How could preventive therapy affect the prevalence of drug resistance? Causes and consequences
Author(s)
Kunkel, A
Colijn, C
Lipsitch, M
Cohen, T
Type
Journal Article
Abstract
Various forms of preventive and prophylactic antimicrobial therapies have been proposed to combat HIV (e.g. pre-exposure prophylaxis), tuberculosis (e.g. isoniazid preventive therapy) and malaria (e.g. intermittent preventive treatment). However, the potential population-level effects of preventative therapy (PT) on the prevalence of drug resistance are not well understood. PT can directly affect the rate at which resistance is acquired among those receiving PT. It can also indirectly affect resistance by altering the rate at which resistance is acquired through treatment for active disease and by modifying the level of competition between transmission of drug-resistant and drug-sensitive pathogens. We propose a general mathematical model to explore the ways in which PT can affect the long-term prevalence of drug resistance. Depending on the relative contributions of these three mechanisms, we find that increasing the level of coverage of PT may result in increases, decreases or non-monotonic changes in the overall prevalence of drug resistance. These results demonstrate the complexity of the relationship between PT and drug resistance in the population. Care should be taken when predicting population-level changes in drug resistance from small pilot studies of PT or estimates based solely on its direct effects.
Date Issued
2015-04-27
Date Acceptance
2015-02-19
Citation
Philosophical Transactions of the Royal Society B: Biological Sciences, 2015, 370 (1670)
ISSN
1471-2970
Publisher
The Royal Society
Journal / Book Title
Philosophical Transactions of the Royal Society B: Biological Sciences
Volume
370
Issue
1670
Copyright Statement
© 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
License URL
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Grant Number
EP/K026003/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Biology
Life Sciences & Biomedicine - Other Topics
prophylaxis
preventive
mathematical model
antibiotic resistance
indirect effects
competition
PREEXPOSURE PROPHYLAXIS
MATHEMATICAL-MODELS
HIV TRANSMISSION
POPULATION
IMPACT
MALARIA
AFRICA
SPREAD
AREAS
PREP
Antibiotic Prophylaxis
Communicable Disease Control
Computer Simulation
Drug Resistance, Microbial
Humans
Infection
Models, Theoretical
Prevalence
Evolutionary Biology
06 Biological Sciences
11 Medical And Health Sciences
Publication Status
Published
Article Number
20140306