Frequent Detection of Respiratory Viruses without Symptoms: Toward Defining Clinically Relevant Cutoff Values

Jansen, R.; Wieringa, Joanne; Koekkoek, Sylvie M.; Visser, Caroline E.; Pajkrt, Dasja; Molenkamp, Richard; Jong, Menno D. de; Schinkel, Janke

doi:10.1128/jcm.02094-10

Cited by 266 publications

(286 citation statements)

References 27 publications

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“…The interpretation of a viral detection is complicated by the fact that infections with multiple viruses are common in children with ARI and that many viruses have lately been reported to be found also in asymptomatic children. [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.…”

Section: Resultsmentioning

confidence: 99%

“…[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. To address these issues, we conducted a matched case-control study outside the influenza season to compare viral qPCR findings in nasopharyngeal aspirates from children with ARI versus population-based asymptomatic control subjects matched on age and calendar time.…”

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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: Resultsmentioning

confidence: 99%

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confidence: 99%

Clinical Utility of PCR for Common Viruses in Acute Respiratory Illness

et al. 2014

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“…Application of a cutoff value to quantitative PCR may identify clinically relevant rhinovirus infections. 12 Largescale longitudinal studies involving rhinovirus strain characterization are lacking, particularly in infants and children without underlying conditions. Most studies involve children with underlying illness or strain characterization is absent or limited.…”

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confidence: 99%

Duration of Rhinovirus Shedding in the Upper Respiratory Tract in the First Year of Life

Loeffelholz¹,

Trujillo

Pyles

et al. 2014

Pediatrics

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WHAT'S KNOWN ON THIS SUBJECT: Rhinoviruses are commonly detected in both acutely ill and asymptomatic infants and children. The finding may represent new infection or prolonged presence of rhinovirus RNA in the respiratory tract. WHAT THIS STUDY ADDS:In young, otherwise healthy infants, shedding of RNA from the same rhinovirus strain rarely persisted longer than 30 days. abstract BACKGROUND: Current molecular diagnostic methods have detected rhinovirus RNA in a high proportion of asymptomatic infants and children, raising the question of the clinical significance of these findings. This study investigates the prevalence of prolonged rhinovirus RNA presence in the upper respiratory tract of infants during the first year of life. METHODS:In a longitudinal study, infants were followed from birth up to 12 months. Nasopharyngeal specimens were collected monthly (months 1-6 and month 9) and during an upper respiratory infection. Rhinoviruses were detected by quantitative reverse-transcription polymerase chain reaction. Presence of repeated rhinovirus RNA was evaluated by nucleotide sequence analysis. RESULTS:A total of 2153 specimens from 362 infants were studied; 341 distinct rhinovirus infections in 216 infants were identified. Follow-up specimens were available within 30 days for 179 infections, creating the sample set to assess prolonged rhinovirus presence. Of the 179 infections, 46 involved the detection of the same rhinovirus strain in repeated specimens, including 8 events of prolonged presence of the same strain (detected in specimens collected .30 days apart), representing 4.5% of the evaluable rhinovirus infections. There were 26 events in which a rhinovirus strain was replaced by a different strain within a 30-day interval, representing 14.5% of the 179 infections. CONCLUSIONS:Although rhinovirus infections are common in healthy infants, prolonged presence of rhinovirus RNA in the respiratory tract after an upper respiratory infection was uncommon (,5%). Detection of rhinovirus RNA in an infant most likely represents an infection within a 30-day period. Dr Loeffelholz co-conceptualized and co-designed the study and wrote the initial manuscript; Dr Trujillo coordinated data collection; Dr Pyles conceptualized and supervised molecular virology studies and reviewed and revised the manuscript; Mr Miller performed molecular virology studies and provided interpretation of the data for inclusion in the manuscript; Dr Alvarez-Fernandez supervised data collection; Dr Pong performed molecular virology studies and performed data collection and analysis; Dr Chonmaitree conceptualized and designed the study, provided overall study supervision, and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. 4,5 A study in adult volunteers showed that cultivatable rhinoviruses were routinely recovered for ∼2 weeks after infection. 6 Recurrent rhinovirus infection has been described in patients with asthma 7 and in those at risk of developing...

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“…Более чувствительные методы лаборатор-ной диагностики, в частности полимеразная цепная реак-ция, позволили зафиксировать факт выделения вирусов из носоглотки до 3-4 нед после начала респиратор-ной инфекции [33]. Респираторные вирусы выявляются и у детей без клинических симптомов болезни, что связы-вают с перенесенной ранее инфекцией, субклиническим течением вирусной инфекции или периодом продромы ОРИ [34]. Известно, что снижение иммуногенной реак-тивности на фоне персистенции вирусов способствует развитию бактериальной инфекции [14,32].…”

Section: респираторные вирусыunclassified

Acute and Recurrent Respiratory Tract Infections: Possible Reduction of the Patient’s Pill Burden

Булгакова¹

2015

Vopr. sovr. pediatr.

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Frequent Detection of Respiratory Viruses without Symptoms: Toward Defining Clinically Relevant Cutoff Values

Cited by 266 publications

References 27 publications

Clinical Utility of PCR for Common Viruses in Acute Respiratory Illness

Clinical Utility of PCR for Common Viruses in Acute Respiratory Illness

Duration of Rhinovirus Shedding in the Upper Respiratory Tract in the First Year of Life

Acute and Recurrent Respiratory Tract Infections: Possible Reduction of the Patient’s Pill Burden

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