Chemotherapy of cerebral malaria: Current recommendations for treatment and prophylaxis

Abstract

Cerebral malaria is a potentially fatal manifestation of 'severe' malaria caused by Plasmodium falciparum. It is an especially important problem for African children because it is a major cause of death due to malaria. The pathophysiology of cerebral disease is characterised by complex host-parasite interactions. Optimal management of cerebral malaria is also complex, requiring accurate diagnosis, prompt treatment with one of the few remaining effective antimalarial drugs, and recognition that cerebral disease is frequently accompanied by other major organ dysfunction requiring additional care. Three classes of antimalarial drugs are useful for cerebral malaria: the 4- aminoquinolines (chloroquine), the cinchona alkaloids (quinine, quinidine) and the artemisinin compounds (artesunate, artemether). Chloroquine is the drug of choice in the few areas of the world where the falciparum parasite remains sensitive. In most malarious regions, however, the cinchona alkaloids and the artemisinin compounds are the only remaining options. In some areas of Southeast Asia, resistance to quinine is established, further limiting treatment options and raising concerns for the future. Artemisinin compounds, an exciting new class of antimalarial drugs developed in China, are the most rapidly acting of all the antimalarial drugs, with little known toxicity. Despite new insight into the pathogenesis of cerebral malaria and powerful antiparasitic therapies, the mortality rates in patients with this disease have remained stable over many years and are unacceptably high, ranging from 10 to 50%. Thus, malaria remains a tremendous public health problem that requires continued efforts to better understand pathophysiology and develop more effective therapies. The best way to prevent cerebral malaria is to prevent infection with P. falciparum. Most approaches are based on a chemoprophylactic regimen in combination with other measures such as repellents and insect screens. Even though no regimen is completely effective, chemoprophylaxis may reduce the subsequent risk of cerebral malaria if a 'breakthrough' falciparum infection is acquired. Additionally, early diagnosis and prompt treatment of individuals with uncomplicated falciparum malaria may diminish the risk of cerebral malaria.