Shrestha, Sourya; Knight, Gwenan M; Fofana, Mariam; Cohen, Ted; White, Richard G; Cobelens, Frank; Dowdy, David W; (2014) Drivers and trajectories of resistance to new first-line drug regimens for tuberculosis. Open forum infectious diseases, 1 (2). ofu073-. ISSN 2328-8957 DOI: https://doi.org/10.1093/ofid/ofu073
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Abstract
BACKGROUND: New first-line drug regimens for treatment of tuberculosis (TB) are in clinical trials: emergence of resistance is a key concern. Because population-level data on resistance cannot be collected in advance, epidemiological models are important tools for understanding the drivers and dynamics of resistance before novel drug regimens are launched. METHODS: We developed a transmission model of TB after launch of a new drug regimen, defining drug-resistant TB (DR-TB) as resistance to the new regimen. The model is characterized by (1) the probability of acquiring resistance during treatment, (2) the transmission fitness of DR-TB relative to drug-susceptible TB (DS-TB), and (3) the probability of treatment success for DR-TB versus DS-TB. We evaluate the effect of each factor on future DR-TB prevalence, defined as the proportion of incident TB that is drug-resistant. RESULTS: Probability of acquired resistance was the strongest predictor of the DR-TB proportion in the first 5 years after the launch of a new drug regimen. Over a longer term, however, the DR-TB proportion was driven by the resistant population's transmission fitness and treatment success rates. Regardless of uncertainty in acquisition probability and transmission fitness, high levels (>10%) of drug resistance were unlikely to emerge within 50 years if, among all cases of TB that were detected, 85% of those with DR-TB could be appropriately diagnosed as such and then successfully treated. CONCLUSIONS: Short-term surveillance cannot predict long-term drug resistance trends after launch of novel first-line TB regimens. Ensuring high treatment success of drug-resistant TB through early diagnosis and appropriate second-line therapy can mitigate many epidemiological uncertainties and may substantially slow the emergence of drug-resistant TB.
Item Type | Article |
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Faculty and Department | Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology & Dynamics (2023-) |
Research Centre | Antimicrobial Resistance Centre (AMR) |
PubMed ID | 25734143 |
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