculty of Medicine, Agostinho Neto University, Luanda, Angola.
Aleixo Panzo
AP
Macaia
National Malaria Control Program, Ministry of Health, Luanda, Angola.
Carolina Miguel
CM
Ferreira
Field Epidemiology and Laboratory Training Programme, Ministry of Health, Luanda, Angola.
Claudete
C
Samutondo
Field Epidemiology and Laboratory Training Programme, Ministry of Health, Luanda, Angola.
Joltim
J
Quivinja
National Malaria Control Program, Ministry of Health, Luanda, Angola.
Marília
M
Afonso
World Health Organization, Luanda, Angola.
Richard
R
Kiniffo
President's Malaria Initiative, USAID, Luanda, Angola.
Eliane
E
Mbounga
Malaria Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30329, USA.|Atlanta Research and Education Foundation, Atlanta, GA, USA.
Julia S
JS
Kelley
Malaria Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30329, USA.
Dhruviben S
DS
Patel
Malaria Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30329, USA.
Yun
Y
He
Malaria Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30329, USA.|Atlanta Research and Education Foundation, Atlanta, GA, USA.
Eldin
E
Talundzic
Malaria Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30329, USA.|President's Malaria Initiative, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Denise O
DO
Garrett
Malaria Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30329, USA.|President's Malaria Initiative, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Eric S
ES
Halsey
Malaria Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30329, USA.
Venkatachalam
V
Udhayakumar
Global Malaria Programme, World Health Organization, Geneva, Switzerland.
Pascal
P
Ringwald
National Malaria Control Program, Ministry of Health, Luanda, Angola.
Filomeno
F
Fortes
D000655:Amodiaquine / Q000627:therapeutic use; D000810:Angola; D000962:Antimalarials / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D011804:Quinolines / Q000627:therapeutic use; D012008:Recurrence; D017211:Treatment Failure; D010879:Piperazines
D000655:Amodiaquine; D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D011804:Quinolines; C515299:amodiaquine, artesunate drug combination; C039060:artenimol; C034759:piperaquine; D010879:Piperazines