title: A randomised, double-blind, placebo-controlled trial of atovaquone-proguanil vs. sulphadoxine-pyrimethamine in the treatment of malarial anaemia in Zambian children.
abstract: OBJECTIVE
  To compare the efficacy of atovaquone-proguanil (AP) and sulphadoxine-pyrimethamine (SP) in the treatment of malarial anaemia in Zambian children.
  
  
  METHODS
  An individually randomised, double-blind, controlled trial was undertaken in Zambian children with moderately severe anaemia and Plasmodium falciparum parasitaemia. The main trial endpoint was treatment failure defined as a need for blood transfusion or treatment with quinine, persistent anaemia or death within 14 days from the start of treatment. Secondary endpoints were parasitological and haematological findings 14 or 28 days after the start of treatment.
  
  
  RESULTS
  A total of 128 children with a packed cell volume of <21% and >9% and P. falciparum parasitaemia received treatment with AP and 127 treatment with SP. Treatment failure occurred in 28 children (22%) who received SP and in 10 (8%) who received AP (OR: 3.34, 95% CI: 1.54, 7.21). Ten children required blood transfusion, all of whom were in the SP treatment group. Six children died, five of whom were in the AP group; none of the deaths were considered to be related directly to treatment.
  
  
  CONCLUSIONS
  Atovaquone-proguanil proved more effective than SP in the treatment of malarial anaemia in an area with a modest level of SP resistance. AP is no longer available through the Malarone Donation Programme and is too expensive for routine use in Africa. However, this study has shown that in an area with a modest level of resistance to SP, use of a more effective antimalaria reduces the need for blood transfusion in children with malarial anaemia.
authors.affiliation: Tropical Diseases Research Centre, Ndola, Zambia.
authors.forename: Modest
authors.initials: M
authors.lastname: Mulenga
authors.forename: Fidelis
authors.initials: F
authors.lastname: Malunga
authors.forename: Steve
authors.initials: S
authors.lastname: Bennett
authors.forename: Philip E
authors.initials: PE
authors.lastname: Thuma
authors.forename: Caroline
authors.initials: C
authors.lastname: Shulman
authors.forename: Katherine
authors.initials: K
authors.lastname: Fielding
authors.forename: Ali
authors.initials: A
authors.lastname: Alloueche
authors.forename: Brian M
authors.initials: BM
authors.lastname: Greenwood
mesh_terms: D000740:Anemia / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D053626:Atovaquone / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D018512:Parasitemia / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D015995:Prevalence; D002727:Proguanil / Q000009:adverse effects / Q000627:therapeutic use*; D011739:Pyrimethamine / Q000009:adverse effects / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D017211:Treatment Failure; D015024:Zambia / Q000453:epidemiology
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002727:Proguanil; D053626:Atovaquone; D011739:Pyrimethamine