Evidence basis for antimalarial policy change in Sierra Leone: five in vivo efficacy studies of chloroquine, sulphadoxine–pyrimethamine and amodiaquine

• Published in: Tropical medicine & international health 2005-02, Vol.10 (2), p.146-153
• Main Authors: Checchi, Francesco, Roddy, Paul, Kamara, Sarian, Williams, Arthur, Morineau, Guy, Wurie, Abdul Rahman, Hora, Bona, Lamotte, Nadine de, Baerwaldt, Tim, Heinzelmann, Annette, Danks, Alison, Pinoges, Loretxu, Oloo, Aggrey, Durand, Rémy, Ranford‐Cartwright, Lisa, Smet, Martin
• Format: Article
• Language: English
• Subjects: amodiaquine; Amodiaquine - therapeutic use; Animals; Antimalarials - therapeutic use; artesunate; Biological and medical sciences; Child, Preschool; chloroquine; Chloroquine - therapeutic use; Developing Countries; Drug Combinations; Drug Resistance; efficacy; Evidence-Based Medicine; Female; General aspects; Health Policy; Human infectious diseases. Experimental studies and models; Humans; Infant; Infectious diseases; malaria; Malaria, Falciparum - drug therapy; Male; Medical sciences; Plasmodium falciparum; Plasmodium falciparum - drug effects; policy; Pyrimethamine - therapeutic use; Sierra Leone; Sulfadoxine - therapeutic use; sulphadoxine–pyrimethamine; Treatment Failure; Treatment Outcome
• ISSN: 1360-2276; 1365-3156
• DOI: 10.1111/j.1365-3156.2004.01367.x

Summary Objectives  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. Conclusion  In a consensus meeting organized by the Ministry of Health and Sanitation, and based on these findings, artesunate (AS) + AQ and artemether–lumefantrine (Coartem™) 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.