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A Multivariate Age-Structured Stochastic Model with Immunization Strategies to Describe Bronchiolitis Dynamics.

ABSTRACT: Bronchiolitis has a high morbidity in children under 2 years old. Respiratory syncytial virus (RSV) is the most common pathogen causing the disease. At present, there is only a costly humanized monoclonal RSV-specific antibody to prevent RSV. However, different immunization strategies are being developed. Hence, evaluation and comparison of their impact is important for policymakers. The analysis of the disease with a Bayesian stochastic compartmental model provided an improved and more natural description of its dynamics. However, the consideration of different age groups is still needed, since disease transmission greatly varies with age. In this work, we propose a multivariate age-structured stochastic model to understand bronchiolitis dynamics in children younger than 2 years of age considering high-quality data from the Valencia health system integrated database. Our modeling approach combines ideas from compartmental models and Bayesian hierarchical Poisson models in a novel way. Finally, we develop an extension of the model that simulates the effect of potential newborn immunization scenarios on the burden of disease. We provide an app tool that estimates the expected reduction in bronchiolitis episodes for a range of different values of uptake and effectiveness.

SUBMITTER: Lopez-Lacort M

PROVIDER: S-EPMC8305028 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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A Multivariate Age-Structured Stochastic Model with Immunization Strategies to Describe Bronchiolitis Dynamics.

López-Lacort Mónica M Corberán-Vallet Ana A Santonja Gómez Francisco J FJ

International journal of environmental research and public health 20210717 14

Bronchiolitis has a high morbidity in children under 2 years old. Respiratory syncytial virus (RSV) is the most common pathogen causing the disease. At present, there is only a costly humanized monoclonal RSV-specific antibody to prevent RSV. However, different immunization strategies are being developed. Hence, evaluation and comparison of their impact is important for policymakers. The analysis of the disease with a Bayesian stochastic compartmental model provided an improved and more natural ...[more]

PMID: 34300058

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Project description:BackgroundTrachoma, the worldwide leading infectious cause of blindness, is due to repeated conjunctival infection with Chlamydia trachomatis. The effects of control interventions on population levels of infection and active disease can be promptly measured, but the effects on severe ocular sequelae require long-term monitoring. We present an age-structured mathematical model of trachoma transmission and disease to predict the impact of interventions on the prevalence of blinding trachoma.Methodology/principal findingsThe model is based on the concept of multiple reinfections leading to progressive conjunctival scarring, trichiasis, corneal opacity and blindness. It also includes aspects of trachoma natural history, such as an increasing rate of recovery from infection and a decreasing chlamydial load with subsequent infections that depend upon a (presumed) acquired immunity that clears infection with age more rapidly. Parameters were estimated using maximum likelihood by fitting the model to pre-control infection prevalence data from hypo-, meso- and hyperendemic communities from The Gambia and Tanzania. The model reproduces key features of trachoma epidemiology: 1) the age-profile of infection prevalence, which increases to a peak at very young ages and declines at older ages; 2) a shift in this prevalence peak, toward younger ages in higher force of infection environments; 3) a raised overall profile of infection prevalence with higher force of infection; and 4) a rising profile, with age, of the prevalence of the ensuing severe sequelae (trachomatous scarring, trichiasis), as well as estimates of the number of infections that need to occur before these sequelae appear.Conclusions/significanceWe present a framework that is sufficiently comprehensive to examine the outcomes of the A (antibiotic) component of the SAFE strategy on disease. The suitability of the model for representing population-level patterns of infection and disease sequelae is discussed in view of the individual processes leading to these patterns.

Project description:BackgroundTuberculosis (TB) is the leading cause of death in South Africa. The burden of disease varies by age, with peaks in TB notification rates in the HIV-negative population at ages 0-5, 20-24, and 45-49 years. There is little variation between age groups in the rates in the HIV-positive population. The drivers of this age pattern remain unknown.MethodsWe developed an age-structured simulation model of Mycobacterium tuberculosis (Mtb) transmission in Cape Town, South Africa. We considered five states of TB progression: susceptible, infected (latent TB), active TB, treated TB, and treatment default. Latently infected individuals could be re-infected; a previous Mtb infection slowed progression to active disease. We further considered three states of HIV progression: HIV negative, HIV positive, on antiretroviral therapy. To parameterize the model, we analysed treatment outcomes from the Cape Town electronic TB register, social mixing patterns from a Cape Town community and used literature estimates for other parameters. To investigate the main drivers behind the age patterns, we conducted sensitivity analyses on all parameters related to the age structure.ResultsThe model replicated the age patterns in HIV-negative TB notification rates of Cape Town in 2009. Simulated TB notification rate in HIV-negative patients was 1000/100,000 person-years (pyrs) in children aged <5 years and decreased to 51/100,000 in children 5-15 years. The peak in early adulthood occurred at 25-29 years (463/100,000 pyrs). After a subsequent decline, simulated TB notification rates gradually increased from the age of 30 years. Sensitivity analyses showed that the dip after the early adult peak was due to the protective effect of latent TB and that retreatment TB was mainly responsible for the rise in TB notification rates from the age of 30 years.ConclusionThe protective effect of a first latent infection on subsequent infections and the faster progression in previously treated patients are the key determinants of the age-structure of TB notification rates in Cape Town.

Dataset Information

A Multivariate Age-Structured Stochastic Model with Immunization Strategies to Describe Bronchiolitis Dynamics.

Publications

A Multivariate Age-Structured Stochastic Model with Immunization Strategies to Describe Bronchiolitis Dynamics.

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