Article,
High-Dose Chloroquine for Treatment of Chloroquine-Resistant Plasmodium falciparum Malaria
The Journal of Infectious Diseases, 213 (8): 1315–1321 (April 2016)
Abstract
Background. Due to development of multidrug-resistant Plasmodium falciparum new antimalarial therapies are needed. In Guinea-Bissau, routinely used triple standard-dose chloroquine remained effective for decades despite the existence of “chloroquine-resistant” P. falciparum. This study aimed to determine the in vivo efficacy of higher chloroquine concentrations against P. falciparum with resistance-conferring genotypes.
Methods. Standard or double-dose chloroquine was given to 892 children aged <15 years with uncomplicated malaria during 3 clinical trials (2001–2008) with ≥35 days follow-up. The P. falciparum resistance–conferring genotype (pfcrt 76T) and day 7 chloroquine concentrations were determined. Data were divided into age groups (<5, 5–9, and 10–14 years) because concentrations increase with age when chloroquine is prescribed according to body weight.
Results. Adequate clinical and parasitological responses were 14%, 38%, and 39% after standard-dose and 66%, 84%, and 91% after double-dose chloroquine in children aged <5, 5–9, and 10–14 years, respectively, and infected with P. falciparum genotypes conferring chloroquine resistance (n = 195, P < .001). In parallel, median chloroquine concentrations were 471, 688, and 809 nmol/L for standard-dose and 1040, 1494, and 1585 nmol/L for double-dose chloroquine.
Conclusions. Chloroquine resistance is dose dependent and can be overcome by higher, still well-tolerated doses.
