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检测阴性设计病例对照研究评价23价肺炎球菌多糖疫苗的儿童保护效果

沈嘉铭 刘肖飞 黄莉莉 陶云珍 郑本锋 赵根明 田健美 栾琳 邵雪君 张涛

沈嘉铭, 刘肖飞, 黄莉莉, 陶云珍, 郑本锋, 赵根明, 田健美, 栾琳, 邵雪君, 张涛. 检测阴性设计病例对照研究评价23价肺炎球菌多糖疫苗的儿童保护效果[J]. 中国公共卫生, 2023, 39(11): 1430-1437. doi: 10.11847/zgggws1141850
引用本文: 沈嘉铭, 刘肖飞, 黄莉莉, 陶云珍, 郑本锋, 赵根明, 田健美, 栾琳, 邵雪君, 张涛. 检测阴性设计病例对照研究评价23价肺炎球菌多糖疫苗的儿童保护效果[J]. 中国公共卫生, 2023, 39(11): 1430-1437. doi: 10.11847/zgggws1141850
SHEN Jiaming, LIU Xiaofei, HUANG Lili, TAO Yunzhen, ZHENG Benfeng, ZHAO Genming, TIAN Jianmei, LUAN Lin, SHAO Xuejun, ZHANG Tao. Effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumococcal disease in children with acute respiratory illness: a hospital- based test-negative design study[J]. Chinese Journal of Public Health, 2023, 39(11): 1430-1437. doi: 10.11847/zgggws1141850
Citation: SHEN Jiaming, LIU Xiaofei, HUANG Lili, TAO Yunzhen, ZHENG Benfeng, ZHAO Genming, TIAN Jianmei, LUAN Lin, SHAO Xuejun, ZHANG Tao. Effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumococcal disease in children with acute respiratory illness: a hospital- based test-negative design study[J]. Chinese Journal of Public Health, 2023, 39(11): 1430-1437. doi: 10.11847/zgggws1141850

检测阴性设计病例对照研究评价23价肺炎球菌多糖疫苗的儿童保护效果

doi: 10.11847/zgggws1141850
基金项目: 国家自然科学基金青年项目(8187006);上海市“重大突发传染病防控关键核心技术研究”市级重大科技专项(ZD2021CY001)
详细信息
    作者简介:

    沈嘉铭(1997 – ),硕士在读,研究方向:疾病预防控制

    通信作者:

    邵雪君,E-mail:xjshao@suda.edu.cn

    张涛,E-mail:tzhang@shmu.edu.cn

Effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumococcal disease in children with acute respiratory illness: a hospital- based test-negative design study

More Information
  • 摘要:   目的   采用检测阴性设计病例对照研究评价23价肺炎球菌多糖疫苗(23-valent pneumococcal polysaccharide vaccine, PPV23)对儿童肺炎球菌[即肺炎链球菌(Streptococcus pneumonia, Spn)]相关呼吸道感染疾病的保护效果。  方法   选取2017年1月1日 — 2020年12月31日因急性呼吸道感染(acute respiratory illness, ARI)在苏州大学附属儿童医院住院治疗的2岁 ≤ 年龄 < 10岁的患儿为研究对象,前瞻性收集呼吸道感染患儿中分离的肺炎链球菌菌株,通过荚膜肿胀实验确定 Spn菌株血清型。采用检测阴性设计病例对照研究,病例组为感染PPV23血清型肺炎球菌的患儿,对照组分别为非疫苗血清型(non-vaccine serotype,NVT)患儿(感染非PPV23血清型肺炎球菌患儿)(NVT对照组)和肺炎球菌阴性(Spn –)患儿(临床样本中未检出感染Spn的患儿)(Spn – 对照组)。在苏州市疾病预防控制中心的疫苗接种登记数据库中查询患儿 PPV23接种的相关信息。采用Logistic回归模型估计PPV23接种的调整比值比,评价PPV23的保护效果(vaccine effectiveness, VE)。  结果   共纳入1 749株Spn菌株,其最常见的血清型依次为19F、6B、23F、6A 和19A;PCV13和PPV23疫苗血清型覆盖率分别为76.56%和72.27%。病例组共纳入1 264例患儿、NVT对照组485例、Spn – 对照组1 590例,平均年龄分别为(3.88 ± 1.27)、(4.02 ± 1.43)、(4.52 ± 1.92)岁;病例组、NVT对照组和Spn – 对照组PPV23的接种率分别为5.4%、6.8%和5.8%,接种疫苗的平均年龄为(2.53 ± 0.61)岁。以NVT患儿为对照时,通过logistic回归模型调整患儿年龄、临床诊断和其他疫苗接种情况后,PPV23对预防儿童疫苗血清型Spn肺炎球菌相关呼吸道感染疾病的总体保护效果(VE)为18.3%(95%CI = – 26.3%~47.1%),对社区获得性肺炎的VE为15.7%,对血清型19F、6B及15B的VE分别为32.8%、16.5%和57.5%,对2~5岁儿童的保护效果(26.0%)优于5岁以上儿童(7.6%)。以Spn – 患儿为对照时,通过logistic回归模型调整患儿年龄、户籍、其他疫苗接种情况、就诊年份、就诊季节及临床诊断后,PPV23对2~5岁儿童的保护效果为29.9%(95%CI = – 22.0%~59.7%)。  结论   PPV23对预防儿童疫苗血清型Spn相关呼吸道感染疾病具有一定的保护效果,但随接种后时间的推移而减弱。
  • 图  1  病例组和对照组研究对象纳入流程图及结果

    Figure  1.  Procedures for the sampling of cases and controls in the test-negative design study

    图  2  2017 — 2020年1 749株肺炎球菌分离株血清型分布

    注:其他:血清型包括15F、10B、13、23B等不足10例的Spn血清型菌株及无法分型的菌株。

    Figure  2.  Serotype-specific number of Spn isolates from 1 749 children (2 – 9 years old) suffering from acute respiratory illness during 2017 – 2020 in Suzhou city

    表  1  病例组与对照组研究对象基本情况

    Table  1.   Gender, age, household registry, year and season of seeking medication, and history of vaccinations for 3 339 ARI children – 1 264 cases (vaccine serotype Spn positive), 485 NVT control (non-vaccine serotype Spn positive), and 1 590 Spn negative control recruited in a hospital during 2017 – 2020 in Suzhou city

    研究对象病例组(N = 1 264)NVT对照组(N = 485)χ2PSpn-对照组(N = 1 590)χ2P
    人数%人数%人数%
    性别 0.4 0.516 1.9 0.167
     女 674 53.3 267 55.1 889 55.9
     男 590 46.7 218 44.9 701 44.1
    年龄(岁) 5.8 0.016 119.0 < 0.001
     2~5 1 067 84.4 386 79.6 1057 66.5
     6~9 197 15.6 99 20.4 533 33.5
    户籍 0.8 0.662 235.9 < 0.001
     苏州 1 193 94.4 463 95.5 1150 72.3
     非苏州 64 5.1 20 4.1 342 21.5
     不详 7 0.6 2 0.4 98 6.2
    就诊时间(年份) 1.0 0.810 367.7 < 0.001
     2017 260 20.6 101 20.8 66 4.3
     2018 159 12.6 64 13.2 621 39.1
     2019 637 50.4 233 48.0 622 39.1
     2020 108 16.5 87 17.9 281 17.7
    就诊季节 7.8 0.051 45.9 < 0.001
     春季(3 — 5月) 319 25.2 135 27.8 337 21.2
     夏季(6 — 8月) 175 13.8 86 17.7 355 22.3
     秋季(9 — 11月) 390 30.9 125 25.8 528 33.2
     冬季(12、1、2月) 380 30.1 139 28.7 370 23.3
    疫苗接种史
     PPV23 68 5.4 33 6.8 1.3 0.253 93 5.8 0.3 0.589
     DTaP 1 256 99.4 479 98.8 1.6 0.204 1162 73.1 375.9 < 0.001
     Hib 280 22.2 110 22.7 0.1 0.812 310 20.7 0.9 0.347
     流感疫苗 90 7.1 20 6.2 0.5 0.489 169 10.6 11.3 0.003
    PPV23平均接种时长(年) 2.07 ± 1.61 2.13 ± 1.84 2.68 ± 2.41
     2~5 1.32 ± 1.12 0.95 ± 0.61 0.98 ± 0.69
     6~9 3.64 ± 1.33 4.49 ± 0.96 5.04 ± 1.89
    下载: 导出CSV

    表  2  病例组与对照组研究对象临床特征

    Table  2.   Diagnosis at discharge, the highest temperature, clinical symptoms, and treatment for 3 339 ARI children – 1 264 cases (vaccine serotype Spn positive), 485 NVT controls (non-vaccine serotype Spn positive), and 1 590 Spn negative controls recruited in a hospital during 2017 – 2020 in Suzhou city

    临床特征病例组(N = 1 264)NVT对照组(N = 485)χ2PSpn-对照组(N = 1 590)χ2P
    病例数%病例数%病例数%
    出院主诊断18.30.00352.7 < 0.001
     CAP a1 10887.743389.31 43890.4
     支气管炎564.4275.6603.8
     上呼吸道感染 b282.2122.5311.9
     哮喘90.751.0422.6
     脓毒血症594.751.0161.0
     其他 c40.330.630.2
    热峰(℃)0.80.66428.2 < 0.001
     < 3919315.37214.832820.6
     39~4079162.630262.385053.5
     > 4014511.5479.71197.5
     未发热13510.76413.229318.4
    临床症状
     咳嗽1 25599.348199.20.10.8061 56998.72.50.113
     咽痛1 74199.548399.60.00.8631 58899.93.10.080
     流涕63850.523147.61.10.28746729.4132.2 < 0.001
     气促443.5153.10.20.687996.211.2 < 0.001
     气短/呼吸困难40.320.40.10.763161.04.80.028
     哮喘/喘息23518.69519.60.20.63441926.424.0 < 0.001
     喂养困难00.000.0--30.23.50.061
     烦躁00.000.0--50.35.90.016
     呕吐28622.610020.60.80.36529318.47.70.060
     抽搐151.261.20.00.93170.45.10.024
    肺部听诊
     无异常171.351.00.30.598110.73.10.079
     异常呼吸音1 22296.747197.10.20.6431 56798.611.1 < 0.001
     干啰音332.681.61.40.234211.36.30.012
     湿啰音46236.618538.10.40.53764540.64.80.029
     痰鸣音23218.410321.21.90.17025015.73.50.062
     喘鸣音23019.010822.32.40.12438624.311.5 < 0.001
    治疗
     吸氧372.9122.50.30.607905.712.4 < 0.001
     转入ICU171.351.00.30.59820.115.8 < 0.001
      注:aCAP:定义为出院诊断ICD编码中含有J09-J18(流感和肺炎)或J20-J22(其他重症下呼吸道感染);b上呼吸道感染:包括鼻窦炎、扁桃体炎、喉炎、喉气管炎;c其他诊断:包括脑炎、传染性单核细胞增多症、EB病毒感染、心肌病、肺挫伤。
    下载: 导出CSV

    表  3  PPV23对儿童肺炎球菌疾病的保护效果

    Table  3.   Effectiveness of PPV23 against pneumococcal disease by age, diagnosis of community acquired pneumonia, and vaccine serotype of Spn infection in ARI children tested positive/negative for vaccine serotype Spn and negative to Spn: a test-negative design study in Suzhou city

    研究对象病例组NVT对照VE(%)(95%CISpn-对照VE(%)(95%CI
    N接种ppv23N接种ppv23N接种ppv23
    n%n%n%
    所有儿童 1 264 68 5.4 485 33 6.8 18.3( – 26.3~47.1) 1 590 93 5.8 – 10.1( – 70.6~28.9)
    年龄(岁)
     2~5 1 067 46 4.3 386 22 5.7 26.0( – 25.6~56.3) 1 057 54 5.1 29.9( – 22.0~59.7)
     6~9 197 22 11.2 99 11 11.1 7.6( – 101.8~57.7) 533 39 7.3 – 157.2( – 479.7~14.1)
    疾病
     CAP 1 108 62 5.6 433 29 6.7 15.7( – 33.5~46.7) 1 438 81 5.6 – 22.1( – 93.4~23.0)
     非CAP 156 6 3.8 52 4 7.7 38.6( – 150.7~84.9) 152 12 7.9 73.3( – 40.4~94.9)
    特定血清型
     19F 564 25 4.4 485 33 6.8 32.8( – 15.5~60.9) 1 590 93 5.8 2.7( – 71.3~44.8)
     6B 245 14 5.7 485 33 6.8 16.5( – 60.3~56.5) 1 590 93 5.8 – 37.2( – 177.9~32.3)
     23F 171 13 7.6 485 33 6.8 – 22.1( – 140.3~37.9) 1 590 93 5.8 – 98.8( – 334.6~-9.0)
     19A 125 8 6.4 485 33 6.8 – 8.6( – 148.3~52.5) 1 590 93 5.8 – 89.2( – 370.9~24.0)
     14 76 6 7.9 485 33 6.8 – 32.3( – 231.0~47.1) 1 590 93 5.8 – 12.7( – 322.9~70.0)
     15B 35 1 2.9 485 33 6.8 57.5( – 222.8~94.4) 1 590 93 5.8 46.6( – 314.4~93.1)
     其他VT 48 1 2.1 485 33 6.8 69.3( – 136.1~96.0) 1 590 93 5.8 47.0( – 322.9~93.3)
    下载: 导出CSV
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  • 接收日期:  2023-03-28
  • 录用日期:  2023-10-09
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