Haeusler Ilsa L, Kagucia E Wangeci, Bottomley Christian, Otiende Mark, Nyiro Joyce, Scott J Anthony G
Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Institute for Global Health, University College London, London, United Kingdom.
PLOS Glob Public Health. 2025 Jul 28;5(7):e0004888. doi: 10.1371/journal.pgph.0004888. eCollection 2025.
Observational evidence suggests that pneumococcal conjugate vaccines (PCVs) are more effective at reducing the incidence of hypoxaemic pneumonia compared to non-hypoxaemic pneumonia. We examined the impact of 10-valent PCV (PCV10, Synflorix) on hypoxaemic pneumonia hospital admissions using data from an existing PCV impact study of clinical and radiographic pneumonia. PCV10 was introduced, with catch-up among children under 5 years, in the Kilifi Health and Demographic Surveillance System (KHDSS) in January 2011. We undertook an interrupted time-series (ITS) analysis using seasonally-adjusted segmented Poisson regression of hypoxaemic and non-hypoxaemic pneumonia, accounting for secular trends, from January 2007 to December 2019 among KHDSS residents aged 2-59 months. The median monthly crude incidence of hypoxaemic pneumonia per 100,000 person-years was 95 (IQR 80-139) in the pre-PCV10 period. Time-series regression estimated PCV10 introduction was associated with an increase in the incidence of hypoxaemic pneumonia in children aged 2-59 months (IRR 1.63, 95% CI 1.10-2.41), whereas it was associated with a decrease in the incidence of non-hypoxaemic pneumonia (IRR 0.61, 95% CI 0.48-0.77). Despite the consistent pneumonia surveillance and robust ITS analysis which accounted for pre-PCV10 secular trend and seasonality, the apparent association with hypoxaemic pneumonia is likely due to unmeasured time-varying confounders around the time of vaccine introduction, such as the epidemiology of other respiratory pathogens. This study highlights limitations in the analysis and interpretation of observational data in vaccine impact studies against pneumonia.
观察性证据表明，与非低氧血症性肺炎相比，肺炎球菌结合疫苗（PCV）在降低低氧血症性肺炎发病率方面更有效。我们利用一项现有的关于临床和影像学肺炎的PCV影响研究的数据，研究了10价PCV（PCV10，Synflorix）对低氧血症性肺炎住院情况的影响。2011年1月，在基利菲健康与人口监测系统（KHDSS）中引入了PCV10，并对5岁以下儿童进行了补种。我们采用中断时间序列（ITS）分析，对2007年1月至2019年12月期间KHDSS中年龄在2至59个月的居民的低氧血症性和非低氧血症性肺炎进行季节性调整的分段泊松回归分析，同时考虑长期趋势。在PCV10引入前，每10万人年的低氧血症性肺炎月粗发病率中位数为95（四分位间距80 - 139）。时间序列回归估计，引入PCV10与2至59个月儿童低氧血症性肺炎发病率增加相关（发病率比1.63，95%置信区间1.10 - 2.41），而与非低氧血症性肺炎发病率降低相关（发病率比0.61，95%置信区间0.48 - 0.77）。尽管进行了持续的肺炎监测和强有力的ITS分析，该分析考虑了PCV10引入前的长期趋势和季节性，但与低氧血症性肺炎的明显关联可能是由于疫苗引入时未测量的随时间变化的混杂因素，如其他呼吸道病原体的流行病学情况。本研究凸显了在肺炎疫苗影响研究中观察性数据的分析和解释方面的局限性。
