Decrease of invasive pneumococcal disease (IPD) in adults after introduction of pneumococcal 13-valent conjugate vaccine in Spain

A prospective laboratory-based multicenter study that collected all adult invasive pneumococcal disease (IPD) episodes from 6 Spanish hospitals before (2008–2009) and after (2012–2013). The 13-valent pneumococcal conjugate vaccine (PCV13) licensure was conducted in order to analyze the impact of PCV13 introduction for children on adult IPD. A total of 1558 IPD episodes were detected. The incidence of IPD decreased significantly in the second period by -33.9% (95% CI, -40.3% to -26.8%). IPD due to PCV7 serotypes (-52.7%; 95% CI, -64.2% to -37.5%) and to PCV13 additional serotypes (-55.0% 95% CI, -62.0% to -46.7%) significantly decreased whereas IPD due to non-PCV13 serotypes remained stable (1.0% 95% CI, -12.9% to 17.2%). IPD due to all PCV13 additional serotypes significantly declined with the exception of serotype 3 (-11.3%; 95%CI -35.0% to 21.1%). IPD due to two non-PCV13 serotypes varied: serotype 6C that rose (301.6%; 95%CI, 92.7% to 733.3%, p6C, and serotype 8 that decreased (-34.9%, 95%CI, -57.1 to -1.2, p = 0.049), related to a decline of the ST638. The recombinant clone ST652111A (variant of ST1569V) increased in frequency. The decrease of serotype 19A IPD was linked to a fall in those antibiotic susceptible clones. In the last period, rates of penicillin- and cefotaxime-resistance remained under 10% and 4%, respectively. Adult IPD decreased after the PCV13 introduction in Spain due to herd protection. The spread of multidrug resistant clones (ST3866C, ST652111A) related to non-PCV13 serotypes needs further surveillance.

本研究为一项基于实验室的前瞻性多中心研究，于2008-2009年（13价肺炎球菌结合疫苗PCV13引入前）及2012-2013年（PCV13引入后），从西班牙6家医院收集了所有成人侵袭性肺炎链球菌病（invasive pneumococcal disease, IPD）病例。本研究以13价肺炎球菌结合疫苗（13-valent pneumococcal conjugate vaccine, PCV13）的获批上市为时间节点，分析儿童群体接种PCV13对成人IPD的影响。本研究共纳入1558例IPD病例。第二阶段的IPD发病率较第一阶段显著降低33.9%（95%置信区间：-40.3% ~ -26.8%）。针对7价肺炎球菌结合疫苗（PCV7）血清型的IPD病例降低52.7%（95%置信区间：-64.2% ~ -37.5%），针对PCV13额外覆盖血清型的IPD病例降低55.0%（95%置信区间：-62.0% ~ -46.7%）；而非PCV13覆盖血清型所致的IPD病例数保持稳定（变化率1.0%，95%置信区间：-12.9% ~ 17.2%）。除血清型3外，所有PCV13额外覆盖血清型所致的IPD病例均显著降低；血清型3所致IPD病例仅降低11.3%（95%置信区间：-35.0% ~ 21.1%）。两种非PCV13覆盖血清型所致的IPD病例数出现变化：血清型6C所致病例数显著上升301.6%（95%置信区间：92.7% ~ 733.3%，p6C），而血清型8所致病例数降低34.9%（95%置信区间：-57.1 ~ -1.2，P=0.049），该变化与ST638克隆的减少相关。重组克隆ST652111A（ST1569V的变异株）的检出频率有所上升。在第二阶段，青霉素耐药株和头孢噻肟耐药株的检出率分别维持在10%和4%以下。西班牙地区成人IPD发病率在PCV13推广接种后出现下降，这一结果得益于群体免疫保护效应。与非PCV13覆盖血清型相关的多重耐药克隆（ST3866C、ST652111A）的传播需要进一步监测。