Aggressive Chemotherapy and the Selection of Drug Resistant Pathogens

PLoS Pathogens

Derek G. Sim¹  Danielle Tomasello¹  Andrew S. Bell¹  Nicole Mideo¹  Silvie Huijben¹  Andrew F. Read¹  Troy Day² 

[1] Center for Infectious Disease Dynamics, Departments of Biology and Entomology, Pennsylvania State University, University Park, Pennsylvania, United States of America;Departments of Mathematics, Statistics and Biology, Jeffery Hall, Queen's University, Kingston, Ontario, Canada

关键词: Parasitic diseases;    Drug therapy;    Aggressive chemotherapy;    Gametocytes;    Cloning;    Parasite evolution;    Malarial parasites;    Red blood cells;   

DOI  :  10.1371/journal.ppat.1003578

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY