Brazilian Journal of Microbiology

, Volume 50, Issue 1, pp 117–125 | Cite as

Viral pathogens associated with acute lower respiratory tract infections in children younger than 5 years of age in Bulgaria

  • Neli KorsunEmail author
  • Svetla Angelova
  • Ivelina Trifonova
  • Irina Georgieva
  • Silvia Voleva
  • Iren Tzotcheva
  • Sirma Mileva
  • Ivan Ivanov
  • Tatiana Tcherveniakova
  • Penka Perenovska
Clinical Microbiology - Research Paper


Acute lower respiratory infections (ALRIs) are a leading cause of morbidity and hospital admissions in children. This study aimed to determine the viral etiology of these infections in children aged < 5 years during three successive epidemic seasons in Bulgaria. Nasopharyngeal and throat specimens were collected from children with bronchiolitis and pneumonia during the 2015/2016, 2016/2017, and 2017/2018 seasons. The viral etiology was determined by individual real-time PCR assays against 11 respiratory viruses. Of the 515 children examined, 402 (78.1%) were positive for at least one virus. Co-infections with two and three viruses were found in 64 (15.9%) of the infected children. Respiratory syncytial virus (RSV) was the predominant pathogen (37.5%), followed by rhinoviruses (13.8%), metapneumovirus (9.1%), adenoviruses (7%), bocaviruses (7%), influenza A(H1N1)pdm09 (4.9%), A(H3N2) (4.3%), type B (4.1%), and parainfluenza viruses 1/2/3 (2.9%). RSV-B were more prevalent than RSV-A during the three seasons. At least one respiratory virus was identified in 82.6% and 70.1% of the children with bronchiolitis and pneumonia, respectively. Respiratory viruses, especially RSV, are principal pathogens of ALRIs in children aged < 5 years. Diagnostic testing for respiratory viruses using molecular methods may lead to the reduced use of antibiotics and may assist in measures to control infection.


Acute lower respiratory infections Bronchiolitis Pneumonia Viral infection 


Authors’ contributions

NK conceptualized and designed the study; ITz, SM, SV, and II were responsible for patient enrollment, assessment, and selection; NK, SA, ITr, IG, and SV performed the experiments; NK, ITr, ITz, SM, and II analyzed the work results; NK wrote the manuscript; TT and PP reviewed the final manuscript. All authors read and approved the final manuscript.


This work was financially supported by the National Science Fund (Project No DH 13-15/20.12.2017) and the Ministry of Health (National Plan of Republic of Bulgaria for Pandemic Influenza Preparedness).

Compliance with ethical standards

This study was carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans

Conflict of interest

The authors declare that they have no conflicts of interest relevant.


  1. 1.
    Nair H, Simões EA, Rudan I et al (2013) Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis. Lancet 381(9875):1380–1390CrossRefGoogle Scholar
  2. 2.
    Wishaupt JO, Versteegh FG, Hartwig NG (2015) PCR testing for paediatric acute respiratory tract infections. Paediatr Respir Rev 16(1):43–48Google Scholar
  3. 3.
    Pavia AT (2011) Viral infections of the lower respiratory tract: old viruses, new viruses, and the role of diagnosis. Clin Infect Dis 52(Suppl 4):S284–S289CrossRefGoogle Scholar
  4. 4.
    WHO (2012) Vaccines against influenza WHO position paper – November 2012. Wkly Epidemiol Rec 47(87):461–476Google Scholar
  5. 5.
    Nair H, Brooks WA, Katz M et al (2011) Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet 378(9807):1917–1930CrossRefGoogle Scholar
  6. 6.
    Shi T, McAllister DA, O’Brien KL et al (2017) Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet 390(10098):946–958CrossRefGoogle Scholar
  7. 7.
    Moe N, Krokstad S, Stenseng IH et al (2017) Comparing human Metapneumovirus and respiratory syncytial virus: viral co-detections, genotypes and risk factors for severe disease. PLoS One 12(1):e0170200CrossRefGoogle Scholar
  8. 8.
    Papenburg J, Hamelin ME, Ouhoummane N et al (2012) Comparison of risk factors for human metapneumovirus and respiratory syncytial virus disease severity in young children. J Infect Dis 206:178–189CrossRefGoogle Scholar
  9. 9.
    Thomazelli LM, Oliveira DBL et al (2017) Human parainfluenza virus surveillance in pediatric patients with lower respiratory tract infections: a special view of parainfluenza type 4. J Pediatr (Rio J)Google Scholar
  10. 10.
    Jacobs SE, Lamson DM, St George K, Walsh TJ (2013) Human rhinoviruses. Clin Microbiol Rev 26(1):135–162CrossRefGoogle Scholar
  11. 11.
    Echevarría M (2008) Adenoviruses in immunocompromised hosts. Clin Microbiol Rev 21:704–715CrossRefGoogle Scholar
  12. 12.
    Longtin J, Bastien M, Gilca R et al (2008) Human bocavirus infections in hospitalized children and adults. Emerg Infect Dis 14(2):217–221CrossRefGoogle Scholar
  13. 13.
    CDC protocol of real-time RTPCR for influenza A(H1N1). Geneva: World Health Organization. 2009.
  14. 14.
    Kodani M, Yang G, Conklin LM et al (2011) Application of TaqMan low-density arrays for simultaneous detection of multiple respiratory pathogens. J Clin Microbiol 49(6):2175–2182CrossRefGoogle Scholar
  15. 15.
    Lu X, Chittaganpitch M, Olsen SJ et al (2006) Real-time PCR assays for detection of bocavirus in human specimens. J Clin Microbiol 44:3231–3235CrossRefGoogle Scholar
  16. 16.
    Zlateva KT, Vijgen L, Dekeersmaeker N et al (2007) Subgroup prevalence and genotype circulation patterns of human respiratory syncytial virus in Belgium during ten successive epidemic seasons. J Clin Microbiol 45(9):3022–3030CrossRefGoogle Scholar
  17. 17.
    Zhou JY, Peng Y, Peng XY et al (2018 Mar) Human bocavirus and human metapneumovirus in hospitalized children with lower respiratorytract illness in Changsha, China. Influenza Other Respir Viruses 12(2):279–286CrossRefGoogle Scholar
  18. 18.
    García-García ML, Calvo C, Rey C et al (2017) Human metapnuemovirus infections in hospitalized children and comparison with other respiratory viruses. 2005–2014 prospective study. PLoS One 12(3):e0173504CrossRefGoogle Scholar
  19. 19.
    Ferone EA, Berezin EN, Durigon GS et al (2014) Clinical and epidemiological aspects related to the detection of adenovirus or respiratory syncytial virus in infants hospitalized for acute lower respiratory tract infection. J Pediatr (Rio J) 90:42–49CrossRefGoogle Scholar
  20. 20.
    Hatipoğlu N, Somer A, Badur S et al (2011) Viral etiology in hospitalized children with acute lower respiratory tract infection. Turk J Pediatr 53(5):508–516Google Scholar
  21. 21.
    Mansbach JM, Piedra PA, Teach SJ et al (2012) Prospective multicenter study of viral etiology and hospital length of stay in children with severe bronchiolitis. Arch Pediatr Adolesc Med 166(8):700–706CrossRefGoogle Scholar
  22. 22.
    Janahi I, Abdulkayoum A, Almeshwesh F et al (2017) Viral aetiology of bronchiolitis in hospitalised children in Qatar. BMC Infect Dis 17(1):139CrossRefGoogle Scholar
  23. 23.
    Calvo C, Pozo F, García-García ML et al (2010) Detection of new respiratory viruses in hospitalized infants with bronchiolitis: a three-year prospective study. Acta Paediatr 99(6):883–887CrossRefGoogle Scholar
  24. 24.
    García-García ML, Calvo C, Pozo F et al (2012) Spectrum of respiratory viruses in children with community-acquired pneumonia. Pediatr Infect Dis J 31(8):808–813CrossRefGoogle Scholar
  25. 25.
    Esposito S, Daleno C, Prunotto G et al (2013) Impact of viral infections in children with community-acquired pneumonia: results of a study of 17 respiratory viruses. Influenza Other Respir Viruses 7(1):18–26CrossRefGoogle Scholar
  26. 26.
    Wong-Chew RM, García-León ML, Noyola DE et al (2017) Respiratory viruses detected in Mexican children younger than 5 years old with community-acquired pneumonia: a national multicenter study. Int J Infect Dis 62:32–38CrossRefGoogle Scholar
  27. 27.
    Jain S, Williams DJ, Arnold SR et al (2015) Community acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med 372(9):835–845CrossRefGoogle Scholar
  28. 28.
    Jiang W, Wu M, Zhou J et al (2017) Etiologic spectrum and occurrence of coinfections in children hospitalized with community-acquired pneumonia. BMC Infect Dis 17(1):787CrossRefGoogle Scholar
  29. 29.
    Hall CB (2001) Respiratory syncytial virus and parainfluenza virus. N Engl J Med 344(25):1917–1928CrossRefGoogle Scholar
  30. 30.
    Feng L, Li Z, Zhao S et al (2014) Viral etiologies of hospitalized acute lower respiratory infection patients in China, 2009-2013. PLoS One 9(6):e99419CrossRefGoogle Scholar
  31. 31.
    Saso A, Kampmann B (2016) Vaccination against respiratory syncytial virus in pregnancy: a suitable tool to combat global infant morbidity and mortality? Lancet Infect Dis 16(8):e153–e163CrossRefGoogle Scholar
  32. 32.
    Mazur NI, Martinón-Torres F, Baraldi E et al (2015) Lower respiratory tract infection caused by respiratory syncytial virus: current management and new therapeutics. Lancet Respir Med 3(11):888–900CrossRefGoogle Scholar
  33. 33.
    Huai Y, Guan X, Liu S et al (2017) Clinical characteristics and factors associated with severe acute respiratory infection and influenza among children in Jingzhou, China. Influenza Other Respir Viruses 11(2):148–156CrossRefGoogle Scholar
  34. 34.
    Lafond KE, Nair H, Rasooly MH et al (2016) Global role and burden of influenza in pediatric respiratory hospitalizations, 1982-2012: a systematic analysis. PLoS Med 13(3):e1001977CrossRefGoogle Scholar
  35. 35.
    Zeng SZ, Xiao NG, Xie ZP et al (2014) Prevalence of human rhinovirus in children admitted to hospital with acute lower respiratory tract infections in Changsha, China. J Med Virol 86(11):1983–1989CrossRefGoogle Scholar
  36. 36.
    García-García ML, Calvo C, Rey C et al (2017) Human metapneumovirus infections in hospitalized children and comparison with other respiratory viruses. 2005–2014 prospective study. PLoS One 12(3):e0173504CrossRefGoogle Scholar
  37. 37.
    Edwards KM, Zhu Y, Griffin MR et al (2013) Burden of human metapneumovirus infection in young children. N Engl J Med 368(7):633–643CrossRefGoogle Scholar
  38. 38.
    Xiao NG, Zhang B, Xie ZP et al (2013) Prevalence of human metapneumovirus in children with acute lower respiratory infection in Changsha, China. J Med Virol 85(3):546–553CrossRefGoogle Scholar
  39. 39.
    Williams JV, Harris PA, Tollefson SJ et al (2004) Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. N Engl J Med 350(5):443–450CrossRefGoogle Scholar
  40. 40.
    Calvo C, García-García ML, Sanchez-Dehesa R et al (2015) Eight year prospective study of adenoviruses infections in hospitalized children. comparison with other respiratory viruses. PLoS One 10(7):e0132162CrossRefGoogle Scholar
  41. 41.
    Liu C, Xiao Y, Zhang J et al (2015) Adenovirus infection in children with acute lower respiratory tract infections in Beijing, China, 2007 to 2012. BMC Infect Dis 15:408CrossRefGoogle Scholar
  42. 42.
    Liu WK, Liu Q, Chen DH et al (2013) Epidemiology and clinical presentation of the four human parainfluenza virus types. BMC Infect Dis 13:28CrossRefGoogle Scholar
  43. 43.
    Xiao NG, Duan ZJ, Xie ZP et al (2016) Human parainfluenza virus types 1-4 in hospitalized children with acute lower respiratory infections in China. J Med Virol 88(12):2085–2091CrossRefGoogle Scholar
  44. 44.
    Ghietto LM, Cámara A, Zhou Y et al (2012) High prevalence of human bocavirus 1 in infants with lower acute respiratory tract disease in Argentina, 2007–2009. Braz J Infect Dis 16(1):38–44Google Scholar
  45. 45.
    Goka EA, Vallely PJ, Mutton KJ, Klapper PE (2014) Single and multiple respiratory virus infections and severity of respiratory disease: a systematic review. Paediatr Respir Rev 15(4):363–370Google Scholar
  46. 46.
    Blessing K, Neske F, Herre U et al (2009) Prolonged detection of human bocavirus DNA in nasopharyngeal aspirates of children with respiratory tract disease. Pediatr Infect Dis J 28(11):1018–1019CrossRefGoogle Scholar
  47. 47.
    Self WH, Williams DJ, Zhu Y et al (2016) Respiratory viral detection in children and adults: comparing asymptomatic controls and patients with community-acquired pneumonia. J Infect Dis 213(4):584–591CrossRefGoogle Scholar
  48. 48.
    Shi T, McLean K, Campbell H, Nair H (2015) Aetiological role of common respiratory viruses in acute lower respiratory infections in children under five years: a systematic review and meta-analysis. J Glob Health 5(1):010408CrossRefGoogle Scholar
  49. 49.
    Rhedin S, Lindstrand A, Rotzén-Östlund M et al (2014) Clinical utility of PCR for common viruses in acute respiratory illness. Pediatrics 133(3):e538–e545CrossRefGoogle Scholar
  50. 50.
    Asner SA, Rose W, Petrich A et al (2015) Is virus coinfection a predictor of severity in children with viral respiratory infections? Clin Microbiol Infect 21:264.e1–264.e6CrossRefGoogle Scholar
  51. 51.
    Harada Y, Kinoshita F, Yoshida LM et al (2013) Does respiratory virus coinfection increases the clinical severity of acute respiratory infection among children infected with respiratory syncytial virus? Pediatr Infect Dis J 32(5):441–445CrossRefGoogle Scholar

Copyright information

© Sociedade Brasileira de Microbiologia 2018

Authors and Affiliations

  • Neli Korsun
    • 1
    Email author
  • Svetla Angelova
    • 1
  • Ivelina Trifonova
    • 1
  • Irina Georgieva
    • 1
  • Silvia Voleva
    • 1
  • Iren Tzotcheva
    • 2
  • Sirma Mileva
    • 1
    • 2
  • Ivan Ivanov
    • 3
  • Tatiana Tcherveniakova
    • 3
  • Penka Perenovska
    • 2
  1. 1.National Center of Infectious and Parasitic DiseasesNational Laboratory “Influenza and ARD”SofiaBulgaria
  2. 2.Medical University, University Hospital Alexandrovska, Pediatric ClinicSofiaBulgaria
  3. 3.Infectious Hospital Prof. Ivan KirovSofiaBulgaria

Personalised recommendations