Evidence basis for antimalarial policy change in Sierra Leone: five in vivo efficacy studies of chloroquine, sulphadoxine-pyrimethamine and amodiaquine.
OBJECTIVE
To provide nationally relevant information on the antimalarial efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) in Sierra Leone, with a view to updating antimalarial policy in the country.


METHODS
Between October 2002 and May 2003, standard WHO methodology for in vivo efficacy assessment was used in five sites to study the therapeutic response of 6-59 months old uncomplicated Plasmodium falciparum malaria cases treated with CQ (n = 247), SP (n = 353) or AQ (n = 434). Follow-up was of 28 days, with polymerase chain reaction genotyping to distinguish late recrudescences from re-infections.


RESULTS
Overall 85.3% of patients reached an analysable endpoint. CQ failure proportions were very high, ranging from 39.5% (95% CI: 25.0-55.6) in Kabala to 78.8% (65.3-88.9) in Kailahun. Early failures under CQ were frequent. SP efficacy was also disappointing, with failure from 23.2% (13.9-34.9) in Kabala to 46.1% (35.4-57.0) in Kailahun. AQ resistance was more moderate, ranging from 5.4% (1.8-12.1) in Makeni to 29.8% (20.3-40.8) in Kailahun, with almost no early failures. AQ also provided more rapid fever and parasite clearance.


CONCLUSIONS
In a consensus meeting organized by the Ministry of Health and Sanitation, and based on these findings, artesunate (AS) + AQ and artemether-lumefantrine (Coartemtrade mark) were identified as the only options to rapidly replace CQ. The choice fell on AS + AQ because of expected high efficacy, lower cost in a blister presentation, and the absence of safety data on artemether-lumefantrine in pregnancy. Donor support is required to support this policy change. Throughout Africa, as SP resistance increases, these two regimens are probably the only options available while newer combinations are developed. Efficacy studies should focus on testing AQ and AS + AQ.
Checchi
Francesco
F
Epicentre, 8 rue Saint-Sabin, 75011 Paris, France. francesco.checchi@lshtm.ac.uk
Roddy
Paul
P
Kamara
Sarian
S
Williams
Arthur
A
Morineau
Guy
G
Wurie
Abdul Rahman
AR
Hora
Bona
B
Lamotte
Nadine de
Nd
Baerwaldt
Tim
T
Heinzelmann
Annette
A
Danks
Alison
A
Pinoges
Loretxu
L
Oloo
Aggrey
A
Durand
Rémy
R
Ranford-Cartwright
Lisa
L
Smet
Martin
M
D000655:Amodiaquine / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use; D003906:Developing Countries; D004338:Drug Combinations; D004351:Drug Resistance; D019317:Evidence-Based Medicine; D005260:Female; D006291:Health Policy; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects; D011739:Pyrimethamine / Q000627:therapeutic use; D012807:Sierra Leone; D013413:Sulfadoxine / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome
D000962:Antimalarials; D004338:Drug Combinations; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine