Ursing Johan, Rombo Lars, Bergqvist Yngve, Rodrigues Amabelia, Kofoed Poul-Erik
Projecto de Saúde de Bandim, Indepth Network, Bissau, Guinea-Bissau Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet Department of Infectious Diseases, Danderyds Hospital, Stockholm.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet Centre for Clinical Research, Sörmland County Council, Eskilstuna, and Uppsala University.
J Infect Dis. 2016 Apr 15;213(8):1315-21. doi: 10.1093/infdis/jiv590. Epub 2015 Dec 11.
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.
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.
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.
Chloroquine resistance is dose dependent and can be overcome by higher, still well-tolerated doses.
由于耐多药恶性疟原虫的出现，需要新的抗疟疗法。在几内亚比绍，尽管存在“耐氯喹”恶性疟原虫，但常规使用的标准剂量三联氯喹数十年来一直有效。本研究旨在确定更高氯喹浓度对具有耐药基因型的恶性疟原虫的体内疗效。
在3项临床试验（2001 - 2008年）中，对892名年龄小于15岁的无并发症疟疾儿童给予标准剂量或双倍剂量氯喹，并进行≥35天的随访。测定了恶性疟原虫耐药基因型（pfcrt 76T）和第7天的氯喹浓度。数据按年龄组（<5岁、5 - 9岁和10 - 14岁）划分，因为按体重开氯喹时浓度会随年龄增加。
在年龄<5岁、5 - 9岁和10 - 14岁且感染具有氯喹耐药基因型的恶性疟原虫的儿童中（n = 195，P <.001），标准剂量氯喹后的充分临床和寄生虫学反应分别为14%、38%和39%，双倍剂量氯喹后的反应分别为66%、84%和91%。同时，标准剂量氯喹的中位氯喹浓度分别为471、688和809 nmol/L，双倍剂量氯喹的中位氯喹浓度分别为1040、1494和1585 nmol/L。
氯喹耐药具有剂量依赖性，可通过更高但仍耐受性良好的剂量克服。
