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[Lancet在线发表]:亚洲和非洲HIV阴性重症肺炎住院患儿的病因:PERCH多国病例对照研究
2019年07月15日 时讯速递, 进展交流 暂无评论

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Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study

The Pneumonia Etiology Research for Child Health (PERCH) Study Group

Lancet Published: June 27, 2019 DOI:https://doi.org/10.1016/S0140-6736(19)30721-4

Summary

Background 背景

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.

肺炎是5岁以上儿童的首要死因。我们将新的分析方法用于临床和微生物学,对非洲和亚洲儿童肺炎的病因进行了研究。

Methods 方法

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.

我们在7个国家(孟加拉国,冈比亚,肯尼亚,马里,南非,泰国和赞比亚)的9个研究中心进行了一项多国、病例对照研究。所有参研中心在24个月的研究期间入选病例。病例为因重症肺炎住院的年龄在1-59个月的儿童。对照组为从参研中心周围社区中随机挑选的年龄组匹配的儿童。对鼻咽部和口咽部(NP-OP)、尿液、血液、诱导痰、肺吸取物、胸水及胃吸取物等标本进行培养和(或)多重PCR。主要分析限于无HIV感染且胸片异常的病例,以及无HIV感染的对照。我们根据采用病例组和对照组数据,Baysien部分潜类别分析评估个体及群体水平各种病原微生物的概率。

Findings 结果

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% (23·3–31·6) 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.

2011年8月15日至2014年1月30日间,我们共纳入4232名病例和5119名对照。主要分析组由无HIV感染且胸片异常的1769名病例(4232名病例的41·8%)和5102名无HIV感染的对照(5119名对照的99·7%)组成。1752名病例中的555名(31·7%)患者有喘鸣(各中心罹患率 10·6–97·3%)。30天病死率为6·4% (114/1769)。1749名病例中56名(3·2%)血培养阳性,肺炎链球菌是最常见的细菌(19/56 [33·9%])。几乎所有病例(98·9%)及对照(98·0%)的NP-OP标本PCR检测至少检测到一种微生物。病例组NP-OP标本检出呼吸道合胞病毒(RSV)、副流感病毒、人偏肺病毒、流感病毒、肺炎链球菌、流感嗜血杆菌b型(Hib)、流感嗜血杆菌非b型和肺孢子虫。病因学分析提示,病毒占61·4% (95% 可信区间 [CrI] 57·3–65·6),细菌占27·3% (23·3–31·6),结核分枝杆菌占5·9% (3·9–8·3)。与重症病例相比,最严重肺炎组病毒较少(54·5%, 95% CrI 47·4–61·5 vs 68·0%, 62·7–72·7),细菌更为常见(33·7%, 27·2–40·8 vs 22·8%, 18·3–27·6)。在所有病原微生物中,RSV比例最高(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分别占5% 或更多。我们发现,不同年龄组患儿百日咳杆菌、副流感病毒1和3型、双埃可病毒—肠道病毒、肺孢子虫、鼻病毒、金黄色葡萄球菌和肺炎链球菌比例不同,且病情严重程度不同时,RSV、金黄色葡萄球菌、肺炎链球菌和副流感病毒3型的比例不同。各个中心最常见的10中病原微生物占所有病原微生物的79%或更多。

Interpretation 结论

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.

本研究显示,少数微生物占需要住院治疗的肺炎病例中大部分。预防并治疗这些微生物可能显著影响肺炎患儿的预后。

Funding

Bill & Melinda Gates Foundation.

评论[仅代表个人观点]

  • 重症社区获得性肺炎是ICU的常见病之一
  • ICU医生应当熟知重症社区获得性肺炎的常见病原微生物
  • 了解常见病原微生物真的能够改变滥用广谱抗生素的现状吗?对此深表怀疑
  • 碳青霉烯、糖肽类及噁唑烷酮等针对耐药菌的抗生素不应该成为治疗重症社区获得性肺炎的常规用药

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