Inadequacy of chlorproguanil 20 mg per week as chemoprophylaxis for falciparum malaria in Kenya.

Abstract

After treatment with chloroquine and pyrimethamine/sulfadoxine, 118 school children aged 6 to 10 years living near the Kenyan coast were enrolled in a malaria chemoprophylaxis study and followed up for 20 weeks. Children were randomly assigned to receive either chlorproguanil 20 mg weekly (n = 78) or placebo (n = 37). The attack rate of Plasmodium falciparum infection was 42% in chlorproguanil recipients (39.8 episodes per 1000 person-weeks of prophylaxis) and 73% in placebo recipients (69.2 episodes per 1000 person-weeks, p less than 0.02). Sensitivity tests on 36 isolates successfully cultured in vitro showed that all 21 isolates from chloroproguanil recipients were resistant to dihydrofolate-reductase inhibitors, whereas only 3 of 15 isolates from the placebo group were resistant (p less than 10(-6)). Chlorproguanil in a weekly adult dose of 40 mg does not provide adequate prophylaxis against P falciparum in Kenya, probably because drug levels between doses fall below those required to suppress parasites resistant to dihydrofolate-reductase inhibitors.

• Authors: W M Watkins, A D Brandling-Bennett, A J Oloo, R E Howells, H M Gilles, D K Koech
• Journal: Lancet (London, England) (Lancet) Vol. 1 Issue 8525 Pg. 125-8 (Jan 17 1987) ISSN: 0140-6736 [Print] England
• PMID: 2879970 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Sulfadoxine
• chlorproguanil
• Proguanil
• Pyrimethamine

Topics

• Adolescent
• Child
• Clinical Trials as Topic
• Drug Resistance, Microbial
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Humans
• In Vitro Techniques
• Kenya
• Malaria (prevention & control)
• Male
• Plasmodium falciparum (drug effects)
• Proguanil (administration & dosage, analogs & derivatives, therapeutic use)
• Pyrimethamine (administration & dosage)
• Random Allocation
• Sulfadoxine (administration & dosage)