Global and Regional Burden of Attributable and Associated Bacterial Antimicrobial Resistance Avertable by Vaccination: Modelling Study

Abstract

Background: Antimicrobial resistance (AMR) is a global health threat with 1.27 million deaths attributable to bacterial AMR and 4.95 million deaths associated with bacterial AMR in 2019. Our aim is to estimate the vaccine avertable bacterial AMR burden based on profiles of existing and future vaccines at the regional and global levels by pathogen and infectious syndromes.

Methods: We developed a static proportional impact model to estimate the vaccination impact in terms of reduction in age-specific AMR burden estimates for 2019 from the Global Research on AntiMicrobial resistance project in direct proportion to efficacy, coverage, target population for protection, and duration of protection of existing and potential future vaccines. We estimated vaccine avertable deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 15 bacterial pathogens by region, infectious syndrome, and pathogen with 95% uncertainty intervals (UIs) for two scenarios – baseline scenario for primary vaccination of specific age-groups and high-potential scenario that includes additional age groups at risk.

Findings: In the baseline scenario, we estimated that vaccines against the 15 pathogens could avert 0.49 (0.47 - 0.51) million deaths and 28 (27 - 29) million DALYs associated with bacterial AMR, and 0.15 (0.14 - 0.16) million deaths and 7.5 (7.0 - 7.9) million DALYs attributable to AMR globally in 2019. We estimated vaccine avertable deaths associated with AMR to be highest for an improved vaccine against Streptococcus pneumoniae with 0.12 (0.11 - 0.14) million deaths averted, by infectious syndrome for lower respiratory infections with 0.16 (0.15 - 0.17) million deaths averted, and in the WHO Africa region with 0.16 (0.15 - 0.17) million deaths averted. In the high-potential scenario, we estimated that vaccines against a subset of 7 pathogens could avert an additional 1.0 (0.99 - 1.0) million deaths and 30 (30 - 31) million DALYs associated with AMR, and 0.27 (0.27 - 0.28) million deaths and 8.2 (8.0 - 8.5) million DALYs attributable to AMR globally in 2019.

Interpretation: Increased coverage of existing vaccines and the development of new vaccines are effective means to reduce AMR. We recommend that the vaccine avertable burden of AMR be included in the full value of vaccine assessments, and that stakeholders include this evidence to inform and prioritise decisions throughout the end-to-end continuum from discovery and clinical development to investment, development, introduction, and sustainability of new vaccines with equitable access.

Funding Information: This study was funded by the Bill & Melinda Gates Foundation (INV-006816).

Declaration of Interests: We declare no competing interests. Where authors are identified as personnel of the WHO, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the WHO.

Ethics Approval Statement: This study was approved by the ethics committee (Ref 26896) of the London School of Hygiene & Tropical Medicine. All authors had full access to all the data in the study and final responsibility for the decision to submit for publication. We conducted our analysis using the R programming 205 language for statistical computing,24 and the repository for the data and software code of this modelling study are publicly accessible at https://github.com/vaccine-impact/vaccine_amr.

Keywords: Antimicrobial resistance, Vaccination, Modelling