OBJECTIVES: Several products of artesunate plus amodiaquine (AS + AQ) are being deployed in malaria-endemic countries for treating uncomplicated falciparum malaria but dosing accuracy and consequential effects on efficacy and tolerability have not been examined. METHODS: Patients with parasitologically confirmed, uncomplicated falciparum malaria were treated and followed by research teams or local health centre staff in Casamance, Senegal. AS + AQ was given as: (i) loose combination (AS 50 mg, AQ 200 mg), dosed on body weight, or (ii) co-blistered product (AS 50 mg, AQ 153 mg) dosed by weight or age. Target doses were: (i) AS 4 (2-10) mg/kg/day and (ii) AQ 10 (7.5-15) mg/kg/day. Patients receiving therapeutic doses defined dosing accuracy. Treatment-emergent signs and symptoms (TESS) were recorded. RESULTS: A total of 3277 patients were treated with loose (n = 1972, weight-dosed) or co-blistered (n = 1305, 962 age-dosed, 343 weight-dosed) AS + AQ by the research team (n = 966) or clinic staff (n = 2311). AS was dosed correctly in >99% with all regimens. Loose AQ by weight was 98% correct. The co-blister AQ overdosed 18% of patients when dosed by age and underdosed 13% by weight. Low weight was an independent risk factor for overdosing. The co-blister had significantly more TESS than the loose product [117/1305 (9%) vs. 41/1972 (2%), relative risk = 4.3 (95% CI: 3.0-6.1, P < 0.0001)]. Age-based dosing accounted for the difference. TESS occurred mostly within one day (72%) and were mild or moderate (75%). CONCLUSION: Artesunate is easier to dose than AQ. Currently available age-dosed, co-blistered AS + AQ tends to overdose AQ and is less well tolerated than loose tablets. It is not the optimal presentation of AS + AQ.
OBJECTIVES: Several products of artesunate plus amodiaquine (AS + AQ) are being deployed in malaria-endemic countries for treating uncomplicated falciparum malaria but dosing accuracy and consequential effects on efficacy and tolerability have not been examined. METHODS:Patients with parasitologically confirmed, uncomplicated falciparum malaria were treated and followed by research teams or local health centre staff in Casamance, Senegal. AS + AQ was given as: (i) loose combination (AS 50 mg, AQ 200 mg), dosed on body weight, or (ii) co-blistered product (AS 50 mg, AQ 153 mg) dosed by weight or age. Target doses were: (i) AS 4 (2-10) mg/kg/day and (ii) AQ 10 (7.5-15) mg/kg/day. Patients receiving therapeutic doses defined dosing accuracy. Treatment-emergent signs and symptoms (TESS) were recorded. RESULTS: A total of 3277 patients were treated with loose (n = 1972, weight-dosed) or co-blistered (n = 1305, 962 age-dosed, 343 weight-dosed) AS + AQ by the research team (n = 966) or clinic staff (n = 2311). AS was dosed correctly in >99% with all regimens. Loose AQ by weight was 98% correct. The co-blister AQ overdosed 18% of patients when dosed by age and underdosed 13% by weight. Low weight was an independent risk factor for overdosing. The co-blister had significantly more TESS than the loose product [117/1305 (9%) vs. 41/1972 (2%), relative risk = 4.3 (95% CI: 3.0-6.1, P < 0.0001)]. Age-based dosing accounted for the difference. TESS occurred mostly within one day (72%) and were mild or moderate (75%). CONCLUSION:Artesunate is easier to dose than AQ. Currently available age-dosed, co-blistered AS + AQ tends to overdose AQ and is less well tolerated than loose tablets. It is not the optimal presentation of AS + AQ.
Authors: M Cairns; B Cisse; C Sokhna; C Cames; K Simondon; E H Ba; J-F Trape; O Gaye; B M Greenwood; P J M Milligan Journal: Antimicrob Agents Chemother Date: 2010-01-11 Impact factor: 5.191
Authors: Martin A Adjuik; Richard Allan; Anupkumar R Anvikar; Elizabeth A Ashley; Mamadou S Ba; Hubert Barennes; Karen I Barnes; Quique Bassat; Elisabeth Baudin; Anders Björkman; François Bompart; Maryline Bonnet; Steffen Borrmann; Philippe Brasseur; Hasifa Bukirwa; Francesco Checchi; Michel Cot; Prabin Dahal; Umberto D'Alessandro; Philippe Deloron; Meghna Desai; Graciela Diap; Abdoulaye A Djimde; Grant Dorsey; Ogobara K Doumbo; Emmanuelle Espié; Jean-Francois Etard; Caterina I Fanello; Jean-François Faucher; Babacar Faye; Jennifer A Flegg; Oumar Gaye; Peter W Gething; Raquel González; Francesco Grandesso; Philippe J Guerin; Jean-Paul Guthmann; Sally Hamour; Armedy Ronny Hasugian; Simon I Hay; Georgina S Humphreys; Vincent Jullien; Elizabeth Juma; Moses R Kamya; Corine Karema; Jean R Kiechel; Peter G Kremsner; Sanjeev Krishna; Valérie Lameyre; Laminou M Ibrahim; Sue J Lee; Bertrand Lell; Andreas Mårtensson; Achille Massougbodji; Hervé Menan; Didier Ménard; Clara Menéndez; Martin Meremikwu; Clarissa Moreira; Carolyn Nabasumba; Michael Nambozi; Jean-Louis Ndiaye; Frederic Nikiema; Christian Nsanzabana; Francine Ntoumi; Bernhards R Ogutu; Piero Olliaro; Lyda Osorio; Jean-Bosco Ouédraogo; Louis K Penali; Mbaye Pene; Loretxu Pinoges; Patrice Piola; Ric N Price; Cally Roper; Philip J Rosenthal; Claude Emile Rwagacondo; Albert Same-Ekobo; Birgit Schramm; Amadou Seck; Bhawna Sharma; Carol Hopkins Sibley; Véronique Sinou; Sodiomon B Sirima; Jeffery J Smith; Frank Smithuis; Fabrice A Somé; Doudou Sow; Sarah G Staedke; Kasia Stepniewska; Todd D Swarthout; Khadime Sylla; Ambrose O Talisuna; Joel Tarning; Walter R J Taylor; Emmanuel A Temu; Julie I Thwing; Emiliana Tjitra; Roger C K Tine; Halidou Tinto; Michel T Vaillant; Neena Valecha; Ingrid Van den Broek; Nicholas J White; Adoke Yeka; Issaka Zongo Journal: BMC Med Date: 2015-03-31 Impact factor: 8.775
Authors: Christina Faust; Jonathan Zelner; Philippe Brasseur; Michel Vaillant; Malick Badiane; Moustafa Cisse; Bryan Grenfell; Piero Olliaro Journal: Am J Trop Med Hyg Date: 2015-05-11 Impact factor: 2.345