H2020Индивидуална стипендия2019–2021

PolyPath · Insights from within-host dynamics on the coexistence of antibiotic resistant and sensitive pathogens

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-11-01 → 2021-10-31
Финансиране от ЕС: 184 708 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Механизмите, чрез които бактерии, чувствителни и устойчиви на антибиотици, съществуват заедно в един организъм и се предават между хора, са в центъра на анализа. Това помага за определяне на по-добри стратегии за лечение и намаляване на риска от развитие на резистентност.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Insights from within-host dynamics on the coexistence of antibiotic resistant and sensitive pathogens

The project PolyPath aimed at understanding the coexistence-maintaining mechanisms of antimicrobial resistant and sensitive strains within a pathogen by accounting for randomness on the scale of within-host bacterial growth and the scale of between-host disease transmission. The new insights that are generated both on within-host dynamics of antimicrobial resistance dynamics as well as their impact on the between-host transmission of resistant strains are useful to tackle the societal problem of antibiotic drug resistance of multiple pathogens. In addition, the results on within-host dynamics might help identify favorable treatment strategies to reduce the risk of resistance evolution during antibiotic treatment. Overall, the scientific objectives were as follows: (1) Understanding the within-host dynamics of the pathogen under antibiotic treatment and during bacterial colonization of uninfected hosts. (2) Resolving the problem of coexistence of antibiotic sensitive and resistant strains in a single pathogen by coupling within- and between-host dynamics to account for selective advantages of strains on different scales. (3) Simulating the within-between-host model and confronting it to epidemiological datasets. In view of the ongoing COVID-19 pandemic, the focus of the project shifted in March 2020 (4 months into the funding period) to address questions related to the propagation of COVID-19. The investigations that were conducted were diverse and ranged from the viral replication mechanism within an infected individual to transmission dynamics of this novel disease in the population. Specifically, I have worked on the following objectives: (A) Assessing the potential of prophylactic antiviral treatment as a tool to prevent infection of people at high risk, e.g. health care workers. (B) Analysis of an epidemiological model that accounts for a time-varying infectiousness of infected individuals over the course of their infection. (C) Study of early epidemic dynamics and public health related consequences, e.g. an estimate for the minimal testing frequency in a population to detect infection clusters before they exceed a certain size. These research questions provided important information on the potential of repurposing existing antiviral drugs as a potential treatment against COVID-19 (objective (A)) and an accurate description of infection cluster dynamics, which can be used to inform policy making with respect to COVID-19 containment and detection strategies (objective (C)).

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Understanding and controlling the evolution of antibiotic resistant strains is one of the biggest public health challenges of our time. Despite a vast amount of data gathered and models being developed, coexistence of antibiotic resistant and sensitive genotypes within the same bacterial pathogen is still an unresolved problem. Simple epidemiological models predict the dominance of either of the two strains while more complex models suffer from generality. Using empirical evidence, I set out to resolve this problem by coupling within-host pathogen dynamics and between-host transmission of bacteria. First, stochastically modelling the within-host system I will develop predictions for the rate of resistance emergence and abundance of sensitive and resistant individuals in hosts with or without antibiotic treatment. While resistant bacteria thrive under antibiotic treatment, the sensitive strain has an advantage in invading and colonising untreated hosts. The outcomes help to get a more detailed understanding of the within-host dynamics, e.g. identification of optimal treatment strategies to confine the evolution of antibiotic resistance. Feeding these results into the dynamics on the population level, the between-host level, will result in a within-between-host feedback. Fitting and confronting the model to empirical data on prevalence and resistance emergence in Streptococcus pneuomoniae and Escherichia coli will conclude this project. The mechanistic implementation of the dynamics can immediately be linked to data which is of great importance given the increasing amount of empirical studies in the field of epidemiology. Through the theoretical and applied results, the study will add new insights and predictions in the field of infectious disease evolution and be able to identify factors enabling the stable coexistence of antibiotic resistant and sensitive bacteria.

Оригинален текст от CORDIS (на английски).

Участници

SORBONNE UNIVERSITE · ParisКоординаторФранция