Global and regional burden of attributable and associated bacterial antimicrobial resistance avertable by vaccination: modelling study

Abstract

Introduction: Antimicrobial resistance (AMR) is a global health threat with 1.27 million and 4.95 million deaths attributable to and associated with bacterial AMR, respectively, in 2019. Our aim is to estimate the vaccine avertable bacterial AMR burden based on 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 on 15 bacterial pathogens 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 future vaccines.

Results: The AMR burden avertable by vaccination in 2019 was highest for the WHO Africa and South-East Asia regions, for lower respiratory infections, tuberculosis, and bloodstream infections by infectious syndromes, and for Mycobacterium tuberculosis and Streptococcus pneumoniae by pathogen. In the baseline scenario for vaccination of primary age groups against 15 pathogens, we estimated vaccine-avertable AMR burden of 0.51 (95% UI 0.49-0.54) million deaths and 28 (27-29) million disability-adjusted life-years (DALYs) associated with bacterial AMR, and 0.15 (0.14-0.17) million deaths and 7.6 (7.1-8.0) million DALYs attributable to AMR globally in 2019. In the high-potential scenario for vaccination of additional age groups against seven pathogens, we estimated vaccine-avertable AMR burden of an additional 1.2 (1.18-1.23) million deaths and 37 (36-39) million DALYs associated with AMR, and 0.33 (0.32-0.34) million deaths and 10 (9.8-11) million DALYs attributable to AMR globally in 2019.

Conclusion: Increased coverage of existing vaccines and development of new vaccines are effective means to reduce AMR, and this evidence should inform the full value of vaccine assessments.

Keywords: Immunisation; Vaccines.

Figure 1

Vaccine impact on antimicrobial resistance model. Static proportional impact model to estimate the reduction in pre-vaccine AMR burden after vaccination in direct proportion to efficacy, coverage, target population for protection, and duration of protection of existing and potential future vaccines. The AMR burden among the infants could be higher or lower than the AMR burden among the elderly depending on the pathogen. For example, AMR burden for Streptococcus pneumoniae and Haemophilus influenzae are higher among the infants compared to the elderly, while AMR burden for Staphylococcus aureus and Acinetobacter baumannii are lower among the infants compared to the elderly.

Figure 2

Vaccine impact on AMR burden by (pathogen-specific) vaccine profile, infectious syndrome, and region. The estimates (median and 95% uncertainty intervals) of the vaccine avertable deaths attributable to and associated with bacterial antimicrobial resistance in 2019 were aggregated by (pathogen-specific) vaccine profile, infectious syndrome, and WHO region in the baseline scenario. (Bone+ = infections of bones, joints, and related organs; BSI = bloodstream infections; cardiac = endocarditis and other cardiac infections; CNS = meningitis and other bacterial CNS infections; intra-abdominal = peritoneal and intra-abdominal infections; LRI+ = lower respiratory infections and all related infections in the thorax; skin = bacterial infections of the skin and subcutaneous systems; TF–PF–iNTS = typhoid fever, paratyphoid fever, and invasive non-typhoidal Salmonella spp; UTI = urinary tract infections and pyelonephritis).

Figure 2

Vaccine impact on AMR burden by (pathogen-specific) vaccine profile, infectious syndrome, and region. The estimates (median and 95% uncertainty intervals) of the vaccine avertable deaths attributable to and associated with bacterial antimicrobial resistance in 2019 were aggregated by (pathogen-specific) vaccine profile, infectious syndrome, and WHO region in the baseline scenario. (Bone+ = infections of bones, joints, and related organs; BSI = bloodstream infections; cardiac = endocarditis and other cardiac infections; CNS = meningitis and other bacterial CNS infections; intra-abdominal = peritoneal and intra-abdominal infections; LRI+ = lower respiratory infections and all related infections in the thorax; skin = bacterial infections of the skin and subcutaneous systems; TF–PF–iNTS = typhoid fever, paratyphoid fever, and invasive non-typhoidal Salmonella spp; UTI = urinary tract infections and pyelonephritis).

Figure 3

Vaccine avertable AMR burden by infectious syndrome and pathogen. Vaccine avertable deaths associated with AMR by infectious syndrome and pathogen in the baseline scenario. (“Others” include infections of bones, joints, and related organs, bloodstream infections, endocarditis and other cardiac infections, meningitis and other bacterial CNS infections, peritoneal and intra-abdominal infections, lower respiratory infections and all related infections in the thorax, bacterial infections of the skin and subcutaneous systems, typhoid fever, paratyphoid fever, and invasive non-typhoidal Salmonella spp, and urinary tract infections and pyelonephritis)