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Respiratory Viral Panels in Young Infants

Anne Blaschke, MD, Solomon Behar, MD, and Ilene Claudius, MD
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IIene and Sol interview ID expert Anne Blaschke about the clinical utility of respiratory viral panels in working up young febrile infants.

Pearls:

  • Infants aged 1-28 days who are febrile and rhinovirus positive should still get a full serious bacterial infection (SBI) work-up.  Infants aged 29-90 days old who are febrile, well appearing and rhinovirus positive should get a CBC, blood culture, and UA, but are deemed low risk for invasive disease and LP may not be needed.

  • Rhinovirus Polymerase Chain Reaction (PCR) tests can often be positive even in the asymptomatic individual

  • Given that the Respiratory Viral Panels (RVP’s)  have become so extensive and sensitive/specific, if an infant has a negative RVP but is febrile, the risk for SBI goes up.

 

  • How does PCR testing work and how sensitive and specific is it?  PCR tests work by looking at the nucleic acid, either DNA or RNA, of a pathogen.  The tests are very specific and very sensitive; the sensitivity is about 80-100% for most of the pathogens tested.  PCR is much more sensitive than an antigen test.

    • There are a number of technologies that laboratories use to check for viruses.  Over the last several years, several panels have been introduced with multiple viruses per panel.  Dr. Blaschke worked to develop the panel that they use at her hospital; this panel consists of 17 viruses and 3 bacteria that are known to cause respiratory illness.  

  • How long are RVP’s  expected to be positive for?  The length of positivity varies by virus.  RSV and influenza have positive tests for about a week whereas rhinovirus, for example, may be positive for 2-4 weeks.  Therefore, if a PCR test is positive for rhinovirus, one can’t be sure that that virus is active and actually causing disease, especially if you are suspicious for something else.

    • In an ill appearing child, who maybe has respiratory distress and/or hypoxemia, for example, and is rhinovirus positive, a CXR to look for pneumonia should still be considered.

  • How long after exposure does a PCR panel become positive?  This is a hard question to answer as generally PCR panels are performed once a person is symptomatic and therefore, it is hard to know when the test will become positive.

  • Do children with positive RVP tests for viral infections and pneumonia (either clinically or on CXR) need antibiotics?  This question has not been easy to answer, particularly with retrospective data.  The CDC has put together a multicenter network to study pneumonia in hospitalized children (Etiology of Pneumonia in the Community - EPIC).  The studies that have been published to date have prospectively enrolled children with pneumonia and extensively looked for respiratory pathogens.  As is known, most of the causes of pneumonia were viral and for most of these children, bacterial infections were not found.

    • As is done in adults, procalcitonin was looked as a marker for differentiating children with viral vs bacterial pneumonias.  Interestingly, when samples from the EPIC study were analyzed, most of the children with viral pneumonias had very low procalcitonin.  

    • In summary, a child with a known viral infection, as indicated by a positive RVP, and pneumonia, probably does not need antibiotics; in practice, however, this may be a hard clinical decision to make since bacterial superinfection can occur.

Jain S, et al. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med. 2015;372:835-45. DOI: 10.1056/NEJMoa.1405870

  • How much does an RVP cost?  The cost of an RVP is different at every hospital and differs by insurance carriers.  Most RVPs are at least in the hundreds of dollars and certainly more expensive than the rapid tests.

    • The decision of whether to order an RVP should be dictated by how one would use the results of the test.  In a child who, if RVP positive, would not be given antibiotics than ordering this test is reasonable. Data shows that children are discharged earlier from the hospital if found to be RVP positive and therefore, not given antibiotics.  Similarly, for influenza, if knowing whether the virus was present affects disposition, than an RVP is reasonable.

  • What is the cost effectiveness of the Rapid Multiplex PCR viral testing in children with influenza?  Ultimately, as above, it matters what the provider does with a positive or negative result.  The Rapid Multiplex PCR test is expensive, but very sensitive and specific. If hospitalizations were prevented by a positive test, than the model was shown to be cost effective.  

Nelson RE et al.  Economic analysis of rapid and sensitive polymerase chain reaction testing in the emergency department for influenza infections in children.  Pediatr Infect Dis J 2015. Jun;34(6):577-82. PMID ID: 25973935

 

Paper Discussion

Blaschke AJ et al.  Rhinovirus in Febrile Infants and Risk of Bacterial Infection.  Pediatrics. 2018 Feb;141(2). PMID 29343585

 

  • One goal of the above study was to risk stratify well appearing febrile infants with rhinovirus, aged 1-90 days of age, to see whether or not these infants also needed a full serious bacterial infection (SBI) evaluation.

    • Based on the study results, in infants 1-29 days of age with positive rhinovirus and fever, a full SBI evaluation should be completed.  

    • Interestingly, infants aged 29-90 days with a positive rhinovirus in this study population had lower rates of bloodstream infections and/or meningitis and therefore, were deemed “low risk” for developing sepsis.  They had the same rates of UTIs as other febrile infants who were not rhinovirus positive.

      • The authors came to the conclusion that an LP could be avoided in an infant aged 29-90 days who was febrile, well appearing, rhinovirus positive with a negative CBC and UA.

  • In this study, for all infants aged 1-90 days, the risk of bacterial infection in a virus negative infant was 13.4 percent.  The majority of these infections were UTIs. So, while the risk of invasive bacterial infection is still fairly low, it is higher in babies who are RVP negative.

  • This study only included children who were in the ED or admitted to the hospital and therefore, didn’t specifically address how RVPs should be used in the outpatient setting.

 

  • In infants, 29-90 days old who are RSV positive and well appearing, is any further work up needed?  In the Utah system where Blaschke practices, if these infants have temperatures less than or equal to 38.5, no additional lab testing is needed and the infant may be treated as low risk for serious bacterial infection (SBI).  The risk is cited as less than 2% for SBI.

    • In the same Utah system, for infants 28 days or younger with confirmed RSV, the physician may elect to test blood and urine and observe patient without antibiotics.  The most common cause of SBI in this group is UTI with or without bacteremia. Bacterial meningitis is very rare in infants with confirmed RSV.

      • Of course, in any baby who is getting antibiotics and/or is ill appearing, a full SBI evaluation should be completed.      

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The Ministry of Pediatric Sillywalks Full episode audio for MD edition 186:24 min - 87 MB - M4AHippo Peds RAP September 2018 Written Summary 392 KB - PDF

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