Project information:
ACRONYM: EMerGE-NeT
Title: Effectiveness of infection control strategies against intra- and
inter-hospital transmission of MultidruG-resistant
Enterobacteriaceae – insights from a multi-level mathematical
NeTwork model
Keywords: Network modelling, multidrug-resistant Enterobacteriaceae, transmission
dynamics, infection control, healthcare network
Realization period: 2017-2020 (extended till 2021)
Budget: Polish team 1 047 068 PLN
Consortium members:
- Helmholtz Centre for Infection Research/Department for Epidemiology, Germany (Mikolajczyk, Rafael)
- Charité- University Medicine Berlin/Institute of Hygiene and Environmental Medicine, Germany (Gastmeier, Petra)
- Nicolaus Copernicus University/Dept. of Microbiology, Poland (Deptula, Aleksander)
- UMC Utrecht/Julius Centre for Health Sciences & Primary Care, Netherlands (Kretzschmar, Mirjam)
- Rabin Medical Center, Beilinson Hospital/Dept. of Medicine, Israel (Leibovici, Leonard)
- Hospital Universitario Virgen Macarena Sevilla./Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Spain (López Cortés, L. Eduardo)
- University of Warsaw/Institute of Applied Mathematics and Mechanics, Poland (Piotrowska, Monika J.)
Warsaw team:
- Monika J. Piotrowska, University of Warsaw, coordinator of Polish teams (University of Warsaw, Institute of Applied Mathematics and Mechanics and Nicolaus Copernicus University,
Dept. of Microbiology)
- Konrad Sakowski, University of Warsaw and Institute of High Pressure Physics, Polish Academy of Sciences, researcher
- Students (University of Warsaw):
- Agata Lonc, M.Sc. student (stipend)
- Julia Rymuza, M.Sc. student (stipend)
- Paweł Brachaczek, M.Sc. student
- Piotr Byrski, B.Sc. student
- Paweł Włodarczyk-Pruszyński, B.Sc. student
Short description:
Multidrug-resistant Enterobacteriaceae (MDR-E) have become a major public health threat in many European countries. While traditional infection control strategies primarily target the containment of intra-hospital transmission, there is growing evidence highlighting the importance of inter-hospital patient traffic for the spread of MDR-E within healthcare systems. Going substantially beyond previous research, the EMerGE-NeT consortium will unite expertise in theoretical modelling, numerical simulation studies, epidemiology, clinical medicine, and microbiology in order to develop a generic network modelling platform, which combines inter- and intra-hospital transmission of MDR-E in a single framework. This multi-level network model will reflect patient traffic in various European healthcare systems and thus provide the framework to systematically study the transmission dynamics of MDR-E and the effectiveness of infection control strategies to contain their spread within and across healthcare systems. Corresponding to the requirements of this modelling approach, we will conduct specific molecular studies assessing the transmissibility of different MDR-E species and strains. In these studies, we will apply a novel cutting-edge methodology of targeted sequencing, which makes the large studies planned in this project economically feasible. Based on a systematic literature review and a formal Delphi process for collating evidence, we will identify promising infection control strategies for containing MDR-E and assess their effectiveness in simulation studies in the multi-level network model using species and strain-specific transmission parameters. The multidisciplinary character of this project will create a unique opportunity to evaluate the results of computer simulations against practical knowledge and experience, thus allowing researchers to determine whether targeted, unified infection control strategies could stop or reduce the spread of MDR-E and whether they are practically feasible.Work Packages
The project is designed to be conducted in three highly interconnected work packages (WPs 1-3) which will be supplemented by a separate WP for the management of the project and the dissemination of the project results (WP 4).- WP 1: Aims to design a multi-level network model that reflects patient traffic
in various European healthcare systems. It will provide the framework to study the transmission
dynamics of MDR-E and the effectiveness of infection control strategies to contain their
spread within and across healthcare systems.
- WP 2: Will conduct specific molecular studies assessing the transmissibility of different MDR-E
species and strains will be conducted. In these studies, we will apply a
novel cutting-edge methodology of targeted sequencing, which makes the large studies planned in this project
economically feasible.
- WP 3: Based on a systematic literature review and a formal Delphi process for collating evidence, we will
identify promising infection control strategies for containing MDR-E and
assess their effectiveness in simulation studies in the multi-level network model using species and
strain-specific transmission parameters.
- WP 4: Project organisation and dissemination of results
Warsaw team is involved in WP 1, WP 3 and WP 4 while the Bydgoszcz team in WP 2 (as a leader), WP3 and WP 4. In particular, the Warsaw team will develop computational models and numerical algorithms to model the dispersion of the pathogens within inter-hospital networks taking into account the transfer of patients. Next, the derived algorithms will be used to broaden the current knowledge about that phenomenon. One of the main objectives would be to analyse and verify such models using the available data. The initial part of these analyses will be based on archival data, e.g. from Germany and from Israel, provided by the members of the consortium and next on collected prospective data from Poland. On the other hand Bydgoszcz, the team will collect the data on potential transmission events based on screening for MDR-E of patients together with the information on patients’ movement within the hospital. Moreover, transmission events will be confirmed with phenotypic and molecular methods. Collected data will be included into the intra-hospital network developed by a Dutch member of the consortium. Next, both models will be combined to obtain a multi-level network model reflecting patient traffic in various European healthcare systems and will thus provide the framework for the systematic study of the transmission dynamics of MDR-E and of the effectiveness of potential interventions to contain their spread within and across healthcare systems. Within the project, we will identify the promising infection control strategies for containing MDR-E and assess their effectiveness in simulation studies based on the multi-level network model using species and strain specific transmission information.
Developed code
EMerGE-NeT Package
The developed code may be used for simulating the pathogen spread in the system of healthcare facilities. It consists of several modules for accomplishing the following tasks:- Analysis of hospital admissions databases and derivation of healthcare transfer networks.
- Automatic estimation of transfer model parameters.
- Parallel simulations of patient transfers between healthcare facilities (interhospital models).
- Serial simulations of pathogen spread inside healthcare facilities (intrahospital models).
- Analysis of simulation results.
- Visualisation of obtained results.
The code is designed for both deterministic models as well as stochastic agent-based variants. After the EMerGE-Net project was completed, the code was further developed and additional functionalities were implemented, for details click here.
The main objective is to simulate hospital infections, which develop mostly during stays in healthcare facilities and do not transmit well in the environment. The typical usage of this software is supposed to be as follows. A healthcare admission data set should be provided in the standardised database format, as required by the module. Then, inter-hospital and corresponding intra-hospital models must be chosen. The models require an initial network state to be specified, determining the initial susceptible/infectious patient distribution, etc. Then, the simulations can be performed. The inter-hospital module provides parallelisation by MPI library. It is assumed that the number of healthcare facilities in the considered systems is high so that the distribution of the facilities between processors and then executing serial intra-hospital models is enough to provide adequate speedup. Finally, simulation results may be processed with the aid of the auxiliary utilities provided by this module. Please note that this code has a form of library, so there is no GUI application provided for the management of the tasks described above. Access to algorithms provided by this code is through the provided Python API.
For the description of the inter-hospital models provided by this library, please refer to submodule emergenet.inter. On the other hand, intra-hospital models are implemented in submodule emergenet.intra.
Requirements
Hardware requirements: any decent desktop computer; RAM usage may vary depending on input database size and the number of healthcare facilities in simulations.Software requirements:
- Python 2 (version 2.7.13 or later) for release 0.5
- Python 3 (version 3.6.7 or later) for release >=1.0
- Python modules: argparse, attrdict, base64, colander, collections, csv, datetime, dateutil, enum, io, itertools, json, ksiterate, math, matplotlib, mpi4py, msgpack, networkx, numpy, os, pandas, pint, pprint, pygraphviz, random, scipy, shutil, sqlalchemy, sys, time, types.
EMerGE-NeT Package Code and Documentation
To download the code and documentation (release 0.5, 1.0 and 2.0) please fill out the details in the form. Then the link to the download page will be provided.Related preprints/publications
- M.J. Piotrowska, K. Sakowski,
Analysis of the AOK Lower Saxony hospitalisation records data (years 2008 – 2015) , arXiv:1903.04701 - A. Lonc, M.J. Piotrowska, K. Sakowski,
Analysis of the hospital records from AOK Plus , arXiv:1909.08169 - A. Lonc, M.J. Piotrowska, K. Sakowski,
Analysis of the AOK Plus data and derived hospital network , Mathematica Applicanda, 47(1), 2019, 127-139, DOI - M.J. Piotrowska, K. Sakowski, A. Karch, H. Tahir, J. Horn, M.E. Kretzschmar, R.T. Mikolajczyk,
Modelling pathogen spread in a healthcare network: indirect patient movements , arXiv:2001.05875 - M.J. Piotrowska, K. Sakowski, A. Karch, H. Tahir, J. Horn, M.E. Kretzschmar, R.T. Mikolajczyk: 'Modelling pathogen spread in a healthcare network: indirect patient movements', PLOS Computational Biology, 16 (11), 2020, e1008442, DOI.
- M.J. Piotrowska, K. Sakowski, A. Lonc, H. Tahir, M.E. Kretzschmar: 'Impact of inter-hospital transfers on the prevalence of resistant pathogens in a hospital-community system', Epidemics, 33, Dec. 2020, 100408, DOI.
- H. Tahir, L.E. López Cortés, A. Kola, D. Yahav, A. Karch, H. Xia, J. Horn, K. Sakowski, M.J. Piotrowska, L. Leibovici, R.T. Mikolajczyk, M.E. Kretzschmar: 'Relevance of intra-hospital patient movements for the spread of healthcare-associated infections within hospitals - a mathematical modeling study', PLOS Computational Biology, 17(2), 2021, e1008600, DOI.
- H. Xia H, J. Horn, M.J. Piotrowska, K. Sakowski, A. Karch A, H. Tahir, M.E. Kretzschmar, R.T. Mikolajczyk: 'Effects of incomplete inter-hospital network data on the assessment of transmission dynamics of hospital-acquired infections', PLOS Computational Biology, 17(5), 2021, e1008941, DOI.
-
M.J. Piotrowska, J. Rymuza, K. Sakowski,
Analysis of the hospital claims data from Germany (years 2013-2018) and derivation of transfer matrices , arXiv:2206.07380, DOI - M.J. Piotrowska, K. Sakowski, J. Horn, R. Mikolajczyk, A. Karch: 'The effect of re-directed patient flow in combination with targeted infection control measures on the spread of multi-drug-resistant Enterobacteriaceae in the German health-care system: a mathematical modelling approach', Clinical Microbiology and Infection, 29(1), P109.E1-109.E7, 2023, published on-line: August 11, 2022, DOI. For a personalized URL providing 50 days' (till Oct. 31, 2022) free access to the article click here.
- M.J. Piotrowska, A. Puchalska, K. Sakowski: 'On network suppression of multidrug-resistant pathogen spread', (preprint), 2022 DOI
-
M.J. Piotrowska, A. Puchalska, K. Sakowski:
'On the network suppression of the pathogen spread within the
healthcare system', Applied Mathematics and Computation, 457, 2023, 128169, DOI.
- H. Xia H, J. Horn, M.J. Piotrowska, K. Sakowski, A. Karch A, H. Tahir, M.E. Kretzschmar, R.T. Mikolajczyk: 'Effects of incomplete inter-hospital network data on the assessment of transmission dynamics of hospital-acquired infections', PLOS Computational Biology, 17(5), 2021, e1008941, DOI.
- P. Brachaczek, A.Lonc, M.E. Kretzschmar, R.T. Mikolajczyk, J. Horn, A. Karch, K. Sakowski, M.J. Piotrowska: 'Transmission of drug-resistant bacteria in a hospital-community model stratified by patient risk', Scientific Reports, 13, Article number: 18593, 2023, DOI.
- A. Weber, L. Neffe, L.A.P. Diaz, N. Thoma, S.J.S. Aghdassi, L.A. Denkel, F. Maechler, M. Behnke, S. Häussler, P. Gastmeier, A. Kola, on behalf of the EMerGE-NeT Consortium: 'Analysis of transmission-related third-generation cephalosporin-resistant Enterobacterales by electronic data mining and core genome multi-locus sequence typing' Journal of Hospital Infection, 140, 2023, 96-101, DOI.
- H. Xia, J. Horn, M.J. Piotrowska, K. Sakowski, A. Karch, M. Kretzschmar, R. Mikolajczyk: 'Regional patient transfer patterns matter for the spread of hospital-acquired pathogens' Scientific Reports, 14, 2024, Article number: 929, DOI.
Popularization
- Interview with Monika J. Piotrowska, "Matematyka vs bakterie" (in Polish), published on portal Rzeczo.pl, 2020.
- Interview in German published on portal www.sporlastic.de, 2017.
More information on partners and realization of the project can be found at the official project web page.