Curdlan sulphate in human severe/cerebral Plasmodium falciparum malaria.
Preclinical studies have shown that curdlan sulphate (CRDS), a sulphated 1-->3-beta-D glucan, inhibits Plasmodium falciparum in vitro and down-modulates the immune response. A direct, non-specific effect on cytoadherence and rosetting may be predicted, as has been described with other sulphated polysaccharides, e.g. heparin. The anticoagulant effect of CRDS is 10-fold lower than heparin. Curdlan sulphate has, therefore, emerged as a candidate for adjunct medication in the treatment of severe/cerebral malaria. Two clinical studies were conducted using CRDS as adjunct medication to conventional therapy (artesunate) in patients with severe and severe/cerebral malaria. Both studies were double-blind and placebo-controlled to evaluate the efficacy and safety of the combination. Curdlan sulphate appeared to reduce the severity of the disease process, e.g. fever clearance time was shortened. Due to the small number of patients, there was no difference in mortality. The two treatment arms in both studies showed similar results for all laboratory parameters. The only adverse event recorded during CRDS treatment was an increase in activated partial thromboplastin time. This can be monitored easily. It seems that the patients who may benefit most are severe/cerebral cases with no organ damage on admission.
Havlik
I
I
Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown 2193, South Africa. havlikiv@therapy.wits.ac.za
Looareesuwan
S
S
Vannaphan
S
S
Wilairatana
P
P
Krudsood
S
S
Thuma
P E
PE
Kozbor
D
D
Watanabe
N
N
Kaneko
Y
Y
D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use; D000077332:Artesunate; D002648:Child; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005334:Fever / Q000188:drug therapy; D006801:Humans; D016779:Malaria, Cerebral / Q000188:drug therapy; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018512:Parasitemia / Q000188:drug therapy; D012717:Sesquiterpenes / Q000627:therapeutic use; D016896:Treatment Outcome; D047071:beta-Glucans / Q000009:adverse effects / Q000627:therapeutic use*
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D047071:beta-Glucans; D000077332:Artesunate; C063130:curdlan sulfate