Symptomatic and asymptomatic respiratory viral infections in the first year of life: association with acute otitis media development

Tasnee Chonmaitree, Pedro Alvarez-Fernandez, Kristofer Jennings, Rocio Trujillo, Tal Marom, Michael J Loeffelholz, Aaron L Miller, David P McCormick, Janak A Patel, Richard B Pyles, Tasnee Chonmaitree, Pedro Alvarez-Fernandez, Kristofer Jennings, Rocio Trujillo, Tal Marom, Michael J Loeffelholz, Aaron L Miller, David P McCormick, Janak A Patel, Richard B Pyles

Abstract

Background: Sensitive diagnostic assays have increased the detection of viruses in asymptomatic individuals. The clinical significance of asymptomatic respiratory viral infection in infants is unknown.

Methods: High-throughput, quantitative polymerase chain reaction assays were used to detect 13 common respiratory viruses from nasopharyngeal specimens collected during 2028 visits from 362 infants followed from near birth up to 12 months of age. Specimens were collected at monthly interval (months 1-6 and month 9) and during upper respiratory tract infection (URTI) episodes. Subjects were followed closely for acute otitis media (AOM) development.

Results: Viruses were detected in 76% of 394 URTI specimens and 27% of asymptomatic monthly specimens. Rhinovirus was detected most often; multiple viruses were detected in 29% of the specimens. Generalized mixed-model analyses associated symptoms with increasing age and female sex; detection of respiratory syncytial virus (RSV), influenza, rhinovirus, metapneumovirus, and adenovirus was highly associated with symptoms. Increasing age was also associated with multiple virus detection. Overall, 403 asymptomatic viral infections in 237 infants were identified. Viral load was significantly higher in URTI specimens than asymptomatic specimens but did not differentiate cases of URTI with and without AOM complication. The rate of AOM complicating URTI was 27%; no AOM occurred following asymptomatic viral infections. AOM development was associated with increasing age and infection with RSV, rhinovirus, enterovirus, adenovirus, and bocavirus.

Conclusions: Compared to symptomatic infection, asymptomatic viral infection in infants is associated with young age, male sex, low viral load, specific viruses, and single virus detection. Asymptomatic viral infection did not result in AOM.

Keywords: acute otitis media; asymptomatic infection; common cold; respiratory viruses; rhinovirus.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.
Figure 1.
Proportion of respiratory viruses in 795 respiratory samples (1079 viruses) detected singly or in combination with other viruses. Rhinovirus was the most common and accounted for 40% of all detected viruses. In 567 (71%) specimens, a single virus was detected; 2 viruses were detected in 181 (23%) specimens; ≥3 viruses were identified in 47 (6%) specimens. Abbreviation: RSV, respiratory syncytial virus.
Figure 2.
Figure 2.
Percentage of virus-positive samples (asymptomatic vs symptomatic infections) by month (combined data 2009–2013). Symptomatic infection includes upper respiratory tract infection episodes and monthly visits with symptom history.
Figure 3.
Figure 3.
Viral load by specimen type; the median is represented by the heavy horizontal line. The interquartile range is shown by the boxes. The number of specimens in each category is shown at the bottom of each column. Abbreviations: AOM, acute otitis media; URTI, upper respiratory tract infection.

References

    1. Alper CM, Winther B, Mandel EM, Hendley JO, Doyle WJ. Rate of concurrent otitis media in upper respiratory tract infections with specific viruses. Arch Otolaryngol Head Neck Surg. 2009;135:17–21.
    1. Chonmaitree T, Revai K, Grady JJ, et al. Viral upper respiratory tract infection and otitis media complication in young children. Clin Infect Dis. 2008;46:815–23.
    1. Marom T, Alvarez-Fernandez PE, Jennings K, Patel JA, McCormick DP, Chonmaitree T. Acute bacterial sinusitis complicating viral upper respiratory tract infections in young children. Pediatr Infect Dis J. 2014;33:803–8.
    1. Kvaerner KJ, Nafstad P, Hagen JA, Mair IW, Jaakkola JJ. Recurrent acute otitis media: the significance of age at onset. Acta Otolaryngol. 1997;117:578–84.
    1. Teele DW, Klein JO, Rosner B. Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective cohort study. J Infect Dis. 1989;160:83–94.
    1. Jansen RR, Wieringa J, Koekkoek SM, et al. Frequent detection of respiratory viruses without symptoms: toward defining clinically relevant cutoff values. J Clin Microbiol. 2011;49:2631–6.
    1. Singleton RJ, Bulkow LR, Miernyk K, et al. Viral respiratory infections in hospitalized and community control children in Alaska. J Med Virol. 2010;82:1282–90.
    1. Van der Zalm MM, van Ewijk BE, Wilbrink B, Uiterwaal CS, Wolfs TF, van der Ent CK. Respiratory pathogens in children with and without respiratory symptoms. J Pediatr. 2009;154:396–400.
    1. Van Gageldonk-Lafeber AB, Heijnen ML, Bartelds AI, Peters MF, van der Plas SM, Wilbrink B. A case-control study of acute respiratory tract infection in general practice patients in the Netherlands. Clin Infect Dis. 2005;41:490–7.
    1. Advani S, Sengupta A, Forman M, Valsamakis A, Milstone AM. Detecting respiratory viruses in asymptomatic children. Pediatr Infect Dis J. 2012;31:1221–6.
    1. Patel JA, Nair S, Revai K, et al. Association of proinflammatory cytokine gene polymorphisms with susceptibility to otitis media. Pediatrics. 2006;118:2273–9.
    1. Revai K, Patel JA, Grady JJ, Nair S, Matalon R, Chonmaitree T. Association between cytokine gene polymorphisms and risk for upper respiratory tract infection and acute otitis media. Clin Infect Dis. 2009;49:257–61.
    1. Loeffelholz MJ, Pong DL, Pyles RB, et al. Comparison of the Filmarray(R) respiratory panel and prodesse(R) real-time PCR assays for detection of respiratory pathogens. J Clin Microbiol. 2011;49:4083–8.
    1. Kalu SU, Loeffelholz M, Beck E, et al. Persistence of adenovirus nucleic acids in nasopharyngeal secretions: a diagnostic conundrum. Pediatr Infect Dis J. 2010;29:746–50.
    1. Nokso-Koivisto J, Pitkaranta A, Blomqvist S, et al. Viral etiology of frequently recurring respiratory tract infections in children. Clin Infect Dis. 2002;35:540–6.
    1. Martin ET, Fairchok MP, Kuypers J, et al. Frequent and prolonged shedding of bocavirus in young children attending daycare. J Infect Dis. 2010;201:1625–32.
    1. Rodrigues F, Foster D, Nicoli E, et al. Relationships between rhinitis symptoms, respiratory viral infections and nasopharyngeal colonization with Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus in children attending daycare. Pediatr Infect Dis J. 2013;32:227–32.
    1. Butler CC, Hood K, Kinnersley P, Robling M, Prout H, Houston H. Predicting the clinical course of suspected acute viral upper respiratory tract infection in children. Fam Pract. 2005;22:92–5.
    1. Rotzén-Östlund M, Eriksson M, Tiveljung Lindell A, Allander T, Zweygberg Wirgart B, Grillner L. Children with multiple viral respiratory infections are older than those with single viruses. Acta Paediatr. 2014;103:100–4.
    1. Jartti T, Lee WM, Pappas T, Evans M, Lemanske RF, Jr, Gern JE. Serial viral infections in infants with recurrent respiratory illnesses. Eur Respir J. 2008;32:314–20.
    1. Miller EK, Gebretsadik T, Carroll KN, et al. Viral etiologies of infant bronchiolitis, croup and upper respiratory illness during 4 consecutive years. Pediatr Infect Dis J. 2013;32:950–5.
    1. Rhedin S, Lindstrand A, Rotzén-Östlund M, et al. Clinical utility of PCR for common viruses in acute respiratory illness. Pediatrics. 2014;133:e538–45.
    1. Martin ET, Kuypers J, Heugel J, Englund JA. Clinical disease and viral load in children infected with respiratory syncytial virus or human metapneumovirus. Diagn Microbiol Infect Dis. 2008;62:382–8.
    1. Houben ML, Coenjaerts FE, Rossen JW, et al. Disease severity and viral load are correlated in infants with primary respiratory syncytial virus infection in the community. J Med Virol. 2010;82:1266–71.
    1. Franz A, Adams O, Willems R, et al. Correlation of viral load of respiratory pathogens and co-infections with disease severity in children hospitalized for lower respiratory tract infection. J Clin Virol. 2010;48:239–45.
    1. Fuller JA, Njenga MK, Bigogo G, et al. Association of the CT values of real-time PCR of viral upper respiratory tract infection with clinical severity, Kenya. J Med Virol. 2013;85:924–32.
    1. Nokso-Koivisto J, Pyles RB, Miller AL, Patel JA, Loeffelholz M, Chonmaitree T. Viral load and acute otitis media development after human metapneumovirus upper respiratory tract infection. Pediatr Infect Dis J. 2012;31:763–6.
    1. Nokso-Koivisto J, Pyles RB, Miller A, Jennings K, Loeffelholz MJ, Chonmaitree T. Role of human bocavirus in upper respiratory tract infections and acute otitis media. J Pediatr Infect Dis Soc. 2014;3:98–103.
    1. Revai K, Mamidi D, Chonmaitree T. Association of nasopharyngeal bacterial colonization during upper respiratory tract infection and the development of acute otitis media. Clin Infect Dis. 2008;46:e34–7.
    1. Hoffman HJ, Daly KA, Bainbridge KE, et al. Panel 1: Epidemiology, natural history, and risk factors. Report of the 10th Research Conference on Recent Advances in Otitis Media. Otolaryngol Head Neck Surg. 2013;148(4 suppl):E1–25.

Source: PubMed

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