Temime Laura, Boelle Pierre-Yves, Opatowski Lulla, Guillemot Didier
CNAM, Paris, France.
PLoS One. 2008 Sep 19;3(9):e3244. doi: 10.1371/journal.pone.0003244.
Despite the dramatic decline in the incidence of invasive pneumococcal disease (IPD) observed since the introduction of conjugate vaccination, it is feared that several factors may undermine the future effectiveness of the vaccines. In particular, pathogenic pneumococci may switch their capsular types and evade vaccine-conferred immunity.
METHODOLOGY/PRINCIPAL FINDINGS: Here, we first review the literature and summarize the available epidemiological data on capsular switch for S. pneumoniae. We estimate the weekly probability that a persistently carried strain may switch its capsule from four studies, totalling 516 children and 6 years of follow-up, at 1.5x10(-3)/week [4.6x10(-5)-4.8x10(-3)/week]. There is not enough power to assess an increase in this frequency in vaccinated individuals. Then, we use a mathematical model of pneumococcal transmission to quantify the impact of capsular switch on the incidence of IPD in a vaccinated population. In this model, we investigate a wide range of values for the frequency of vaccine-selected capsular switch. Predictions show that, with vaccine-independent switching only, IPD incidence in children should be down by 48% 5 years after the introduction of the vaccine with high coverage. Introducing vaccine-selected capsular switch at a frequency up to 0.01/week shows little effect on this decrease; yearly, at most 3 excess cases of IPD per 10(6) children might occur due to switched pneumococcal strains.
Based on all available data and model predictions, the existence of capsular switch by itself should not impact significantly the efficacy of pneumococcal conjugate vaccination on IPD incidence. This optimistic result should be tempered by the fact that the selective pressure induced by the vaccine is currently increasing along with vaccine coverage worldwide; continued surveillance of pneumococcal populations remains of the utmost importance, in particular during clinical trials of the new conjugate vaccines.
尽管自引入结合疫苗以来侵袭性肺炎球菌病(IPD)的发病率显著下降,但人们担心若干因素可能会削弱疫苗未来的有效性。特别是,致病性肺炎球菌可能会改变其荚膜类型,从而逃避疫苗赋予的免疫力。
方法/主要发现:在此,我们首先回顾文献并总结关于肺炎链球菌荚膜转换的现有流行病学数据。我们从四项研究中估计持续携带菌株每周转换其荚膜的概率,这些研究共有516名儿童,随访6年,结果为1.5×10⁻³/周[4.6×10⁻⁵ - 4.8×10⁻³/周]。没有足够的能力评估接种疫苗个体中这种频率的增加情况。然后,我们使用肺炎球菌传播的数学模型来量化荚膜转换对接种疫苗人群中IPD发病率的影响。在这个模型中,我们研究了疫苗选择的荚膜转换频率的广泛取值。预测表明,仅考虑与疫苗无关的转换,在高覆盖率疫苗引入5年后,儿童IPD发病率应下降48%。引入频率高达0.01/周的疫苗选择的荚膜转换对这种下降影响不大;每年每10⁶名儿童中因转换的肺炎球菌菌株可能最多额外出现3例IPD病例。
基于所有现有数据和模型预测,荚膜转换本身的存在不应显著影响肺炎球菌结合疫苗对IPD发病率的疗效。这一乐观结果应因以下事实而有所缓和:目前随着全球疫苗覆盖率的提高,疫苗引起的选择压力正在增加;对肺炎球菌群体的持续监测仍然至关重要,特别是在新结合疫苗临床试验期间。