Have you herd? Indirect flu vaccine effects are critically important

Seasonal epidemics of influenza virus infection occur frequently. These viruses infect the respiratory tract and typically cause fever, cough, and muscle and joint pain. In some individuals, particularly infants and elderly people, influenza infection can lead to severe illness or death.1Simonsen L Fukuda K Schonberger LB Cox NJ The impact of influenza epidemics on hospitalizations.J Infect Dis. 2000; 181: 831-837Crossref PubMed Scopus (424) Google Scholar Seasonal influenza also places a strain on economic productivity due to employee absenteeism and exhaustion of health-care resources due to increased hospital admissions.2Molinari NA Ortega-Sanchez IR Messonnier ML et al.The annual impact of seasonal influenza in the US: measuring disease burden and costs.Vaccine. 2007; 25: 5086-5096Crossref PubMed Scopus (1284) Google Scholar Seasonal immunisation programmes are an important component of influenza prevention strategies, but several factors combine to make seasonal vaccination programmes less impactful than might be expected. First, viral mutation (also known as drift) is an ongoing process, resulting in vaccine mismatch with circulating strains in some years and therefore decreased vaccine efficacy. Furthermore, influenza epidemiology is unfortunately characterised by dissociation between populations most likely to have severe disease (infants and elderly people), and populations most likely to benefit from vaccination (older children and adolescents—ie, those aged 2–16 years).3Galvani AP Reluga TC Chapman GB Long-standing influenza vaccination policy is in accord with individual self-interest but not with the utilitarian optimum.Proc Natl Acad Sci USA. 2007; 104: 5692-5697Crossref PubMed Scopus (203) Google Scholar Older children and adolescents seem to be important for the early propagation of influenza in populations, and the efficacy of influenza vaccines is greater in these populations than in elderly people, but they are generally not prioritised for immunisation because of their lower risk of morbidity and mortality from this infection.3Galvani AP Reluga TC Chapman GB Long-standing influenza vaccination policy is in accord with individual self-interest but not with the utilitarian optimum.Proc Natl Acad Sci USA. 2007; 104: 5692-5697Crossref PubMed Scopus (203) Google Scholar This paradoxical state of affairs has led some researchers to suggest that the best way to minimise the burden of seasonal influenza would be to focus immunisation programmes on children, adolescents, and young adults, with benefit accrued by elderly people and infants as a result of herd immunity.3Galvani AP Reluga TC Chapman GB Long-standing influenza vaccination policy is in accord with individual self-interest but not with the utilitarian optimum.Proc Natl Acad Sci USA. 2007; 104: 5692-5697Crossref PubMed Scopus (203) Google Scholar Herd immunity is the additional protection provided to both unvaccinated and vaccinated individuals in a population, and results from the inability of successfully vaccinated individuals to propagate disease. Such an approach would be supported by both observational data,4Reichert TA Sugaya N Fedson DS Glezen WP Simonsen L Tashiro M The Japanese experience with vaccinating schoolchildren against influenza.N Engl J Med. 2001; 344: 889-896Crossref PubMed Scopus (725) Google Scholar and more recent randomised trials5Loeb M Russell ML Moss L et al.Effect of influenza vaccination of children on infection rates in Hutterite communities: a randomized trial.JAMA. 2010; 303: 943-950Crossref PubMed Scopus (290) Google Scholar, 6Loeb M Russell ML Manning V et al.Live attenuated versus inactivated influenza vaccine in Hutterite children: a cluster randomized blinded trial.Ann Intern Med. 2016; 165: 617-624Crossref PubMed Scopus (28) Google Scholar suggesting that protection of all age groups results when children and adolescents are immunised against influenza. Such an approach might raise ethical questions: individuals who bear the discomfort and risk of immunisation provide the benefit of herd immunity to others at the extremes of age, who are less likely to benefit from direct immunisation. Although such an approach would be consistent with a utilitarian optimum, and with a communitarian approach to health and medicine, it might be a difficult sell in a health context that embraces an individualistic focus on health-care decision making.3Galvani AP Reluga TC Chapman GB Long-standing influenza vaccination policy is in accord with individual self-interest but not with the utilitarian optimum.Proc Natl Acad Sci USA. 2007; 104: 5692-5697Crossref PubMed Scopus (203) Google Scholar In The Lancet Public Health, David Hodgson and colleagues7Hodgson D Baguelin M van Leeuwen E et al.Effect of mass paediatric influenza vaccination on existing influenza vaccination programmes in England and Wales: a modelling and cost-effectiveness analysis.Lancet Public Health. 2017; (published online Jan 10.)http://dx.doi.org/10.1016/S2468-2667(16)30044-5Google Scholar provide a model-based cost-effectiveness analysis of emerging live-attenuated influenza virus (LAIV)-based seasonal influenza programmes targeting people aged 2–16 years. Although the efficacy of LAIV had been the subject of controversy, the most recent randomised trial6Loeb M Russell ML Manning V et al.Live attenuated versus inactivated influenza vaccine in Hutterite children: a cluster randomized blinded trial.Ann Intern Med. 2016; 165: 617-624Crossref PubMed Scopus (28) Google Scholar showed efficacy equivalent to that seen with a more traditional trivalent subunit vaccine, providing the same herd effects. Intranasal administration of LAIV has the benefit of making parenteral injection unnecessary, a benefit that can be readily appreciated by parents of young children. Importantly, and in accordance with best practices,8Pitman R Fisman D Zaric GS et al.ISPOR-SMDM Modeling Good Research Practices Task ForceDynamic transmission modeling: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force–5.Value Health. 2012; 15: 828-834Summary Full Text Full Text PDF PubMed Scopus (127) Google Scholar Hodgson and colleagues use a well calibrated dynamic mathematical model that allows them to evaluate the cost-effectiveness of vaccinating one group in the population (aged 2–16 years) on disease risk in another (elderly people).7Hodgson D Baguelin M van Leeuwen E et al.Effect of mass paediatric influenza vaccination on existing influenza vaccination programmes in England and Wales: a modelling and cost-effectiveness analysis.Lancet Public Health. 2017; (published online Jan 10.)http://dx.doi.org/10.1016/S2468-2667(16)30044-5Google Scholar They project that LAIV programmes focused on young individuals are in themselves highly cost-effective health interventions. However, their analysis highlights the importance of herd effects for decision makers: a rapidly implemented LAIV programme focused on children aged 2–16 years is actually more effective at preventing disease in elderly people than a more slowly implemented programme that includes both LAIV and direct immunisation of elderly people themselves. This finding is because a rapid, early focus on young individuals, in whom the vaccine is more effective, stops the influenza epidemic in its tracks. Furthermore, when young individuals are vaccinated, seasonal vaccination programmes targeted at low-risk elderly individuals might cease to be cost-effective (depending on the notoriously murky definition of cost-effectiveness threshold) because herd effects already effectively reduce risk for these individuals. The Article by Hodgson and colleagues,7Hodgson D Baguelin M van Leeuwen E et al.Effect of mass paediatric influenza vaccination on existing influenza vaccination programmes in England and Wales: a modelling and cost-effectiveness analysis.Lancet Public Health. 2017; (published online Jan 10.)http://dx.doi.org/10.1016/S2468-2667(16)30044-5Google Scholar although focusing on influenza, has implications for other emerging vaccines. For example, conjugate pneumococcal vaccines administered to children have important effects on mortality in older individuals.9Lexau CA Lynfield R Danila R et al.Active Bacterial Core Surveillance TeamChanging epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine.JAMA. 2005; 294: 2043-2051Crossref PubMed Scopus (597) Google Scholar The existence of these herd effects could erode the cost-effectiveness of direct immunisation of older individuals. If health-care providers are to use the increasingly wide array of vaccines optimally, they need to acknowledge that epidemics are implicitly processes that involve populations rather than individuals. A degree of fluency with disease dynamics and health economics as applied to communicable diseases is increasingly a key component of the public health practitioner's skill set. DNF has received grants from Sequirus Vaccines, GlaxoSmithKline Vaccines, Sanofi Pasteur Vaccines, and Pfizer Vaccines, outside the submitted work. IIB declares no competing interests. Effect of mass paediatric influenza vaccination on existing influenza vaccination programmes in England and Wales: a modelling and cost-effectiveness analysisWith the likely move to decreased cost-effectiveness thresholds, reassessment of existing risk group-based vaccine programme cost-effectiveness in the presence of the paediatric vaccination programme is needed. Full-Text PDF Open Access

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