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High-Dose Chloroquine for Treatment of Chloroquine-Resistant Plasmodium falciparum Malaria
Indepth Network, Projecto Saude Bandim, Bissau, Guinea Bissau.;Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. Danderyd Hosp, Dept Infect Dis, Stockholm, Sweden. Sormland Cty Council, Clin Res Ctr, Eskilstuna, Sweden. Uppsala Univ, Borlange, Sweden. Dalarna Univ Coll, Borlange, Sweden. Kolding Cty Hosp, Dept Paediat, Kolding, Denmark..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. Danderyd Hosp, Dept Infect Dis, Stockholm, Sweden.
Borlange, Sweden. Dalarna Univ Coll, Borlange, Sweden..
Indepth Network, Projecto Saude Bandim, Bissau, Guinea Bissau..
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2016 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 213, no 8, 1315-1321 p.Article in journal (Refereed) PublishedText
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 213, no 8, 1315-1321 p.
Keyword [en]
Plasmodium falciparum, pfcrt, resistance, chloroquine, efficacy
National Category
Infectious Medicine Microbiology in the medical area Immunology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-297370DOI: 10.1093/infdis/jiv590ISI: 000375298700016PubMedID: 26656124OAI: oai:DiVA.org:uu-297370DiVA: diva2:941840
Funder
Stockholm County Council
Available from: 2016-06-23 Created: 2016-06-22 Last updated: 2016-06-23Bibliographically approved

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