Pneumococcal conjugate vaccines (PCVs) have been shown in randomised controlled trials and epidemiological studies to prevent acute otitis media caused by vaccine serotype pneumococci, although their role in preventing complications of acute otitis media is less clear. We hypothesised that the 11-valent PCV would reduce the long-term sequelae of acute otitis media, including moderate-to-severe ear disease and hearing loss. This prospective cohort study, referred to as 11PCV study, included follow-up after 16–20 years of children previously enrolled in 2000–04, at age 6 weeks to 6 months, in the randomised, placebo-controlled, ARIVAC trial of 11-valent PCV for the prevention of radiographical pneumonia. The ARIVAC trial and this 11PCV study were conducted at six study centres in Bohol, Philippines. Ear disease was classified using video-otoscopy review and observations derived from the ear exam. The final classification of the worst ear disease was mild (ie, acute otitis media, otitis media with effusion, healed perforation, or tympanosclerosis), moderate (ie, dry perforation or adhesive otitis media), or severe (chronic suppurative otitis media). Hearing loss was assessed following a standard schema and classified according to the worst ear as mild (>15 to 30 dB puretone average) or moderate-to-profound (>30 dB pure tone average). We calculated the relative and absolute risk reduction in the primary outcome of moderate-to-severe ear disease and the secondary outcomes of mild or moderate-to-profound hearing loss in adolescents who previously received the 11-valent PCV compared with those who received placebo during infancy in ARIVAC. Of the 15 593 children assessed for eligibility in ARIVAC, 12 194 were randomly assigned and 8926 were alive and could be located for enrolment in this 11PCV study between Sept 19, 2016, and Dec 13, 2019. 8321 (4188 in the vaccine group and 4133 in the placebo group) completed follow-up of the 11PCV study by March 30, 2020, and had sufficient data to classify ear disease and be included in the primary outcome analysis. The primary outcome of the absolute risk reduction in moderate-to-severe ear disease in the vaccine group (310 [7·4%] of 4188) versus those in the placebo group (356 [8·6%] of 4133) was 1·2% (95% CI 0·0–2·4; p=0·046) and the relative risk reduction was 14·1% (0·0 to 26·0). There were no differences in secondary outcomes of mild hearing loss or moderate-to-profound hearing loss between the vaccine and placebo groups. The absolute risk reduction for moderate-to-severe ear disease in adolescence of 1·2% (12 per 1000 children) was almost three times higher than the 0·45% reduction (4·5 per 1000 children) in radiographical pneumonia in the first 2 years of life shown in ARIVAC. Administration of 11-valent PCV in infancy was associated with absolute and relative risk reductions in the sequelae of acute otitis media 16–20 years after the original ARIVAC trial. Bill & Melinda Gates Foundation.

中文翻译：

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婴儿期注射 11 价肺炎球菌结合疫苗后的中耳炎后遗症和青春期听力：一项对 ARIVAC 试验进行长期随访的前瞻性队列研究


随机对照试验和流行病学研究表明，肺炎球菌结合疫苗（PCV）可预防由疫苗血清型肺炎球菌引起的急性中耳炎，但其在预防急性中耳炎并发症中的作用尚不清楚。我们假设 11 价 PCV 将减少急性中耳炎的长期后遗症，包括中度至重度耳病和听力损失。这项前瞻性队列研究被称为 11PCV 研究，包括对 2000 年 4 月入组的 6 周至 6 个月大的 16-20 岁儿童进行随访，这些儿童参加了随机、安慰剂对照、ARIVAC 试验，该试验对 11-价 PCV 用于预防放射学肺炎。 ARIVAC 试验和这项 11PCV 研究是在菲律宾保和岛的六个研究中心进行的。使用视频耳镜检查和耳部检查观察结果对耳部疾病进行分类。最严重耳部疾病的最终分类为轻度（即急性中耳炎、渗出性中耳炎、愈合的穿孔或鼓室硬化）、中度（即干性穿孔或粘连性中耳炎）或重度（慢性化脓性中耳炎）。听力损失按照标准方案进行评估，并根据最差的耳朵分为轻度（>15 至 30 dB 纯音平均）或中度至极重（>30 dB 纯音平均）。我们计算了与接受安慰剂的青少年相比，先前接受 11 价 PCV 的青少年中度至重度耳病的主要结局以及轻度或中度至极重度听力损失的次要结局的相对和绝对风险降低情况在 ARIVAC 的婴儿期。 在 2016 年 9 月 19 日至 2019 年 12 月 13 日期间，评估了 ARIVAC 资格的 15 593 名儿童中，有 12 194 名被随机分配，其中 8926 名儿童还活着，可以找到参加这项 11PCV 研究的机会。8321 名儿童（疫苗组 4188 名，疫苗组 4188 名）安慰剂组的 4133 名患者）于 2020 年 3 月 30 日完成了 11PCV 研究的随访，并有足够的数据对耳部疾病进行分类并纳入主要结果分析。与安慰剂组（4133 人中的 356 人 [8·6%]）相比，疫苗组（4188 人中的 310 人 [7·4%]）中度至重度耳病绝对风险降低的主要结果为 1 ·2%（95% CI 0·0–2·4；p=0·046），相对风险降低为 14·1%（0·0 至 26·0）。疫苗组和安慰剂组之间的轻度听力损失或中度至重度听力损失的次要结果没有差异。青春期中度至重度耳病的绝对风险降低 1·2%（每 1000 名儿童 12 名），几乎是 2017 年放射学肺炎降低 0·45%（每 1000 名儿童 4·5 名）的三倍。 ARIVAC 中显示了生命的前 2 年。在最初的 ARIVAC 试验后 16-20 年，婴儿期给予 11 价 PCV 与急性中耳炎后遗症的绝对和相对风险降低相关。比尔及梅琳达·盖茨基金会。