Modeling Interventions Against Antimicrobial Resistance

Antimicrobial resistance (AMR) poses a serious public health threat that affects people all around the globe. Although methicillin-resistant Staphylococcus aureus (MRSA) poses a well-understood risk, problems with AMR span beyond that bacteria. Predicting the Impact of Monoclonal Antibodies and Vaccines on Antimicrobial Resistance (PrIMAVeRa) is a program that seeks to help estimate the burden of disease attributable to AMR, which is a complex problem that requires high-quality surveillance data. A recent global study linked 4.95 million deaths to bacterial AMR in 2019, including 38,710 in the European Union/European Economic Area (EU/EEA) (1, 2). The PrIMAVeRa project conducted three systematic reviews to demonstrate the burden of AMR, assessing frequency measures, health, and economic outcomes.

The project focused on six drug-resistant pathogens drawn from priority lists from the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO): S. aureus, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus faecium, Escherichia coli, and Klebsiella pneumoniae. The lists were compared with availability and development data for vaccines and monoclonal antibodies (MAbs) targeting those pathogens (3).

Developing Vaccines and MAbs To Mitigate AMR
Antibiotic misuse drives the development of AMR. But vaccines can be used to prevent infectious disease by inducing immunity against AMR pathogens, stopping their spread among people (4). Vaccines developed to prevent the spread of viral pathogens could achieve similar effects; people vaccinated against a viral pathogen are less likely to contract a secondary bacterial infection, decreasing antibiotic usage.

MAbs rapidly protect patients from contracting infections when they cannot wait for vaccine-induced immunity or when vaccines are unavailable. Both interventions protect individuals from infection, lowering the spread of infectious agents and decreasing the need for antibiotics.

Investing in vaccine/MAb development is important, because for many AMR pathogens, vaccines and MAbs do not exist, have low efficacy, or are in early clinical development. To guide resource prioritization, decision-makers need a tool to estimate the health and economic value of developing vaccines and MAbs to reduce AMR. PrIMAVeRa seeks to provide such a tool.

The PrIMAVeRa Project
PrIMAVeRa was designed to leverage private–public partnerships through a consortium of academics, small and medium-sized enterprises (SMEs), and industry partners from epidemiology, health economics, mathematical modeling, and vaccine/MAb development. Its scientific advisory board consists of experts from organizations such as the World Health Organization (WHO) and Wellcome Trust. PrIMAVeRa is also part of the Innovative Medicines Initiative (IMI) AMR Accelerator, a group of projects that are developing new medicines against AMR pathogens.

PrIMAVeRa will build upon the success of the Epi-Net epidemiological-surveillance database and contribute data that are gathered during the project. Epi-Net is an open-platform repository used to perform data visualization for hosts and pathogens of interest. It enables policy-makers to visualize disease burdens in specific countries. Such information will facilitate data-driven decisions regarding AMR-related agenda prioritization, policies, and investments.

PrIMAVeRa is working on case studies to develop structures for E. coli, S. aureus, and P. aeruginosa models. Input based on granular, high-quality epidemiological data is needed to validate theoretical models. Gaps remain in publicly available data, and gathering data from existing studies can be difficult. During the project’s first year, a systematic review of existing models defined parameters for the minimum and optimum data required to create a model. Such models can be used to mitigate AMR by filling gaps in epidemiological data with theoretical assumptions.

References
1  Murray CJL, et al. Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis. Lancet 399(10325) 2022: 629–655; https://doi.org/10.1016/S0140-6736(21)02724-0.

2  Assessing the Health Burden of Infections with Antibiotic-Resistant Bacteria in the EU/EEA, 2016-2020. European Centre for Disease Prevention and Control: Stockholm, Sweden, November 2022; https://www.ecdc.europa.eu/sites/default/files/documents/Health-burden-infections-antibiotic-resistant-bacteria.pdf.

3  Tacconelli E, et al. Discovery, Research, and Development of New Antibiotics: The WHO Priority List of Antibiotic-Resistant Bacteria and Tuberculosis. Lancet Infect. Dis. 18(3) 2018: 318–327; https://doi.org/10.1016/S1473-3099(17)30753-3.

4  Micoli F, et al. The Role of Vaccines in Combatting Antimicrobial Resistance. Nat. Rev. Microbiol. 19, 2021: 287–302; https://doi.org/10.1038/s41579-020-00506-3.

Irina Meln, PhD, is senior innovation manager; Daniel Reem is project & IT administrative manager; Ole F. Olesen, PhD, is executive director; and Romina Di Marzo is communication and advocacy manager at the European Vaccine Initiative; https://www.primavera-amr.eu/consortium. This work has received support from the IMI2/EU/EFPIA Joint Undertaking PrIMAVeRa grant n° 101034420.