Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria.
To examine the effect of iron chelation on mortality in cerebral malaria, we enrolled 352 children in a trial of deferoxamine in addition to standard quinine therapy at 2 centres in Zambia, one rural and one urban. Entrance criteria included age < 6 years, Plasmodium falciparum parasitaemia, normal cerebral spinal fluid, and unrousable coma. Deferoxamine (100 mg/kg/d infused for a total of 72 h) or placebo was added to a 7 d regimen of quinine that included a loading dose. Mortality overall was 18.3% (32/175) in the deferoxamine group and 10.7% (19/177) in the placebo group (adjusted odds ratio 1.8; 95% confidence interval 0.9-3.6; P = 0.074). At the rural study site, mortality was 15.4% (18/117) with deferoxamine compared to 12.7% (15/118) with placebo (P = 0.78, adjusted for covariates). At the urban site, mortality was 24.1% (14/58) with deferoxamine and 6.8% (4/59) with placebo (P = 0.061, adjusted for covariates). Among survivors, there was a non-significant trend to faster recovery from coma in the deferoxamine group (adjusted odds ratio 1.2; 95% confidence interval 0.97-1.6; P = 0.089). Hepatomegaly was significantly associated with higher mortality, while splenomegaly was associated with lower mortality. This study did not provide evidence for a beneficial effect on mortality in children with cerebral malaria when deferoxamine was added to quinine, given in a regimen that included a loading dose.
Pennsylvania State University, Hershey Medical Center, USA.
P E
PE
Thuma
G F
GF
Mabeza
G
G
Biemba
G J
GJ
Bhat
C E
CE
McLaren
V M
VM
Moyo
S
S
Zulu
H
H
Khumalo
P
P
Mabeza
A
A
M'Hango
D
D
Parry
A A
AA
Poltera
G M
GM
Brittenham
V R
VR
Gordeuk
D000931:Antidotes / Q000627:therapeutic use*; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003128:Coma / Q000188:drug therapy; D003676:Deferoxamine / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005334:Fever / Q000188:drug therapy; D006801:Humans; D007223:Infant; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D016779:Malaria, Cerebral / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D018512:Parasitemia / Q000188:drug therapy* / Q000401:mortality*; D011446:Prospective Studies; D011803:Quinine / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome; D015024:Zambia / Q000453:epidemiology
D000931:Antidotes; D000962:Antimalarials; D007502:Iron Chelating Agents; D011803:Quinine; D003676:Deferoxamine