BACKGROUND: In 2008, Guinea-Bissau introduced artemether-lumefantrine for treatment of uncomplicated malaria. Previously, 3 times the standard dose of chloroquine, that was probably efficacious against Plasmodium falciparum with the resistance-associated chloroquine-resistance transporter (pfcrt) 76T allele, was routinely used. The present study compared the efficacy and tolerability of a double standard dose of chloroquine with the efficacy and tolerability of artemether-lumefantrine. METHODS: In a randomized open-label clinical trial, artemether-lumefantrine or chloroquine (50 mg/kg) were given as 6 divided doses over 3 days to children aged 6 months--15 years who had uncomplicated P. falciparum monoinfection. Drug concentrations were measured on day 7. P. falciparum multidrug resistance gene N86Y and pfcrt K76T alleles were identified. RESULTS: The polymerase chain reaction-adjusted day 28 and 42 treatment efficacies were 162 (97%) of 168 and 155 (97%) of 161, respectively, for artemether-lumefantrine and 150 (95%) of 158 and 138 (94%) of 148, respectively, for chloroquine. When parasites with resistance-associated pfcrt 76T were treated, the day 28 efficacy of chloroquine was 87%. No severe drug-related adverse events were detected. Symptom resolution was similar with both treatments. CONCLUSIONS: Both treatments achieved the World Health Organization-recommended efficacy for antimalarials that will be adopted as policy. High-dose chloroquine treatment regimes should be further evaluated with the aim of assessing chloroquine as a potential partner drug to artemisinin derivatives. Clinical trials registration. NCT00426439.
RCT Entities:
BACKGROUND: In 2008, Guinea-Bissau introduced artemether-lumefantrine for treatment of uncomplicated malaria. Previously, 3 times the standard dose of chloroquine, that was probably efficacious against Plasmodium falciparum with the resistance-associated chloroquine-resistance transporter (pfcrt) 76T allele, was routinely used. The present study compared the efficacy and tolerability of a double standard dose of chloroquine with the efficacy and tolerability of artemether-lumefantrine. METHODS: In a randomized open-label clinical trial, artemether-lumefantrine or chloroquine (50 mg/kg) were given as 6 divided doses over 3 days to children aged 6 months--15 years who had uncomplicated P. falciparum monoinfection. Drug concentrations were measured on day 7. P. falciparum multidrug resistance gene N86Y and pfcrt K76T alleles were identified. RESULTS: The polymerase chain reaction-adjusted day 28 and 42 treatment efficacies were 162 (97%) of 168 and 155 (97%) of 161, respectively, for artemether-lumefantrine and 150 (95%) of 158 and 138 (94%) of 148, respectively, for chloroquine. When parasites with resistance-associated pfcrt 76T were treated, the day 28 efficacy of chloroquine was 87%. No severe drug-related adverse events were detected. Symptom resolution was similar with both treatments. CONCLUSIONS: Both treatments achieved the World Health Organization-recommended efficacy for antimalarials that will be adopted as policy. High-dose chloroquine treatment regimes should be further evaluated with the aim of assessing chloroquine as a potential partner drug to artemisinin derivatives. Clinical trials registration. NCT00426439.
Authors: E Pussard; J P Lepers; F Clavier; L Raharimalala; J Le Bras; M Frisk-Holmberg; Y Bergqvist; F Verdier Journal: Antimicrob Agents Chemother Date: 1991-03 Impact factor: 5.191
Authors: Christin Sisowath; Johan Strömberg; Andreas Mårtensson; Mwinyi Msellem; Christine Obondo; Anders Björkman; José P Gil Journal: J Infect Dis Date: 2005-02-08 Impact factor: 5.226
Authors: Poul-Erik Kofoed; Johan Ursing; Anja Poulsen; Amabelia Rodrigues; Yngve Bergquist; Peter Aaby; Lars Rombo Journal: Trans R Soc Trop Med Hyg Date: 2006-08-14 Impact factor: 2.184
Authors: Patrice Piola; Carole Fogg; Francis Bajunirwe; Samuel Biraro; Francesco Grandesso; Eugene Ruzagira; Joseph Babigumira; Isaac Kigozi; James Kiguli; Juliet Kyomuhendo; Laurent Ferradini; Walter Taylor; Francesco Checchi; Jean-Paul Guthmann Journal: Lancet Date: 2005 Apr 23-29 Impact factor: 79.321
Authors: A Djimdé; O K Doumbo; J F Cortese; K Kayentao; S Doumbo; Y Diourté; D Coulibaly; A Dicko; X Z Su; T Nomura; D A Fidock; T E Wellems; C V Plowe Journal: N Engl J Med Date: 2001-01-25 Impact factor: 91.245
Authors: Ric N Price; Anne-Catrin Uhlemann; Michele van Vugt; Al Brockman; Robert Hutagalung; Shalini Nair; Denae Nash; Pratap Singhasivanon; Tim J C Anderson; Sanjeev Krishna; Nicholas J White; François Nosten Journal: Clin Infect Dis Date: 2006-04-26 Impact factor: 9.079
Authors: Colin J Sutherland; Hamza Babiker; Margaret J Mackinnon; Lisa Ranford-Cartwright; Badria Babiker El Sayed Journal: Parasitology Date: 2011-08-03 Impact factor: 3.234
Authors: Brioni R Moore; Madhu Page-Sharp; Jillian R Stoney; Kenneth F Ilett; Jeffrey D Jago; Kevin T Batty Journal: Antimicrob Agents Chemother Date: 2011-06-06 Impact factor: 5.191
Authors: Robert L Summers; Anurag Dave; Tegan J Dolstra; Sebastiano Bellanca; Rosa V Marchetti; Megan N Nash; Sashika N Richards; Valerie Goh; Robyn L Schenk; Wilfred D Stein; Kiaran Kirk; Cecilia P Sanchez; Michael Lanzer; Rowena E Martin Journal: Proc Natl Acad Sci U S A Date: 2014-04-11 Impact factor: 11.205
Authors: Alejandro L Antonia; Steve M Taylor; Mark Janko; Michael Emch; Antoinette K Tshefu; Steven R Meshnick Journal: Am J Trop Med Hyg Date: 2014-04-14 Impact factor: 2.345