title: Chloroquine blood concentrations and molecular markers of chloroquine-resistant Plasmodium falciparum in febrile children in northern Ghana.
abstract: Plasmodium falciparum malaria is a predominant reason for health care utilization among children in sub-Saharan Africa. Despite the spread of resistance, chloroquine (CQ) is the most commonly used antimalarial. Little is known about the pattern of CQ use and resistance to the drug prior to attendance at a health care facility, and its impact on clinical presentation in children attending health care facilities in endemic regions. In a cross-sectional study among 840 febrile children presenting at a primary health care facility in northern Ghana from September to December 2000, CQ blood levels were measured by enzyme-linked immunosorbent assay and parasite isolates were genotyped for the CQ resistance markers pfcrt T76 and pfmdr1 Y86. Plasmodium falciparum was present in 95% by polymerase chain reaction and CQ was detected in 64% of the children. Concentrations of CQ in blood ranged from 31 to 3897 nmol/L (median 198 nmol/L). The pfcrt T76 and pfmdr1 Y86 resistance markers were detected in 84% and 57% of the isolates, respectively, and were selected by CQ. A significant trend for higher frequencies of the resistance markers with increasing CQ concentrations was observed. In this typical primary health care setting in sub-Saharan Africa, CQ use prior to attendance at a health care facility and CQ-resistant P. falciparum are frequent. As CQ selects resistant P. falciparum genotypes, CQ should be omitted as a first-line drug even in primary health care facilities when self-treatment with CQ is common.
authors.affiliation: Institut für Tropenmedizin Berlin, Charité, Humboldt-Universität zu Berlin, Spandauer Damm 130, 14050 Berlin, Germany. ehrhardt@bni-hamburg.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Ehrhardt
authors.forename: Frank P
authors.initials: FP
authors.lastname: Mockenhaupt
authors.forename: Teunis A
authors.initials: TA
authors.lastname: Eggelte
authors.forename: Patrick
authors.initials: P
authors.lastname: Agana-Nsiire
authors.forename: Karsten
authors.initials: K
authors.lastname: Stollberg
authors.forename: Sylvester D
authors.initials: SD
authors.lastname: Anemana
authors.forename: Rowland N
authors.initials: RN
authors.lastname: Otchwemah
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bienzle
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000097:blood / Q000627:therapeutic use*; D002675:Child, Preschool; D002738:Chloroquine / Q000097:blood / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D004351:Drug Resistance; D005260:Female; D005334:Fever / Q000469:parasitology; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D026901:Membrane Transport Proteins; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D015800:Protozoan Proteins
chemical_list: D000962:Antimalarials; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine