美国儿童健康肺炎病原学（PERCH）研究组最近分析了亚洲和非洲未感染艾滋病毒的儿童需住院治疗的重症肺炎的病因。 该项研究成果发表在2019年8月30日出版的《柳叶刀》上。

研究人员在孟加拉国、冈比亚、肯尼亚、马里、南非、泰国和赞比亚等7个国家的9个研究地点进行了多地点的国际病例对照研究。病患组为1 ~ 59个月因重症肺炎而住院的儿童。对照组是从周围社区中随机选择的年龄匹配的儿童。分别采用细菌培养或多重PCR（或两者兼用）对受试者的鼻咽和口咽（NP-OP）拭子、尿液、血液、诱导痰、肺吸液、胸膜液和胃吸液等标本进行检测。

2011年8月15日至2014年1月30日，研究团队共登记了4232例患儿和5119例社区对照儿。病患组中有1769例（41.8%）患儿未感染艾滋病毒但胸片呈阳性，对照组中有5102例儿童（99.7%）未感染艾滋病毒。1752例患儿中有555例（31.7%）出现喘息。1769例患儿中有114例30天内病死（6.4%）。1749例患儿中有56例（3.2%）血培养阳性，其中肺炎链球菌是最常见的分离菌（19例，33.9%）。

几乎所有患儿（98.9%）和对照组（98.0%）均至少在NP-OP标本中检测到一种病原体。NP-OP标本中检测到的呼吸道合胞病毒（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型流感嗜血杆菌和卡氏肺囊虫与患者状况有关。病原学分析估计，病毒占病因的61.4%，细菌占27.3%，结核分枝杆菌占5.9%。

与重症肺炎相比，超重症肺炎患儿中病毒较少见（54.5% vs 68.0%），细菌较常见（33.7% vs 22.8%）。其中RSV在所有病原体中的致病率最高（31.1%）。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因学分布的5%或更多。百日咳博德特氏菌、1型和3型副流感病毒、双埃可病毒-肠病毒、卡氏肺囊虫、RSV、鼻病毒、金黄色葡萄球菌和肺炎链球菌的发病率随年龄出现差异，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亦存在差异。每个研究地点前十种病原体约占该点病因学分布的79%及以上。

该研究表明大多数需要住院的肺炎病例是由一小部分病原体导致的。对这部分病原体进行防治可在很大程度上改善儿童肺炎的预后。

附：英文原文

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

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

Issue&Volume: Volume 394 Number 10200,30 August 2019

Summary:

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% (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.

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.

DOI: https://doi.org/10.1016/S0140-6736(19)30721-4

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30721-4/fulltext