{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Knight GM"],"funding":["Medical Research Council","PEPFAR","PHS HHS","NIGMS NIH HHS","Engineering and Physical Sciences Research Council"],"pagination":["S147-54"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4583567"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["61Suppl 3"],"pubmed_abstract":["<h4>Background</h4>Drug resistance poses a serious challenge for the control of tuberculosis in many settings. It is well established that the expected future trend in resistance depends on the reproductive fitness of drug-resistant Mycobacterium tuberculosis. However, the variability in fitness between strains with different resistance-conferring mutations has been largely ignored when making these predictions.<h4>Methods</h4>We developed a novel approach for incorporating the variable fitness costs of drug resistance-conferring mutations and for tracking this distribution of fitness costs over time within a transmission model. We used this approach to describe the effects of realistic fitness cost distributions on the future prevalence of drug-resistant tuberculosis.<h4>Results</h4>The shape of the distribution of fitness costs was a strong predictor of the long-term prevalence of resistance. While, as expected, lower average fitness costs of drug resistance-conferring mutations were associated with more severe epidemics of drug-resistant tuberculosis, fitness distributions with greater variance also led to higher levels of drug resistance. For example, compared to simulations in which the fitness cost of resistance was fixed, introducing a realistic amount of variance resulted in a 40% increase in prevalence of drug-resistant tuberculosis after 20 years.<h4>Conclusions</h4>The differences in the fitness costs associated with drug resistance-conferring mutations are a key determinant of the future burden of drug-resistant tuberculosis. Future studies that can better establish the range of fitness costs associated with drug resistance-conferring mutations will improve projections and thus facilitate better public health planning efforts."],"journal":["Clinical infectious diseases : an official publication of the Infectious Diseases Society of America"],"pubmed_title":["The Distribution of Fitness Costs of Resistance-Conferring Mutations Is a Key Determinant for the Future Burden of Drug-Resistant Tuberculosis: A Model-Based Analysis."],"pmcid":["PMC4583567"],"funding_grant_id":["T32 GM007309","U2GPS0008111","EP/K026003/1","MR/J005088/1"],"pubmed_authors":["White RG","Knight GM","Colijn C","Cobelens F","Fofana M","Shrestha S","Cohen T","Dowdy DW"],"additional_accession":[]},"is_claimable":false,"name":"The Distribution of Fitness Costs of Resistance-Conferring Mutations Is a Key Determinant for the Future Burden of Drug-Resistant Tuberculosis: A Model-Based Analysis.","description":"<h4>Background</h4>Drug resistance poses a serious challenge for the control of tuberculosis in many settings. It is well established that the expected future trend in resistance depends on the reproductive fitness of drug-resistant Mycobacterium tuberculosis. However, the variability in fitness between strains with different resistance-conferring mutations has been largely ignored when making these predictions.<h4>Methods</h4>We developed a novel approach for incorporating the variable fitness costs of drug resistance-conferring mutations and for tracking this distribution of fitness costs over time within a transmission model. We used this approach to describe the effects of realistic fitness cost distributions on the future prevalence of drug-resistant tuberculosis.<h4>Results</h4>The shape of the distribution of fitness costs was a strong predictor of the long-term prevalence of resistance. While, as expected, lower average fitness costs of drug resistance-conferring mutations were associated with more severe epidemics of drug-resistant tuberculosis, fitness distributions with greater variance also led to higher levels of drug resistance. For example, compared to simulations in which the fitness cost of resistance was fixed, introducing a realistic amount of variance resulted in a 40% increase in prevalence of drug-resistant tuberculosis after 20 years.<h4>Conclusions</h4>The differences in the fitness costs associated with drug resistance-conferring mutations are a key determinant of the future burden of drug-resistant tuberculosis. Future studies that can better establish the range of fitness costs associated with drug resistance-conferring mutations will improve projections and thus facilitate better public health planning efforts.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Oct","modification":"2021-02-25T09:36:19Z","creation":"2019-03-27T01:58:59Z"},"accession":"S-EPMC4583567","cross_references":{"pubmed":["26409276"],"doi":["10.1093/cid/civ579"]}}