Aggressive chemotherapy and the selection of drug resistant pathogens.
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 s...
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doaj-0adf4f17574f44b1b92dc7eb29d683812020-11-25T00:12:00ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-09-0199e100357810.1371/journal.ppat.1003578Aggressive chemotherapy and the selection of drug resistant pathogens.Silvie HuijbenAndrew S BellDerek G SimDanielle TomaselloNicole MideoTroy DayAndrew F ReadDrug 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.http://europepmc.org/articles/PMC3771897?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Silvie Huijben Andrew S Bell Derek G Sim Danielle Tomasello Nicole Mideo Troy Day Andrew F Read |
spellingShingle |
Silvie Huijben Andrew S Bell Derek G Sim Danielle Tomasello Nicole Mideo Troy Day Andrew F Read Aggressive chemotherapy and the selection of drug resistant pathogens. PLoS Pathogens |
author_facet |
Silvie Huijben Andrew S Bell Derek G Sim Danielle Tomasello Nicole Mideo Troy Day Andrew F Read |
author_sort |
Silvie Huijben |
title |
Aggressive chemotherapy and the selection of drug resistant pathogens. |
title_short |
Aggressive chemotherapy and the selection of drug resistant pathogens. |
title_full |
Aggressive chemotherapy and the selection of drug resistant pathogens. |
title_fullStr |
Aggressive chemotherapy and the selection of drug resistant pathogens. |
title_full_unstemmed |
Aggressive chemotherapy and the selection of drug resistant pathogens. |
title_sort |
aggressive chemotherapy and the selection of drug resistant pathogens. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2013-09-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3771897?pdf=render |
work_keys_str_mv |
AT silviehuijben aggressivechemotherapyandtheselectionofdrugresistantpathogens AT andrewsbell aggressivechemotherapyandtheselectionofdrugresistantpathogens AT derekgsim aggressivechemotherapyandtheselectionofdrugresistantpathogens AT danielletomasello aggressivechemotherapyandtheselectionofdrugresistantpathogens AT nicolemideo aggressivechemotherapyandtheselectionofdrugresistantpathogens AT troyday aggressivechemotherapyandtheselectionofdrugresistantpathogens AT andrewfread aggressivechemotherapyandtheselectionofdrugresistantpathogens |
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1725401876636106752 |