8 results found
Hogan AB, Winskill P, Verity R, et al., 2018, Modelling population-level impact to inform target product profiles for childhood malaria vaccines, BMC Medicine, Vol: 16, ISSN: 1741-7015
BackgroundThe RTS,S/AS01 vaccine for Plasmodium falciparum malaria demonstrated moderate efficacy in 5–17-month-old children in phase 3 trials, and from 2018, the vaccine will be evaluated through a large-scale pilot implementation program. Work is ongoing to optimise this vaccine, with higher efficacy for a different schedule demonstrated in a phase 2a challenge study. The objective of our study was to investigate the population-level impact of a modified RTS,S/AS01 schedule and dose amount in order to inform the target product profile for a second-generation malaria vaccine.MethodsWe used a mathematical modelling approach as the basis for our study. We simulated the changing anti-circumsporozoite antibody titre following vaccination and related the titre to vaccine efficacy. We then implemented this efficacy profile within an individual-based model of malaria transmission. We compared initial efficacy, duration and dose timing, and evaluated the potential public health impact of a modified vaccine in children aged 5–17 months, measuring clinical cases averted in children younger than 5 years.ResultsIn the first decade of delivery, initial efficacy was associated with a higher reduction in childhood clinical cases compared to vaccine duration. This effect was more pronounced in high transmission settings and was due to the efficacy benefit occurring in younger ages where disease burden is highest. However, the low initial efficacy and long duration schedule averted more cases across all age cohorts if a longer time horizon was considered. We observed an age-shifting effect due to the changing immunological profile in higher transmission settings, in scenarios where initial efficacy was higher, and the fourth dose administered earlier.ConclusionsOur findings indicate that, for an imperfect childhood malaria vaccine with suboptimal efficacy, it may be advantageous to prioritise initial efficacy over duration. We predict that a modified vaccine could outpe
Hogan A, Winskill P, Verity R, et al., 2018, INFORMING TARGET PRODUCT PROFILES FOR A SECOND-GENERATION CHILDHOOD MALARIA VACCINE: A MODELLING STUDY, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 583-583, ISSN: 0002-9637
Hogan AB, Campbell PT, Blyth CC, et al., 2017, Potential impact of a maternal vaccine for RSV: A mathematical modelling study., Vaccine, Vol: 35, Pages: 6172-6179
Respiratory syncytial virus (RSV) is a major cause of respiratory morbidity and one of the main causes of hospitalisation in young children. While there is currently no licensed vaccine for RSV, a vaccine candidate for pregnant women is undergoing phase 3 trials. We developed a compartmental age-structured model for RSV transmission, validated using linked laboratory-confirmed RSV hospitalisation records for metropolitan Western Australia. We adapted the model to incorporate a maternal RSV vaccine, and estimated the expected reduction in RSV hospitalisations arising from such a program. The introduction of a vaccine was estimated to reduce RSV hospitalisations in Western Australia by 6-37% for 0-2month old children, and 30-46% for 3-5month old children, for a range of vaccine effectiveness levels. Our model shows that, provided a vaccine is demonstrated to extend protection against RSV disease beyond the first three months of life, a policy using a maternal RSV vaccine could be effective in reducing RSV hospitalisations in children up to six months of age, meeting the objective of a maternal vaccine in delaying an infant's first RSV infection to an age at which severe disease is less likely.
Smith RJ, Hogan AB, Mercer GN, 2017, Unexpected infection spikes in a model of Respiratory Syncytial Virus vaccination, Vaccines, Vol: 5, ISSN: 2076-393X
Respiratory Syncytial Virus (RSV) is an acute respiratory infection that infects millions of children and infants worldwide. Recent research has shown promise for the development of a vaccine, with a range of vaccine types now in clinical trials or preclinical development. We extend an existing mathematical model with seasonal transmission to include vaccination. We model vaccination both as a continuous process, applying the vaccine during pregnancy, and as a discrete one, using impulsive differential equations, applying pulse vaccination. We develop conditions for the stability of the disease-free equilibrium and show that this equilibrium can be destabilised under certain extreme conditions, even with 100% coverage using an (unrealistic) vaccine. Using impulsive differential equations and introducing a new quantity, the impulsive reproduction number, we showed that eradication could be acheived with 75% coverage, while 50% coverage resulted in low-level oscillations. A vaccine that targets RSV infection has the potential to significantly reduce the overall prevalence of the disease, but appropriate coverage is critical.
Hogan AB, Anderssen RS, Davis S, et al., 2016, Time series analysis of RSV and bronchiolitis seasonality in temperate and tropical Western Australia, Epidemics, Vol: 16, Pages: 49-55, ISSN: 1878-0067
Respiratory syncytial virus (RSV) causes respiratory illness in young children and is most commonly associated with bronchiolitis. RSV typically occurs as annual or biennial winter epidemics in temperate regions, with less pronounced seasonality in the tropics. We sought to characterise and compare the seasonality of RSV and bronchiolitis in temperate and tropical Western Australia. We examined over 13 years of RSV laboratory identifications and bronchiolitis hospitalisations in children, using an extensive linked dataset from Western Australia. We applied mathematical time series analyses to identify the dominant seasonal cycle, and changes in epidemic size and timing over this period. Both the RSV and bronchiolitis data showed clear winter epidemic peaks in July or August in the southern Western Australia regions, but less identifiable seasonality in the northern regions. Use of complex demodulation proved very effective at comparing disease epidemics. The timing of RSV and bronchiolitis epidemics coincided well, but the size of the epidemics differed, with more consistent peak sizes for bronchiolitis than for RSV. Our results show that bronchiolitis hospitalisations are a reasonable proxy for the timing of RSV detections, but may not fully capture the magnitude of RSV epidemics.
Hogan AB, Glass K, Moore HC, et al., 2016, Exploring the dynamics of respiratory syncytial virus (RSV) transmission in children, Theoretical Population Biology, Vol: 110, Pages: 78-85, ISSN: 1096-0325
Respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in children. Whilst highly seasonal, RSV dynamics can have either one-year (annual) or two-year (biennial) cycles. Furthermore, some countries show a ‘delayed biennial’ pattern, where the epidemic peak in low incidence years is delayed. We develop a compartmental model for RSV infection, driven by a seasonal forcing function, and conduct parameter space and bifurcation analyses to document parameter ranges that give rise to these different seasonal patterns. The model is sensitive to the birth rate, transmission rate, and seasonality parameters, and can replicate RSV dynamics observed in different countries. The seasonality parameter must exceed a threshold for the model to produce biennial cycles. Intermediate values of the birth rate produce the greatest delay in these biennial cycles, while the model reverts to annual cycles if the duration of immunity is too short. Finally, the existence of period doubling and period halving bifurcations suggests robust model dynamics, in agreement with the known regularity of RSV outbreaks. These findings help explain observed RSV data, such as regular biennial dynamics in Western Australia, and delayed biennial dynamics in Finland. From a public health perspective, our findings provide insight into the drivers of RSV transmission, and a foundation for exploring RSV interventions.
Moore HC, Jacoby P, Hogan AB, et al., 2014, Modelling the seasonal epidemics of respiratory syncytial virus in young children, PLOS One, Vol: 9, Pages: e100422-e100422, ISSN: 1932-6203
BackgroundRespiratory syncytial virus (RSV) is a major cause of paediatric morbidity. Mathematical models can be used to characterise annual RSV seasonal epidemics and are a valuable tool to assess the impact of future vaccines.ObjectivesConstruct a mathematical model of seasonal epidemics of RSV and by fitting to a population-level RSV dataset, obtain a better understanding of RSV transmission dynamics.MethodsWe obtained an extensive dataset of weekly RSV testing data in children aged less than 2 years, 2000–2005, for a birth cohort of 245,249 children through linkage of laboratory and birth record datasets. We constructed a seasonally forced compartmental age-structured Susceptible-Exposed-Infectious-Recovered-Susceptible (SEIRS) mathematical model to fit to the seasonal curves of positive RSV detections using the Nelder-Mead method.ResultsFrom 15,830 specimens, 3,394 were positive for RSV. RSV detections exhibited a distinct biennial seasonal pattern with alternating sized peaks in winter months. Our SEIRS model accurately mimicked the observed data with alternating sized peaks using disease parameter values that remained constant across the 6 years of data. Variations in the duration of immunity and recovery periods were explored. The best fit to the data minimising the residual sum of errors was a model using estimates based on previous models in the literature for the infectious period and a slightly lower estimate for the immunity period.ConclusionsOur age-structured model based on routinely collected population laboratory data accurately captures the observed seasonal epidemic curves. The compartmental SEIRS model, based on several assumptions, now provides a validated base model. Ranges for the disease parameters in the model that could replicate the patterns in the data were identified. Areas for future model developments include fitting climatic variables to the seasonal parameter, allowing parameters to vary according to age and implementing a newb
Hogan AB, Mercer GN, Glass K, et al., Modelling the seasonality of respiratory syncytial virus in young children, 20th International Congress on Modelling and Simulation (MODSIM), ISSN: 1932-6203
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