title: Predictors of the failure of treatment with chloroquine plus chlorpheniramine, in children with acute, uncomplicated, Plasmodium falciparum malaria.
abstract: Resistance to chloroquine in Plasmodium falciparum can be reversed, both in vitro and in vivo, by chlorpheniramine, a histamine H(1) receptor antagonist. This reversal raises the possibility of using chlorpheniramine to prolong the clinical usefulness of chloroquine in resource-poor communities. The factors that identify children at risk of treatment failure after being given chloroquine plus chlorpheniramine have now been evaluated in 281 children with uncomplicated, P. falciparum malaria. The children, who had taken part in six trials of antimalarial drugs between February 1996 and September 1999, in a hyper-endemic area of south-western Nigeria, were enrolled prospectively for the present study. Following treatment with chloroquine plus chlorpheniramine, 13 (5%) of the children failed treatment by day 7 or 14. In a multivariate analysis, an age of < or =3 years (adjusted odds ratio = 11.1; 95% confidence interval = 2.2-55.3; P = 0.003) and a parasitaemia that took >3 days to clear (adjusted odds ratio=7.9; 95% confidence interval = 1.3-49.4; P = 0.027) were found to be independent predictors of treatment failure. In addition, compared with the children who had a lower axillary temperature then, the children who had an axillary temperature of > or =38 degrees C 2 days after commencing treatment were significantly more likely to be treatment failures. In resource-poor communities using chloroquine plus chlorpheniramine, the easily identifiable predictors of treatment failure might be used to identify children requiring alternative antimalarial drugs.
authors.affiliation: Department of Pharmacology and Therapeutics and Malaria Research Group, Institute for Medical Research and Training, University of Ibadan, Nigeria. malaria.iba@alpha.linkserve.com
authors.forename: A
authors.initials: A
authors.lastname: Sowunmi
authors.forename: B A
authors.initials: BA
authors.lastname: Fateye
authors.forename: A A
authors.initials: AA
authors.lastname: Adedeji
authors.forename: F A
authors.initials: FA
authors.lastname: Fehintola
authors.forename: G O
authors.initials: GO
authors.lastname: Gbotosho
authors.forename: T C
authors.initials: TC
authors.lastname: Happi
authors.forename: A M J
authors.initials: AM
authors.lastname: Oduola
mesh_terms: D000208:Acute Disease; D000367:Age Factors; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use*; D002744:Chlorpheniramine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D018512:Parasitemia / Q000188:drug therapy; D011446:Prospective Studies; D012307:Risk Factors; D013223:Statistics as Topic; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D006634:Histamine H1 Antagonists; D002744:Chlorpheniramine; D002738:Chloroquine