Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study
Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study
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DOI：
10.1016/s0140-6736(19)30721-4
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发表时间：
2019-08-31
期刊：
影响因子：
168.9
通讯作者：
Mitchell, Joanne L.
中科院分区：
文献类型：
--
作者：
O'Brien, Katherine L.;Levine, Orin S.;Mitchell, Joanne L.
背景肺炎是5岁以下儿童死亡的主要原因。在这项研究中，我们使用应用于临床和微生物学发现的新型分析方法估计了非洲和亚洲幼儿肺炎的原因。方法我们在七个国家的九个研究地点进行了一项多地点、国际病例对照研究：孟加拉国、冈比亚、肯尼亚、马里、南非、泰国和赞比亚。所有临床试验机构入组研究24个月。病例为1至59个月的儿童，因严重肺炎入院。对照组是从研究地点周围的社区随机选择的年龄组匹配的儿童。鼻咽和口咽（NP-OP）、尿液、血液、诱导痰、肺抽吸物、胸膜液和胃抽吸物均采用培养物、多重PCR或两者进行检测。初步分析仅限于无HIV感染和胸部X线检查异常的病例以及无HIV感染的对照组。我们应用贝叶斯，部分潜在类分析，估计在个人和人口水平的病原体的概率，将病例和对照data.Findings之间的2011年8月15日，2014年1月30日，我们招募了4232例和5119社区控制。主要分析组包括1769例（41.8%的4232）无HIV感染且胸部X线检查阳性的病例和5102例（99.7%的5119）无HIV感染的社区对照。1752例病例中有555例（31.7%）存在喘鸣（部位范围10.6-97.3%）。30-日病死率为6.4%（114/1769例）。1749例病例中56例（3.2%）血培养阳性，肺炎链球菌是最常见的细菌分离株（19/56 [33.9%]）。几乎所有病例（98.9%）和对照（98.0%）在NP-OP标本中通过PCR检测到至少一种病原体。NP-OP标本中呼吸道合胞病毒（RSV）、副流感病毒、人偏肺病毒、流感病毒、肺炎链球菌、B型流感嗜血杆菌（HiB）、非B型流感嗜血杆菌和耶氏肺孢子虫的检出与病例状态相关。病原学分析估计病毒占61.4%（95%可信区间[CrI] 57.3-65.6），而细菌占27.3%（2.3-31.6），结核分枝杆菌占5.9%（3.9-8.3）。与重症病例相比，极重症肺炎病例中病毒较不常见（54.5%，95%CrI 47.4-61.5 vs 68.0%，62.7-72.7），细菌较常见（33.7%，27.2-40.8 vs 22.8%，18.3-27.6）。RSV在所有病原体中具有最大的病原学分数（31.1%，95%CrI 28.4-34.2）。人鼻病毒、人偏肺病毒A或B、人副流感病毒、肺炎链球菌、结核分枝杆菌和流感嗜血杆菌各占病原学分布的5%或以上。我们观察到百日咳博德特氏菌、1型和3型副流感病毒、肠道副埃柯病毒、耶氏肺孢子虫、RSV、鼻病毒、金黄色葡萄球菌和肺炎链球菌的病原学分数随年龄的差异，以及RSV、金黄色葡萄球菌、肺炎链球菌和3型副流感病毒的严重程度的差异。每个站点的前10个病原体占该站点的病因fraction.Interpretation的79%或更多在我们的研究中，一小部分病原体占大多数需要住院的肺炎病例。预防和治疗病原体的一个子集可以大大影响儿童肺炎的结果。版权所有（C）2019作者。爱思唯尔有限公司出版
Background Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings.Methods We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1-59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data.Findings Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41.8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99.7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31.7%) of 1752 cases (range by site 10.6-97.3%). 30-day case-fatality ratio was 6.4% (114 of 1769 cases). Blood cultures were positive in 56 (3.2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33.9%] of 56). Almost all cases (98.9%) and controls (98.0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61.4% (95% credible interval [CrI] 57.3-65.6) of causes, whereas bacteria accounted for 27.3% (2.3-31.6) and Mycobacterium tuberculosis for 5.9% (3.9-8.3). Viruses were less common (54.5%, 95% CrI 47.4-61.5 vs 68.0%, 62.7-72.7) and bacteria more common (33.7%, 27.2-40.8 vs 22.8%, 18.3-27.6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31.1%, 95% CrI 28.4-34.2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus-enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction.Interpretation In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.