RSV, hMPV, parainfluenza virus likely causes of acute respiratory illness

Rhedin S. Pediatrics. 2014;doi:10.1542/peds.2013-3042.

  • March 6, 2014

Respiratory syncytial virus, metapneumovirus or parainfluenza virus are likely the causative agents of acute respiratory illness in children, although other respiratory viruses also may be detected with quantitative real-time PCR, according to recent study findings published in Pediatrics.

“We found that these viruses were almost exclusively found in cases making them likely causes of acute respiratory illness, and indicating that the current diagnostic method is capable of distinguishing infection from asymptomatic infection,” Samuel Rhedin, an MD-PhD student in the unit of infectious diseases at the Center for Molecular Medicine at Karolinksa Institutet in Stockholm, told Infectious Diseases in Children. “Other viruses were detected frequently in asymptomatic children making it hard to interpret the clinical significance of a finding. However, we still believe that rhinovirus is the most common cause of acute respiratory illness.”

Samuel Rhedin

Rhedin and colleagues evaluated children aged 5 years and younger with acute respiratory illness and matched controls from Sept. 1, 2011, to Jan. 20, 2012. The investigators compared quantitative real-time PCR (qPCR) findings from patients with acute respiratory illness with asymptomatic controls.

Overall, 72.3% of case patients had respiratory virus detected compared with 35.4% of control patients.

Nearly 8% of case patients had parainfluenza virus (PIV) detected vs. 0.5% of controls, and PIV1 was detected in 4.3% of case patients. PIV2 was detected among two case patients and PIV3 was detected among five case patients; however, PIV1 and PIV2 were not detected among any control patients. Five percent of case patients had RSV detected compared with 0.5% of controls. Nearly 5% of case patients had human metapneumovirus (hMPV) detected compared with 1% of controls. Nearly 16% of case patients had human bocavirus (hBoV) detected compared with 4.3% of controls. The most commonly detected virus was human rhinovirus (HRV) for both case patients (47.9%) and controls (21.5%).

Fever (P=.003), increased respiratory rate (P=.035), tachycardia (P=.01), and decreased O2 saturation (P=.05) were most commonly associated with hMPV infection. Decreased O2 saturation (P=.05) also was associated with human adenovirus (HAdV); increased respiratory rate (P=.003), tachycardia (P=.01), and reported coughing (P=.017) were associated with HBoV; coryza (P=.04) and absence of fever (P=.008) were associated with HRV; and RSV was associated with increased respiratory rate (P=.04) and wheezing (P=.03).

More than one virus was detected in 20.1% of case patients. Of those, 15.2% had two viruses, 4.3% had three viruses and 0.5% had four viruses. Patients with coinfections were more likely to have severe disease compared with case patients with single infections.

“Our study provides further evidence that hMPV is a pathogen associated with severe respiratory disease in children and indicate that PCR is a reliable method for diagnosing the virus,” Rhedin said. — by Amber Cox

Samuel Rhedin can be reached at the Department of Medicine Solna Infectious Diseases Unit (CMM L8:01), Karolinska University Hospital, 171 76 Stockholm, Sweden; email: samual.rhedin@ki.se.

Disclosure: The study was funded in part by the Karolinska Institutet.

Perspective

Christy Beneri

  • This study assessed the clinical utility of PCRs for the diagnosis of respiratory viral infections in cases with acute respiratory illness (ARIs) compared with asymptomatic controls, attempting to understand the relevance of viral detection in the context of sick vs. well child exams. In particular, viral detection in asymptomatic controls identifies the challenges to assign relevance; could this be prolonged shedding of virus or perhaps an early indication of illness to come?

    Not surprisingly, rhinovirus was the most common virus identified. Viral co-infection was detected in 20.1% of cases and 5.3% of controls. Cases with coinfections were more likely to have severe disease compared to cases with single infections. Further study will be needed to understand the role of each virus as causative of symptoms in cases of coinfection, especially given data on coinfections in controls.

    Interestingly, cases were more likely to attend daycare and less likely to be breast-fed. Case patients were also more likely to be treated with an antibiotic in the last year, suggesting that severity of symptoms more frequently brought these children to medical attention.

    Although some viral infections were associated with specific clinical features, such as fever or tachypnea, they are not specific enough to distinguish individual viral etiology. Rather, one needs to link the clinical presentation, such as croup or bronchiolitis, with the seasonality of viruses and age of the child.

    This study reminds us that given viral shedding in asymptomatic patients, good infection control practices will continue to be important. Lastly, viral diagnostic testing should be done only when clinically indicated.

    • Christy Beneri, DO
    • Assistant Professor, Department of Pediatrics, Stony Brook University Medical Center
  • Disclosures: Beneri reports no relevant financial disclosures.
Perspective
Ellen R. Wald, MD

Ellen Wald

  • The availability of sensitive tools such as quantitative real-time PCR (qPCR) for nucleic acids has dramatically increased our ability to identify viruses in children with acute respiratory infections especially compared to virus culture or antigen detection. The recent awareness that virus identification is also common in 19% to 40% of asymptomatic children has heightened our understanding that the significance of this identification must be carefully evaluated in the context of clinical findings. In this study, the investigators sampled children <5 years of age presenting to the ED with acute respiratory symptoms and had a unique population-based control group of asymptomatic subjects, matched for season and age, presenting for well-child care. Virus was identified in 72.3% of children with acute illness and 35.4% of control subjects. Identification of multiple viruses was associated with more severe disease. The identification of respiratory syncytial virus, parainfluenza virus and human metapneumovirus were strongly associated with acute respiratory illness. In contrast, bocavirus, human rhinovirus, coronaviruses, adenovirus and enterovirus were detected at such high frequency in control subjects that it might be hard to interpret the clinical significance of a positive qPCR finding. Accordingly, it is essential to know the background rate of asymptomatic virus detection in the population to appropriately interpret the results of testing in acutely ill children. Virus identification does not always indicate causality.
    • Ellen Wald, MD
    • Infectious Diseases in Children Editorial Board member
  • Disclosures: Wald reports no relevant financial disclosures.

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