Is the role of rhinoviruses as causative agents of pediatric community-acquired pneumonia over-estimated?

Tatyana V Spichak, Svetlana B Yatsyshina, Lubov К Кatosova, Svetlana S Кim, Matti O Korppi, Tatyana V Spichak, Svetlana B Yatsyshina, Lubov К Кatosova, Svetlana S Кim, Matti O Korppi

Abstract

The role that rhinoviruses, enteroviruses, parainfluenza viruses, coronaviruses and human bocavirus play in pediatric pneumonia is insufficiently studied. We used polymerase chain reaction (PCR) to study 9 virus groups, including 16 different viruses or viral strains, in 56 ambulatory children with radiologically confirmed community-acquired pneumonia (CAP). The same tests were carried out on 474 apparently healthy control children of the same age and sex. The mean age of children with CAP was 6.5 years (SD 4.2). Respiratory syncytial virus (RSV) was found in 19.6 % of 56 cases and in 2.1 % of 474 controls. Adenoviruses were present in 12.5 % of cases (0.2 % controls) and metapneumovirus and influenza A virus each in 10.7 % of cases (0.2 % controls). Interestingly, rhinoviruses were less common in cases (10.7 %) than in controls (22.4 %): odds ratio 0.36 (95%CI) 0.15-0.87) in conditional logistic regression including 56 cases and 280 controls matched for age, sex and sampling month. The prevalence of parainfluenza viruses, enteroviruses, coronaviruses and human bocavirus were similar in both groups.

Conclusion: We conclude that the role of rhinoviruses as an etiology of pediatric CAP has been over-estimated, mainly due to the non-controlled designs of previous studies. What is Known: • In non-controlled studies, rhinovirus detection has been common, next to respiratory syncytial virus, in children with viral community-acquired pneumonia (CAP). • Enteroviruses, coronaviruses and the human bocavirus have been found less frequently. What is New: • In this controlled study, rhinoviruses were detected more often in healthy controls than in children with CAP, and enteroviruses, coronaviruses and human bocavirus were detected equally often in cases and controls. • We conclude that previous studies have over-estimated the role of rhinoviruses in the etiology of CAP in children.

Keywords: Adenoviruses; Child; Community-acquired pneumonia; Human bocavirus; Respiratory syncytial virus; Rhinoviruses.

Conflict of interest statement

The authors declare that they have no conflict of interest.

References

    1. Douros K, Kotzia D, Kottaridi C, Giotas A, Boutopoulou B, Karakitsos P, Priftis KΝ. Many children aged two to five years old have a persistent presence of respiratory viruses in their nasopharynx. Acta Paediatr. 2016;105:e89–e92. doi: 10.1111/apa.13259.
    1. Elemraid MA, Sails AD, Eltringham GJ, Perry JD, Rushton SP, Spencer DA, Thomas MF, Eastham KM, Hampton F, Gennery AR, Clark JE, North East of England Paediatric Respiratory Infection Study Group Aetiology of paediatric pneumonia after the introduction of pneumococcal conjugate vaccine. Eur Respir J. 2013;42:1595–1603. doi: 10.1183/09031936.00199112.
    1. Esposito S, Daleno C, Prunotto G, Scala A, Tagliabue C, Borzani I, Fossali E, Pelucchi C, Principi N. Impact of viral infections in children with community-acquired pneumoniae: results of a study of 17 respiratory viruses. Influenza Other Respir Viruses. 2013;7:18–26. doi: 10.1111/j.1750-2659.2012.00340.x.
    1. Fabbiani M, Terrosi C, Martorelli B, Valentini M, Bernini L, Cellesi C, Cusi MG. Epidemiological and clinical study of viral respiratory tract infections in children from Italy. J Medical Virol. 2009;81:750–756. doi: 10.1002/jmv.21457.
    1. Gern JE. The ABCs of rhinovirus, wheezing, and asthma. J Virol. 2010;84:7418–7426. doi: 10.1128/JVI.02290-09.
    1. Gilla G, Onate E, Perez-Yarza EG, Montes M, Vicente D, Perez-Trallero E. Viruses in community-acquired pneumonia in children aged less than 3 years old: high rate of viral coinfection. J Med Virol. 2008;80:1843–1849. doi: 10.1002/jmv.21271.
    1. Harris M, Clarc J, Coote N, Fletcher P, Harnden A, McKean M, Thomson A. British Thoracic Society guidelines for the management of community acquired pneumoniae in children; update 2011. Thorax. 2011;66:548–569. doi: 10.1136/thoraxjnl-2011-200598.
    1. Hershenson MB, Johnstom SL. Rhinovirus infections more than a common cold. Am J Respir Crit Care Med. 2006;174:1284–1285. doi: 10.1164/rccm.200609-1387ED.
    1. Honkinen M, Lahti F, Osterback R, Ruuskanen O, Waris M. Viruses and bacteria in sputum samples of children with community-acquired pneumoniae. Clin Microbiol Infect. 2012;18:300–307. doi: 10.1111/j.1469-0691.2011.03603.x.
    1. Iatsyshina SB, Evseeva EL, Shvec EU, Praded MN, Minenko AN, Gorelov AV. The etiological diagnosis of acute respiratory infections in children using molecular techniques (in Russian) Infect Dis (Moscow) 2009;1:244–245.
    1. Iatsyshina SB, Konovalov AV, Magkoeva ZG, Praded MN, Shelkovskaia LP, Perevozchikova LA, Andronova MM, Gorelov AV. Laboratory diagnostics in evaluation of acute respiratory viral infection morbidity in 2010-2011 epidemic season (in Russian) ZH mikrobiol Epidemiol Immuniobiol. 2013;1:33–38.
    1. Jacques J, Bouscambert-Duchamp M, Moret H, Carquin J, Brodard V, Lina B, Motte J, Andreoletti L. Association of respiratory picornaviruses with acute bronchiolitis in French infants. J Clin Virol. 2006;35:463–466. doi: 10.1016/j.jcv.2005.11.009.
    1. Jain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C, Stockmann C, Anderson EJ, Grijalva CG, Self WH, Zhu Y, Patel A, Hymas W, Chappell JD, Kaufman RA, Kan JH, Dansie D, Lenny N, Hillyard DR, Haynes LM, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, Wunderink RG, Edwards KM, Pavia AT, McCullers JA, Finelli L, Study Team CDCEPIC. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med. 2015;372:835–845. doi: 10.1056/NEJMoa1405870.
    1. Jansen RR, Wieriga J, Koekkoek SM, Visser CE, Pajkrt D, Molenkamp R, de Jong MD, Schinkel J. Frequent detection of respiratory viruses without symptoms: toward defining clinically relevant cutoff values. J Clin Microbiol. 2011;49:2631–2636. doi: 10.1128/JCM.02094-10.
    1. Jartti T, Lehtinen P, Vuorinen T, Koskenvuo M, Ruuskanen O. Persistence of rhinovirusand enterovirus RNA after acute respiratory ilness in children. J Med Virol. 2004;72:695–699. doi: 10.1002/jmv.20027.
    1. Juven T, Mertsola J, Waris M, Leinonen M, Meurman O, Roivainen M, Eskola J, Saikku P, Ruuskanen O. Etiology of community-aquired pneumonia in 254 hospitalized children. Pediatr Infect Dis J. 2000;19:293–298. doi: 10.1097/00006454-200004000-00006.
    1. Karalar L, Linder J, Schimanski S, Kertai M, Segerer H, Modrow S. Prevalence and clinical aspects of human bocavirus infection in children. Clin Microbiol Infect. 2010;16:633–639. doi: 10.1111/j.1469-0691.2009.02889.x.
    1. Loeffelholz MJ, Trujillo R, Pyles RB, Miller AL, Alvarez-Fernandez P, Pong DL, Chonmaitree T. Duration of rhinovirus shedding in the upper respiratory tract in the first year of life. Pediatrics. 2014;134:1144–1150. doi: 10.1542/peds.2014-2132.
    1. Midulla F, Scagnolari C, Bonchi E, Pierangeli A, Antonelli G, De Angelis D, Berardi R, Moretti C. Respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants. Arch Dis Child. 2010;95:35–41. doi: 10.1136/adc.2008.153361.
    1. Nilsson AC, Björkman P, Persson K. Polymerase chain reaction is superior to serology for the diagnosis of acute mycoplasma pneumoniae infection and reveals a high rate of persistent infection. BMC Microbiol. 2008;8:93. doi: 10.1186/1471-2180-8-93.
    1. Okada T, Morozumi M, Sakata H, Takayanagi R, Ishiwada N, Sato Y, Oishi T, Tajima T, Haruta T, Kawamura N, Ouchi K, Matsubara K, Chiba N, Takahashi T, Iwata S, Ubukata K. A practical approach estimating aetiologic agents using real-time PCR in pediatric inpatients with community-acquired pneumoniae. J Infect Chemother. 2012;18:832–884. doi: 10.1007/s10156-012-0422-7.
    1. Piralla A, Baldanti F, Gerna G. Phylogenetic patterns of human respiratory picornavirus species, including the newly identified group C rhinoviruses, during a 1-year surveillance of a hospitalized patient population in Italy. J Clin Microbiol. 2011;49:373–376. doi: 10.1128/JCM.01814-10.
    1. Pyrc K, Berkhout B, van der Hoek L. The novel human coronaviruses NL63 and HKU1. J Virolog. 2007;81:3051–3057. doi: 10.1128/JVI.01466-06.
    1. Regamay N, Kaiser L, Roiha HL, Deffernez C, Kuehni CE, Latzin P, Aebi C, Frey U, Swiss Paediatric Respiratory Research Group Viral etiology of acute respiratory infections with cough in infancy – a community-based birth cohort study. Pediatr Infect Dis J. 2008;27:100–105.
    1. Rhedin S, Lindstrand A, Rotzen-Oslund M, Tolfvenstam T, Ohrmalm L, Rinder MR, Zweygberg-Wirgart B, Ortqvist A, Henriques-Normark B, Broliden K, Naucler P. Clinical utility of PCR for common viruses in acute respiratory illness. Pediatrics. 2014;133:e538–e545. doi: 10.1542/peds.2013-3042.
    1. Rhedin S, Lindstrand A, Hjelmgren A, Ryd-Rinder M, Öhrmalm L, Tolfvenstam T, Örtqvist Å, Rotzén-Östlund M, Zweygberg-Wirgart B, Henriques-Normark B, Broliden K, Naucler P. Respiratory viruses associated with community-acquired pneumonia in children: matched case-control study. Thorax. 2015;70:847–853. doi: 10.1136/thoraxjnl-2015-206933.
    1. Rohde GGU. The role of viruses in CAP. Eur Respir Monogr. 2014;63:74–87.
    1. Schroth MK, Grimm E, Frindt P, Galagan DM, Konno SI, Love R, Gern JE. Rhinovirus replication causes RANTES production in primary bronchial epitjelial cells. Am J Respir Cell Mol Biol. 1999;20:1220–1228. doi: 10.1165/ajrcmb.20.6.3261.
    1. Spuesens EB, Fraaij PL, Visser EG, Hoogenboezem T, Hop WC, van Adrichem LN, Weber F, Moll HA, Broekman B, Berger MY, van Rijsoort-Vos T, van Belkum A, Schutten M, Pas SD, Osterhaus AD, Hartwig NG, Vink C, van Rossum AM. Carriage of mycoplasma pneumoniae in the upper respiratory tract of symptomatic and asymptomatic children: an observational study. PLoS Med. 2013;10:e1001444. doi: 10.1371/journal.pmed.1001444.
    1. Toivonen L, Schuez-Havupalo L, Rulli M, Ilonen J, Pelkonen J, Melen K, Julkunen I, Peltola V, Waris M. Blood MxA protein as a marker for respiratory virus infections in young children. J Clin Virol. 2015;62:8–13. doi: 10.1016/j.jcv.2014.11.018.
    1. Wang K, Wang W, Yan H, Ren P, Zhang J, Shen J, Deubel V. Correlation between bocavirus infection and humoral response, and co- infection with other respiratory viruses in children with acute respiratory infection. J Clin Virol. 2010;47:148–155. doi: 10.1016/j.jcv.2009.11.015.
    1. Williams JV, Harris PA, Tollefson SJ, Halburnt-Rush LL, Pingsterhaus JM, Edwards KM, Wright PF, Crowe JE., Jr Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. N Engl J Med. 2004;350:443–450. doi: 10.1056/NEJMoa025472.
    1. Woo PCY, Lau SKP, Yip CCY, Huang Y, Yuen K-Y. More and more coronaviruses: human coronaviruses HKU1. Viruses. 2009;1:57–71. doi: 10.3390/v1010057.
    1. Zar HJ, Barnett W, Stadler A, Gardner-Lubbe S, Myer L, Nicol MP. Aetiology of childhood pneumonia in a well vaccinated South African birth cohort: a nested case-control study of the Drakenstein Child Health Study. Lancet Respir Med. 2016;4:463–472. doi: 10.1016/S2213-2600(16)00096-5.
    1. Zhou L, Zheng S, Xiao Q, Ren L, Xie X, Luo J, Wang L, Huang A, Liu W, Liu E. Single detection of human bocavirus 1 with a high viral load in severe respiratory tract infections in previously healthy children. BMC Infect Dis. 2014;14:424. doi: 10.1186/1471-2334-14-424.

Source: PubMed

3
Abonnere