Aggressive Chemotherapy and the Selection of Drug Resistant Pathogens

Silvie Huijben, Andrew S. Bell, Derek G. Sim, Danielle Tomasello, Nicole Mideo, Troy Day, Andrew F. Read

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere1003578
JournalPLoS Pathogens
Volume9
Issue number9
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

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Drug Therapy
Pharmaceutical Preparations
Health
Drug Resistance
Malaria
Rodentia
Public Health
Outcome Assessment (Health Care)
Pressure
Therapeutics
Population

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Huijben, S., Bell, A. S., Sim, D. G., Tomasello, D., Mideo, N., Day, T., & Read, A. F. (2013). Aggressive Chemotherapy and the Selection of Drug Resistant Pathogens. PLoS Pathogens, 9(9), [e1003578]. https://doi.org/10.1371/journal.ppat.1003578

Aggressive Chemotherapy and the Selection of Drug Resistant Pathogens. / Huijben, Silvie; Bell, Andrew S.; Sim, Derek G.; Tomasello, Danielle; Mideo, Nicole; Day, Troy; Read, Andrew F.

In: PLoS Pathogens, Vol. 9, No. 9, e1003578, 01.09.2013.

Research output: Contribution to journalArticle

Huijben, S, Bell, AS, Sim, DG, Tomasello, D, Mideo, N, Day, T & Read, AF 2013, 'Aggressive Chemotherapy and the Selection of Drug Resistant Pathogens', PLoS Pathogens, vol. 9, no. 9, e1003578. https://doi.org/10.1371/journal.ppat.1003578
Huijben, Silvie ; Bell, Andrew S. ; Sim, Derek G. ; Tomasello, Danielle ; Mideo, Nicole ; Day, Troy ; Read, Andrew F. / Aggressive Chemotherapy and the Selection of Drug Resistant Pathogens. In: PLoS Pathogens. 2013 ; Vol. 9, No. 9.
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