Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria

• Published in: Transactions of the Royal Society of Tropical Medicine and Hygiene Vol. 92; no. 2; pp. 214 - 218
• Main Authors: Thuma, Philip E., Mabeza, George F., Biemba, Godfrey, Bhat, G.J., McLaren, Christine E., Moyo, Victor M., Zulu, Stenford, Khumalo, Hlosukwazi, Mabeza, Patricia, M'Hango, Abraham, Parry, Dean, Poltera, Anton A., Brittenham, Gary M., Gordeuk, Victor R.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.03.1998; Royal Society of Tropical Medicine and Hygiene; Elsevier
• Subjects: Antidotes - therapeutic use; Antimalarials - therapeutic use; Biological and medical sciences; chemotherapy; Child; Child, Preschool; Coma - drug therapy; deferoxamine; Deferoxamine - therapeutic use; Double-Blind Method; Drug Therapy, Combination; Female; Fever - drug therapy; Human protozoal diseases; Humans; Infant; Infectious diseases; Iron Chelating Agents - therapeutic use; iron chelation; Malaria; Malaria, Cerebral - drug therapy; Malaria, Cerebral - mortality; Male; Medical sciences; Parasitemia - drug therapy; Parasitemia - mortality; Parasitic diseases; Plasmodium falciparum; Prospective Studies; Protozoal diseases; quinine; Quinine - therapeutic use; Survival Rate; Treatment Outcome; Tropical medicine; Zambia; Zambia - epidemiology; Zambia; Africa; iron chelation; Plasmodium falciparum; deferoxamine; malaria; quinine; chemotherapy; Human; Protozoa; Antimalarial; Apicomplexa; Protozoal disease; Drug combination; Malaria; Treatment efficiency; Iron; Parasitosis; Quinine; Deferoxamine; Infection; Chemotherapy; Pernicious attack; Chelating agent; Double blind study; Child
• ISSN: 0035-9203; 1878-3503
• DOI: 10.1016/S0035-9203(98)90753-2

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.