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Philos Trans R Soc Lond B Biol Sci. 2015 Jun 5;370(1670):20140306. doi: 10.1098/rstb.2014.0306.

How could preventive therapy affect the prevalence of drug resistance? Causes and consequences.

Author information

1
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06520, USA agkunkel@gmail.com.
2
Department of Mathematics, Imperial College, London SW7 2AZ, UK.
3
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
4
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06520, USA.

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.

KEYWORDS:

antibiotic resistance; competition; indirect effects; mathematical model; preventive; prophylaxis

PMID:
25918446
PMCID:
PMC4424438
DOI:
10.1098/rstb.2014.0306
[Indexed for MEDLINE]
Free PMC Article
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