Vaccination to reduce antimicrobial resistance
Authors: Katherine E Atkins, Stefan Flasche
Journal: The Lancet Global Health (2018)

With the pipeline of new antibiotics running dry, vaccines are being proposed as a key part of the toolkit used to fight antimicrobial resistance.1Review on Antimicrobial ResistanceVaccines and alternative approaches: reducing our dependence on antimicrobials.https://amr-review.org/sites/default/files/Vaccines%20and%20alternatives_v4_LR.pdfGoogle Scholar Amy Ginsburg and Keith Klugman (November 2017, e1176–77)2Ginsburg AS Klugman KP Vaccination to reduce antimicrobial resistance.Lancet Glob Health. 2017; 5: e1176-e1177Summary Full Text Full Text PDF PubMed Scopus (39) Google Scholar suggest that a reduction in resistant pathogens might be easier to achieve in many countries via vaccines than through other interventions, such as improved hygiene and sanitation. However, vaccines are rarely designed to target resistant pathogens directly, with the notable exception of pneumococcal conjugate vaccines (PCVs) that protect against serotypes of Streptococcus pneumoniae displaying high resistance frequency. Hence, vaccines' effect of reducing antimicrobial resistance has been mostly regarded as a highly desirable byproduct. The scale of the problem of antimicrobial resistance now requires us to formally integrate the effect of vaccines on antimicrobial resistance into decision-making in public health. Vaccines, arguably more than any other public health intervention, are subject to rigorous evaluations before integration into national immunisation programmes. Because of the non-linear effects of transmission-reducing vaccines, embedding mathematical modelling forecasts in economic evaluations is the gold standard for impact predictions.3Wilder-Smith A Longini I Zuber PL et al.The public health value of vaccines beyond efficacy: methods, measures and outcomes.BMC Med. 2017; 15: 138Crossref PubMed Scopus (50) Google Scholar Similarly, the interplay between vaccination and the emergence and spread of antimicrobial resistance will probably yield complex dynamics that require mathematical modelling analysis. The characteristics and efficacy of a particular vaccine will influence the linked direct and indirect reductions in resistance burden and antibiotic use.4Atkins KE Lafferty E Deeny SR Davies NG Robotham JV Jit M Use of mathematical modelling to assess the impact of vaccines on antibiotic resistance.Lancet Infect Dis. 2017; (published online Nov 13.)https://doi.org/10.1016/S1473-3099(17)30478-4Summary Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 5Lipsitch M Siber GR How can vaccines contribute to solving the antimicrobial resistance problem?.MBio. 2016; 7: e00428-e00516Crossref PubMed Scopus (127) Google Scholar Meanwhile, vaccines against non-focal pathogens (ie, pathogens which themselves are not the targets of resistance control) might have similar and substantial benefits.4Atkins KE Lafferty E Deeny SR Davies NG Robotham JV Jit M Use of mathematical modelling to assess the impact of vaccines on antibiotic resistance.Lancet Infect Dis. 2017; (published online Nov 13.)https://doi.org/10.1016/S1473-3099(17)30478-4Summary Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 5Lipsitch M Siber GR How can vaccines contribute to solving the antimicrobial resistance problem?.MBio. 2016; 7: e00428-e00516Crossref PubMed Scopus (127) Google Scholar However, there is a scarcity of modelling studies that aim to quantify the public health effect of vaccines on antimicrobial resistance. Furthermore, none of these models have integrated an economic framework.4Atkins KE Lafferty E Deeny SR Davies NG Robotham JV Jit M Use of mathematical modelling to assess the impact of vaccines on antibiotic resistance.Lancet Infect Dis. 2017; (published online Nov 13.)https://doi.org/10.1016/S1473-3099(17)30478-4Summary Full Text Full Text PDF PubMed Scopus (31) Google Scholar Mathematical models have been able to reflect both the fall of penicillin-resistant S pneumoniae and the subsequent rise in resistance in non-vaccine serotypes after the introduction of PCVs.6Opatowski L Mandel J Varon E Boëlle PY Temime L Guillemot D Antibiotic dose impact on resistance selection in the community: a mathematical model of beta-lactams and streptococcus pneumoniae dynamics.Antimicrob Agents Chemother. 2010; 54: 2330-2337Crossref PubMed Scopus (41) Google Scholar Notwithstanding these post-hoc studies, developing mechanistic models that show the empirical relation between an antibiotic's use and the rising frequency of resistance against the antibiotic has been challenging.7Lehtinen S Blanquart F Croucher NJ Turner P Lipsitch M Fraser C Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage.Proc Natl Acad Sci USA. 2017; 114: 1075-1080Crossref PubMed Scopus (78) Google Scholar, 8Lipsitch M Colijn C Cohen T Hanage WP Fraser C No coexistence for free: neutral null models for multistrain pathogens.Epidemics. 2009; 1: 2-13Crossref PubMed Scopus (94) Google Scholar, 9Davies NG Flasche S Jit M Atkins KE Within-host dynamics explain the coexistence of antibiotic-sensitive and resistant bacteria.bioRxiv. 2017; (published online Nov 10.)DOI:10.1101/217232Google Scholar Without an accurate quantification of the selection mechanisms through which resistance frequency is maintained, it will be impossible to base policy decisions on model forecasts. To couple vaccine programmes with an evidence-based strategy for antimicrobial resistance, we must now move from blanket recommendations of vaccine use for antimicrobial resistance control to a vaccine-specific, pathogen-specific, and setting-specific quantification of vaccine policy. This crucial shift will rely on a new generation of mathematical models and of the economic frameworks in which these models will be embedded. We declare no competing interests. Vaccination to reduce antimicrobial resistancePneumonia remains the leading infectious cause of death in children worldwide, and how best to reduce this burden is worth consideration on World Pneumonia Day on November 12. Antibiotics are effective in treating bacterial pneumonia and access to appropriate antibiotics can be lifesaving. Universal provision of antibiotics to children younger than 5 years could prevent an estimated mean of 445 000 deaths per year due to community-acquired pneumonia—a 75·4% reduction across 101 countries.1 Antibiotics need to be available and accessible to effectively treat pneumonia; however, inappropriate use of antibiotics can lead to the emergence and progression of antibiotic resistance, a serious public health threat. Full-Text PDF Open Access