Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children.

Fleur M Moesker,Matthijs De Hoog,Pieter L A Fraaij,Marion P G Koopmans,Annemarie M C Van Rossum,Albert D M E Osterhaus,Jeroen J A Van Kampen,Oliver Schildgen

doi:10.1371/journal.pone.0150776

Abstract

BackgroundRespiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections.ObjectiveThe study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities.Study DesignBetween April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed.ResultsWe identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients.ConclusionBoth SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified.

Highlights

Worldwide acute respiratory tract infections (ARTIs) are among the most important causes of morbidity and mortality in children [1,2]
We identified 44 patients admitted to paediatric intensive care unit (PICU) with severe acute respiratory tract infections (SARIs) and 40 patients admitted to medium care (MC) with ARTI
Twelve viruses were associated with SARI, ten of which were associated with ARTI in the absence of typical bacterial and viral co-infections, with respiratory syncytial virus (RSV) and human rhinoviruses (HRVs) being the PLOS ONE | DOI:10.1371/journal.pone

Summary

Introduction

Worldwide acute respiratory tract infections (ARTIs) are among the most important causes of morbidity and mortality in children [1,2]. SARIs are characterized by respiratory failure and are an indication for admission to a paediatric intensive care unit (PICU) because of the need of respiratory support Some viruses such as respiratory syncytial virus (RSV) and influenza viruses have been shown to be the single cause of SARI, but for other viruses like human rhinoviruses (HRVs) and human coronavirus-NL63 (HCoV-NL63) this is under debate [3,4,5]. It may be that these viruses cause minimal or mild disease only, but in combination with bacterial co-infections, viral co-infections or alternatively, underlying high-risk conditions infection may result into SARI [6,7,8] This hypothesis follows observations of detection of viruses in the nasopharynx of children in absence of clinical signs and symptoms [9,10,11,12]. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections

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