Antimalarial drug resistance and combination chemotherapy

被引:335
作者
White, N
机构
[1] Mahidol Univ, Fac Trop Med, Bangkok 10400, Thailand
[2] Ctr Trop Dis, Wellcome Trust Clin Res Unit, Ho Chi Minh City, Vietnam
[3] John Radcliffe Hosp, Nuffield Dept Clin Med, Ctr Trop Dis, Oxford OX3 9DU, England
关键词
antimalarials; resistance; combinations; artemisinin;
D O I
10.1098/rstb.1999.0426
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Antimarial drug resistance develops when spontaneously occurring parasite mutants with reduced susceptibility are selected, and are then transmitted. Drugs for which a single point mutation confers a marked reduction in susceptibility are particularly vulnerable. Low clearance and a shallow concentration-effect relationship increase the chance of selection. Use of combinations of antimalarials that do not share the same resistance mechanisms will reduce the chance of selection because the chance of a resistant mutant surviving is the product of the per parasite mutation rates for the individual drugs, multiplied by the number of parasites in an infection that are exposed to the drugs. Artemisinin derivatives are particularly effective combination partners because (i) they are very active antimalarials, producing up to 10 000-fold reductions in parasite biomass per asexual cycle; (ii) they reduce malaria transmissibility; and (iii) no resistance to these drugs has been reported yet. There are good arguments for no longer using antimalarial drugs alone in treatment, and instead always using a combination with artemisinin or one of its derivatives.
引用
收藏
页码:739 / 749
页数:11
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