title: Effect of quinine and artesunate combination therapy on platelet count of children with severe malaria.
abstract: BACKGROUND
  There are several case reports of quinine-induced thrombocytopenia but no clinical trials to ascertain its incidence and significance in severe malaria.
  
  
  OBJECTIVE
  The primary objective was to assess the effect of quinine on the platelet count in children with severe malaria and to compare it with artesunate combination therapy (ACT), and the secondary objective was to assess outcome of treatment with quinine and ACT.
  
  
  METHODS
  An open-labelled, randomised, controlled trial was undertaken in 100 children aged 6 months to 12 years who were diagnosed with malaria by microscopy and/or rapid diagnostic test kits with at least one WHO clinical or laboratory criterion for severe malaria. All subjects were commenced on either quinine or ACT. Clindamycin was added to artesunate as a combination drug (ACT). It was also given to patients on quinine to avoid its confounding effect on the results. Platelet counts were undertaken every 24 hours for 7 consecutive days, temperature and coma score (Blantyre coma score ≥3 in children <4 years or Glasgow coma score ≥13 in children >4 years) was recorded 6-hourly and peripheral smears were taken 12-hourly until two consecutively negative smears were obtained. The primary outcome was a fall in the platelet count by ≥20% from the time of drug initiation until day 7. The secondary outcome was comparison of the efficacy, parasite clearance time, fever clearance time, coma recovery time and adverse effects of quinine vs ACT.
  
  
  RESULTS
  30.4% patients in the quinine group (n = 48) had ≥20% fall in platelet count and 10.8% of patients in the ACT group (n = 46) (P = 0.02). Despite the fall in platelet count, there was no bleeding. The efficacy of ACT was significantly better than quinine but the other treatment outcomes showed insignificant difference.
  
  
  CONCLUSIONS
  Quinine should be used with caution in patients with severe malaria because of the potential risk of quinine-induced thrombocytopenia.
authors.affiliation: a Department of Paediatrics , University College of Medical Sciences and Guru Tegh Bahadur Hospital, University of Delhi , Delhi , India.
authors.forename: Parul
authors.initials: P
authors.lastname: Gupta
authors.affiliation: a Department of Paediatrics , University College of Medical Sciences and Guru Tegh Bahadur Hospital, University of Delhi , Delhi , India.
authors.forename: Manish
authors.initials: M
authors.lastname: Narang
authors.affiliation: a Department of Paediatrics , University College of Medical Sciences and Guru Tegh Bahadur Hospital, University of Delhi , Delhi , India.
authors.forename: Sunil
authors.initials: S
authors.lastname: Gomber
authors.affiliation: b Department of Microbiology , University College of Medical Sciences and Guru Tegh Bahadur Hospital, University of Delhi , Delhi , India.
authors.forename: Rumpa
authors.initials: R
authors.lastname: Saha
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects*; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D003128:Coma; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D008288:Malaria / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D010976:Platelet Count; D011803:Quinine / Q000008:administration & dosage / Q000009:adverse effects*; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D011803:Quinine
keywords: Artemisinins; Child; Malaria; Platelet count; Quinine; Thrombocytopenia