背景下呼吸道感染(LRTI)是全球婴儿发病和死亡的主要原因。LRTI可能由病毒或细菌感染引起,单独或组合。我们调查了南非出生队列中LRTI与婴儿鼻咽(NP)病毒和细菌之间的关联。方法在Drakenstein儿童健康研究(DCHS)的婴儿的病例对照研究中,对LRTI病例进行前瞻性鉴定,并与队列中的对照组进行年龄匹配。使用定量实时聚合酶链反应(qPCR)和16SrRNA基因扩增子测序测试NP拭子。我们计算了qPCR靶标的调整后条件赔率比(aOR),并使用混合效应模型来识别LRTI病例和对照之间的差异丰富分类单元,并探索病毒-细菌相互作用。结果呼吸道合胞病毒(RSV)[aOR:5.69,95%CI:3.03-10.69],人鼻病毒(HRV)[1.47,1.03-2.09],副流感病毒[3.46,1.64-7.26],腺病毒[1.99,1.08-3.68],肠道病毒[2.32,1.20-4.46],流感嗜血杆菌[1.72,1.25-2.37],肺炎克雷伯菌[2.66,1.59-4.46],或高密度(>6.9log10拷贝/mL)肺炎链球菌[1.53,1.01-2.32]与LRTI相关。使用16S测序,LRTI与嗜血杆菌的相对丰度增加(q=0.0003)和Dolosigranulum的相对丰度减少(q=0.001)相关,棒杆菌(q=0.091)和奈瑟菌(q=0.004)。在RSV阳性的样本中,在病例中,葡萄球菌和Alloprevotella的相对丰度低于对照组。在副流感病毒或HRV阳性的样本中,病例中嗜血杆菌的相对丰度较高。结论细菌分类群和LRTI之间的关联与高收入国家中发现的关联非常相似,提示一种保守的表型。RSV是与LRTI相关的主要病毒。流感嗜血杆菌似乎是LRTI的主要细菌驱动因素,与病毒协同作用。革兰氏阳性菌Dolosigranulum和棒状杆菌可以预防LRTI,而葡萄球菌与RSV相关LRTI风险降低相关。资助美国国立卫生研究院,比尔和梅林达·盖茨基金会,南非国家研究基金会,南非医学研究理事会,L\'Oréal-UNESCOforWomeninScienceSouthAfrica,澳大利亚国家健康与医学研究委员会。
UNASSIGNED: Lower respiratory tract infection (LRTI) is a leading cause of infant morbidity and mortality globally. LRTI may be caused by viral or bacterial infections, individually or in combination. We investigated associations between LRTI and infant
nasopharyngeal (NP) viruses and bacteria in a South African birth cohort.
UNASSIGNED: In a case-control study of infants enrolled in the Drakenstein Child Health Study (DCHS), LRTI cases were identified prospectively and age-matched with controls from the cohort. NP swabs were tested using quantitative real-time polymerase chain reaction (qPCR) and 16S rRNA gene amplicon sequencing. We calculated adjusted Conditional Odds Ratios (aORs) for qPCR targets and used mixed effects models to identify differentially abundant taxa between LRTI cases and controls and explore viral-bacterial interactions.
UNASSIGNED: Respiratory Syncytial Virus (RSV) [aOR: 5.69, 95% CI: 3.03-10.69], human rhinovirus (HRV) [1.47, 1.03-2.09], parainfluenza virus [3.46, 1.64-7.26], adenovirus [1.99, 1.08-3.68], enterovirus [2.32, 1.20-4.46], Haemophilus influenzae [1.72, 1.25-2.37], Klebsiella pneumoniae [2.66, 1.59-4.46], or high-density (> 6.9 log10 copies/mL) Streptococcus pneumoniae [1.53, 1.01-2.32] were associated with LRTI. Using 16S sequencing, LRTI was associated with increased relative abundance of Haemophilus (q = 0.0003) and decreased relative abundance of Dolosigranulum (q = 0.001), Corynebacterium (q = 0.091) and Neisseria (q = 0.004). In samples positive for RSV, Staphylococcus and Alloprevotella were present at lower relative abundance in cases than controls. In samples positive for parainfluenza virus or HRV, Haemophilus was present at higher relative abundance in cases.
UNASSIGNED: The associations between bacterial taxa and LRTI are strikingly similar to those identified in high-income countries, suggesting a conserved phenotype. RSV was the major virus associated with LRTI. H. influenzae appears to be the major bacterial driver of LRTI, acting synergistically with viruses. The Gram-positive bacteria Dolosigranulum and Corynebacteria may protect against LRTI, while Staphylococcus was associated with reduced risk of RSV-related LRTI.
UNASSIGNED: National Institutes of Health of the USA, Bill and Melinda Gates Foundation, National Research Foundation South Africa, South African Medical Research Council, L\'Oréal-UNESCO For Women in Science South Africa, Australian National Health and Medical Research Council.