ORCID Profile
0000-0003-1332-332X
Current Organisation
James Cook University
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Biological Mathematics | Applied Mathematics | Phylogeny and Comparative Analysis | Stochastic Analysis and Modelling |
Expanding Knowledge in the Biological Sciences | Expanding Knowledge in the Mathematical Sciences
Publisher: Cold Spring Harbor Laboratory
Date: 11-10-2020
DOI: 10.1101/2020.10.08.20208108
Abstract: In anticipation of COVID-19 vaccine deployment, we use an age-structured mathematical model to investigate the benefits of optimizing age-specific dose allocation to suppress the transmission, morbidity and mortality of SARS-CoV-2 and the associated disease, COVID-19. To minimize transmission, we find that the highest priority in iduals across 179 countries are typically those between 30 and 59 years of age because of their high contact rates and higher risk of infection and disease. Conversely, morbidity and mortality are initially most effectively reduced by targeting 60+ year olds who are more likely to experience severe disease. However, when population-level coverage is sufficient — such that herd immunity can be achieved through targeted dose allocation — prioritizing middle-aged in iduals becomes the most effective strategy to minimize hospitalizations and deaths. For each metric considered, we show that optimizing the allocation of vaccine doses can more than double their effectiveness.
Publisher: Cold Spring Harbor Laboratory
Date: 19-07-2021
DOI: 10.1101/2021.07.16.21260642
Abstract: The Australian National Cabinet four-step plan to transition to post-pandemic re-opening begins with vaccination to achieve herd protection and protection of the health system against a surge in COVID-19 cases. Assuming a pre-vaccination reproduction number for the Delta variant of 5, we show that for the current Mixed program of vaccinating over 60s with AstraZeneca and 16-60s with Pfizer we would not achieve herd immunity. We would need to cover 85% of the population (including many 5-16 year-olds to achieve herd immunity). At lower reproduction number of 3 and our current Mixed strategy, we can achieve herd immunity without vaccinating 5-15 year olds. This will be achieved at a 60% coverage pursuing a strategy targetting high transmitters or 70% coverage using a strategy targetting the vulnerable first. A reproduction number of 7 precludes achieving herd immunity, however vaccination is able to prevent 75% of deaths compared with no vaccination. We also examine the impact of vaccination on death in the event that herd immunity is not achieved. Direct effects of vaccination on reducing death are very good for both Pfizer and AstraZeneca vaccines. However we estimate that the Mixed or Pfizer program performs better than the AstraZeneca program. Furthermore, vaccination levels below the herd immunity threshold can lead to substantial (albeit incomplete) indirect protection for both vaccinated and unvaccinated populations. Given the potential for not reaching herd immunity, we need to consider what level of severe disease and death is acceptable, balanced against the consequences of ongoing aggressive control strategies.
Publisher: Elsevier BV
Date: 02-2020
Publisher: Elsevier BV
Date: 2019
Publisher: Cold Spring Harbor Laboratory
Date: 19-05-2020
DOI: 10.1101/2020.05.12.20099036
Abstract: Australia is one of a few countries which has managed to control COVID-19 epidemic before a major epidemic took place. Currently with just under 7000 cases and 100 deaths, Australia is seeing less than 20 new cases per day. This is a positive outcome, but makes estimation of current effective reproduction numbers difficult to estimate. Australia, like much of the world is poised to step out of lockdown and looking at which measures to relax first. We use age-based contact matrices, calibrated to Chinese data on reproduction numbers and difference in infectiousness and susceptibility of children to generate next generation matrices (NGMs) for Australia. These matrices have a spectral radius of 2.49, which is hence our estimated basic reproduction number for Australia. The effective reproduction number (Reff) for Australia during the April/May lockdown period is estimated by other means to be around 0.8. We simulate the impact of lockdown on the NGM by first applying observations through Google Mobility Report for Australia at 3 locations: home (increased contacts by 18%), work (reduced contacts by 34%) and other (reduced contacts by 40%), and we reduce schools to 3% reflecting attendance rates during lockdown. Applying macro-distancing to the NGM leads to a spectral radius of 1.76. We estimate that the further reduction of the reproduction number to current levels of Reff = 0.8 is achieved by a micro-distancing factor of 0.26. That is, in a given location, people are 26% as likely as usual to have an effective contact with another person. We apply both macro and micro-distancing to the NGMs to examine the impact of different exit strategies. We find that reopening schools is estimated to reduce Reff from 0.8 to 0.78. This is because increase in school contact is offset by decrease in home contact. The NGMs all estimate that adults aged 30-50 are responsible for the majority of transmission. We also find that micro-distancing is critically important to maintain Reff . There is considerable uncertainty in these estimates and a sensitivity and uncertainty analysis is presented.
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.IJID.2017.01.031
Abstract: Multidrug-resistant tuberculosis (MDR-TB) is a threat to tuberculosis (TB) control. To guide TB control, it is essential to understand the extent to which and the circumstances in which MDR-TB will replace drug-susceptible TB (DS-TB) as the dominant phenotype. The issue was examined by assessing evidence from genomics, pharmacokinetics, and epidemiology studies. This evidence was then synthesized into a mathematical model. This model considers two TB strains, one with and one without an MDR phenotype. It was considered that intrinsic transmissibility may be different between the two strains, as may the control response including the detection, treatment failure, and default rates. The outcomes were explored in terms of the incidence of MDR-TB and time until MDR-TB surpasses DS-TB as the dominant strain. The ability of MDR-TB to dominate DS-TB was highly sensitive to the relative transmissibility of the resistant strain however, MDR-TB could dominate even when its transmissibility was modestly reduced (to between 50% and 100% as transmissible as the DS-TB strain). This model suggests that it may take decades or more for strain replacement to occur. It was also found that while the lification of resistance is the early cause of MDR-TB, this will rapidly give way to person-to-person transmission.
Publisher: IOP Publishing
Date: 09-06-2014
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.EPIDEM.2017.06.002
Abstract: Although different structures are used in modern tuberculosis (TB) models to simulate TB latency, it remains unclear whether they are all capable of reproducing the particular activation dynamics empirically observed. We aimed to determine which of these structures replicate the dynamics of progression accurately. We reviewed 88 TB-modelling articles and classified them according to the latency structure employed. We then fitted these different models to the activation dynamics observed from 1352 infected contacts diagnosed in Victoria (Australia) and Amsterdam (Netherlands) to obtain parameter estimates. Six different model structures were identified, of which only those incorporating two latency compartments were capable of reproducing the activation dynamics empirically observed. We found important differences in parameter estimates by age. We also observed marked differences between our estimates and the parameter values used in many previous models. In particular, when two successive latency phases are considered, the first period should have a duration that is much shorter than that used in previous studies. In conclusion, structures incorporating two latency compartments and age-stratification should be employed to accurately replicate the dynamics of TB latency. We provide a catalogue of parameter values and an approach to parameter estimation from empiric data for calibration of future TB-models.
Publisher: Springer Science and Business Media LLC
Date: 09-02-2019
DOI: 10.1007/S00285-018-01324-1
Abstract: We investigate the global dynamics of a general Kermack-McKendrick-type epidemic model formulated in terms of a system of renewal equations. Specifically, we consider a renewal model for which both the force of infection and the infected removal rates are arbitrary functions of the infection age, [Formula: see text], and use the direct Lyapunov method to establish the global asymptotic stability of the equilibrium solutions. In particular, we show that the basic reproduction number, [Formula: see text], represents a sharp threshold parameter such that for [Formula: see text], the infection-free equilibrium is globally asymptotically stable whereas the endemic equilibrium becomes globally asymptotically stable when [Formula: see text], i.e. when it exists.
Publisher: IOP Publishing
Date: 16-12-2014
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.MBS.2017.12.006
Abstract: We introduce and analyze coupled, multi-strain epidemic models designed to simulate the emergence and dissemination of mutant (e.g. drug-resistant) pathogen strains. In particular, we investigate the mathematical and biological properties of a general class of multi-strain epidemic models in which the infectious compartments of each strain are coupled together in a general manner. We derive explicit expressions for the basic reproduction number of each strain and highlight their importance in regulating the system dynamics (e.g. the potential for an epidemic outbreak) and the existence of nonnegative endemic solutions. Importantly, we find that the basic reproduction number of each strain is independent of the mutation rates between the strains - even under quite general assumptions for the form of the infectious compartment coupling. Moreover, we verify that the coupling term promotes strain coexistence (as an extension of the competitive exclusion principle) and demonstrate that the strain with the greatest reproductive capacity is not necessarily the most prevalent. Finally, we briefly discuss the implications of our results for public health policy and planning.
Publisher: Oxford University Press (OUP)
Date: 05-10-2019
DOI: 10.1093/JAC/DKY403
Abstract: Latent tuberculosis infection (LTBI) is a critical driver of the global burden of active TB, and therefore LTBI treatment is key for TB elimination. Treatment regimens for LTBI include self-administered daily isoniazid for 6 (6H) or 9 (9H) months, self-administered daily rif icin plus isoniazid for 3 months (3RH), self-administered daily rif icin for 4 months (4R) and weekly rifapentine plus isoniazid for 3 months self-administered (3HP-SAT) or administered by a healthcare worker as directly observed therapy (3HP-DOT). Data on the relative cost-effectiveness of these regimens are needed to assist policymakers and clinicians in selecting an LTBI regimen. To evaluate the cost-effectiveness of all regimens for treating LTBI. We developed a Markov model to investigate the cost-effectiveness of 3HP-DOT, 3HP-SAT, 4R, 3RH, 9H and 6H for LTBI treatment in a cohort of 10000 adults with LTBI. Cost-effectiveness was evaluated from a health system perspective over a 20 year time horizon. Compared with no preventive treatment, 3HP-DOT, 3HP-SAT, 4R, 3RH, 9H and 6H prevented 496, 470, 442, 418, 370 and 276 additional cases of active TB per 10000 patients, respectively. All regimens reduced costs and increased QALYs compared with no preventive treatment. 3HP was more cost-effective under DOT than under SAT at a cost of US$27948 per QALY gained. Three months of weekly rifapentine plus isoniazid is more cost-effective than other regimens. Greater recognition of the benefits of short-course regimens can contribute to the scale-up of prevention and achieving the 'End TB' targets.
Publisher: IOP Publishing
Date: 04-12-2015
Publisher: Proceedings of the National Academy of Sciences
Date: 02-11-2022
Abstract: Community-associated, methicillin-resistant Staphylococcus aureus (MRSA) lineages have emerged in many geographically distinct regions around the world during the past 30 y. Here, we apply consistent phylodynamic methods across multiple community-associated MRSA lineages to describe and contrast their patterns of emergence and dissemination. We generated whole-genome sequencing data for the Australian sequence type (ST) ST93-MRSA-IV from remote communities in Far North Queensland and Papua New Guinea, and the Bengal Bay ST772-MRSA-V clone from metropolitan communities in Pakistan. Increases in the effective reproduction number (R e ) and sustained transmission (R e 1) coincided with spread of progenitor methicillin-susceptible S. aureus (MSSA) in remote northern Australian populations, dissemination of the ST93-MRSA-IV genotype into population centers on the Australian East Coast, and subsequent importation into the highlands of Papua New Guinea and Far North Queensland. Applying the same phylodynamic methods to existing lineage datasets, we identified common signatures of epidemic growth in the emergence and epidemiological trajectory of community-associated S. aureus lineages from America, Asia, Australasia, and Europe. Surges in R e were observed at the ergence of antibiotic-resistant strains, coinciding with their establishment in regional population centers. Epidemic growth was also observed among drug-resistant MSSA clades in Africa and northern Australia. Our data suggest that the emergence of community-associated MRSA in the late 20th century was driven by a combination of antibiotic-resistant genotypes and host epidemiology, leading to abrupt changes in lineage-wide transmission dynamics and sustained transmission in regional population centers.
Start Date: 2021
End Date: 05-2024
Amount: $364,981.00
Funder: Australian Research Council
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