BACKGROUND There is limited empiric evidence on the coverage of pneumococcal conjugate vaccines (PCVs) required to generate substantial indirect protection. We investigate the association between population PCV coverage and indirect protection against invasive pneumococcal disease (IPD) and pneumonia hospitalisations among undervaccinated Australian children. METHODS AND FINDINGS Birth and vaccination records, IPD notifications, and hospitalisations were individually linked for children aged <5 years, born between 2001 and 2012 in 2 Australian states (New South Wales and Western Australia; 1.37 million children). Using Poisson regression models, we examined the association between PCV coverage, in small geographical units, and the incidence of (1) 7-valent PCV (PCV7)-type IPD; (2) all-cause pneumonia; and (3) pneumococcal and lobar pneumonia hospitalisation in undervaccinated children. Undervaccinated children received <2 doses of PCV at <12 months of age and no doses at ≥12 months of age. Potential confounding variables were selected for adjustment a priori with the assistance of a directed acyclic graph. There were strong inverse associations between PCV coverage and the incidence of PCV7-type IPD (adjusted incidence rate ratio [aIRR] 0.967, 95% confidence interval [CI] 0.958 to 0.975, p-value < 0.001), and pneumonia hospitalisations (all-cause pneumonia: aIRR 0.991 95% CI 0.990 to 0.994, p-value < 0.001) among undervaccinated children. Subgroup analyses for children <4 months old, urban, rural, and Indigenous populations showed similar trends, although effects were smaller for rural and Indigenous populations. Approximately 50% coverage of PCV7 among children <5 years of age was estimated to prevent up to 72.5% (95% CI 51.6 to 84.4) of PCV7-type IPD among undervaccinated children, while 90% coverage was estimated to prevent 95.2% (95% CI 89.4 to 97.8). The main limitations of this study include the potential for differential loss to follow-up, geographical misclassification of children (based on residential address at birth only), and unmeasured confounders. CONCLUSIONS In this study, we observed substantial indirect protection at lower levels of PCV coverage than previously described-challenging assumptions that high levels of PCV coverage (i.e., greater than 90%) are required. Understanding the association between PCV coverage and indirect protection is a priority since the control of vaccine-type pneumococcal disease is a prerequisite for reducing the number of PCV doses (from 3 to 2). Reduced dose schedules have the potential to substantially reduce program costs while maintaining vaccine impact.

中文翻译：

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澳大利亚肺炎球菌结合疫苗覆盖率和对侵袭性肺炎球菌疾病和肺炎住院的间接保护水平：一项观察性研究。

背景 关于产生大量间接保护所需的肺炎球菌结合疫苗 (PCV) 覆盖率的经验证据有限。我们调查了人口 PCV 覆盖率与针对侵袭性肺炎球菌疾病 (IPD) 的间接保护以及未接种疫苗的澳大利亚儿童肺炎住院之间的关联。方法和发现 2001 年至 2012 年在澳大利亚 2 个州（新南威尔士州和西澳大利亚州；137 万名儿童）出生的 5 岁以下儿童的出生和疫苗接种记录、IPD 通知和住院情况分别相关。使用泊松回归模型，我们检查了小地理单位中 PCV 覆盖率与 (1) 7 价 PCV (PCV7) 型 IPD 发病率之间的关联；(2)全因肺炎；(3) 接种疫苗不足的儿童因肺炎球菌和大叶性肺炎住院。未接种疫苗的儿童在 <12 个月大时接种了 <2 剂 PCV，而在 12 个月大时未接种过 PCV。在有向无环图的帮助下，选择潜在的混杂变量进行先验调整。PCV 覆盖率与 PCV7 型 IPD 的发病率（调整后发病率比 [aIRR] 0.967，95% 置信区间 [CI] 0.958 至 0.975，p 值 < 0.001）和肺炎住院率（所有-引起肺炎：aIRR 0.991 95% CI 0.990 至 0.994，p 值 < 0.001）在未接种疫苗的儿童中。对小于 4 个月大的儿童、城市、农村和土著人口的亚组分析显示出类似的趋势，尽管对农村和土著人口的影响较小。据估计，5 岁以下儿童中大约 50% 的 PCV7 覆盖率可以预防疫苗接种不足儿童中高达 72.5%（95% CI 51.6 至 84.4）的 PCV7 型 IPD，而 90% 的覆盖率预计可预防 95.2%（95 % CI 89.4 至 97.8)。本研究的主要局限性包括可能导致不同的失访、儿童的地理错误分类（仅基于出生时的住址）以及无法测量的混杂因素。结论 在这项研究中，我们观察到在较低水平的 PCV 覆盖率下的实质性间接保护比先前描述的具有挑战性的假设需要高水平的 PCV 覆盖率（即大于 90%）。了解 PCV 覆盖率与间接保护之间的关联是一个优先事项，因为控制疫苗型肺炎球菌疾病是减少 PCV 接种次数（从 3 次到 2 次）的先决条件。减少剂量计划有可能大幅降低计划成本，同时保持疫苗的影响。