title: Pre-treatment with chloroquine and parasite chloroquine resistance in Ghanaian children with severe malaria.
abstract: BACKGROUND
  Self-medication with anti-malarial drugs is widespread, and chloroquine (CQ) resistance is increasing. The effect of these factors on the incidence and presentation of severe malaria is uncertain.
  
  
  OBJECTIVE
  To investigate subtype of severe malaria, duration of illness, previous CQ treatment and prevalence of Plasmodium falciparum CQ-resistance markers among children presenting with severe malaria to a teaching hospital in Ghana.
  
  
  METHODS
  Prospective clinical study.
  
  
  METHODS
  Consecutive patients (n = 189) presenting with severe malaria were examined clinically, and blood was taken for routine haematology and malaria films. Plasma and blood cells were stored and subsequently analysed by ELISA for CQ levels (n = 168) and by PCR and restriction digest for P. falciparum chloroquine resistance transporter gene (pfcrt) mutations (n = 139).
  
  
  RESULTS
  Of 47 presenting with cerebral malaria, 21 had severe anaemia and 13 respiratory distress (RDS). Twenty-nine had prostration or RDS alone, 41 severe anaemia with prostration or RDS, and 72 severe anaemia not associated with coma, prostration or RDS. Of the patients studied, 77% had CQ in their plasma, and 88% were carrying P. falciparum with a CQ-resistance genotype. Significant associations were found (i) between the CQ-resistance genotype of parasites and plasma CQ levels, (ii) between the presence of CQ in plasma and the reported duration of illness, and (iii) between the reported duration of illness and the occurrence of severe but otherwise uncomplicated anaemia.
  
  
  CONCLUSIONS
  There was extensive prior CQ use in our patients presenting with severe malaria, and a high prevalence of parasites with the CQ-resistance genotype. CQ resistance in P. falciparum may contribute to the development of severe but otherwise uncomplicated anaemia in this setting.
authors.affiliation: Kumasi Centre for Collaborative Research, Kwame Nkrumah University of Science and Technology, Ghana. evans@kccr.de
authors.forename: J A
authors.initials: JA
authors.lastname: Evans
authors.forename: J
authors.initials: J
authors.lastname: May
authors.forename: D
authors.initials: D
authors.lastname: Tominski
authors.forename: T
authors.initials: T
authors.lastname: Eggelte
authors.forename: F
authors.initials: F
authors.lastname: Marks
authors.forename: H H
authors.initials: HH
authors.lastname: Abruquah
authors.forename: C G
authors.initials: CG
authors.lastname: Meyer
authors.forename: C
authors.initials: C
authors.lastname: Timmann
authors.forename: T
authors.initials: T
authors.lastname: Agbenyega
authors.forename: R D
authors.initials: RD
authors.lastname: Horstmann
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005838:Genotype; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D011446:Prospective Studies; D015800:Protozoan Proteins
chemical_list: D000962:Antimalarials; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine