Pentoxifylline as an adjunct therapy in children with cerebral malaria.

BACKGROUND: Pentoxifylline (PTX) affects many processes that may contribute to the pathogenesis of severe malaria and it has been shown to reduce the duration of coma in children with cerebral malaria. This pilot study was performed to assess pharmacokinetics, safety and efficacy of PTX in African children with cerebral malaria. METHODS: Ten children admitted to the high dependency unit of the Kilifi District Hospital in Kenya with cerebral malaria (Blantyre coma score of 2 or less) received quinine plus a continuous infusion of 10 mg/kg/24 hours PTX for 72 hours. Five children were recruited as controls and received normal saline instead of PTX. Plasma samples were taken for PTX and tumour necrosis factor (TNF) levels. Blantyre Coma Score, parasitemia, hematology and vital signs were assessed 4 hourly. RESULTS: One child (20%) in the control group died, compared to four children (40%) in the PTX group. This difference was not significant (p = 0.60). Laboratory parameters and clinical data were comparable between groups. TNF levels were lower in children receiving PTX. CONCLUSIONS: The small sample size does not permit definitive conclusions, but the mortality rate was unexpectedly high in the PTX group.

Carboxyhemoglobin levels in Kenyan children with Plasmodium falciparum malaria.

Heme oxygenase (HO) is thought to be induced in severe malaria, but the pathophysiologic consequences have not been examined. It is induced by hemolysis, oxidative stress, and inflammation. It degrades heme, producing carbon monoxide (CO), which causes elevated levels of carboxyhemoglobin (COHb). In a prospective study of 1,520 children admitted to a Kenyan district hospital, COHb levels were no higher in children with malaria than with other infections. The COHb levels in children with severe malarial anemia were higher than in other children with malaria, but significantly lower than in children with other causes of severe anemia such as sickle cell disease. Levels of COHb were not significantly higher in children with cerebral malaria or in those dying of malaria. These results do not support a systemic increase in HO activity in malaria compared with other infectious diseases, but the roles of HO and CO in malaria require further study.

Cerebral malaria: optimising management.

Cerebral malaria is one of the most common nontraumatic encephalopathies in the world. Children living in sub-Saharan Africa bear the brunt of the disease, but cerebral malaria is being seen increasingly in adults throughout the world, including outside malarious areas. There are differences in the clinical presentation and pathophysiology between African children and nonimmune adults from any region. Mortality is high (10-20%). Parenteral antimalarials are the only interventions that have been shown to affect outcome. The cinchona alkaloids (quinine and quinidine) are the mainstay of antimalarial treatment, but the artemisinin derivatives are increasingly being used. Aggressive treatment and prevention of convulsions may be important, particularly in children. Other ancillary treatments that can be used to augment standard antimalarial drugs, such as exchange blood transfusions, osmotic diuretics and pentoxifylline, may improve outcome but have not been subjected to rigorous clinical trials. There is little support for corticosteroids or deferoxamine (desferrioxamine) in cerebral malaria. Other adjuncts have not been adequately tested. Further research is required on drugs that interfere with the pathophysiological processes to prevent neurological complications and death.