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Evolutionary Epidemiology of Drug-Resistance in Space

By Florence Débarre, Thomas Lenormand and Sylvain Gandon


The spread of drug-resistant parasites erodes the efficacy of therapeutic treatments against many infectious diseases and is a major threat of the 21st century. The evolution of drug-resistance depends, among other things, on how the treatments are administered at the population level. “Resistance management” consists of finding optimal treatment strategies that both reduce the consequence of an infection at the individual host level, and limit the spread of drug-resistance in the pathogen population. Several studies have focused on the effect of mixing different treatments, or of alternating them in time. Here, we analyze another strategy, where the use of the drug varies spatially: there are places where no one receives any treatment. We find that such a spatial heterogeneity can totally prevent the rise of drug-resistance, provided that the size of treated patches is below a critical threshold. The range of parasite dispersal, the relative costs and benefits of being drug-resistant compared to being drug-sensitive, and the duration of an infection with drug-resistant parasites are the main factors determining the value of this threshold. Our analysis thus provides some general guidance regarding the optimal spatial use of drugs to prevent or limit the evolution of drug-resistance

Topics: Research Article
Publisher: Public Library of Science
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Provided by: PubMed Central

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  30. (1990). On the definition and the computation of the basic reproduction ratio R0 in models for infectious diseases in heterogeneous populations.
  31. (2005). Outpatient antibiotic use in Europe and association with resistance: a crossnational database study.
  32. (2004). Persistent colonization and the spread of antibiotic resistance in nosocomial pathogens: resistance is a regional problem.
  33. (2005). Perspectives on the basic reproductive ratio.
  34. (1998). Population dynamics of tuberculosis treatment: mathematical models of the roles of non-compliance and bacterial heterogeneity in the evolution of drug resistance.
  35. (1998). Resistance management: the stable zone strategy.
  36. (2005). Small-scale fungicide spray heterogeneity and the coexistence of resistant and sensitive pathogen trains.
  37. (1969). Some demographic and genetic consequences of environmental heterogeneity for biological control.
  38. (1982). Spartial Heterogeneity and Interspecific Competition.
  39. (2007). Structure of the scientific community modelling the evolution of resistance.
  40. (1974). Sufficient Conditions for Protected Polymorphism in a Subdivided Popula-tion.
  41. (1999). The biological cost of antibiotic resistance.
  42. (1977). The development of insecticide resistance in the presence of migration.
  43. (2004). The effect of local prevention in an SIS model with diffusion.
  44. (1994). The evolution of virulence in parasites and pathogens: reconciliation between two competing hypotheses.
  45. (2007). The evolutionary epidemiology of vaccination.
  46. (2007). The pluses and minuses of r0.
  47. (1997). The population dynamics of antimicrobial chemotherapy.
  48. (1999). The relationship between the volume of antimi-crobial consumption in human communities and the frequency of resistance.
  49. (2006). The role of compensatory mutations in the emergence of drug resistance.
  50. (1948). The theory of a cline.
  51. (2003). Tsetse y population genetics: an indirect approach to dispersal.
  52. (2006). Vaccination, within-host dynamics, and virulence evolution.

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