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dc.contributor.authorColijn, Caroline
dc.contributor.authorCohen, Ted
dc.contributor.authorFraser, Christophe
dc.contributor.authorHanage, William P.
dc.contributor.authorGoldstein, Edward
dc.contributor.authorGivon-Lavi, Noga
dc.contributor.authorDagan, Ron
dc.contributor.authorLipsitch, Marc
dc.date.accessioned2010-11-22T16:27:40Z
dc.date.issued2009
dc.identifier.citationColijn, Caroline, Ted Cohen, Christophe Fraser, William Hanage, Edward Goldstein, Noga Givon-Lavi, Ron Dagan, and Marc Lipsitch. 2010. What is the mechanism for persistent coexistence of drug-susceptible and drug-resistant strains of Streptococcus pneumoniae? Journal of the Royal Society Interface 7(47): 905-919.en_US
dc.identifier.issn1742-5689en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4584791
dc.description.abstractThe rise of antimicrobial resistance in many pathogens presents a major challenge to the treatment and control of infectious diseases. Furthermore, the observation that drug-resistant strains have risen to substantial prevalence but have not replaced drug-susceptible strains despite continuing (and even growing) selective pressure by antimicrobial use presents an important problem for those who study the dynamics of infectious diseases. While simple competition models predict the exclusion of one strain in favour of whichever is ‘fitter’, or has a higher reproduction number, we argue that in the case of Streptococcus pneumoniae there has been persistent coexistence of drug-sensitive and drug-resistant strains, with neither approaching 100 per cent prevalence. We have previously proposed that models seeking to understand the origins of coexistence should not incorporate implicit mechanisms that build in stable coexistence ‘for free’. Here, we construct a series of such ‘structurally neutral’ models that incorporate various features of bacterial spread and host heterogeneity that have been proposed as mechanisms that may promote coexistence. We ask to what extent coexistence is a typical outcome in each. We find that while coexistence is possible in each of the models we consider, it is relatively rare, with two exceptions: (i) allowing simultaneous dual transmission of sensitive and resistant strains lets coexistence become a typical outcome, as does (ii) modelling each strain as competing more strongly with itself than with the other strain, i.e. self-immunity greater than cross-immunity. We conclude that while treatment and contact heterogeneity can promote coexistence to some extent, the in-host interactions between strains, particularly the interplay between coinfection, multiple infection and immunity, play a crucial role in the long-term population dynamics of pathogens with drug resistance.en_US
dc.language.isoen_USen_US
dc.publisherThe Royal Societyen_US
dc.relation.isversionofdoi:10.1098/rsif.2009.0400en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871802/pdf/en_US
dash.licenseLAA
dc.subjectepidemiologyen_US
dc.subjectdrug resistanceen_US
dc.subjectmathematical modelen_US
dc.subjectcoexistenceen_US
dc.titleWhat is the Mechanism for Persistent Coexistence of Drug-susceptible and Drug-resistant Strains of Streptococcus pneumoniae?en_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalJournal of the Royal Society Interfaceen_US
dash.depositing.authorLipsitch, Marc
dc.date.available2010-11-22T16:27:40Z
dash.affiliation.otherSPH^Epidemiologyen_US
dc.identifier.doi10.1098/rsif.2009.0400*
dash.contributor.affiliatedHanage, William
dash.contributor.affiliatedGoldstein, Edward
dash.contributor.affiliatedLipsitch, Marc


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