Antibodies (Abs) are critical for immunity to malaria. However, Plasmodium falciparum specific Abs decline rapidly in absence of reinfection, suggesting impaired immunological memory. This study determines whether residents of Sweden that were treated for malaria following international travel maintained long-lasting malaria-specific Abs and memory B cells (MBCs).
A new generation of strategies is evolving that aim to block malaria transmission by employing genetically modified vectors or mosquito pathogens or symbionts that express anti-parasite molecules. Whilst transgenic technologies have advanced rapidly, there is still a paucity of effector molecules with potent anti-malaria activity whose expression does not cause detrimental effects on mosquito fitness. Our objective was to examine a wide range of antimicrobial peptides (AMPs) for their toxic effects on Plasmodium and anopheline mosquitoes.
The outcome of the Phase IIb trial of RTS,S (a vaccine comprising the polypeptides RTS and S) in young Mozambican children consolidated hopes that effective vaccination against malaria is a step nearer, and even elicited a generous promise of commitment from the Chancellor of the Exchequer of the UK. However, it seems that both optimism and generosity should be moderated by the failure of this vaccine to induce meaningful protection against infection by Plasmodium falciparum and that we should await confirmation of its efficacy in diminishing the incidence of severe malaria.
The vast majority of the 1-2 million malaria associated deaths that occur each year are due to anemia and cerebral malaria (the attachment of erythrocytes containing mature forms of Plasmodium falciparum to the endothelial cells that line the vascular beds of the brain). A "model system" for the study of cerebral malaria employs amelanotic melanoma cells as the "target" cells in an in vitro cytoadherence assay.
Artemisinin is an important new antimalarial agent containing a bridged endoperoxide. The in vitro antimalarial activity of an artemisinin derivative, arteether, is antagonized by two iron chelators, pyridoxal benzoylhydrazone and 1,2-dimethyl-3-hydroxypyrid-4-one. Similarly, the acute toxicity of artemisinin in mice is antagonized by another chelator, deferoxamine-hydroxyethylstarch. A combination of artemisinin and hemin oxidizes erythrocyte membrane thiols in vitro, and this oxidation is also inhibited by an iron chelator.
A randomized comparative trial of the pharmacokinetics and pharmacodynamics of oral doses of mefloquine and of mefloquine in combination with artesunate was carried out on 20 Thai male patients with acute, uncomplicated falciparum malaria. The patients were randomized to receive either mefloquine alone (8 patients; 1250 mg of mefloquine--initial dose, 750 mg; followed 6 hours later by 500 mg), or in combination with oral artesunate (12 patients--initial dose, 200 mg of artesunate; followed by 750 mg and 500 mg of mefloquine 6 hours and 12 hours later, respectively).
In Thailand Plasmodium falciparum malaria is highly resistant to available antimalarials. Investigations on the efficacy of existing antimalarials and of alternative drugs are urgently needed. Artesunate has been shown to be effective against falciparum malaria, but is associated with a high recrudescence rate. We have carried out a comparative clinical trial of the standard regimen of quinine + tetracycline versus oral artesunate at a 700-mg total dose given over 5 days to patients with acute uncomplicated falciparum malaria.
1. The pharmacokinetics of artemether were investigated (a) in six healthy male Thai volunteers after single 200 mg oral doses and (b) in eight male Thai patients with acute uncomplicated falciparum malaria after an initial 200 mg oral dose followed by 100 mg at 12 h then 100 mg daily for 4 days. 2. In the healthy subjects, median (range) maximum plasma concentrations of artemether of 118 (112-127) ng ml-1 were reached at 3 (1-10) h. Thereafter, drug concentrations declined monoexponentially with a median (range) t1/2.z of 3.1 (1.0-9.6) h.
The in vivo and in vitro effects of antimalarials on cytoadherence and rosette formation were studied in 17 patients with severe and 46 with uncomplicated falciparum malaria. Cytoadherence was increased in severe malaria (P<.001). Artesunate and artemether were more potent than quinine in inhibiting both adherence properties. Artesunate was the most rapidly acting drug tested, producing >50% inhibition of both cytoadherence and rosetting in vivo and in vitro within 2 hr of drug exposure.
Plasma concentrations of big endothelin-1 were determined by ELISA in 18 patients with complicated Plasmodium falciparum malaria in Bangkok. Before therapy, elevated levels were recorded (21 +/- 12 vs. 2.9 +/- 1.1 pmol/L in age- and sex-matched healthy subjects; P < .001). Even 7 days after therapy, elevated concentrations were seen (25 +/- 14 pmol/L). Plasma endothelin levels were correlated with levels of tumor necrosis factor-alpha (r = .632, P < .01), and a negative correlation with platelet counts was seen (r = .783, P < .005).