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Biology subjects

McBryde, E. S.

Publications and source records attributed to McBryde, E. S..

3 recordsLinked to original sources

Capturing heterogeneous infectiousness in transmission dynamic models of tuberculosis: a compartmental modelling approach

Infectiousness heterogeneity among individuals with tuberculosis (TB) is substantial and is likely to have a significant impact on the long-term dynamics of TB and the effectiveness of interventions. However, there is a gap in capturing heterogeneous infectiousness and evaluating its impact on the effectiveness of interventions. Informed by observed distribution of secondary infections, we constructed a deterministic model of TB transmission using ordinary differential equations. The model incorporated assumption of heterogeneous infectiousness with three levels of infectivity, namely non-spreaders, low-spreaders and super-spreaders. We evaluated the effectiveness of dynamic transmission untargeted and targeted implementation of an intervention intended to represent active case finding with a point-of-care diagnostic tool. The simulated intervention detected 20% of all TB patients who would otherwise have been missed by the health system during their disease episode and was compared across four epidemiological scenarios. Our model suggested that targeting the active case finding intervention towards super-spreaders was more effective than untargeted intervention in all setting scenarios, with more effectiveness in settings with low case detection and high transmission intensity. For instance, a targeted intervention achieved a 42.2% reduction in TB incidence, while the untargeted intervention achieved only a 20.7% reduction over 20 years, given the same number of people treated. Although the most marked impact on equilibrium TB incidence came from the rate of late reactivation, the proportion of super-spreaders and their relative infectiousness had shown substantial impact. Targeting active case-finding interventions to highly infectious cases likely to be particularly beneficial in settings where case detection is poor. Heterogeneity-related parameters had an equivalent effect to several other parameters that have been established as being very important to TB transmission dynamics.

microbiology↗

Revisiting the Natural History of Pulmonary Tuberculosis: a Bayesian Estimation of Natural Recovery and Mortality rates

BackgroundTuberculosis (TB) natural history remains poorly characterised and new investigations are impossible as it would be unethical to follow up TB patients without treating them. Estimates of TB burden and mortality rely heavily on TB self-recovery and mortality rates, as around 40% of individuals with TB are never detected, making their prognosis entirely dependent on the disease natural history.\n\nMethodsWe considered the reports identified in a previous systematic review of studies from the prechemotherapy era, and extracted detailed data on mortality over time. We used a continuous-time Markov model in a Bayesian framework to estimate the rates of TB-induced mortality and self-cure. A hierarchical model was employed to allow estimates to vary by cohort. Inference was performed separately for smear-positive TB (SP-TB) and smear-negative TB (SN-TB).\n\nResultsWe included 41 cohorts of SP-TB patients and 19 cohorts of pulmonary SN-TB patients in the analysis. No data were available on extrapulmonary TB. The posterior median estimates of the TB-specific mortality rates were 0.390 year-1 (0.329-0.452, 95% credible interval) and 0.025 year-1 (0.016-0.036) for SP-TB and SN-TB patients, respectively. The estimates for self-recovery rates were 0.233 year-1 (0.179-0.293) and 0.147 year-1 (0.087-0.248) for SP-TB and SN-TB patients, respectively. These rates correspond to average durations of untreated TB of 1.57 years (1.37-1.81) and 5.35 years (3.42-8.23) for SP-TB and SN-TB, respectively, when assuming a natural mortality rate of 0.014 year-1 (i.e. a 70-year life expectancy).\n\nConclusionsTB-specific mortality rates are around 15 times higher for SP-TB than for SN-TB patients. This difference was underestimated dramatically in previous TB modelling studies that parameterised models based on the ratio of 3.3 between the 10-year case fatality of SP-TB and SN-TB. Our findings raise important concerns about the accuracy of past and current estimates of TB mortality and predicted impact of control interventions on TB mortality.

bioinformatics↗

Predicting the Outcomes of New Short-Course Regimens for Multi-Drug Resistant Tuberculosis Using Intrahost and Pharmacokinetic-Pharmacodynamic Modelling

Short-course regimens for multi-drug resistant tuberculosis (MDR-TB) are urgently needed. Limited data suggest that the new drug, bedaquiline (BDQ), may have the potential to shorten MDR-TB treatment to less than six months when used in conjunction with standard anti-TB drugs. However, the feasibility of BDQ in shortening MDR-TB treatment duration remains to be established. Mathematical modelling provides a platform to investigate different treatment regimens and predict their efficacy. We developed a mathematical model to capture the immune response to TB inside a human host environment. This model was then combined with a pharmacokinetic-pharmacodynamic model to simulate various short-course BDQ-containing regimens. Our modelling suggests that BDQ could reduce MDR-TB treatment duration to just 18 weeks (four months) while still maintaining a very high treatment success rate (100% for daily BDQ for two weeks, or 95% for daily BDQ for one week during the intensive phase). The estimated time to bacterial clearance of these regimens ranges from 27 to 33 days. Our findings provide the justification for empirical evaluation of short-course BDQ-containing regimens. If short-course BDQ-containing regimens are found to improve outcomes then we anticipate clear cost-savings and a subsequent improvement in the efficiency of national TB programs.

systems biology↗