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Mathematical modelling of biological processes

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http://hdl.handle.net/10400.7/331

Our research lies in mathematical biology with a special focus on multi-scale infectious disease modeling. Adopting mechanistic approaches, the aim is to develop a deeper quantitative understanding of how system behavior emerges from the interaction of its components, and how processes at one biological scale affect patterns we observe at another. At the genetics-ecology-epidemiology interface, we study processes from the individual to the population level. Data-driven mathematical modeling is applied to a variety of topics, including antibiotic resistance management, multi-type pathogen ecology, within-host interactions in health and disease, and evolutionary diversification. We combine analysis with computer simulations, and we are particularly interested in dynamical systems, stochastic processes and Bayesian inference. The insights gained from our interdisciplinary research can have practical implications for medical settings and public health policy, and provide innovative frameworks for the interpretation of biological data.

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Browsing Mathematical modelling of biological processes by Author "Gjini, Erida"

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  • Expanding vaccine efficacy estimation with dynamic models fitted to cross-sectional prevalence data post-licensure
    Publication . Gjini, Erida; Gomes, M. Gabriela M.
    The efficacy of vaccines is typically estimated prior to implementation, on the basis of randomized controlled trials. This does not preclude, however, subsequent assessment post-licensure, while mass-immunization and nonlinear transmission feedbacks are in place. In this paper we show how cross-sectional prevalence data post-vaccination can be interpreted in terms of pathogen transmission processes and vaccine parameters, using a dynamic epidemiological model. We advocate the use of such frameworks for model-based vaccine evaluation in the field, fitting trajectories of cross-sectional prevalence of pathogen strains before and after intervention. Using SI and SIS models, we illustrate how prevalence ratios in vaccinated and non-vaccinated hosts depend on true vaccine efficacy, the absolute and relative strength of competition between target and non-target strains, the time post follow-up, and transmission intensity. We argue that a mechanistic approach should be added to vaccine efficacy estimation against multi-type pathogens, because it naturally accounts for inter-strain competition and indirect effects, leading to a robust measure of individual protection per contact. Our study calls for systematic attention to epidemiological feedbacks when interpreting population level impact. At a broader level, our parameter estimation procedure provides a promising proof of principle for a generalizable framework to infer vaccine efficacy post-licensure.
    2016-03Journal article Open access Show more
  • Geographic variation in pneumococcal vaccine efficacy estimated from dynamic modeling of epidemiological data post-PCV7
    Publication . Gjini, Erida
    Although mean efficacy of multivalent pneumococcus vaccines has been intensively studied, variance in vaccine efficacy (VE) has been overlooked. Different net individual protection across settings can be driven by environmental conditions, local serotype and clonal composition, as well as by socio-demographic and genetic host factors. Understanding efficacy variation has implications for population-level effectiveness and other eco-evolutionary feedbacks. Here I show that realized VE can vary across epidemiological settings, by applying a multi-site-one-model approach to data post-vaccination. I analyse serotype prevalence dynamics following PCV7, in asymptomatic carriage in children attending day care in Portugal, Norway, France, Greece, Hungary and Hong-Kong. Model fitting to each dataset provides site-specific estimates for vaccine efficacy against acquisition, and pneumococcal transmission parameters. According to this model, variable serotype replacement across sites can be explained through variable PCV7 efficacy, ranging from 40% in Norway to 10% in Hong-Kong. While the details of how this effect is achieved remain to be determined, here I report three factors negatively associated with the VE readout, including initial prevalence of serotype 19F, daily mean temperature, and the Gini index. The study warrants more attention on local modulators of vaccine performance and calls for predictive frameworks within and across populations.
    2017-06-12Journal article Open access Show more
  • Integrating Antimicrobial Therapy with Host Immunity to Fight Drug-Resistant Infections: Classical vs. Adaptive Treatment
    Publication . Gjini, Erida; Brito, Patricia H.
    Antimicrobial resistance of infectious agents is a growing problem worldwide. To prevent the continuing selection and spread of drug resistance, rational design of antibiotic treatment is needed, and the question of aggressive vs. moderate therapies is currently heatedly debated. Host immunity is an important, but often-overlooked factor in the clearance of drug-resistant infections. In this work, we compare aggressive and moderate antibiotic treatment, accounting for host immunity effects. We use mathematical modelling of within-host infection dynamics to study the interplay between pathogen-dependent host immune responses and antibiotic treatment. We compare classical (fixed dose and duration) and adaptive (coupled to pathogen load) treatment regimes, exploring systematically infection outcomes such as time to clearance, immunopathology, host immunization, and selection of resistant bacteria. Our analysis and simulations uncover effective treatment strategies that promote synergy between the host immune system and the antimicrobial drug in clearing infection. Both in classical and adaptive treatment, we quantify how treatment timing and the strength of the immune response determine the success of moderate therapies. We explain key parameters and dimensions, where an adaptive regime differs from classical treatment, bringing new insight into the ongoing debate of resistance management. Emphasizing the sensitivity of treatment outcomes to the balance between external antibiotic intervention and endogenous natural defenses, our study calls for more empirical attention to host immunity processes.
    2016-04-14Journal article Open access Show more