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Abstract：
BACKGROUND: Chronic lung disease is a major cause of morbidity in African children with HIV infection; however, the microbial determinants of HIV-associated chronic lung disease (HCLD) remain poorly understood. We conducted a case-control study to investigate the prevalence and densities of respiratory microbes among pneumococcal conjugate vaccine (PCV)-naive children with (HCLD +) and without HCLD (HCLD-) established on antiretroviral treatment (ART).
METHODS: Nasopharyngeal swabs collected from HCLD + (defined as forced-expiratory-volume/second < -1.0 without reversibility postbronchodilation) and age-, site-, and duration-of-ART-matched HCLD- participants aged between 6-19 years enrolled in Zimbabwe and Malawi (BREATHE trial-NCT02426112) were tested for 94 pneumococcal serotypes together with twelve bacteria, including Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), Moraxella catarrhalis (MC), and eight viruses, including human rhinovirus (HRV), respiratory syncytial virus A or B, and human metapneumovirus, using nanofluidic qPCR (Standard BioTools formerly known as Fluidigm). Fisher\'s exact test and logistic regression analysis were used for between-group comparisons and risk factors associated with common respiratory microbes, respectively.
RESULTS: A total of 345 participants (287 HCLD + , 58 HCLD-; median age, 15.5 years [IQR = 12.8-18], females, 52%) were included in the final analysis. The prevalence of SP (40%[116/287] vs. 21%[12/58], p = 0.005) and HRV (7%[21/287] vs. 0%[0/58], p = 0.032) were higher in HCLD + participants compared to HCLD- participants. Of the participants positive for SP (116 HCLD + & 12 HCLD-), 66% [85/128] had non-PCV-13 serotypes detected. Overall, PCV-13 serotypes (4, 19A, 19F: 16% [7/43] each) and NVT 13 and 21 (9% [8/85] each) predominated. The densities of HI (2 × 104 genomic equivalents [GE/ml] vs. 3 × 102 GE/ml, p = 0.006) and MC (1 × 104 GE/ml vs. 1 × 103 GE/ml, p = 0.031) were higher in HCLD + compared to HCLD-. Bacterial codetection (≥ any 2 bacteria) was higher in the HCLD + group (36% [114/287] vs. (19% [11/58]), (p = 0.014), with SP and HI codetection (HCLD + : 30% [86/287] vs. HCLD-: 12% [7/58], p = 0.005) predominating. Viruses (predominantly HRV) were detected only in HCLD + participants. Lastly, participants with a history of previous tuberculosis treatment were more likely to carry SP (adjusted odds ratio (aOR): 1.9 [1.1 -3.2], p = 0.021) or HI (aOR: 2.0 [1.2 - 3.3], p = 0.011), while those who used ART for ≥ 2 years were less likely to carry HI (aOR: 0.3 [0.1 - 0.8], p = 0.005) and MC (aOR: 0.4 [0.1 - 0.9], p = 0.039).
CONCLUSIONS: Children with HCLD + were more likely to be colonized by SP and HRV and had higher HI and MC bacterial loads in their nasopharynx. The role of SP, HI, and HRV in the pathogenesis of CLD, including how they influence the risk of acute exacerbations, should be studied further.
BACKGROUND: The BREATHE trial (ClinicalTrials.gov Identifier: NCT02426112 , registered date: 24 April 2015).
METHODS: Nasopharyngeal swabs collected from HCLD + (defined as forced-expiratory-volume/second < -1.0 without reversibility postbronchodilation) and age-, site-, and duration-of-ART-matched HCLD- participants aged between 6-19 years enrolled in Zimbabwe and Malawi (BREATHE trial-NCT02426112) were tested for 94 pneumococcal serotypes together with twelve bacteria, including Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), Moraxella catarrhalis (MC), and eight viruses, including human rhinovirus (HRV), respiratory syncytial virus A or B, and human metapneumovirus, using nanofluidic qPCR (Standard BioTools formerly known as Fluidigm). Fisher\'s exact test and logistic regression analysis were used for between-group comparisons and risk factors associated with common respiratory microbes, respectively.
RESULTS: A total of 345 participants (287 HCLD + , 58 HCLD-; median age, 15.5 years [IQR = 12.8-18], females, 52%) were included in the final analysis. The prevalence of SP (40%[116/287] vs. 21%[12/58], p = 0.005) and HRV (7%[21/287] vs. 0%[0/58], p = 0.032) were higher in HCLD + participants compared to HCLD- participants. Of the participants positive for SP (116 HCLD + & 12 HCLD-), 66% [85/128] had non-PCV-13 serotypes detected. Overall, PCV-13 serotypes (4, 19A, 19F: 16% [7/43] each) and NVT 13 and 21 (9% [8/85] each) predominated. The densities of HI (2 × 104 genomic equivalents [GE/ml] vs. 3 × 102 GE/ml, p = 0.006) and MC (1 × 104 GE/ml vs. 1 × 103 GE/ml, p = 0.031) were higher in HCLD + compared to HCLD-. Bacterial codetection (≥ any 2 bacteria) was higher in the HCLD + group (36% [114/287] vs. (19% [11/58]), (p = 0.014), with SP and HI codetection (HCLD + : 30% [86/287] vs. HCLD-: 12% [7/58], p = 0.005) predominating. Viruses (predominantly HRV) were detected only in HCLD + participants. Lastly, participants with a history of previous tuberculosis treatment were more likely to carry SP (adjusted odds ratio (aOR): 1.9 [1.1 -3.2], p = 0.021) or HI (aOR: 2.0 [1.2 - 3.3], p = 0.011), while those who used ART for ≥ 2 years were less likely to carry HI (aOR: 0.3 [0.1 - 0.8], p = 0.005) and MC (aOR: 0.4 [0.1 - 0.9], p = 0.039).
CONCLUSIONS: Children with HCLD + were more likely to be colonized by SP and HRV and had higher HI and MC bacterial loads in their nasopharynx. The role of SP, HI, and HRV in the pathogenesis of CLD, including how they influence the risk of acute exacerbations, should be studied further.
BACKGROUND: The BREATHE trial (ClinicalTrials.gov Identifier: NCT02426112 , registered date: 24 April 2015).
摘要：
背景：慢性肺病是感染艾滋病毒的非洲儿童发病的主要原因；然而，HIV相关慢性肺病(HCLD)的微生物决定因素仍然知之甚少.我们进行了一项病例对照研究，以调查在抗逆转录病毒治疗（ART）上建立的肺炎球菌结合疫苗（PCV）初治儿童（HCLD）和无HCLD（HCLD-）的呼吸道微生物的患病率和密度。
方法：从HCLD收集的鼻咽拭子（定义为支气管扩张后无可逆性的用力呼气量/秒<-1.0）和年龄-，Site-,在津巴布韦和马拉维（BREATHE试验-NCT02426112）招募的年龄在6-19岁之间的参与者进行了94种肺炎球菌血清型和12种细菌的检测，包括肺炎链球菌（SP），金黄色葡萄球菌(SA),流感嗜血杆菌(HI),卡他莫拉氏菌（MC），和八种病毒，包括人鼻病毒（HRV），呼吸道合胞病毒A或B，和人类偏肺病毒，使用纳米流体qPCR（以前称为Fluidigm的标准BioTools）。Fisher精确检验和logistic回归分析用于组间比较和与常见呼吸道微生物相关的危险因素。分别。
结果：共有345名参与者（287HCLD+，58HCLD-；中位年龄，15.5年[IQR=12.8-18]，女性,52%)包括在最终分析中。SP的患病率(40%[116/287]与21%[12/58]，p=0.005）和HRV（7%[21/287]与0%[0/58]，p=0.032）与HCLD-参与者相比，HCLD+参与者更高。在SP呈阳性的参与者中(116HCLD+和12HCLD-)，66%[85/128]检测到非PCV-13血清型。总的来说,PCV-13血清型（4，19A，19F：各16%[7/43]）和NVT13和21（各9%[8/85]）占主导地位。HI的密度（2×104基因组当量[GE/ml]与3×102GE/ml，p=0.006）和MC（1×104GE/mlvs.1×103GE/ml，p=0.031）在HCLD+中高于HCLD-。HCLD+组的细菌共检测（≥2种细菌）较高（36%[114/287]vs.（19%[11/58]），（p=0.014），SP和HI共检测(HCLD+：30%[86/287]与HCLD-：12%[7/58]，p=0.005）占优势。仅在HCLD+参与者中检测到病毒(主要是HRV)。最后,既往有结核病治疗史的参与者更有可能携带SP（校正比值比（AOR）：1.9[1.1-3.2]，p=0.021)或HI(AOR:2.0[1.2-3.3]，p=0.011),而那些使用ART≥2年的人不太可能携带HI(aOR：0.3[0.1-0.8]，p=0.005)和MC(aOR：0.4[0.1-0.9]，p=0.039)。
结论：HCLD+患儿更容易被SP和HRV定植，鼻咽部HI和MC细菌负荷较高。SP的作用,HI,和HRV在CLD发病机制中，包括它们如何影响急性加重的风险，应该进一步研究。
背景：BREATHE试验（ClinicalTrials.gov标识符：NCT02426112，注册日期：2015年4月24日）。
方法：从HCLD收集的鼻咽拭子（定义为支气管扩张后无可逆性的用力呼气量/秒<-1.0）和年龄-，Site-,在津巴布韦和马拉维（BREATHE试验-NCT02426112）招募的年龄在6-19岁之间的参与者进行了94种肺炎球菌血清型和12种细菌的检测，包括肺炎链球菌（SP），金黄色葡萄球菌(SA),流感嗜血杆菌(HI),卡他莫拉氏菌（MC），和八种病毒，包括人鼻病毒（HRV），呼吸道合胞病毒A或B，和人类偏肺病毒，使用纳米流体qPCR（以前称为Fluidigm的标准BioTools）。Fisher精确检验和logistic回归分析用于组间比较和与常见呼吸道微生物相关的危险因素。分别。
结果：共有345名参与者（287HCLD+，58HCLD-；中位年龄，15.5年[IQR=12.8-18]，女性,52%)包括在最终分析中。SP的患病率(40%[116/287]与21%[12/58]，p=0.005）和HRV（7%[21/287]与0%[0/58]，p=0.032）与HCLD-参与者相比，HCLD+参与者更高。在SP呈阳性的参与者中(116HCLD+和12HCLD-)，66%[85/128]检测到非PCV-13血清型。总的来说,PCV-13血清型（4，19A，19F：各16%[7/43]）和NVT13和21（各9%[8/85]）占主导地位。HI的密度（2×104基因组当量[GE/ml]与3×102GE/ml，p=0.006）和MC（1×104GE/mlvs.1×103GE/ml，p=0.031）在HCLD+中高于HCLD-。HCLD+组的细菌共检测（≥2种细菌）较高（36%[114/287]vs.（19%[11/58]），（p=0.014），SP和HI共检测(HCLD+：30%[86/287]与HCLD-：12%[7/58]，p=0.005）占优势。仅在HCLD+参与者中检测到病毒(主要是HRV)。最后,既往有结核病治疗史的参与者更有可能携带SP（校正比值比（AOR）：1.9[1.1-3.2]，p=0.021)或HI(AOR:2.0[1.2-3.3]，p=0.011),而那些使用ART≥2年的人不太可能携带HI(aOR：0.3[0.1-0.8]，p=0.005)和MC(aOR：0.4[0.1-0.9]，p=0.039)。
结论：HCLD+患儿更容易被SP和HRV定植，鼻咽部HI和MC细菌负荷较高。SP的作用,HI,和HRV在CLD发病机制中，包括它们如何影响急性加重的风险，应该进一步研究。
背景：BREATHE试验（ClinicalTrials.gov标识符：NCT02426112，注册日期：2015年4月24日）。
