Highly frequent infections with human rhinovirus in healthy young children: a longitudinal cohort study.

Department of Pediatrics, Respiratory Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, The Netherlands.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology (Impact Factor: 3.12). 12/2011; 52(4):317-20. DOI: 10.1016/j.jcv.2011.09.003
Source: PubMed

ABSTRACT Human rhinoviruses (HRVs) are an important cause of respiratory tract infections.
We questioned whether the high prevalence rates of HRVs found in epidemiological studies is due to long-term individual continuity or a result of frequent infections with different HRV subtypes.
In a 6-month winter period 18 healthy controls, aged 0-7 years, were at least sampled every two weeks for HRV-PCR, irrespective of respiratory symptoms. All HRV positive samples were genotyped to determine HRV diversity.
In total 272 samples were collected. HRV was found in 101/272 (37%) samples. Genotyping revealed 27 different HRV subtypes. A median of 3.0 different HRV subtypes was found per child. Re-infections and continuity with identical HRV sequences were observed. The number of HRVs were higher in the youngest age group (p=0.01) and they had more different HRV subtypes (p=0.05) compared to oldest age group.
We found a high HRV exposition with a considerable diverse population of HRV subtypes in young children. These results have major implications for future research into the pathogenic role of HRV in respiratory diseases. Characterisation of subtypes will be necessary to discriminate between prolonged continuity and re-infections in patients with respiratory diseases.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The comparative yield of respiratory virus detection from nasopharyngeal aspirate (NPA) versus bronchoalveolar lavage (BAL) is uncertain. Furthermore, the significance of virus detection and its relationship to lower airway neutrophilic inflammation is poorly studied. To evaluate the sensitivity, specificity and predictive values of NPA for detecting respiratory viruses in BAL; and to determine the relationship between viruses and lower airway neutrophilia in children with non-acute respiratory illness. 150 paired NPA and BAL samples were obtained from 75 children aged <18 years undergoing flexible bronchoscopy for investigation of chronic respiratory symptoms. Viral studies were performed using polymerase chain reaction (PCR). Cellularity studies were performed on BALs. Diagnostic parameters of NPA compared to BAL and associations between viruses and lower airway %neutrophils were evaluated. NPA had a higher yield than BAL for detection of any respiratory virus (52 versus 38, respectively). NPA had a high sensitivity (92%) and low specificity (57%) for detecting HRV in BAL with poor kappa agreement value of 0.398 (95% CI 0.218-0.578, p<0.001). NPA had a fair sensitivity (69%) and good specificity (90.3%) for detecting HAdV on BAL, kappa agreement was 0.561 (95% CI 0.321-0.801, p<0.001). HAdV positivity on NPA, compared to negativity, was independently associated with heightened airway neutrophilia [mean difference (95% CI): 18 (1,35); p=0.042]. NPA has a higher yield for respiratory virus detection than BAL, however its diagnostic accuracy is dependent on viral species. Adenovirus positivity is associated with significantly heightened lower airway neutrophilia in children with chronic respiratory symptoms.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 09/2013; · 3.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The relative impact of human rhino/enteroviruses (HRV/EV) compared to influenza viruses on hospitalized children is unknown. OBJECTIVES: This retrospective study compared the epidemiology and clinical characteristics of hospitalized patients with HRV/EV to patients hospitalized with influenza virus. STUDY DESIGN: Respiratory specimens from hospitalized children submitted between January 1, 2009 and December 31, 2009 to Children's Hospital Colorado Virology Laboratory in Aurora, CO were tested by a commercial multiplex PCR for 16 respiratory viruses and subtypes. Patients with specimens positive for HRV/EV or influenza virus without bacterial or viral co-infection were selected for retrospective chart review. RESULTS: Of the 2299 patients with specimens tested during the study period, 427 (18.6%) were singly positive for HRV/EV and 202 (8.8%) for influenza virus (p<0.01). Children with HRV/EV were more likely to present with increased work of breathing (67.9% vs. 52.5%, p<0.01) with crackles (36.3% vs. 23.3%, p<0.01) and wheezing (41.7% vs. 22.8%, p<0.01) noted on exam. Children hospitalized with HRV/EV had a shorter median length of stay (2 days vs. 3 days, p<0.01), duration of fever (1 days vs. 3 days, p<0.01), and duration of hypoxemia (2 days vs. 3 days, p<0.01) than children with influenza virus. Similar percentages of children with HRV/EV and influenza virus were admitted to the PICU and required positive pressure ventilation. There were no deaths in children hospitalized with HRV/EV, whereas 6 children with influenza virus expired. CONCLUSIONS: HRV/EVs are common pathogens in hospitalized children associated with serious lower respiratory tract disease and significant morbidity, similar to influenza viruses.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 10/2012; · 3.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Carefully conducted, community-based, longitudinal studies are required to gain further understanding of the nature and timing of respiratory viruses causing infections in the population. However, such studies pose unique challenges for field specimen collection, including as we have observed the appearance of mould in some nasal swab specimens. We therefore investigated the impact of sample collection quality and the presence of visible mould in samples upon respiratory virus detection by real-time polymerase chain reaction (PCR) assays. Anterior nasal swab samples were collected from infants participating in an ongoing community-based, longitudinal, dynamic birth cohort study. The samples were first collected from each infant shortly after birth and weekly thereafter. They were then mailed to the laboratory where they were catalogued, stored at -80[degree sign]C and later screened by PCR for 17 respiratory viruses. The quality of specimen collection was assessed by screening for human deoxyribonucleic acid (DNA) using endogenous retrovirus 3 (ERV3). The impact of ERV3 load upon respiratory virus detection and the impact of visible mould observed in a subset of swabs reaching the laboratory upon both ERV3 loads and respiratory virus detection was determined. In total, 4933 nasal swabs were received in the laboratory. ERV3 load in nasal swabs was associated with respiratory virus detection. Reduced respiratory virus detection (odds ratio 0.35; 95% confidence interval 0.27-0.44) was observed in samples where the ERV3 could not be identified. Mould was associated with increased time of samples reaching the laboratory and reduced ERV3 loads and respiratory virus detection. Suboptimal sample collection and high levels of visible mould can impact negatively upon sample quality. Quality control measures, including monitoring human DNA loads using ERV3 as a marker for epithelial cell components in samples should be undertaken to optimize the validity of real-time PCR results for respiratory virus investigations in community-based studies.
    BMC Infectious Diseases 01/2014; 14(1):15. · 3.03 Impact Factor