Are we missing respiratory viral infections in infants and children? Comparison of a hospital-based quality management system with standard of care

Clin Microbiol Infect. 2019 Mar;25(3):380.e9-380.e16. doi: 10.1016/j.cmi.2018.05.023. Epub 2018 Jun 12.


Objectives: Hospital-based surveillance of influenza and acute respiratory infections relies on International Classification of Diseases (ICD) codes and hospital laboratory reports (Standard-of-Care). It is unclear how many cases are missed with either method, i.e. remain undiagnosed/coded as influenza and other respiratory virus infections. Various influenza-like illness (ILI) definitions co-exist with little guidance on how to use them. We compared the diagnostic accuracy of standard surveillance methods with a prospective quality management (QM) programme at a Berlin children's hospital with the Robert Koch Institute.

Methods: Independent from routine care, all patients fulfilling pre-defined ILI-criteria (QM-ILI) participated in the QM programme. A separate QM team conducted standardized clinical assessments and collected nasopharyngeal specimens for blinded real-time quantitative PCR for influenza A/B viruses, respiratory syncytial virus, adenovirus, rhinovirus and human metapneumovirus.

Results: Among 6073 individuals with ILI qualifying for the QM programme, only 8.7% (528/6073) would have undergone virus diagnostics during Standard-of-Care. Surveillance based on ICD codes would have missed 61% (359/587) of influenza diagnoses. Of baseline ICD codes, 53.2% (2811/5282) were non-specific, most commonly J06 ('acute upper respiratory infection'). Comparison of stakeholder case definitions revealed that QM-ILI and the WHO ILI case definition showed the highest overall sensitivities (84%-97% and 45%-68%, respectively) and the CDC ILI definition had the highest sensitivity for influenza infections (36%, 95% CI 31.4-40.8 for influenza A and 48%, 95% CI 40.5-54.7 for influenza B).

Conclusions: Disease-burden estimates and surveillance should account for the underreporting of cases in routine care. Future studies should explore the effect of ILI screening and surveillance in various age groups and settings. Diagnostic algorithms should be based on the WHO ILI case definition combined with targeted testing.

Keywords: Case definitions; Children; Diagnostics; Influenza; Influenza-like illness; International classification of disease coding; Quality management; Respiratory viruses.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Female
  • Hospitals
  • Humans
  • Infant
  • Infant, Newborn
  • Influenza, Human / classification
  • Influenza, Human / diagnosis
  • International Classification of Diseases / standards
  • Male
  • Nasopharynx / virology
  • Population Surveillance
  • Prospective Studies
  • Quality Assurance, Health Care / standards
  • Quality Assurance, Health Care / statistics & numerical data*
  • Real-Time Polymerase Chain Reaction
  • Respiratory Tract Infections / classification
  • Respiratory Tract Infections / diagnosis*
  • Respiratory Tract Infections / virology
  • Standard of Care / standards
  • Standard of Care / statistics & numerical data*
  • Virus Diseases / classification
  • Virus Diseases / diagnosis*
  • Viruses / isolation & purification*