Modeling the impact of bedaquiline treatment strategies on the multidrug-resistant tuberculosis burden in India

Mehra, Maneesha; Kambili, Chrispin; Potluri, Ravi; Rhines, Allison S.; Singh, Vikram; Thomas, Adrian

doi:10.5588/ijtld.16.0717

Cited by 5 publications

(2 citation statements)

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“…As would be expected, PK/PD models were used almost exclusively for “treatment interventions”, with one model being used for parameter estimation. Six models used a combination of methods: transmission and state transition [ 27 , 28 ], transmission and operational [ 29 ]and state transition and statistical [ 30 – 32 ]. “Bacterial dynamics” type models were used for “treatment interventions”, “theoretical” and “parameter estimation” aims only.…”

Section: Resultsmentioning

confidence: 99%

Mathematical models of drug-resistant tuberculosis lack bacterial heterogeneity: A systematic review

Fuller,

McQuaid,

Harker

et al. 2024

PLoS Pathog

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Drug-resistant tuberculosis (DR-TB) threatens progress in the control of TB. Mathematical models are increasingly being used to guide public health decisions on managing both antimicrobial resistance (AMR) and TB. It is important to consider bacterial heterogeneity in models as it can have consequences for predictions of resistance prevalence, which may affect decision-making. We conducted a systematic review of published mathematical models to determine the modelling landscape and to explore methods for including bacterial heterogeneity. Our first objective was to identify and analyse the general characteristics of mathematical models of DR-mycobacteria, including M. tuberculosis. The second objective was to analyse methods of including bacterial heterogeneity in these models. We had different definitions of heterogeneity depending on the model level. For between-host models of mycobacterium, heterogeneity was defined as any model where bacteria of the same resistance level were further differentiated. For bacterial population models, heterogeneity was defined as having multiple distinct resistant populations. The search was conducted following PRISMA guidelines in five databases, with studies included if they were mechanistic or simulation models of DR-mycobacteria. We identified 195 studies modelling DR-mycobacteria, with most being dynamic transmission models of non-treatment intervention impact in M. tuberculosis (n = 58). Studies were set in a limited number of specific countries, and 44% of models (n = 85) included only a single level of “multidrug-resistance (MDR)”. Only 23 models (8 between-host) included any bacterial heterogeneity. Most of these also captured multiple antibiotic-resistant classes (n = 17), but six models included heterogeneity in bacterial populations resistant to a single antibiotic. Heterogeneity was usually represented by different fitness values for bacteria resistant to the same antibiotic (61%, n = 14). A large and growing body of mathematical models of DR-mycobacterium is being used to explore intervention impact to support policy as well as theoretical explorations of resistance dynamics. However, the majority lack bacterial heterogeneity, suggesting that important evolutionary effects may be missed.

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Section: Resultsmentioning

confidence: 99%

Mathematical models of drug-resistant tuberculosis lack bacterial heterogeneity: A systematic review

Fuller,

McQuaid,

Harker

et al. 2024

PLoS Pathog

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“…(5) Deferring access to bedaquiline until onset of treatment failure could be detrimental to patients and public health…”

Section: Mdr‐tb: Repurposed and Novel Drugsmentioning

confidence: 99%

New drugs and regimens for tuberculosis

et al. 2018

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Since standardized rifampin-based first-line regimens and fluoroquinolone-based second-line regimens were used to treat tuberculosis (TB), unfortunately without timely modification according to the drug resistance profile, TB and drug-resistant disease are still important public health threats worldwide. Although the last decade has witnessed advances in rapid diagnostic tools and use of repurposed and novel drugs for better managing drug-resistant TB, we need an appropriate TB control strategy and a well-functioning health infrastructure to ensure optimal operational use of rapid tests, judicious use of effective treatment regimens that can be rapidly tailored according to the drug resistance profile and timely management of risk factors and co-morbidities that promote infection and its progression to disease. We searched the published literature to discuss (i) standardized versus individualized therapies, including the choice between a single one-size-fit-all regimen versus different options with different key drugs determined mainly by rapid drug susceptibility testing, (ii) alternative regimens for managing drug-susceptible TB, (iii) evidence for using the World Health Organization (WHO) longer and shorter regimens for multidrug-resistant TB and (iv) evidence for using repurposed and novel drugs. We hope an easily applicable combination of biomarkers that accurately predict individual treatment outcome will soon be available to ultimately guide individualized therapy.

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Tuberculosis: a Persistent Health Challenge for India

Huddart

Nafade

2018

Curr Epidemiol Rep

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Modeling the impact of bedaquiline treatment strategies on the multidrug-resistant tuberculosis burden in India

Abstract: Our study suggests that deferring patient access to new drugs such as BDQ until front-line regimens have failed, in order to 'save' these drugs for later use, could be detrimental to patients and to public health, and could reduce the economic benefit of treating MDR-TB.

Cited by 5 publications

References 0 publications

Mathematical models of drug-resistant tuberculosis lack bacterial heterogeneity: A systematic review

Mathematical models of drug-resistant tuberculosis lack bacterial heterogeneity: A systematic review

New drugs and regimens for tuberculosis

Tuberculosis: a Persistent Health Challenge for India

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