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 three clinical trials (2001-2008) with at least 35 days follow up. The P. falciparum resistance conferring genotype (pfcrt 76T) and day seven chloroquine concentrations were determined. Data were divided into age groups <5, 5-9 and 10-14 years as 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 and infected with P. falciparum with chloroquine resistance conferring genotypes (n=195, p<0.001). In parallel, median chloroquine concentrations were 471, 688, and 809 (standard dose), 1040, 1494 and 1585 (double dose) nmol/l.
CONCLUSIONS: Chloroquine resistance is dose dependent and can be overcome by higher still well tolerated doses.
2016. Vol. 213, no 8, 1315-1321 p.