Thorrington Dominic, Andrews Nick, Stowe Julia, Miller Elizabeth, van Hoek Albert Jan
Public Health England, London, UK.
London School of Hygiene and Tropical Medicine, London, UK.
BMC Med. 2018 Feb 8;16(1):13. doi: 10.1186/s12916-018-1004-z.
The seven-valent pneumococcal conjugate vaccine (PCV) was introduced in England in September 2006, changing to the 13-valent vaccine in April 2010. PCV impact on invasive pneumococcal disease (IPD) has been extensively reported, but less described is its impact on the burden of pneumonia, sepsis and otitis media in the hospital.
Using details on all admissions to hospitals in England, we compared the incidence of pneumococcal-specific and syndromic disease endpoints in a 24-month pre-PCV period beginning April 2004 to the 24-month period ending March 2015 to derive incidence rate ratios (IRRs). To adjust for possible secular trends in admission practice, IRRs were compared to the IRRs for five control conditions over the same period and the relative change assessed using the geometric mean of the five control IRRs as a composite, and individually for each control condition to give the min-max range. Relative changes were also compared with IRRs for IPD from the national laboratory database. The effect of stratifying cases into those with and without clinical risk factors for pneumococcal infection was explored.
Relative reductions in pneumococcal pneumonia were seen in all age groups and in those with and without risk factors; in children under 15 years old reductions were similar in magnitude to reductions in IPD. For pneumonia of unspecified cause, relative reductions were seen in those under 15 years old (maximum reduction in children under 2 years of 34%, min-max: 11-49%) with a relative increase in 65+ year olds most marked in those with underlying risk conditions (41%, min-max: 0-82%). Reductions in pneumococcal sepsis were seen in all age groups, with the largest reduction in children younger than 2 years (67%, min-max 56-75%). Reductions in empyema and lung abscess were also seen in under 15 year olds. Results for other disease endpoints were varied. For disease endpoints showing an increase in raw IRR, the increase was generally reduced when expressed as a relative change.
Use of a composite control and stratification by risk group status can help elucidate the impact of PCV on non-IPD disease endpoints and in vulnerable population groups. We estimate a substantial reduction in the hospitalised burden of pneumococcal pneumonia in all age groups and pneumonia of unspecified cause, empyema and lung abscess in children under 15 years of age since PCV introduction. The increase in unspecified pneumonia in high-risk 65+ year olds may in part reflect their greater susceptibility to develop pneumonia from less pathogenic serotypes that are replacing vaccine types in the nasopharynx.
七价肺炎球菌结合疫苗（PCV）于2006年9月在英国引入，2010年4月更换为13价疫苗。PCV对侵袭性肺炎球菌疾病（IPD）的影响已有广泛报道，但对其在医院中肺炎、败血症和中耳炎负担的影响描述较少。
利用英格兰所有医院的入院详细信息，我们比较了2004年4月开始的24个月PCV接种前时期与2015年3月结束的24个月期间肺炎球菌特异性和综合征疾病终点的发病率，以得出发病率比值（IRR）。为了调整入院实践中可能存在的长期趋势，将IRR与同期五种对照情况的IRR进行比较，并使用五种对照IRR的几何平均值作为综合指标评估相对变化，同时针对每种对照情况单独评估以给出最小-最大范围。还将相对变化与国家实验室数据库中IPD的IRR进行比较。探讨了将病例分为有和无肺炎球菌感染临床危险因素的效果。
在所有年龄组以及有和无危险因素的人群中均观察到肺炎球菌肺炎的相对减少；在15岁以下儿童中，减少幅度与IPD的减少幅度相似。对于病因不明的肺炎，15岁以下人群出现了相对减少（2岁以下儿童最大减少34%，最小-最大范围：11%-49%），65岁及以上人群中病因不明肺炎的相对增加在有潜在危险因素的人群中最为明显（41%，最小-最大范围：0%-82%）。所有年龄组均观察到肺炎球菌败血症的减少，2岁以下儿童减少幅度最大（67%，最小-最大范围56%-75%）。15岁以下儿童的脓胸和肺脓肿也有所减少。其他疾病终点的结果各不相同。对于原始IRR增加的疾病终点，以相对变化表示时增加幅度通常会降低。
使用综合对照和按风险组状态分层有助于阐明PCV对非IPD疾病终点和弱势群体的影响。我们估计自引入PCV以来，所有年龄组的肺炎球菌肺炎住院负担以及15岁以下儿童病因不明的肺炎、脓胸和肺脓肿均大幅减少。65岁及以上高危人群中病因不明肺炎的增加可能部分反映了他们更容易因鼻咽部致病性较低的血清型取代疫苗型而发生肺炎。
