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

Abstract

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.

Undernutrition, infection and immune function

“…Since reduced Fe availability decreases the number of erythrocytes, low Fe status should protect against malaria (indeed, the incidence of malaria in Fe-de®cient individuals is less than in Fe-replete individuals; Oppenheimer et al 1986) and giving Fe to malaria-infected individuals should make the disease worse. Indeed, it could be argued that lowering Fe status might improve malaria outcome: this is borne out by the observation that Fe chelation therapy enhanced the clearance of parasites and speeded up the effect of anti-malarials (Thuma et al 1998). Earlier studies showed that levels of malaria infection and the severity of the disease were increased by Fe supplementation (Murray et al 1978a,b).…”

Association of hepatomegaly and jaundice with acute renal failure but not with cerebral malaria in severe falciparum malaria in Thailand.

“…1 Few studies have focused on hepatomegaly during severe malaria. 5 Hepatic failure is exceptional, but decreased hepatic blood flow 6 and microsomal activity are common during severe malaria. 7 There are several clinical manifestations of severe malaria, which may differ in pathophysiology.…”

Effects of Synthetic Siderophores on Proliferation ofPlasmodium falciparumin Infected Human Erythrocytes

“…Although these studies showed some clinical benefit, the overall mortality was not reduced (16). However, these studies suggested that iron deprivation is a useful therapeutic approach for malaria.…”