Respiratory Viruses in Hospitalized Children with Influenza-Like Illness during the H1n1 2009 Pandemic in Sweden

Rhedin, Samuel; Hamrin, Johan; Nauclér, Pontus; Bennet, Rutger; Rotzén-Östlund, Maria; Färnert, Anna; Eriksson, Margareta

doi:10.1371/journal.pone.0051491

Cited by 26 publications

(32 citation statements)

References 24 publications

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“…19 In our data, coinfections were associated with increased risk of ARI compared with single infections, and they were also associated with more severe disease. However, we did not have sufficient power to fully address how different respiratory viruses interact in the development of ARI, which is of great importance when assessing the potential impact of targeted interventions.…”

Section: Discussionsupporting

confidence: 52%

“…[12][13][14][15][16][17] Numerous case series investigating respiratory viruses in hospitalized children with ARI have been published. [18][19][20] However, data are available from only a few case-control studies that examined to what extent specific respiratory viruses cause disease. 12,14,15,21 Furthermore, these studies had limitations in that they used hospital-based control subjects, which might have biased the results.…”

Section: Resultsmentioning

confidence: 99%

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Clinical Utility of PCR for Common Viruses in Acute Respiratory Illness

et al. 2014

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WHAT'S KNOWN ON THIS SUBJECT: Quantitative real-time polymerase chain reaction allows sensitive detection of respiratory viruses. The clinical significance of detection of specific viruses is not fully understood, however, and several viruses have been detected in the respiratory tract of asymptomatic children. WHAT THIS STUDY ADDS:Our results indicate that quantitative real-time polymerase chain reaction is limited at distinguishing acute infection from detection in asymptomatic children for rhinovirus, bocavirus, adenovirus, enterovirus, and coronavirus. abstract BACKGROUND: Acute respiratory illness (ARI) accounts for a large proportion of all visits to pediatric health facilities. Quantitative real-time polymerase chain reaction (qPCR) analyses allow sensitive detection of viral nucleic acids, but it is not clear to what extent specific viruses contribute to disease because many viruses have been detected in asymptomatic children. Better understanding of how to interpret viral findings is important to reduce unnecessary use of antibiotics. OBJECTIVE:To compare viral qPCR findings from children with ARI versus asymptomatic control subjects.METHODS: Nasopharyngeal aspirates were collected from children aged #5 years with ARI and from individually matched, asymptomatic, population-based control subjects during a noninfluenza season. Samples were analyzed by using qPCR for 16 viruses. RESULTS:Respiratory viruses were detected in 72.3% of the case patients (n 5 151) and 35.4% of the control subjects (n 5 74) (P 5 .001). Rhinovirus was the most common finding in both case patients and control subjects (47.9% and 21.5%, respectively), with a population-attributable proportion of 0.39 (95% confidence interval: 0.01 to 0.62). Metapneumovirus, parainfluenza viruses, and respiratory syncytial virus were highly overrepresented in case patients. Bocavirus was associated with ARI even after adjustment for coinfections with other viruses and was associated with severe disease. Enterovirus and coronavirus were equally common in case patients and control subjects.CONCLUSIONS: qPCR detection of respiratory syncytial virus, metapneumovirus, or parainfluenza viruses in children with ARI is likely to be causative of disease; detection of several other respiratory viruses must be interpreted with caution due to high detection rates in asymptomatic children. Although acute respiratory illness (ARI) in childrenaccountsfora large part ofall visits to pediatric health facilities and is a great economic burden on society, 1,2 our tools to diagnose the etiologic agents have until recently been limited. 3 Treatment with antibiotics induces development of antibiotic resistance in bacteria 4 and has a negligible effect on most ARIs, which generally are of viral origin. 5,6 Nevertheless, antibiotics are frequently prescribed due to lack of clinically valid diagnostic tests verifying a viral etiology. 7 Sensitive methods, such as quantitative real-time polymerase chain reaction (qPCR) analyses on nasopharyngeal samples, for a number of viru...

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Section: Discussionsupporting

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Clinical Utility of PCR for Common Viruses in Acute Respiratory Illness

et al. 2014

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“…Note: N = number, CI = confidence interval, GRADE [31] = Grading of Recommendations Assessment, Development and Evaluation, RR = risk ratio, SD = standard deviation, CI = confidence interval.GRADE Working Group grades of evidence. High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.aSerious design limitations: Eight [15], [19], [21], [32], [22], [35], [23] [24] of the eleven studies had serious design limitations including the absence of notification or adjustment for important prognostic factors and the absence of evidence provided on the similarity of co-interventions between both groups.bSerious Inconsistency: There was high statistical heterogeneity ( I 2 = 72%, p<0.001), which was not explained on further subgroup analysis.cSerious indirectness of the comparison: Only three [33] [19] [24] of the eleven studies focused primarily on the comparison of disease severity between single vs viral co-infections.dNo serious imprecision: The assumption of our a priori hypothesis of no difference was met. Cumulative sample size was appropriate.…”

Section: Methodsmentioning

confidence: 99%

Clinical Disease Severity of Respiratory Viral Co-Infection versus Single Viral Infection: A Systematic Review and Meta-Analysis

Asner¹,

Tran

Śmieja³

et al. 2014

PLoS ONE

139

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BackgroundResults from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections.MethodsWe searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses.ResultsTwenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) −0.20 days, 95% CI −0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p<0.001) with viral co-infection as compared to other age groups (I2 for subgroup analysis 64%, p = 0.04).ConclusionsNo differences in clinical disease severity between viral co-infections and single respiratory infections were documented. The suggested increased risk of mortality observed amongst children with viral co-infections requires further investigation.

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“…In a large study conducted in England, co-infection with influenza A virus and HAdV was associated with increased risk of admission to the general ward (14). In a Swedish study, no correlation was observed between the severity of symptoms in children hospitalized with influenza A infection with or without coinfection (27). Consistent with this finding, no difference was found between the severity of influenza A infection and the presence of respiratory viral co-infections in Spain and Brazil (28,29).…”

Section: Discussionmentioning

confidence: 70%

Detection of Respiratory Co-Infections in Children Less Than Five Years With Adenovirus Infection

Malekshahi

Shafiei-Jandaghi

Yavarian

et al. 2016

Arch Pediatr Infect Dis

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Background: Acute respiratory tract infection is associated with significant morbidity, mortality, and economic loss worldwide. Viral infections seem to be responsible for 80% of the cases. There are several reports on the influence of dual or multiple respiratory viral infections on the severity of disease in childhood. Objectives: A limited number of studies have been conducted on co-infection of Adenovirus (AdV) with coxsackievirus, human bocavirus (HBoV) and Mycoplasma pneumoniae (MP) in Iran. To address this, the present article focuses on both the etiology and epidemiology of multiple microbial respiratory infections (coxsackievirus, HBoV, MP and influenza virus) and their clinical significance in young Iranian children with confirmed AdV infection. Patients and Methods: Molecular detection of HBoV, coxsackievirus, MP and influenza virus was performed by conventional PCR in 71 respiratory adenovirus-positive samples obtained from children younger than 5 years of age. Results: Among the 71 adenovirus-positive samples, 6 (8.4%) were co-infected, three were co-infected with MP and three of which were co-infected with influenza A/H3N2. Of the six patients with co-infection, four were male and two were female; three patients were less than 1 year of age and the remaining were 2, 3 and 4 years of age. Moreover, there were two inpatients and four outpatients. Conclusions: Although several studies have investigated viral respiratory co-infection, no study has evaluated the rate of respiratory co-infections in adenovirus-positive samples from children younger than 5 years. However, this study has filled this gap, the the number of co-infections were too small to draw any definite conclusions. Therefore, large-scale studies using bigger samples are required to understand the clinical significance of polymicrobial acute respiratory infections.

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Respiratory Viruses in Hospitalized Children with Influenza-Like Illness during the H1n1 2009 Pandemic in Sweden

Cited by 26 publications

References 24 publications

Clinical Utility of PCR for Common Viruses in Acute Respiratory Illness

Clinical Utility of PCR for Common Viruses in Acute Respiratory Illness

Clinical Disease Severity of Respiratory Viral Co-Infection versus Single Viral Infection: A Systematic Review and Meta-Analysis

Detection of Respiratory Co-Infections in Children Less Than Five Years With Adenovirus Infection

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