Aetiology of childhood pneumonia in a well vaccinated South African birth cohort: a nested case-control study of the Drakenstein Child Health Study.
Aetiology of childhood pneumonia in a well vaccinated South African birth cohort: a nested case-control study of the Drakenstein Child Health Study.
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DOI：
10.1016/s2213-2600(16)00096-5
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Nicol MP
中科院分区：
文献类型：
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作者：
Zar HJ;Barnett W;Stadler A;Gardner-Lubbe S;Myer L;Nicol MP
肺炎是全球儿童死亡和发病的主要原因。在低收入和中等收入国家，引入13价肺炎球菌结合疫苗（PCV 13）后的肺炎原因尚未得到充分研究，大多数数据来自住院儿童的横断面研究。我们的目的是纵向调查南非出生队列儿童肺炎的发病率和原因。我们在Drakenstein儿童健康研究中对2012年5月29日至2014年12月1日发生肺炎的儿童进行了巢式病例对照研究。儿童接受了包括无细胞百日咳疫苗和PCV 13在内的免疫接种。一个嵌套亚组在整个婴儿期每2周采集一次鼻咽拭子。我们确定了肺炎发作，并收集了血液、鼻咽拭子和诱导痰标本。我们采用多重实时PCR检测肺炎病例的鼻咽拭子和诱导痰以及年龄匹配和地点匹配的对照的鼻咽拭子中的病原体。为了显示微生物与肺炎之间的关联，我们使用了条件logistic回归;结果以比值比（OR）和95% CI表示。在1145个儿童年的随访中，967名儿童发生了314例肺炎病例（发病率为0.27次/儿童年，95% CI 0.24 - 0.31;中位年龄5个月[IQR 3-9]）。60例（21%）肺炎为重度（发病率0.05次/儿童年[95%CI 0.04 - 0.07]），病死率为1%（3例死亡）。病例和对照组鼻咽拭子中检出的微生物中位数为5个（IQR 4-6），诱导痰中记录的微生物中位数为6个（4-7）（与鼻咽拭子相比，p= 0.48）。百日咳杆菌（OR 11.08，95% CI 1.33 - 92.54）、呼吸道合胞病毒（8.05，4.21 - 15.38）或流感病毒（4.13，2.06 - 8.26）与肺炎的相关性最强;博卡病毒、腺病毒、副流感病毒、流感嗜血杆菌和巨细胞病毒也与肺炎相关。在病例中，除鼻咽拭子外，诱导痰的检测为B型百日咳和几种病毒的检测提供了增量。肺炎在这个高度接种疫苗的人群中仍然很常见。呼吸道合胞病毒是最常检测到的与肺炎相关的病原体;流感病毒和B型百日咳也与肺炎密切相关。诱导痰的检测增加了几种微生物的检出率。需要新的疫苗和战略来解决儿童肺炎的负担。，和。
Pneumonia is a leading cause of mortality and morbidity in children globally. The cause of pneumonia after introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) has not been well studied in low-income and middle-income countries, and most data are from cross-sectional studies of children admitted to hospital. We aimed to longitudinally investigate the incidence and causes of childhood pneumonia in a South African birth cohort. We did a nested case-control study of children in the Drakenstein Child Health Study who developed pneumonia from May 29, 2012, to Dec 1, 2014. Children received immunisations including acellular pertussis vaccine and PCV13. A nested subgroup had nasopharyngeal swabs collected every 2 weeks throughout infancy. We identified pneumonia episodes and collected blood, nasopharyngeal swabs, and induced sputum specimens. We used multiplex real-time PCR to detect pathogens in nasopharyngeal swabs and induced sputum of pneumonia cases and in nasopharyngeal swabs of age-matched and site-matched controls. To show associations between organisms and pneumonia we used conditional logistic regression; results are presented as odds ratios (ORs) with 95% CIs. 314 pneumonia cases occurred (incidence of 0·27 episodes per child-year, 95% CI 0·24–0·31; median age 5 months [IQR 3–9]) in 967 children during 1145 child-years of follow-up. 60 (21%) cases of pneumonia were severe (incidence 0·05 episodes per child-year [95% CI 0·04–0·07]) with a case fatality ratio of 1% (three deaths). A median of five organisms (IQR 4–6) were detected in cases and controls with nasopharyngeal swabs, and a median of six organisms (4–7) recorded in induced sputum (p=0·48 compared with nasopharyngeal swabs). Bordetella pertussis (OR 11·08, 95% CI 1·33–92·54), respiratory syncytial virus (8·05, 4·21–15·38), or influenza virus (4·13, 2·06–8·26) were most strongly associated with pneumonia; bocavirus, adenovirus, parainfluenza virus, Haemophilus influenzae, and cytomegalovirus were also associated with pneumonia. In cases, testing of induced sputum in addition to nasopharyngeal swabs provided incremental yield for detection of B pertussis and several viruses. Pneumonia remains common in this highly vaccinated population. Respiratory syncytial virus was the most frequently detected pathogen associated with pneumonia; influenza virus and B pertussis were also strongly associated with pneumonia. Testing of induced sputum increases the yield for detection of several organisms. New vaccines and strategies are needed to address the burden of childhood pneumonia. , , , , and .