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Quantifying the Benefits of Vaccines in Combating Antimicrobial Resistance

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Quantifying the Benefits of Vaccines in Combating Antimicrobial Resistance 16 Eurohealth Observer QUANTIFYING THE BENEFITS OF VACCINESINCOMBATING ANTIMICROBIALRESISTANCE By: Mark Jit, Michael Anderson and Ben Cooper Summary: Vaccination is one of the most effective measures to reduce antimicrobial resistance. As vaccines are highly specific to their targeted pathogens, they are less likely to induce resistance compared to antibiotics. Their impact on resistance or antibiotic prescriptions has already been demonstrated for vaccines against pathogens such as Streptococcus pneumonia and influenza, but greater investment and development is needed for vaccines which target pathogens such as Vibrio cholerae, Salmonella typhi, Escherichia coli, common health care-associated infections and respiratory and diarrhoeal viruses. To value vaccines correctly, economic evaluations need to take account of multiple health system, ecological and epidemiological pathways through which vaccination affects antimicrobial resistance and use. Keywords: Vaccines, Economic Evaluation, Antimicrobial Resistance Introduction strains. This is because vaccines work by enabling the immune system to recognise The development and use of vaccines is antigens that are highly specific to their a key strategy to combat antimicrobial targeted pathogens. In contrast, antibiotics resistance (AMR). A recently published can impose selective pressure on both Mark Jit is Professor, Vaccine chapter ‘The role of vaccines in combating targeted and non-targeted microorganisms Epidemiology, Department of antimicrobial resistance’ within the book; Infectious Disease Epidemiology, to develop resistance. Second, due to the Challenges in Tackling Antimicrobial London School of Hygiene & specific nature of vaccines, vaccines can Tropical Medicine, and Principal Resistance: Economics and Policy be developed that target specific strains Mathematical Modeller, Statistics, Responses offers a comprehensive review Modelling and Economics Unit, of a pathogen that are most pathogenic of this summary. 1 In this article we National Infections Service, Public or prone to developing resistance. This provide an overview of the key issues Health England, London, UK; has been the case with pneumococcal Michael Anderson is Research discussed in the chapter. Officer, Department of Health conjugate vaccines, where the serotypes Policy, London School of Economics selected for vaccine development were Vaccines have a number of characteristics and Political Science, London, UK; generally the ones most likely to cause Ben Cooper is Associate Professor, which make them particularly effective invasive disease. 2 Thirdly, vaccines and Nuffield Department of Medicine, at combating AMR. First, vaccines University of Oxford, Oxford, UK. antimicrobials can work in a synergistic usually have little effect on the evolution Email: [email protected] fashion – vaccines can reduce the rate of microorganisms besides the targeted Eurohealth — Vol.26 | No.1 | 2020 Eurohealth Observer 17 at which populations are infected and not targeted by the vaccine, such as the resistant strain, leading to declines hence extend the time until a pathogen commensal bacterial pathogens, as a in resistance in both hospitals and evolves resistance to an antimicrobial. result of reduced antibiotic selection the community. Finally, vaccines can be administered pressure. For example, since influenza only a few times and provide long-lasting infections are frequently treated with Priorities for vaccine investment and population-wide effects by preventing antibiotics (either inappropriately for the development to tackle AMR the onset of disease. In contrast, primary viral infection, or for a secondary antimicrobials need to be continuously bacterial infection), an effective and Vaccines are already used effectively to administered with each infection. While widely used vaccine that reduces the tackle AMR in many countries. In the they can be used prophylactically to number of influenza infections should United States, the introduction of the prevent disease onset, more commonly result in population-wide reductions in seven-valent pneumococcal conjugate they are used to treat rather than prevent antibiotic use. vaccine (PCV7) was associated with infections. They also have less potential to an 84% reduction in multidrug-resistant prevent onward transmission of resistant Pathway 3: Infection severity effects invasive pneumococcal disease. 5 In microorganisms, as there is usually a delay the Canadian province of Ontario, the Vaccines that reduce the risk of between the onset of infectiousness and introduction of a universal influenza symptomatic infection without reducing receiving treatment. immunisation programme was associated the risk of carriage/asymptomatic with reductions in prescriptions of infection can lead to reductions in the antimicrobials for respiratory tract proportion of infections which are treated infections. 6 However, to fully capitalise with antimicrobials and therefore a on the benefits of vaccines to tackle The reduction in the selection pressure for AMR there are a number of vaccine resistant phenotypes. potentialbenefit investment and development needs which need to be prioritised. ofvaccinesto Pathway 4: Subtype selection effects Some vaccines may target subtypes of Vibrio cholerae a pathogen population which are more reduceAMRis Resistant and multi-resistant cholera is likely to be resistant. As a result, overall a significant issue for many health care resistance may decrease. However, it is frequently systems. An oral cholera vaccine which is also possible that vaccines may target effective at preventing medically-attended subtypes which are less likely to be underestimated cholera already exists. 7 Use of this resistant. In these circumstances, overall vaccine clearly has the potential to reduce resistance may increase. Pathways by which vaccines can AMR through its direct effect on cholera; reduce AMR‘‘ however, there is a need for greater Pathway 5: Interspecific effects investment to increase access to this The potential benefit of vaccines to Bacteria and viruses interact in vaccine, particularly in low and middle reduce AMR is frequently underestimated complex ways. For example, influenza income countries (LMICs). because people only consider a subset or respiratory syncytial virus (RSV) of the pathways by which vaccines can infections may increase the risk of Salmonella typhi affect antimicrobial use and resistance. secondary bacterial infections and In total, we consider six pathways by A ciprofloxacin-resistant lineage of patients with certain viral infections which vaccines can reduce the burden of Salmonella typhi infection has emerged may transmit more bacterial pathogens. AMR. 3 4 in many countries. Two vaccines have Vaccination against one organism could been available since the 1990s and are therefore reduce transmission of another, Pathway 1: Preventing infections by focal recommended by the World Health leading to declines in both resistant and pathogens Organization (WHO): the live Ty21a sensitive phenotypes. vaccine and the Vi-polysaccharide Vaccines may reduce the incidence vaccine. 8 While they are both effective, of infection by a resistant pathogen. Pathway 6: Selective targeting effects their protection is partial and relatively This can occur both through direct Interventions, such as hygiene short-lived, typically up to two years. protection to those vaccinated, and improvements or vaccination, could However, there are several promising through indirect protection resulting from lead to differential effects if targeted to next-generation conjugate vaccines in reduced exposure to the infection in the certain population groups. For example, development, including two vaccine unvaccinated (herd immunity). if a resistant strain of a given pathogen candidates having received licensure in transmits preferentially in hospitals India. 9 Gavi, the Vaccine Alliance, has Pathway 2: Bystander effects (where antibiotic use is high), targeting opened a funding window for this vaccine, Any vaccines that lead to changes in the hospital population with a vaccine which will help increase access to these antibiotic use could potentially have could have a greater overall effect on vaccines in LMICs. an impact on AMR in organisms Eurohealth — Vol.26 | No.1 | 2020 18 Eurohealth Observer Escherichia coli severe AMR problems. Yet, with the article, AMR reduction is a key benefit of exception of P. aeruginosa, there is little vaccines but a recent review of published Infections caused by E. coli are activity in developing vaccines or other models of the impact of vaccines on the a major cause of morbidity and immunotherapies for these pathogens that dynamics of AMR did not find any studies associated antibiotic use. In particular, has extended beyond animal models and that considered the economic value of enterotoxigenic E. coli (ETEC) is a it is thought unlikely that these vaccines this benefit. 4 leading cause of diarrhoea in children will be available within the next 10 years. in developing countries. Ciprofloxacin- Major technical hurdles to developing The simplest way to estimate the benefit resistant ETEC strains represent a major vaccines for these “ESKAPE” pathogens of vaccines that prevent AMR is to challenge for ETEC treatment strategies exist such as limited understanding multiply the reduction in risk of acquiring in some parts of the world. While there of pathogen biology including natural a resistant strain in vaccinated individuals are no licensed vaccines for ETEC,
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