Effectiveness and safety of artemether-lumefantrine versus artesunate-amodiaquine for unsupervised treatment of uncomplicated falciparum malaria in patients of all age groups in Nanoro, Burkina Faso: a randomized open label trial.
BACKGROUND
Several studies have reported high efficacy and safety of artemisinin-based combination therapy (ACT) mostly under strict supervision of drug intake and limited to children less than 5 years of age. Patients over 5 years of age are usually not involved in such studies. Thus, the findings do not fully reflect the reality in the field. This study aimed to assess the effectiveness and safety of ACT in routine treatment of uncomplicated malaria among patients of all age groups in Nanoro, Burkina Faso.


METHODS
A randomized open label trial comparing artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) was carried out from September 2010 to October 2012 at two primary health centres (Nanoro and Nazoanga) of Nanoro health district. A total of 680 patients were randomized to receive either ASAQ or AL without any distinction by age. Drug intake was not supervised as pertains in routine practice in the field. Patients or their parents/guardians were advised on the time and mode of administration for the 3 days treatment unobserved at home. Follow-up visits were performed on days 3, 7, 14, 21, and 28 to evaluate clinical and parasitological resolution of their malaria episode as well as adverse events. PCR genotyping of merozoite surface proteins 1 and 2 (msp-1, msp-2) was used to differentiate recrudescence and new infection.


RESULTS
By day 28, the PCR corrected adequate clinical and parasitological response was 84.1 and 77.8 % respectively for ASAQ and AL. The cure rate was higher in older patients than in children under 5 years old. The risk of re-infection by day 28 was higher in AL treated patients compared with those receiving ASAQ (p < 0.00001). Both AL and ASAQ treatments were well tolerated.


CONCLUSIONS
This study shows a lowering of the efficacy when drug intake is not directly supervised. This is worrying as both rates are lower than the critical threshold of 90 % required by the WHO to recommend the use of an anti-malarial drug in a treatment policy.


BACKGROUND
NCT01232530.
IRSS, Clinical Research Unit of Nanoro (CRUN), CMA Saint Camille of Nanoro, BP 218 Ouagadougou CMS 11, Nanoro, Burkina Faso. paulsondo@yahoo.fr.
Paul
P
Sondo
IRSS, Clinical Research Unit of Nanoro (CRUN), CMA Saint Camille of Nanoro, BP 218 Ouagadougou CMS 11, Nanoro, Burkina Faso. kderra@crun.bf.
Karim
K
Derra
IRSS, Clinical Research Unit of Nanoro (CRUN), CMA Saint Camille of Nanoro, BP 218 Ouagadougou CMS 11, Nanoro, Burkina Faso. naksaid2006@yahoo.fr.
Seydou
S
Diallo-Nakanabo
IRSS, Clinical Research Unit of Nanoro (CRUN), CMA Saint Camille of Nanoro, BP 218 Ouagadougou CMS 11, Nanoro, Burkina Faso. zekibat@yahoo.fr.
Zekiba
Z
Tarnagda
Centre Muraz of Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso. hatoodile@yahoo.fr.
Odile
O
Zampa
IRSS, Clinical Research Unit of Nanoro (CRUN), CMA Saint Camille of Nanoro, BP 218 Ouagadougou CMS 11, Nanoro, Burkina Faso. kazienga_adama@yahoo.fr.
Adama
A
Kazienga
IRSS, Clinical Research Unit of Nanoro (CRUN), CMA Saint Camille of Nanoro, BP 218 Ouagadougou CMS 11, Nanoro, Burkina Faso. valinno@yahoo.fr.|Centre Muraz of Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso. valinno@yahoo.fr.
Innocent
I
Valea
IRSS, Clinical Research Unit of Nanoro (CRUN), CMA Saint Camille of Nanoro, BP 218 Ouagadougou CMS 11, Nanoro, Burkina Faso. hsorgho@hotmail.com.
Hermann
H
Sorgho
Kumasi Center for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana. owusudabo@kccr.de.
Ellis
E
Owusu-Dabo
IRSS, Clinical Research Unit of Nanoro (CRUN), CMA Saint Camille of Nanoro, BP 218 Ouagadougou CMS 11, Nanoro, Burkina Faso. jbouedraogo@gmail.com.
Jean-Bosco
JB
Ouedraogo
Centre Muraz of Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso. rguiguemde@yahoo.fr.
Tinga Robert
TR
Guiguemde
IRSS, Clinical Research Unit of Nanoro (CRUN), CMA Saint Camille of Nanoro, BP 218 Ouagadougou CMS 11, Nanoro, Burkina Faso. tintohalidou@yahoo.fr.|Centre Muraz of Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso. tintohalidou@yahoo.fr.
Halidou
H
Tinto
D000655:Amodiaquine / Q000009:adverse effects / Q000627:therapeutic use*; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D002050:Burkina Faso / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D012008:Recurrence
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine