Introduction Viral acute respiratory infections (ARIs) cause substantial child morbidity. Sensitive molecular-based assays aid virus detection, but the clinical significance of positive tests remains uncertain as some viruses may be found in both acutely ill and healthy children. We describe disease-pathogen associations of respiratory viruses and quantify virus-specific attributable risk of ARIs in healthy children during the first 2 years of life.
Methods One hundred fifty-eight term newborn babies in Brisbane, Australia, were recruited progressively into a longitudinal, community-based, birth cohort study conducted between September 2010 and October 2014. A daily tick-box diary captured predefined respiratory symptoms from birth until their second birthday. Weekly parent-collected nasal swabs were batch-tested for 17 respiratory viruses by PCR assays, allowing calculation of virus-specific attributable fractions in the exposed (AFE) to determine the proportion of virus-positive children whose ARI symptoms could be attributed to that particular virus.
Results Of 8100 nasal swabs analysed, 2646 (32.7%) were virus-positive (275 virus codetections, 3.4%), with human rhinoviruses accounting for 2058/2646 (77.8%) positive swabs. Viruses were detected in 1154/1530 (75.4%) ARI episodes and in 984/4308 (22.8%) swabs from asymptomatic periods. Respiratory syncytial virus (AFE: 68% (95% CI 45% to 82%)) and human metapneumovirus (AFE: 69% (95% CI 43% to 83%)) were strongly associated with higher risk of lower respiratory symptoms.
Discussion The strong association of respiratory syncytial virus and human metapneumovirus with ARIs and lower respiratory symptoms in young children managed within the community indicates successful development of vaccines against these two viruses should provide substantial health benefits.
- respiratory infection
- viral infection
- clinical epidemiology
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Contributors MS had full access to all of the data in the study and had the final responsibility for the decision to submit for publication.Study concept and design: KG, SBL, RSW, TPS, MDN, DW, DMW. Analysis and interpretation of data: MS, SBL, RSW, KG, TPS, AA, LM, SB. Drafting of the manuscript: MS, SBL, RSW, KG. Critical revision of the manuscript for important intellectual content: MS, RSW, TPS, DMW, AA, LM, SB, DW, MDN, SBL, KG. Statistical analysis: MS, RSW. Administrative and technical support: MS, RSW, SBL. Study supervision: SBL, RSW, KG.
Funding This study was supported by a National Health and Medical Research Council (NHMRC) (Australia) project grant (APP 615700) and a Children’s Hospital Foundation Queensland (CHFQ) (programme grant number: 50006). MS is the recipient of an NHMRC Dora Lush Clinical Scholarship and a CHFQ PhD Clinical Scholarship. SBL is the recipient of an NHMRC Early Career Fellowship and a CHFQ Mid-career Fellowship . DMW reports a Career Development Fellowship from the NHMRC. SB is the recipient of a CHFQ Early Career Fellowship.
Competing interests After completion of data collection for this study, MDN became a full-time employee of GlaxoSmithKline, GlaxoSmithKline Vaccines Value Health Science, 150 Beach Road, Gateway West #7, Singapore 189720, Singapore. Other authors have no competing interest to declare.
Ethics approval Children’s Health Queensland, Royal Brisbane and Women’s Hospital and The University of Queensland Human Research Ethics Committees.
Provenance and peer review Not commissioned; externally peer reviewed.
Correction notice This article has been corrected since it was published Online First. Figure 2 has been updated to include the missing figure legend.
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