The impact of within-host ecology on the fitness of a drug-resistant parasite

Silvie Huijben, Brian H.K. Chan, William A. Nelson, Andrew F. Read

Research output: Contribution to journalArticle

Abstract

Background and objectives: The rate of evolution of drug resistance depends on the fitness of resistant pathogens. The fitness of resistant pathogens is reduced by competition with sensitive pathogens in untreated hosts and so enhanced by competitive release in drug-treated hosts. We set out to estimate the magnitude of those effects on a variety of fitness measures, hypothesizing that competitive suppression and competitive release would have larger impacts when resistance was rarer to begin with. Methodology: We infected mice with varying densities of drug-resistant Plasmodium chabaudi malaria parasites in a fixed density of drug-sensitive parasites and followed infection dynamics using strain-specific quantitative PCR. Results: Competition with susceptible parasites reduced the absolute fitness of resistant parasites by 50–100%. Drug treatment increased the absolute fitness from 2- to >10 000-fold. The ecological context and choice of fitness measure was responsible for the wide variation in those estimates. Initial population growth rates poorly predicted parasite abundance and transmission probabilities. Conclusions and implications: (i) The sensitivity of estimates of pathogen fitness to ecological context and choice of fitness measure make it difficult to derive field-relevant estimates of the fitness costs and benefits of resistance from experimental settings. (ii) Competitive suppression can be a key force preventing resistance from emerging when it is rare, as it is when it first arises. (iii) Drug treatment profoundly affects the fitness of resistance. Resistance evolution could be slowed by developing drug use policies that consider in-host competition.

Original languageEnglish (US)
Pages (from-to)127-137
Number of pages11
JournalEvolution, Medicine and Public Health
Volume2018
Issue number1
DOIs
StatePublished - Jan 1 2018

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Ecology
parasite
Parasites
drug
fitness
ecology
parasites
drugs
Pharmaceutical Preparations
pathogens
drug therapy
pathogen
Plasmodium chabaudi
Plasmodium malariae
Parasitic Diseases
Population Growth
drug resistance
Drug Resistance
malaria
Cost-Benefit Analysis

Keywords

  • Cost of resistance
  • Drug resistance
  • Epidemiological models
  • Plasmodium chabaudi
  • Selection coefficient
  • Within-host ecology

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Ecology, Evolution, Behavior and Systematics
  • Health, Toxicology and Mutagenesis

Cite this

The impact of within-host ecology on the fitness of a drug-resistant parasite. / Huijben, Silvie; Chan, Brian H.K.; Nelson, William A.; Read, Andrew F.

In: Evolution, Medicine and Public Health, Vol. 2018, No. 1, 01.01.2018, p. 127-137.

Research output: Contribution to journalArticle

Huijben, Silvie ; Chan, Brian H.K. ; Nelson, William A. ; Read, Andrew F. / The impact of within-host ecology on the fitness of a drug-resistant parasite. In: Evolution, Medicine and Public Health. 2018 ; Vol. 2018, No. 1. pp. 127-137.
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