Application of Human Adenovirus Genotyping by Phylogenetic Analysis in an Outbreak to Identify Nosocomial Infection

Chuanyu Yang; Chunmei Zhu; Yuan Qian; Jie Deng; Baoyuan Zhang; Runan Zhu; Fang Wang; Yu Sun; Dongmei Chen; Qi Guo; Yutong Zhou; Lei Yu; Ling Cao; Linqing Zhao

doi:10.1007/s12250-020-00299-y

June 2021

Chuanyu Yang, Chunmei Zhu, Yuan Qian, Jie Deng, Baoyuan Zhang, Runan Zhu, Fang Wang, Yu Sun, Dongmei Chen, Qi Guo, Yutong Zhou, Lei Yu, Ling Cao and Linqing Zhao. Application of Human Adenovirus Genotyping by Phylogenetic Analysis in an Outbreak to Identify Nosocomial Infection[J]. Virologica Sinica, 2021, 36(3): 393-401. doi: 10.1007/s12250-020-00299-y

Citation: Chuanyu Yang, Chunmei Zhu, Yuan Qian, Jie Deng, Baoyuan Zhang, Runan Zhu, Fang Wang, Yu Sun, Dongmei Chen, Qi Guo, Yutong Zhou, Lei Yu, Ling Cao, Linqing Zhao. Application of Human Adenovirus Genotyping by Phylogenetic Analysis in an Outbreak to Identify Nosocomial Infection .VIROLOGICA SINICA, 2021, 36(3) : 393-401. http://dx.doi.org/10.1007/s12250-020-00299-y

基于系统进化树分析的基因分型在腺病毒暴发鉴别院内感染中的应用

杨传宇 ¹ ,
朱春梅 ² ,
钱渊 ¹ ,
邓洁 ¹ ,
张宝元 ³ ,
朱汝南 ¹ ,
王芳 ¹ ,
孙宇 ¹ ,
陈冬梅 ¹ ,
郭琪 ¹ ,
周禹彤 ¹ ,
于磊 ³ ,
曹玲 ^2,, ,
赵林清 ^1,,

cstr: 32224.14.s12250-020-00299-y

1.
首都儿科研究所，病毒研究室，儿童病毒病病原学研究北京市重点实验室
2.
首都儿科研究所附属儿童医院呼吸内科
3.
首都儿科研究所附属儿童医院院感科

通讯作者： 曹玲, caoling9919@163.com, ORCID: 0000-0001-5633-1202
; 赵林清, linqingz525@163.com, ORCID: 0000-0002-5622-1959
收稿日期： 2020-05-14
录用日期： 2020-08-05
出版日期： 2020-10-01

摘要

院内感染是儿科常见问题，对婴儿及免疫功能低下者可能致命。在2018年9月，首都儿科研究所附属儿童医院住院儿童中发现人腺病毒（HAdV）的高阳性检出率。为调查本次HAdV暴发是院内感染？还是社区感染？收集2018年6月至12月呼吸病房收治的急性呼吸道感染患儿呼吸道标本，进行呼吸道病毒筛查。在1840例患者中，95例（5.2%，95/1840）为HAdV阳性，81例进行了系统进化树分析，其中7例为HAdV-1（8.6%），30例为HAdV-3（37.0%），2例HAdV-6（2.5%），42例HAdV-7（51.9%）。8月（4.7%，12/255）、9月（15.0%，41/274）和10月（6.9%，17/247）采集到的HAdV阳性样本更多，9月达到高峰。将HAdV系统进化树分析结果与患者临床资料相结合，排除院内感染的有77例（4.2%，77/1840；81.1%，77/95）；剩余的18例中8例可能是探视者或家长传播的；3例未得到HAdV序列，无法确定为HAdV阳性室友传播；另有1例因HAdV阳性室友未得到序列，无法确定是否为院内感染；有6例与室友具有高度同源的HAdV序列，考虑可能为院内感染。由此可见基于系统进化树分析的HAdVs基因分型结合临床资料，可为区分院内感染和社区获得性感染提供有力证据，尤其是在追踪院内感染起源时。
- 急性呼吸道感染
- , 人腺病毒
- , 系统进化树分析
- , 基因分型
- , 院内感染

Application of Human Adenovirus Genotyping by Phylogenetic Analysis in an Outbreak to Identify Nosocomial Infection

Chuanyu Yang ¹ ,
Chunmei Zhu ² ,
Yuan Qian ¹ ,
Jie Deng ¹ ,
Baoyuan Zhang ³ ,
Runan Zhu ¹ ,
Fang Wang ¹ ,
Yu Sun ¹ ,
Dongmei Chen ¹ ,
Qi Guo ¹ ,
Yutong Zhou ¹ ,
Lei Yu ³ ,
Ling Cao ^2,, ,
Linqing Zhao ^1,,

1.
Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing 100020, China
2.
Department of Respiratory Medicine, Affiliated Children's Hospital, Capital Institute of Pediatrics, Beijing 100020, China
3.
Hospital Infection-Control Department, Affiliated Children's Hospital, Capital Institute of Pediatrics, Beijing 100020, China

Corresponding author: Ling Cao, caoling9919@163.com Linqing Zhao, linqingz525@163.com
ORCID: 0000-0001-5633-1202; 0000-0002-5622-1959
Received Date: 14 May 2020
Accepted Date: 05 August 2020
Published Date: 01 October 2020

Abstract

Nosocomial infections are common in pediatric patients and can be fatal in infants and immunocompromised patients. In September 2018, a high positive rate of human adenovirus HAdV was occurred among hospitalized children in the Children's Hospital Affiliated to the Capital Institute of Paediatrics in Beijing. To investigate whether this outbreak of HAdV was related to nosocomial infections or the result of community infections, we collected respiratory specimens from patients with acute respiratory infections in a respiratory ward during June to December 2018, and screened for respiratory viruses. Among 1, 840 cases included, 95 (5.2%, 95/1840) were positive for HAdV and 81 were genotyped based on phylogenetic analysis, including seven as HAdV-1 (8.6%), 30 HAdV-3 (37.0%), two HAdV-6 (2.5%), and 42 HAdV-7 (51.9%). More HAdV-positive samples were collected in August (4.7%, 12/255), September (15.0%, 41/274) and October (6.9%, 17/247), with a peak in September 2018. By combining the results of HAdV phylogenetic analysis with clinical data of patients, there were 77 cases (4.2%, 77/1840; 81.1%, 77/95) excluded from nosocomial infections, eight cases representing possible infections transmitted by visitors or attending parents, three cases without sequences that might have been due to infection transmitted by roommates positive for HAdV, one case of a roommate without an HAdV sequence, and six cases that shared highly homologous sequences with those of their roommates, for which nosocomial infections might be considered. In conclusion, genotyping of HAdVs based on phylogenetic analysis combined with clinical information provides a powerful method to distinguish nosocomial infections from community acquired infection, especially when tracing the origins of nosocomial infections.
- Acute respiratory tract infection
- , Human adenovirus (HAdV)
- , Phylogenetic analysis
- , Nosocomial infection

References
1. Allard A, Girones R, Juto P, Wadell G (1990) Polymerase chain reaction for detection of adenoviruses in stool samples. J Clin Microbiol 28:2659-2667
  doi: 10.1128/JCM.28.12.2659-2667.1990
2. Allard A, Albinsson B, Wadell G (2001) Rapid typing of human adenoviruses by a general PCR combined with restriction endonuclease analysis. J Clin Microbiol 39:498-505
  doi: 10.1128/JCM.39.2.498-505.2001
3. Bautista-Gogel J, Madsen CM, Lu X, Sakthivel SK, Froh I, Kamau E, Gerber SI, Watson JT, Cooper SS, Schneider E (2020) Outbreak of respiratory illness associated with human adenovirus type 7 among persons attending officer candidates school, Quantico, Virginia, 2017. J Infect Dis 221:697-700
  doi: 10.1093/infdis/jiz060
4. Chen M, Zhu Z, Huang F, Liu D, Zhang T, Ying D, Wu J, Xu W (2015) Adenoviruses associated with acute respiratory diseases reported in Beijing from 2011 to 2013. PLoS ONE 10:e0121375
  doi: 10.1371/journal.pone.0121375
5. Civardi E, Tzialla C, Baldanti F, Strocchio L, Manzoni P, Stronati M (2013) Viral outbreaks in neonatal intensive care units:what we do not know. Am J Infect Control 41:854-856
  doi: 10.1016/j.ajic.2013.01.026
6. Dare RK, Talbot TR (2016) Health care-acquired viral respiratory diseases. Infect Dis Clin North Am 30:1053-1070
  doi: 10.1016/j.idc.2016.07.004
7. Deng J, Qian Y, Zhao L, Zhu R, Sun Y, Tian R (2013) Identification and typing of adenovirus from acute respiratory infections in pediatric patients in Beijing from 2003 to 2012. Bing Du Xue Bao 29:615-620
8. Dhingra A, Hage E, Ganzenmueller T, Böttcher S, Hofmann J, Hamprecht K, Obermeier P, Rath B, Hausmann F, Dobner T, Heim A (2019) Molecular evolution of human adenovirus (HAdV) species C. Sci Rep 9:1039
  doi: 10.1038/s41598-018-37249-4
9. Ding YX, Tian R, Qian Y, Sun Y, Deng J, Wang F, Zhu RN, Zhao LQ (2017) Clinical value of a rapid respiratory syncytial virus antigen detection in point-of-care testing. ZhongHua Er Ke Za Zhi 55:139-143 (in Chinese)
10. Hung KH, Lin L (2015) Adenovirus pneumonia complicated with acute respiratory distress syndrome:a case report. Medicine 94:e776
  doi: 10.1097/MD.0000000000000776
11. Kobayashi H, Shinjoh M, Sudo K, Kato S, Morozumi M, Koinuma G, Takahashi T, Takano Y, Tamura Y, Hasegawa N (2019) Nosocomial infection by human bocavirus and human rhinovirus among paediatric patients with respiratory risks. J Hosp Infect 103:341-348
  doi: 10.1016/j.jhin.2019.05.002
12. Kumar S, Stecher G, Li M, Knyaz C, Tamura K (2018) MEGA X:molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol 35:1547-1549
  doi: 10.1093/molbev/msy096
13. Lai CY, Lee CJ, Lu CY, Lee PI, Shao PL, Wu ET, Wang CC, Tan BF, Chang HY, Hsia SH, Lin JJ, Chang LY, HUang YC, Huang LM, Taiwan Pediatric Infectious Disease Alliance, (2013) Adenovirus serotype 3 and 7 infection with acute respiratory failure in children in Taiwan, 2010-2011. PLoS ONE 8: e53614
14. Lessler J, Reich NG, Brookmeyer R, Perl TM, Nelson KE, Cummings DA (2009) Incubation periods of acute respiratory viral infections:a systematic review. Lancet Infect Dis 9:291-300
  doi: 10.1016/S1473-3099(09)70069-6
15. Li Y, Zhou W, Zhao Y, Wang Y, Xie Z, Loou Y, Tan W (2015) Molecular typing and epidemiology profiles of human adenovirus infection among paediatric patients with severe acute respiratory infection in China. PLoS ONE 10:e0123234
  doi: 10.1371/journal.pone.0123234
16. Lion T (2014) Adenovirus infections in immunocompetent and immunocompromised patients. Clin Microbiol Rev 27:441-462
  doi: 10.1128/CMR.00116-13
17. Liu LY, Zhang Y, Deng J, Qian Y (2009) Developing of a method for detection and identification of entero-adenovirus in fecal specimens from infantile diarrhea. ZhongHua Jian Yan Yi Xue Za Zhi 32:857-860
18. Lu G, Shi W, Zhang D, Liu Y, Zhang L, Sun Y, Yang P, Wang Q (2019) The epidemiological and etiological features of human adenovirus outbreaks among children in Beijing in 2016. ZhongGou Yu Fang Yi Xue Za Zhi 20:21-26 (In Chinese)
19. Mao N, Zhu Z, Rivailler P, Yang J, Li Q, Han G, Yin J, Yu D, Sun L, Jiang H, Zhan Z, Xiang X, Mei H, Wang X, Zhang B, Yu P, Li H, Lei Z, Xu W (2019) Multiple divergent human mastadenovirus C co-circulating in mainland of China. Infect Genet Evol 76:104035
  doi: 10.1016/j.meegid.2019.104035
20. Potter RN, Cantrell JA, Mallak CT, Gaydos J (2012) Adenovirus-associated deaths in US military during postvaccination period, 1999-2010. Emerg Infect Dis 18:507-509
  doi: 10.3201/eid1803.111238
21. Quach C, Shah R, Rubin LG (2018) Burden of healthcare-associated viral respiratory infections in children's hospitals. J Pediatric Infect Dis Soc 7:18-24
  doi: 10.1093/jpids/piw072
22. Rutledge-Taylor K, Matlow A, Gravel D, Embree J, Le Saux N, Johnston L, Suh K, Embil J, Henderson E, John M, Roth V, Wong A, Shurgold J, Taylor G, Program Canadian Nosocomial Infection Surveillance (2012) A point prevalence survey of health care-associated infections in Canadian pediatric inpatients. Am J Infect Control 40:491-496
  doi: 10.1016/j.ajic.2011.08.008
23. Saitou N, Nei M (1987) The neighbor-joining method:a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406-425
  doi: 10.1093/oxfordjournals.molbev.a040454
24. Sun J, Xiao Y, Zhang M, Ao T, Lang S, Wang J (2018) Serum inflammatory markers in patients with adenovirus respiratory infection. Med Sci Monit 24:3848-3855
  doi: 10.12659/MSM.910692
25. Tamura K, Suzuki K (2004) Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci USA 101:11030-11035
  doi: 10.1073/pnas.0404206101
26. Topoulos S, Giesa C, Gatermann S, Fussen R, Lemmen S, Ewig S (2019) Analysis of acute respiratory infections due to influenza virus A, B and RSV during an influenza epidemic 2018. Infection 47:425-433
  doi: 10.1007/s15010-018-1262-x
27. Wang L, Zhou KH, Chen W, Yu Y, Feng SF (2019) Epidemiology and risk factors for nosocomial infection in the respiratory intensive care unit of a teaching hospital in China:a prospective surveillance during 2013 and 2015. BMC Infect Dis 19:145
  doi: 10.1186/s12879-019-3772-2
28. Wen S, Lv F, Chen X, Zhu L, Li H, Lin L, Zhang H (2019) Application of a nucleic acid-based multiplex kit to identify viral and atypical bacterial aetiology of lower respiratory tract infection in hospitalized children. J Med Microbiol 68:1211-1218
  doi: 10.1099/jmm.0.001006
29. Xu L, Liu J, Liu C, Duan Y, Zhu Y, Xu B, Xie Z (2018) Case-control study of the epidemiological and clinical features of human adenovirus 55 and human adenovirus 7 infection in children with acute lower respiratory tract infections in Beijing, China, 2008-2013. BMC Infect Dis 18:634
  doi: 10.1186/s12879-018-3520-z
30. Zhang J, Sridhar S, Lau Susanna KP, Liu J, Ou J, Yan Y, Zhao S, Lan W, Guan W, Wu J, Woo Patrick CY, Seto D, Zhang Q (2020) Molecular typing of human respiratory adenoviruses with universal PCR and sequencing primers for three major capsid genes:penton base, hexon, and fiber. BioRxiv. https://doi.org/10.1101/2020.03.17.995373
  doi: 10.1101/2020.03.17.995373
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