Knight, Gwenan M; Colijn, Caroline; Shrestha, Sourya; Fofana, Mariam; Cobelens, Frank; White, Richard G; Dowdy, David W; Cohen, Ted; (2015) 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. Clinical infectious diseases, 61Supp (Suppl ). S147-S154. ISSN 1058-4838 DOI: https://doi.org/10.1093/cid/civ579
Permanent Identifier
Use this Digital Object Identifier when citing or linking to this resource.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Item Type | Article |
---|---|
Faculty and Department | Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology & Dynamics (2023-) |
Research Centre | Antimicrobial Resistance Centre (AMR) |
PubMed ID | 26409276 |
ISI | 362952900007 |
Related URLs |
Download
Filename: Redraft manuscript.docx
Licence: Creative Commons: Attribution-Noncommercial-No Derivative Works 3.0
Download