title: Effects of antifolates--co-trimoxazole and pyrimethamine-sulfadoxine--on gametocytes in children with acute, symptomatic, uncomplicated, Plasmodium falciparum malaria.
abstract: Antimalarial drugs including the antifolate, pyrimethamine-sulfadoxine (PS), can modulate the prevalence and intensities of gametocytaemia following treatment of acute malaria infections. They may also directly influence the transmission and spread of drug insensitivity. Little is known of the effects of co-trimoxazole (Co-T), another antifolate antimalarial, on gametocytes in children with acute malaria infections. We compared the effects of Co-T and PS on the prevalence and intensities of gametocytaemia and gametocyte sex ratios in 102 children aged 0.5-12 years presenting with acute and uncomplicated falciparum malaria. Compared to pre-treatment, both drugs significantly increased gametocyte carriage post-initiation of treatment. However, gametocyte carriage was significantly lower on day 14 in those treated with Co-T than PS. Significant increase in gametocytaemia with time occurred in PS--but not Co-T-treated children. Kaplan-Meier survival curve of the cumulative probability of remaining gametocyte-free in children who were agametocytaemic at enrollment showed that by day 7 of follow up, children treated with PS had a significantly higher propensity to have developed gametocytes than in Co-T-treated children (Log-rank statistic 5.35, df = 1, P = 0.02). Gametocyte sex ratio changes were similar following treatment with both drugs. PS and Co-T treatment of acute malaria infections in children from this endemic area is associated with significant increases in prevalence and intensities of gametocytaemia but these effects are more marked in those treated with PS than Co-T.
authors.affiliation: Department of Pharmacology & Therapeutics, Institute for Medical Research and Training, 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: A E
authors.initials: AE
authors.lastname: Bamgboye
authors.forename: C P
authors.initials: CP
authors.lastname: Babalola
authors.forename: T C
authors.initials: TC
authors.lastname: Happi
authors.forename: G O
authors.initials: GO
authors.lastname: Gbotosho
mesh_terms: D000208:Acute Disease; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects; D011739:Pyrimethamine / Q000627:therapeutic use*; D012744:Sex Ratio; D013413:Sulfadoxine / Q000627:therapeutic use*; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D005493:Folic Acid Antagonists; C001205:fanasil, pyrimethamine drug combination; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D013413:Sulfadoxine; D011739:Pyrimethamine