Effect of Seven-Valent Pneumococcal Conjugate Vaccine on Staphylococcus aureus Colonisation in a Randomised Controlled Trial

BackgroundHeptavalent pneumococcal conjugate vaccine (PCV7) shifts nasopharyngeal colonisation with vaccine serotype pneumococci towards nonvaccine serotypes. Because of the reported negative association of vaccine serotype pneumococci and Staphylococcus aureus in the nasopharynx, we explored the effect of PCV7 on nasopharyngeal colonisation with S. aureus in children and parents. Methodology/Principal FindingsThis study was part of a randomised controlled trial on the effect of PCV7 on pneumococcal carriage, enrolling healthy newborns who were randomly assigned (1∶1∶1) to receive PCV7 (1) at 2 and 4 months of age (2) at 2, 4 and 11 months or (3) no PCV7 (controls). Nasopharyngeal colonisation of S. aureus was a planned secondary outcome. Nasopharyngeal swabs were obtained from all children over a 2-year period with 6-months interval and from one parent at the child's age of 12 and 24 months and cultured for Streptococcus pneumoniae and S. aureus. Between July 2005 and February 2006, 1005 children were enrolled and received either 2-doses of PCV7 (n = 336), 2+1-doses (336) or no dose (n = 333) before PCV7 implementation in the Dutch national immunization program. S. aureus colonisation had doubled in children in the 2+1-dose group at 12 months of age compared with unvaccinated controls (10.1% versus 5.0%; p = 0.019). A negative association for co-colonisation of S. pneumoniae and S. aureus was observed for both vaccine serotype (adjusted odds ratio (aOR) 0.53, 95% confidence interval (CI) 0.38–0.74) and nonvaccine serotype pneumococci (aOR 0.67, 95% CI 0.52–0.88). Conclusions/SignificancePCV7 induces a temporary increase in S. aureus colonisation in children around 12 months of age after a 2+1-dose PCV7 schedule. The potential clinical consequences are unknown and monitoring is warranted. Trial RegistrationClinicalTrials.gov NCT00189020背景 七价肺炎球菌结合疫苗（heptavalent pneumococcal conjugate vaccine, PCV7）可使携带疫苗血清型肺炎球菌的鼻咽部定植向非疫苗血清型转变。鉴于已有研究报道鼻咽部的疫苗血清型肺炎球菌与金黄色葡萄球菌（Staphylococcus aureus）存在负相关关联，本研究探讨了PCV7对儿童及家长鼻咽部金黄色葡萄球菌定植的影响。 方法/主要结果 本研究为一项关于PCV7对肺炎球菌携带率影响的随机对照试验的子研究，纳入健康新生儿并按1∶1∶1的比例随机分为三组：（1）于2月龄和4月龄接种PCV7；（2）于2、4和11月龄接种PCV7；（3）不接种PCV7（对照组）。鼻咽部金黄色葡萄球菌定植为预设的次要结局指标。研究在2年随访周期内每6个月采集所有受试儿童的鼻咽拭子，并在儿童12月龄和24月龄时采集其一名家长的鼻咽拭子，用于培养肺炎链球菌（Streptococcus pneumoniae）与金黄色葡萄球菌。2005年7月至2006年2月期间，共纳入1005名儿童，其中336名接受2剂次PCV7接种，336名接受2+1剂次PCV7接种，333名为未接种对照组，该入组阶段早于荷兰国家免疫规划中PCV7的推广实施时间。在儿童12月龄时，2+1剂次组的金黄色葡萄球菌定植率较未接种对照组翻倍（10.1% vs 5.0%；p=0.019）。同时观察到，无论疫苗血清型（校正比值比（adjusted odds ratio, aOR）0.53，95%置信区间（confidence interval, CI）0.38~0.74）还是非疫苗血清型肺炎球菌，其与金黄色葡萄球菌的共定植均呈负相关关联（aOR 0.67，95%CI 0.52~0.88）。 结论/意义 采用2+1剂次PCV7免疫程序的儿童，其鼻咽部金黄色葡萄球菌定植率会在12月龄左右出现暂时性升高。目前该现象潜在的临床后果尚不明确，因此有必要开展相关监测。试验注册信息：ClinicalTrials.gov NCT00189020