High-Dose Dexamethasone in Quinine-Treated Patients with Cerebral Malaria: A Double-Blind, Placebo-Controlled Trial

Abstract

We compared placebo and dexamethasone (initial dose, 3 mg/kg; total, 11.4 mg/kg per 48 h) in a double-blind trial involving 10 stuporous and 28 comatose patients with cerebral malaria. Patients were 18 mo to 42 y of age (geometric mean, 10.2 y), and the 19 patients in each group were comparable on admission. All patients received intravenous quinine therapy. Four patients (21%) in each group died. There were no significant differences between the placebo- and dexamethasone-treated groups in time until patients became afebrile (median, 51 vs. 19 h), the level of consciousness became normal (mean, 80 vs. 83 h), or parasitemia was cleared (mean, 2.1 vs. 3.4 d) or in the incidence of complications. Coma or hyperparasitemia (greater than or equal to 5% of erythrocytes parasitized) at the time of admission and hypoglycemia at any time during hospitalization were significantly correlated with a fatal outcome, which was not improved by using dexamethasone. We conclude that high-dose dexamethasone is not indicated for treating cerebral malaria.

Plasmodium falciparumMalaria: Reduction of Endothelial Cell Apoptosis In Vitro

“…In human P. falciparum malaria, heparin (21), anti-TNF-␣ antibodies (52), and pentoxifylline (24,35) have failed to provide any therapeutic benefit, while dexamethasone (which is known to induce endothelial apoptosis in vivo [15,53]) was even deleterious (25,54). Activated or apoptotic endothelial cells become procoagulant, reflected by decreased protein C and elevated plasma thrombin-antithrombin III levels in P. falciparum malaria (5,22,44).…”

Presidential address: The American Society of Tropical Medicine and Hygiene in the last half century: from apparent anachronism to international leader and innovator.

“…Our efforts led to a remarkable reduction in mortality on typhoid, 1 but had no impact on the case fatality rate of cerebral malaria. 7 In retrospect, it is hard to believe that 21 years ago, the entire extent of clinical tropical medicine and travelers health at our meeting, the principal venue for tropical medicine in the United States, was perhaps one session devoted to clinical tropical medicine and travelers health, and an evening meeting of the clinicians club. At this meeting there are three scientific sessions, four symposia, a late breakers session, and a meet the professors session all devoted specifically to clinical tropical medicine or travelers health.…”

Pediatric Cerebral Malaria: A Scourge of Africa

“…A second double-blind placebo-controlled trial of adjunctive corticosteroids in children and adults and conducted in southeast Asia used a dexamethasone dose more than five-times higher [73]. Dosage was chosen based on previous success in the treatment of typhoid fever [74].…”