Projects per year
Abstract
Background: Antimicrobial resistance develops following the accrual of mutations in the bacterial genome, and may variably impact organism fitness and hence, transmission risk. Classical representation of tuberculosis (TB) dynamics using a single or two strain (DS/MDR-TB) model typically does not capture elements of this important aspect of TB epidemiology. To understand and estimate the likelihood of resistance spreading in high drug-resistant TB incidence settings, we used epidemiological data to develop a mathematical model of Mycobacterium tuberculosis (Mtb) transmission. Methods: A four-strain (drug-susceptible (DS), isoniazid mono-resistant (INH-R), rifampicin mono-resistant (RIF-R) and multidrug-resistant (MDR)) compartmental deterministic Mtb transmission model was developed to explore the progression from DS- to MDR-TB in The Philippines and Viet Nam. The models were calibrated using data from national tuberculosis prevalence (NTP) surveys and drug resistance surveys (DRS). An adaptive Metropolis algorithm was used to estimate the risks of drug resistance amplification among unsuccessfully treated individuals. Results: The estimated proportion of INH-R amplification among failing treatments was 0.84 (95% CI 0.79–0.89) for The Philippines and 0.77 (95% CI 0.71–0.84) for Viet Nam. The proportion of RIF-R amplification among failing treatments was 0.05 (95% CI 0.04–0.07) for The Philippines and 0.011 (95% CI 0.010–0.012) for Viet Nam. Conclusion: The risk of resistance amplification due to treatment failure for INH was dramatically higher than RIF. We observed RIF-R strains were more likely to be transmitted than acquired through amplification, while both mechanisms of acquisition were important contributors in the case of INH-R. These findings highlight the complexity of drug resistance dynamics in high-incidence settings, and emphasize the importance of prioritizing testing algorithms which allow for early detection of INH-R.
Original language | English |
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Article number | 82 |
Number of pages | 12 |
Journal | BMC Infectious Diseases |
Volume | 22 |
Issue number | 1 |
DOIs | |
Publication status | Published - Dec 2022 |
Keywords
- Drug resistant tuberculosis
- Epidemiological modelling
- Fitness cost
- Resistance amplification
- Tuberculosis transmission dynamics
Projects
- 2 Finished
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AuTuMN: Improving Global Tuberculosis Control with the "AuTuMN" Platform
Trauer, J., McBryde, E., Doan, T. N., Marks, G. B. & Denholm, J. T.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/18 → 31/12/21
Project: Research
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ECF: Plotting a Course to Tuberculosis Elimination in our Lifetime
National Health and Medical Research Council (NHMRC) (Australia)
1/01/18 → 31/12/21
Project: Research