Medicine (RMH) - Research Publications

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    Mathematical analysis of a two-strain disease model with amplification
    Kuddus, MA ; McBryde, ES ; Adekunle, A ; White, LJ ; Meehan, MT (PERGAMON-ELSEVIER SCIENCE LTD, 2021-02-01)
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    Modelling the Economic Impacts of Epidemics in Developing Countries Under Alternative Intervention Strategies
    Geard, N ; Giesecke, JA ; Madden, JR ; McBryde, ES ; Moss, R ; Tran, NH ; Madden, JR ; Shibusawa, H ; Higano, Y (Springer, 2020)
    Modern levels of global travel have intensified the risk of new infectious diseases becoming pandemics. Particularly at risk are developing countries whose health systems may be less well equipped to detect quickly and respond effectively to the importation of new infectious diseases. This chapter examines what might have been the economic consequences if the 2014 West African Ebola epidemic had been imported to a small Asia-Pacific country. Hypothetical outbreaks in two countries were modelled. The post-importation estimations were carried out with two linked models: a stochastic disease transmission (SEIR) model and a quarterly version of the multi-country GTAP model, GTAP-Q. The SEIR model provided daily estimates of the number of persons in various disease states. For each intervention strategy the stochastic disease model was run 500 times to obtain the probability distribution of disease outcomes. Typical daily country outcomes for both controlled and uncontrolled outbreaks under five alternative intervention strategies were converted to quarterly disease-state results, which in turn were used in the estimation of GTAP-Q shocks to country-specific health costs and labour productivity during the outbreak, and permanent reductions in each country’s population and labour force due to mortality. Estimated behavioural consequences (severe reductions in international tourism and crowd avoidance) formed further shocks. The GTAP-Q simulations revealed very large economic costs for each country if they experienced an uncontrolled Ebola outbreak, and considerable economic costs for controlled outbreaks in Fiji due to the importance of the tourism sector to its economy. A major finding was that purely reactive strategies had virtually no effect on preventing uncontrolled outbreaks, but pre-emptive strategies substantially reduced the proportion of uncontrolled outbreaks, and in turn the economic and social costs.
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    Modeling the Cost-Effectiveness of Latent Tuberculosis Screening and Treatment Strategies in Recent Migrants to a Low-Incidence Setting
    Dale, KD ; Abayawardana, MJ ; McBryde, ES ; Trauer, JM ; Carvalho, N (OXFORD UNIV PRESS INC, 2022-01-24)
    Many tuberculosis (TB) cases in low-incidence settings are attributed to reactivation of latent TB infection (LTBI) acquired overseas. We assessed the cost-effectiveness of community-based LTBI screening and treatment strategies in recent migrants to a low-incidence setting (Australia). A decision-analytical Markov model was developed that cycled 1 migrant cohort (≥11-year-olds) annually over a lifetime from 2020. Postmigration/onshore and offshore (screening during visa application) strategies were compared with existing policy (chest x-ray during visa application). Outcomes included TB cases averted and discounted cost per quality-adjusted life-year (QALY) gained from a health-sector perspective. Most recent migrants are young adults and cost-effectiveness is limited by their relatively low LTBI prevalence, low TB mortality risks, and high emigration probability. Onshore strategies cost at least $203,188 (Australian) per QALY gained, preventing approximately 2.3%-7.0% of TB cases in the cohort. Offshore strategies (screening costs incurred by migrants) cost at least $13,907 per QALY gained, preventing 5.5%-16.9% of cases. Findings were most sensitive to the LTBI treatment quality-of-life decrement (further to severe adverse events); with a minimal decrement, all strategies caused more ill health than they prevented. Additional LTBI strategies in recent migrants could only marginally contribute to TB elimination and are unlikely to be cost-effective unless screening costs are borne by migrants and potential LTBI treatment quality-of-life decrements are ignored.
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    Understanding how Victoria, Australia gained control of its second COVID-19 wave
    Trauer, JM ; Lydeamore, MJ ; Dalton, GW ; Pilcher, D ; Meehan, MT ; McBryde, ES ; Cheng, AC ; Sutton, B ; Ragonnet, R (NATURE PORTFOLIO, 2021-11-01)
    During 2020, Victoria was the Australian state hardest hit by COVID-19, but was successful in controlling its second wave through aggressive policy interventions. We calibrated a detailed compartmental model of Victoria's second wave to multiple geographically-structured epidemic time-series indicators. We achieved a good fit overall and for individual health services through a combination of time-varying processes, including case detection, population mobility, school closures, physical distancing and face covering usage. Estimates of the risk of death in those aged ≥75 and of hospitalisation were higher than international estimates, reflecting concentration of cases in high-risk settings. We estimated significant effects for each of the calibrated time-varying processes, with estimates for the individual-level effect of physical distancing of 37.4% (95%CrI 7.2-56.4%) and of face coverings of 45.9% (95%CrI 32.9-55.6%). That the multi-faceted interventions led to the dramatic reversal in the epidemic trajectory is supported by our results, with face coverings likely particularly important.
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    Vaccines and variants: Modelling insights into emerging issues in COVID-19 epidemiology
    Caldwell, JM ; Le, X ; McIntosh, L ; Meehan, MT ; Ogunlade, S ; Ragonnet, R ; O'Neill, GK ; Trauer, JM ; McBryde, ES (ELSEVIER SCI LTD, 2021-09-13)
    Mathematical modelling has played a pivotal role in understanding the epidemiology of and guiding public health responses to the ongoing coronavirus disease of 2019 (COVID-19) pandemic. Here, we review the role of epidemiological models in understanding evolving epidemic characteristics, including the effects of vaccination and Variants of Concern (VoC). We highlight ways in which models continue to provide important insights, including (1) calculating the herd immunity threshold and evaluating its limitations; (2) verifying that nascent vaccines can prevent severe disease, infection, and transmission but may be less efficacious against VoC; (3) determining optimal vaccine allocation strategies under efficacy and supply constraints; and (4) determining that VoC are more transmissible and lethal than previously circulating strains, and that immune escape may jeopardize vaccine-induced herd immunity. Finally, we explore how models can help us anticipate and prepare for future stages of COVID-19 epidemiology (and that of other diseases) through forecasts and scenario projections, given current uncertainties and data limitations.
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    Understanding COVID-19 dynamics and the effects of interventions in the Philippines: A mathematical modelling study
    Caldwell, JM ; de Lara-Tuprio, E ; Robin Teng, T ; Estuar, MRJE ; Sarmiento, RFR ; Abayawardana, M ; Leong, RNF ; Gray, RT ; Wood, JG ; Linh-Vi, L ; McBryde, ES ; Ragonnet, R ; Trauer, JM (ELSEVIER, 2021-07-14)
    BACKGROUND: COVID-19 initially caused less severe outbreaks in many low- and middle-income countries (LMIC) compared with many high-income countries, possibly because of differing demographics, socioeconomics, surveillance, and policy responses. Here, we investigate the role of multiple factors on COVID-19 dynamics in the Philippines, a LMIC that has had a relatively severe COVID-19 outbreak. METHODS: We applied an age-structured compartmental model that incorporated time-varying mobility, testing, and personal protective behaviors (through a "Minimum Health Standards" policy, MHS) to represent the first wave of the Philippines COVID-19 epidemic nationally and for three highly affected regions (Calabarzon, Central Visayas, and the National Capital Region). We estimated effects of control measures, key epidemiological parameters, and interventions. FINDINGS: Population age structure, contact rates, mobility, testing, and MHS were sufficient to explain the Philippines epidemic based on the good fit between modelled and reported cases, hospitalisations, and deaths. The model indicated that MHS reduced the probability of transmission per contact by 13-27%. The February 2021 case detection rate was estimated at ~8%, population recovered at ~9%, and scenario projections indicated high sensitivity to MHS adherence. INTERPRETATION: COVID-19 dynamics in the Philippines are driven by age, contact structure, mobility, and MHS adherence. Continued compliance with low-cost MHS should help the Philippines control the epidemic until vaccines are widely distributed, but disease resurgence may be occurring due to a combination of low population immunity and detection rates and new variants of concern.
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    Vaccination is Australia's most important COVID-19 public health action, even though herd immunity is unlikely
    McBryde, E ; Meehan, M ; Sziklay, J ; Adekunle, A ; Kuddus, A ; Ogunlade, S ; Jayasundara, P ; Ragonnet, R ; Trauer, J ; Cope, R ( 2021-07-19)
    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.
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    Tuberculosis in the Western Pacific Region: Estimating the burden of disease and return on investment 2020-2030 in four countries
    Estill, J ; Islam, T ; Houben, RMGJ ; Rudman, J ; Ragonnet, R ; McBryde, ES ; Trauer, JM ; Orel, E ; Nguyen, AT ; Rahevar, K ; Morishita, F ; Oh, KH ; Raviglione, MC ; Keiser, O (ELSEVIER, 2021-04-29)
    BACKGROUND: We aimed to estimate the disease burden of Tuberculosis (TB) and return on investment of TB care in selected high-burden countries of the Western Pacific Region (WPR) until 2030. METHODS: We projected the TB epidemic in Viet Nam and Lao People's Democratic Republic (PDR) 2020-2030 using a mathematical model under various scenarios: counterfactual (no TB care); baseline (TB care continues at current levels); and 12 different diagnosis and treatment interventions. We retrieved previous modeling results for China and the Philippines. We pooled the new and existing information on incidence and deaths in the four countries, covering >80% of the TB burden in WPR. We estimated the return on investment of TB care and interventions in Viet Nam and Lao PDR using a Solow model. FINDINGS: In the baseline scenario, TB incidence in the four countries decreased from 97•0/100,000/year (2019) to 90•1/100,000/year (2030), and TB deaths from 83,300/year (2019) to 71,100/year (2030). Active case finding (ACF) strategies (screening people not seeking care for respiratory symptoms) were the most effective single interventions. Return on investment (2020-2030) for TB care in Viet Nam and Lao PDR ranged US$4-US$49/dollar spent; additional interventions brought up to US$2•7/dollar spent. INTERPRETATION: In the modeled countries, TB incidence will only modestly decrease without additional interventions. Interventions that include ACF can reduce TB burden but achieving the End TB incidence and mortality targets will be difficult without new transformational tools (e.g. vaccine, new diagnostic tools, shorter treatment). However, TB care, even at its current level, can bring a multiple-fold return on investment. FUNDING: World Health Organization Western Pacific Regional Office; Swiss National Science Foundation Grant 163878.
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    Timing of Mycobacterium tuberculosis exposure explains variation in BCG effectiveness: a systematic review and meta-analysis
    Trauer, JM ; Kawai, A ; Coussens, AK ; Datta, M ; Williams, BM ; McBryde, ES ; Ragonnet, R (BMJ PUBLISHING GROUP, 2021-11-01)
    RATIONALE: The heterogeneity in efficacy observed in studies of BCG vaccination is not fully explained by currently accepted hypotheses, such as latitudinal gradient in non-tuberculous mycobacteria exposure. METHODS: We updated previous systematic reviews of the effectiveness of BCG vaccination to 31 December 2020. We employed an identical search strategy and inclusion/exclusion criteria to these earlier reviews, but reclassified several studies, developed an alternative classification system and considered study demography, diagnostic approach and tuberculosis (TB)-related epidemiological context. MAIN RESULTS: Of 21 included trials, those recruiting neonates and children aged under 5 were consistent in demonstrating considerable protection against TB for several years. Trials in high-burden settings with shorter follow-up also showed considerable protection, as did most trials in settings of declining burden with longer follow-up. However, the few trials performed in high-burden settings with longer follow-up showed no protection, sometimes with higher case rates in the vaccinated than the controls in the later follow-up period. CONCLUSIONS: The most plausible explanatory hypothesis for these results is that BCG protects against TB that results from exposure shortly after vaccination. However, we found no evidence of protection when exposure occurs later from vaccination, which would be of greater importance in trials in high-burden settings with longer follow-up. In settings of declining burden, most exposure occurs shortly following vaccination and the sustained protection observed for many years thereafter represents continued protection against this early exposure. By contrast, in settings of continued intense transmission, initial protection subsequently declines with repeated exposure to Mycobacterium tuberculosis or other pathogens.
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    Hospitalisations related to lower respiratory tract infections in Northern Queensland
    Pak, A ; Adegboye, OA ; Eisen, DP ; McBryde, ES (WILEY, 2021-04-26)
    OBJECTIVE: To investigate the admission characteristics and hospital outcomes for patients admitted with lower respiratory tract infections (LRTI) in Northern Queensland. METHODS: We perform a retrospective analysis of the data covering an 11-year period, 2006-2016. Length of hospital stay (LOS) is modelled by negative binomial regression and heterogeneous effects are checked using interaction terms. RESULTS: A total of 11,726 patients were admitted due to LRTI; 2,430 (20.9%) were of Indigenous descent. We found higher hospitalisations due to LRTI for Indigenous than non-Indigenous patients, with a disproportionate increase in hospitalisations occurring during winter. The LOS for Indigenous patients was higher by 2.5 days [95%CI: -0.15; 5.05] than for non-Indigenous patients. The average marginal effect of 17.5 [95%CI: 15.3; 29.7] implies that the LOS for a patient, who was admitted to ICU, was higher by 17.5 days. CONCLUSIONS: We highlighted the increased burden of LRTIs experienced by Indigenous populations, with this information potentially being useful for enhancing community-level policy making. Implications for public health: Future guidelines can use these results to make recommendations for preventative measures in Indigenous communities. Improvements in engagement and partnership with Indigenous communities and consumers can help increase healthcare uptake and reduce the burden of respiratory diseases.