title: Residual antimalarials in malaria patients from Tanzania--implications on drug efficacy assessment and spread of parasite resistance.
abstract: BACKGROUND
  Repeated antimalarial treatment for febrile episodes and self-treatment are common in malaria-endemic areas. The intake of antimalarials prior to participating in an in vivo study may alter treatment outcome and affect the interpretation of both efficacy and safety outcomes. We report the findings from baseline plasma sampling of malaria patients prior to inclusion into an in vivo study in Tanzania and discuss the implications of residual concentrations of antimalarials in this setting.
  
  
  RESULTS
  In an in vivo study conducted in a rural area of Tanzania in 2008, baseline plasma samples from patients reporting no antimalarial intake within the last 28 days were screened for the presence of 14 antimalarials (parent drugs or metabolites) using liquid chromatography-tandem mass spectrometry. Among the 148 patients enrolled, 110 (74.3%) had at least one antimalarial in their plasma: 80 (54.1%) had lumefantrine above the lower limit of calibration (LLC = 4 ng/mL), 7 (4.7%) desbutyl-lumefantrine (4 ng/mL), 77 (52.0%) sulfadoxine (0.5 ng/mL), 15 (10.1%) pyrimethamine (0.5 ng/mL), 16 (10.8%) quinine (2.5 ng/mL) and none chloroquine (2.5 ng/mL).
  
  
  CONCLUSIONS
  The proportion of patients with detectable antimalarial drug levels prior to enrollment into the study is worrying. Indeed artemether-lumefantrine was supposed to be available only at government health facilities. Although sulfadoxine-pyrimethamine is only recommended for intermittent preventive treatment in pregnancy (IPTp), it was still widely used in public and private health facilities and sold in drug shops. Self-reporting of previous drug intake is unreliable and thus screening for the presence of antimalarial drug levels should be considered in future in vivo studies to allow for accurate assessment of treatment outcome. Furthermore, persisting sub-therapeutic drug levels of antimalarials in a population could promote the spread of drug resistance. The knowledge on drug pressure in a given population is important to monitor standard treatment policy implementation.
authors.affiliation: Swiss Tropical Institute, Basel, Switzerland.
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Hodel
authors.forename: Abdunoor Mulokozi
authors.initials: AM
authors.lastname: Kabanywanyi
authors.forename: Aggrey
authors.initials: A
authors.lastname: Malila
authors.forename: Boris
authors.initials: B
authors.lastname: Zanolari
authors.forename: Thomas
authors.initials: T
authors.lastname: Mercier
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Beck
authors.forename: Thierry
authors.initials: T
authors.lastname: Buclin
authors.forename: Piero
authors.initials: P
authors.lastname: Olliaro
authors.forename: Laurent Arthur
authors.initials: LA
authors.lastname: Decosterd
authors.forename: Blaise
authors.initials: B
authors.lastname: Genton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000962:Antimalarials / Q000097:blood* / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004350:Drug Residues / Q000032:analysis*; D004351:Drug Resistance / Q000187:drug effects; D005260:Female; D005843:Geography; D006801:Humans; D007223:Infant; D008288:Malaria / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010271:Parasites / Q000187:drug effects*; D013413:Sulfadoxine / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D013636:Tanzania; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000962:Antimalarials; D013413:Sulfadoxine