Marshfield Clinic Research Foundation, Marshfield, WI 54449, USA.
Clin Infect Dis. 2013 Sep;57(6):789-93. doi: 10.1093/cid/cit379.
The test-negative control study design is the basis for observational studies of influenza vaccine effectiveness (VE). Recent studies have suggested that influenza vaccination increases the risk of noninfluenza respiratory virus infection. Such an effect could create bias in VE studies using influenza-negative controls. We investigated the association between influenza infection, vaccination, and detection of other respiratory viruses among children <5 years old and adults ≥50 years old with acute respiratory illness who participated in seasonal studies of influenza vaccine effectiveness.
Nasal/nasopharyngeal samples collected from 2004–2005 through 2009–2010 were tested for 19 respiratory virus targets using a multiplex reverse-transcription polymerase chain reaction (RT-PCR) platform. Vaccination status was determined using a validated registry. Adjusted odds ratios for influenza and vaccination status were calculated using three different control groups: influenza-negative, other respiratory virus positive, and pan-negative.
Influenza was detected in 12% of 2010 children and 20% of 1738 adults. Noninfluenza respiratory viruses were detected in 70% of children and 38% of adults without influenza. The proportion vaccinated did not vary between virus-positive controls and pan-negative controls in children (P = .62) or adults (P = .33). Influenza infection was associated with reduced odds of vaccination, but adjusted odds ratios differed by no more than 0.02 when the analysis used influenza-negative or virus-positive controls.
Influenza vaccination was not associated with detection of noninfluenza respiratory viruses. Use of influenza-negative controls did not generate a biased estimate of vaccine effectiveness due to an effect of vaccination on other respiratory virus infections.
病例对照研究设计是流感疫苗效力（VE）观察性研究的基础。最近的研究表明，流感疫苗接种会增加感染非流感呼吸道病毒的风险。这种影响可能会导致使用流感阴性对照的 VE 研究产生偏差。我们调查了在参加季节性流感疫苗效力研究的<5 岁儿童和≥50 岁成人中，急性呼吸道疾病患者中流感感染、疫苗接种与其他呼吸道病毒检测之间的关联。
使用多重逆转录聚合酶链反应（RT-PCR）平台，对 2004-2005 年至 2009-2010 年采集的鼻/鼻咽样本进行了 19 种呼吸道病毒靶标检测。使用经过验证的登记处确定疫苗接种状况。使用三种不同的对照组（流感阴性、其他呼吸道病毒阳性和全阴性）计算流感和疫苗接种状况的调整比值比（OR）。
在 2010 年的儿童中，12%检测到流感，在 1738 名成人中，20%检测到流感。在没有流感的儿童中，70%检测到非流感呼吸道病毒，在成人中，38%检测到非流感呼吸道病毒。在儿童（P =.62）或成人（P =.33）中，病毒阳性对照与全阴性对照之间疫苗接种比例没有差异。流感感染与接种疫苗的可能性降低有关，但当分析使用流感阴性或病毒阳性对照时，调整后的比值比差异不超过 0.02。
流感疫苗接种与非流感呼吸道病毒的检测无关。使用流感阴性对照不会因疫苗接种对其他呼吸道病毒感染的影响而导致疫苗效力的估计产生偏差。
