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Aggressive Chemotherapy and the Selection of Drug Resistant Pathogens
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نویسنده
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huijben s. ,bell a.s. ,sim d.g. ,tomasello d. ,mideo n. ,day t. ,read a.f.
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منبع
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plos pathogens - 2013 - دوره : 9 - شماره : 9
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چکیده
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Drug resistant pathogens are one of the key public health challenges of the 21st century. there is a widespread belief that resistance is best managed by using drugs to rapidly eliminate target pathogens from patients so as to minimize the probability that pathogens acquire resistance de novo. yet strong drug pressure imposes intense selection in favor of resistance through alleviation of competition with wild-type populations. aggressive chemotherapy thus generates opposing evolutionary forces which together determine the rate of drug resistance emergence. identifying treatment regimens which best retard resistance evolution while maximizing health gains and minimizing disease transmission requires empirical analysis of resistance evolution in vivo in conjunction with measures of clinical outcomes and infectiousness. using rodent malaria in laboratory mice,we found that less aggressive chemotherapeutic regimens substantially reduced the probability of onward transmission of resistance (by >150-fold),without compromising health outcomes. our experiments suggest that there may be cases where resistance evolution can be managed more effectively with treatment regimens other than those which reduce pathogen burdens as fast as possible. © 2013 huijben et al.
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آدرس
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center for infectious disease dynamics,departments of biology and entomology,pennsylvania state university,university park,pa,united states,cresib - barcelona centre for international health research,barcelona, Spain, center for infectious disease dynamics,departments of biology and entomology,pennsylvania state university,university park,pa, United States, center for infectious disease dynamics,departments of biology and entomology,pennsylvania state university,university park,pa, United States, center for infectious disease dynamics,departments of biology and entomology,pennsylvania state university,university park,pa,united states,neuroscience program,the state university of new york at buffalo,buffalo,ny, United States, center for infectious disease dynamics,departments of biology and entomology,pennsylvania state university,university park,pa, United States, departments of mathematics,statistics and biology,jeffery hall,queen's university,kingston,on, Canada, center for infectious disease dynamics,departments of biology and entomology,pennsylvania state university,university park,pa,united states,fogarty international center,national institutes of health,bethesda,md, United States
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Authors
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