Abstract. In prospective studies of acute uncomplicated, multidrug-resistant falciparum malaria on the western border of Thailand, the oral artemisinin derivatives were used alone in the treatment of 836 patients (artesunate 630, artemether 206), were combined with mefloquine (15-25 mg base/kg) in 2,826 patients, and mefloquine alone was used in 1,303 patients. The combined regimens of mefloquine plus an artemisinin derivative were associated with more side effects than those with an artemisinin derivative alone; acute nausea (31% versus 16%), vomiting (24% versus 11%), anorexia (51% versus 34%), and dizziness (47% versus 15%) (P Ͻ 0.001). Oral artesunate and artemether alone were very well tolerated. There was no difference in the incidence of possible adverse effects between the two drugs, and no evidence that either derivative caused allergic reactions, neurologic or psychiatric reactions, or cardiovascular or dermatologic toxicity. Blackwater fever occurred in three patients treated with mefloquine plus artesunate regimens. Oral artesunate and artemether are safe and well tolerated antimalarial drugs.
Dengue shock syndrome is a severe complication of dengue hemorrhagic fever (DHF), characterized by a massive increase in vascular permeability. Plasma cytokine concentrations were prospectively studied in 443 Vietnamese children with DHF, of whom 6 died. Shock was present in 188 children on admission to hospital, and in 71 children it developed later. Contrary to expectations, certain inflammatory markers (interleukin-6 and soluble intercellular adhesion molecule-1) were lower in the group with shock, and this may reflect the general loss of protein from the circulation due to capillary leakage. Only soluble tumor necrosis factor receptor (TNFR) levels showed a consistent positive relationship with disease severity. In patients with suspected DHF without shock, admission levels of sTNFR-75 in excess of 55 pg/mL predicted the subsequent development of shock, with a relative risk of 5.5 (95% confidence interval, 2.3-13.2). Large-scale release of soluble TNFR may be an early and specific marker of the endothelial changes that cause dengue shock syndrome.
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