Skip to main content
Top
Published in: BMC Infectious Diseases 1/2021

Open Access 01-12-2021 | Adenovirus | Research article

Broad range detection of viral and bacterial pathogens in bronchoalveolar lavage fluid of children to identify the cause of lower respiratory tract infections

Authors: Heping Wang, Jiali Gu, Xiaonan Li, Christa E. van der Gaast-de Jongh, Wenjian Wang, Xuehui He, Zhi Xu, Yonghong Yang, Ronald de Groot, Marien I. de Jonge, Yuejie Zheng

Published in: BMC Infectious Diseases | Issue 1/2021

Login to get access

Abstract

Background

Knowledge on the etiology of LRTIs is essential for improvement of the clinical diagnosis and accurate treatment. Molecular detection methods were applied to identify a broad range of bacterial and viral pathogens in a large set of bronchial alveolar lavage (BAL) fluid samples. The patterns of detected pathogens were correlated to the clinical symptoms.

Methods

BAL fluid samples and clinical data were collected from 573 hospitalized children between 1 month and 14 years of age with LRTIs, enrolled from January to December 2018. Pathogens were detected using standardized clinical diagnostics, with a sensitive, high-throughput GeXP-based multiplex PCR and with multiplex qPCR. Data were analyzed to describe the correlation between the severity of respiratory tract disease and the pathogens identified.

Results

The pathogen detection rate with GeXP-based PCR and multiplex qPCR was significantly higher than by clinical routine diagnostics (76.09% VS 36.13%,χ2 = 8.191, P = 0.004). The most frequently detected pathogens in the BAL fluid were human adenovirus (HADV)(21.82%), Mycoplasma pneumoniae (20.24%), human rhinovirus (13.96%), Streptococcus pneumoniae (8.90%) and Haemophilus influenzae (8.90%). In 16.4% of the cases co-detection with two or three different pathogens was found. Viral detection rates declined with age, while atypical pathogen detection rates increased with age. Oxygen supply in the HADV and Influenza H1N1 infected patients was more frequent (49.43%) than in patients infected with other pathogens.

Conclusion

Broad range detection of viral and bacterial pathogens using molecular methods is a promising and implementable approach to improve clinical diagnosis and accurate treatment of LRTI in children.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bicer S, Giray T, Çöl D, Erdağ GÇ, Vitrinel A, Gürol Y, Çelik G, Kaspar Ç, Küçük Ö. Virological and clinical characterizations of respiratory infections in hospitalized children. Ital J Pediatr. 2013 Dec;39(1):22.CrossRef Bicer S, Giray T, Çöl D, Erdağ GÇ, Vitrinel A, Gürol Y, Çelik G, Kaspar Ç, Küçük Ö. Virological and clinical characterizations of respiratory infections in hospitalized children. Ital J Pediatr. 2013 Dec;39(1):22.CrossRef
2.
go back to reference UNICEFWHO. Countdown to 2015: a decade of tracking progress for maternal, newborn and child survival—the 2015 report. Geneva/New York: WHO/UNICEF; 2015. UNICEFWHO. Countdown to 2015: a decade of tracking progress for maternal, newborn and child survival—the 2015 report. Geneva/New York: WHO/UNICEF; 2015.
3.
go back to reference Li L, Zhu T, Chen ZR, Yan YD, He LP, Xu HM, Shao XJ, Yin F, Ji W. Detection of human bocavirus in nasopharyngeal aspirates versus in bronchoalveolar lavage fluids in children with lower respiratory tract infections. J Med Virol. 2016;88(2):211–5.CrossRef Li L, Zhu T, Chen ZR, Yan YD, He LP, Xu HM, Shao XJ, Yin F, Ji W. Detection of human bocavirus in nasopharyngeal aspirates versus in bronchoalveolar lavage fluids in children with lower respiratory tract infections. J Med Virol. 2016;88(2):211–5.CrossRef
4.
go back to reference Wurzel DF, Marchant JM, Clark JE, Mackay IM, Wang CY, Sloots TP, Upham JW, Yerkovich ST, Masters IB, Baker PJ, Anderson-James S. Respiratory virus detection in nasopharyngeal aspirate versus bronchoalveolar lavage is dependent on virus type in children with chronic respiratory symptoms. J Clin Virol. 2013;58(4):683–8.CrossRef Wurzel DF, Marchant JM, Clark JE, Mackay IM, Wang CY, Sloots TP, Upham JW, Yerkovich ST, Masters IB, Baker PJ, Anderson-James S. Respiratory virus detection in nasopharyngeal aspirate versus bronchoalveolar lavage is dependent on virus type in children with chronic respiratory symptoms. J Clin Virol. 2013;58(4):683–8.CrossRef
5.
go back to reference Muhlebach MS, Hatch JE, Einarsson GG, McGrath SJ, Gilipin DF, Lavelle G, Mirkovic B, Murray MA, McNally P, Gotman N, Thomas SD. Anaerobic bacteria cultured from cystic fibrosis airways correlate to milder disease: a multisite study. Eur Respir J. 2018;52(1):1800242.CrossRef Muhlebach MS, Hatch JE, Einarsson GG, McGrath SJ, Gilipin DF, Lavelle G, Mirkovic B, Murray MA, McNally P, Gotman N, Thomas SD. Anaerobic bacteria cultured from cystic fibrosis airways correlate to milder disease: a multisite study. Eur Respir J. 2018;52(1):1800242.CrossRef
6.
go back to reference Tsai CM, Wong KS, Lee WJ, Hsieh KS, Hung PL, Niu CK, Yu HR. Diagnostic value of bronchoalveolar lavage in children with nonresponding community-acquired pneumonia. Pediatrics & Neonatology. 2017;58(5):430–6.CrossRef Tsai CM, Wong KS, Lee WJ, Hsieh KS, Hung PL, Niu CK, Yu HR. Diagnostic value of bronchoalveolar lavage in children with nonresponding community-acquired pneumonia. Pediatrics & Neonatology. 2017;58(5):430–6.CrossRef
7.
go back to reference Nadimpalli S, Foca M, Satwani P, Sulis ML, Constantinescu A, Saiman L. Diagnostic yield of bronchoalveolar lavage in immunocompromised children with malignant and non-malignant disorders. Pediatr Pulmonol. 2017;52(6):820–6.CrossRef Nadimpalli S, Foca M, Satwani P, Sulis ML, Constantinescu A, Saiman L. Diagnostic yield of bronchoalveolar lavage in immunocompromised children with malignant and non-malignant disorders. Pediatr Pulmonol. 2017;52(6):820–6.CrossRef
8.
go back to reference Montaner AE, de Lomas JG, Asensi JR, de la Cruz OA, de la Serna BO, Burruchaga MS, López PM, Vernetta AT, Feng Y, Van Dyke MK, Reyes J. Bacteria from bronchoalveolar lavage fluid from children with suspected chronic lower respiratory tract infection: results from a multi-center, cross-sectional study in Spain. Eur J Pediatr. 2018;177(2):181–92.CrossRef Montaner AE, de Lomas JG, Asensi JR, de la Cruz OA, de la Serna BO, Burruchaga MS, López PM, Vernetta AT, Feng Y, Van Dyke MK, Reyes J. Bacteria from bronchoalveolar lavage fluid from children with suspected chronic lower respiratory tract infection: results from a multi-center, cross-sectional study in Spain. Eur J Pediatr. 2018;177(2):181–92.CrossRef
9.
go back to reference Gu W, Jiang W, Zhang X, Chen Z, Yan Y, Huang L, Wang M, Shao X, Wang S, Ji W. Refractory wheezing in Chinese children under 3 years of age: bronchial inflammation and airway malformation. BMC Pediatr. 2016;16(1):145.CrossRef Gu W, Jiang W, Zhang X, Chen Z, Yan Y, Huang L, Wang M, Shao X, Wang S, Ji W. Refractory wheezing in Chinese children under 3 years of age: bronchial inflammation and airway malformation. BMC Pediatr. 2016;16(1):145.CrossRef
10.
go back to reference Guo YL, Yang YX, Dong PP. Pathogens in bronchoalveolar lavage fluid of children with lower respiratory tract infection. Zhongguo dang daierkezazhi=. Chinese journal of contemporary pediatrics. 2019;21(2):144–9.PubMed Guo YL, Yang YX, Dong PP. Pathogens in bronchoalveolar lavage fluid of children with lower respiratory tract infection. Zhongguo dang daierkezazhi=. Chinese journal of contemporary pediatrics. 2019;21(2):144–9.PubMed
11.
go back to reference Wang L, Feng Z, Zhao M, Yang S, Yan X, Guo W, Shi Z, Li G. A comparison study between GeXP-based multiplex-PCR and serology assay for mycoplasma pneumoniae detection in children with community acquired pneumonia. BMC Infect Dis. 2017;17(1):518.CrossRef Wang L, Feng Z, Zhao M, Yang S, Yan X, Guo W, Shi Z, Li G. A comparison study between GeXP-based multiplex-PCR and serology assay for mycoplasma pneumoniae detection in children with community acquired pneumonia. BMC Infect Dis. 2017;17(1):518.CrossRef
12.
go back to reference Gadsby NJ, McHugh MP, Russell CD, Mark H, Morris AC, Laurenson IF, Hill AT, Templeton KE. Development of two real-time multiplex PCR assays for the detection and quantification of eight key bacterial pathogens in lower respiratory tract infections. Clin Microbiol Infect. 2015 Aug 1;21(8):788–e1.CrossRef Gadsby NJ, McHugh MP, Russell CD, Mark H, Morris AC, Laurenson IF, Hill AT, Templeton KE. Development of two real-time multiplex PCR assays for the detection and quantification of eight key bacterial pathogens in lower respiratory tract infections. Clin Microbiol Infect. 2015 Aug 1;21(8):788–e1.CrossRef
13.
go back to reference Wang L, Zhao M, Shi Z, Feng Z, Guo W, Yang S, Liu L, Li G. A GeXP-based assay for simultaneous detection of multiple viruses in hospitalized children with community acquired pneumonia. PLoS One. 2016 Sep 14;11(9):e0162411.CrossRef Wang L, Zhao M, Shi Z, Feng Z, Guo W, Yang S, Liu L, Li G. A GeXP-based assay for simultaneous detection of multiple viruses in hospitalized children with community acquired pneumonia. PLoS One. 2016 Sep 14;11(9):e0162411.CrossRef
14.
go back to reference Liu P, Xu M, He L, Su L, Wang A, Fu P, Lu L, Wang C, Xu J. Epidemiology of respiratory pathogens in children with lower respiratory tract infections in Shanghai, China, from 2013 to 2015. Jpn J Infect Dis. 2018;71(1):39–44.CrossRef Liu P, Xu M, He L, Su L, Wang A, Fu P, Lu L, Wang C, Xu J. Epidemiology of respiratory pathogens in children with lower respiratory tract infections in Shanghai, China, from 2013 to 2015. Jpn J Infect Dis. 2018;71(1):39–44.CrossRef
15.
go back to reference Liu WK, Liu Q, Chen DH, Liang HX, Chen XK, Chen MX, Qiu SY, Yang ZY, Zhou R. Epidemiology of acute respiratory infections in children in Guangzhou: a three-year study. PLoS One. 2014;9(5):e96674.CrossRef Liu WK, Liu Q, Chen DH, Liang HX, Chen XK, Chen MX, Qiu SY, Yang ZY, Zhou R. Epidemiology of acute respiratory infections in children in Guangzhou: a three-year study. PLoS One. 2014;9(5):e96674.CrossRef
16.
go back to reference Xie L, Zhang B, Xiao N, Zhang F, Zhao X, Liu Q, Xie Z, Gao H, Duan Z, Zhong L. Epidemiology of human adenovirus infection in children hospitalized with lower respiratory tract infections in Hunan, China. J Med Virol. 2019;91(3):392–400.CrossRef Xie L, Zhang B, Xiao N, Zhang F, Zhao X, Liu Q, Xie Z, Gao H, Duan Z, Zhong L. Epidemiology of human adenovirus infection in children hospitalized with lower respiratory tract infections in Hunan, China. J Med Virol. 2019;91(3):392–400.CrossRef
17.
go back to reference Wang Y-Q, Chuang-Li H, Wei J, Zheng-Rong C, Xin-Xin Z, Wen-jing G. Etiology and clinical characteristics of community-acquired pneumonia with airway Malacia in children. J Trop Pediatr. 2018;64(4):317–25.CrossRef Wang Y-Q, Chuang-Li H, Wei J, Zheng-Rong C, Xin-Xin Z, Wen-jing G. Etiology and clinical characteristics of community-acquired pneumonia with airway Malacia in children. J Trop Pediatr. 2018;64(4):317–25.CrossRef
18.
go back to reference Fu Y, Tang Z, Ye Z, Mo S, Tian X, Ni K, Ren L, Liu E, Zang N. Human adenovirus type 7 infection causes a more severe disease than type 3. BMC Infect Dis. 2019 Dec;19(1):36.CrossRef Fu Y, Tang Z, Ye Z, Mo S, Tian X, Ni K, Ren L, Liu E, Zang N. Human adenovirus type 7 infection causes a more severe disease than type 3. BMC Infect Dis. 2019 Dec;19(1):36.CrossRef
19.
go back to reference Bao Y, Li Y, Qiu C, Wang W, Yang Z, Huang L, Feng X, Liu Y, Li J, Zhou Q, Wang H, Li D, Wang H, Dai W, Zheng Y. Bronchoalveolar lavage fluid microbiota dysbiosis in infants with protracted bacterial bronchitis. J Thorac Dis. 2018;10(1):168–74.CrossRef Bao Y, Li Y, Qiu C, Wang W, Yang Z, Huang L, Feng X, Liu Y, Li J, Zhou Q, Wang H, Li D, Wang H, Dai W, Zheng Y. Bronchoalveolar lavage fluid microbiota dysbiosis in infants with protracted bacterial bronchitis. J Thorac Dis. 2018;10(1):168–74.CrossRef
20.
go back to reference Wang H, Zheng Y, Deng J, Wang W, Liu P, Yang F, Jiang H. Prevalence of respiratory viruses among children hospitalized from respiratory infections in Shenzhen, China. Virology J. 2016;13(1):39.CrossRef Wang H, Zheng Y, Deng J, Wang W, Liu P, Yang F, Jiang H. Prevalence of respiratory viruses among children hospitalized from respiratory infections in Shenzhen, China. Virology J. 2016;13(1):39.CrossRef
Metadata
Title
Broad range detection of viral and bacterial pathogens in bronchoalveolar lavage fluid of children to identify the cause of lower respiratory tract infections
Authors
Heping Wang
Jiali Gu
Xiaonan Li
Christa E. van der Gaast-de Jongh
Wenjian Wang
Xuehui He
Zhi Xu
Yonghong Yang
Ronald de Groot
Marien I. de Jonge
Yuejie Zheng
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2021
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-021-05834-0

Other articles of this Issue 1/2021

BMC Infectious Diseases 1/2021 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.