Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115 USA.
J Infect. 2017 Jun;74 Suppl 1:S101-S107. doi: 10.1016/S0163-4453(17)30199-8.
Interactions between pathogens and commensal microbes are major contributors to health and disease. Infectious diseases however are most often considered independent, viewed within a one-host one-pathogen paradigm and, by extension, the interventions used to treat and prevent them are measured and evaluated within this same paradigm. Vaccines, especially live vaccines, by stimulating immune responses or directly interacting with other microbes can alter the environment in which they act, with effects that span across pathogen species. Live attenuated infl uenza vaccines for example, while safe, increase upper respiratory tract bacterial carriage density of important human commensal pathogens like Streptococcus pneumoniae and Staphylococcus aureus. Further, by altering the ecological niche and dynamics of phylogenetically distinct microbes within the host, vaccines may unintentionally affect transmission of non-vaccine targeted pathogens. Thus, vaccine effects may span across species and across scales, from the individual to the population level. In keeping with traditional vaccine herd-effects that indirectly protect even unvaccinated individuals by reducing population prevalence of vaccine-targeted pathogens, we call these cross-species cross-scale effects "generalized herd-effects". As opposed to traditional herd-effects, "generalized" relaxes the assumption that the effect occurs at the level of the vaccine-target pathogen and "herd effect" implies, as usual, that the effects indirectly impact the population at large, including unvaccinated bystanders. Unlike traditional herd-effects that decrease population prevalence of the vaccine-target, generalized herd-effects may decrease or increase prevalence and disease by the off-target pathogen. LAIV, for example, by increasing pneumococcal density in the upper respiratory tract of vaccine recipients, especially children, may increase pneumococcal transmission and prevalence, leading to excess pneumococcal invasive disease in the population, especially among the elderly and others most susceptible to pneumococcal disease. However, these effects may also be beneficial, for example the large reductions in all-cause mortality noted following measles vaccines. Here we discuss evidence for these novel vaccine effects and suggest that vaccine monitoring and evaluation programs should consider generalized herd effects to appreciate the full impacts of vaccines, beneficial or detrimental, across species and scales that are inevitably hiding in plain sight, affecting human health and disease.
病原体和共生微生物之间的相互作用是健康和疾病的主要因素。然而，传染病通常被认为是独立的，在一个宿主一种病原体的范式内观察，并且，用于治疗和预防它们的干预措施也是在同一范式内进行衡量和评估的。疫苗，尤其是活疫苗，通过刺激免疫反应或直接与其他微生物相互作用，可以改变它们作用的环境，其影响跨越病原体物种。例如，虽然安全，但减毒活流感疫苗会增加重要的人类共生病原体，如肺炎链球菌和金黄色葡萄球菌在上呼吸道的细菌携带密度。此外，通过改变宿主内系统发育上不同的微生物的生态位和动态，疫苗可能会无意中影响非疫苗靶向病原体的传播。因此，疫苗的效果可能跨越物种和规模，从个体到人群水平。为了与间接通过降低疫苗靶向病原体的人群流行率来保护甚至未接种人群的传统疫苗群体效应保持一致，我们将这些跨物种跨规模的效应称为“广义群体效应”。与传统的群体效应不同，“广义”放宽了效应发生在疫苗靶向病原体水平的假设，而“群体效应”通常意味着这些效应间接影响到包括未接种旁观者在内的整个人群。与降低疫苗靶向病原体的人群流行率的传统群体效应不同，广义群体效应可能会降低或增加非靶向病原体的流行率和疾病。例如，LAIV 通过增加疫苗接种者，尤其是儿童，上呼吸道的肺炎链球菌密度，可能会增加肺炎链球菌的传播和流行率，导致人群中肺炎链球菌侵袭性疾病增加，尤其是在老年人和其他最易患肺炎链球菌疾病的人群中。然而，这些效应也可能是有益的，例如麻疹疫苗接种后观察到的全因死亡率大幅降低。在这里，我们讨论了这些新型疫苗效应的证据，并建议疫苗监测和评估计划应考虑广义群体效应，以了解疫苗在跨越物种和规模上的全部影响，这些影响不可避免地隐藏在显而易见的地方，影响着人类的健康和疾病。
