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CIDRAP- Genetic tests could speed infection diagnosis in infants

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  • CIDRAP- Genetic tests could speed infection diagnosis in infants

    Source: http://www.cidrap.umn.edu/news-persp...gnosis-infants


    Genetic tests could speed infection diagnosis in infants
    Filed Under:
    Antimicrobial Stewardship
    Chris Dall | News Reporter | CIDRAP News
    | Aug 24, 2016
    Two new studies in the Journal of the American Medical Association (JAMA) show the potential of genetics to quickly determine whether feverish infants have a bacterial or a viral infection, a finding that could ultimately aid antibiotic stewardship efforts.
    Host gene response

    In the first of the two studies, an international team of researchers investigated whether bacterial infections can be distinguished from other types of fever-causing infections in young children by observing how host genes respond to an infection. From there, they wanted to determine if a subset of those genes could be used as the basis for a diagnostic test.
    By analyzing RNA expression in a discovery group of 240 febrile children (median age, 19 months) who were hospitalized in the United Kingdom, Spain, the Netherlands, and the United States, the researchers were able to identify a 38-transcript RNA expression signature that could distinguish bacterial from viral infections. They then were able narrow this down to 2 gene transcripts that could differentiate between bacterial and viral infections.
    When tested in a validation group of 130 children (23 with microbiologically confirmed bacterial infections, 28 with confirmed viral infections, and 79 with indeterminate infections), the 2-transcript signature accurately identified bacterial infections in all 23 children who had confirmed bacterial infections (sensitivity 100%), and accurately identified 27 out of 28 children who had confirmed viral infections (specificity 96.4%).
    The signature was also able to distinguish bacterial infections from other conditions, such as childhood inflammatory diseases and juvenile idiopathic arthritis.
    Biosignature test

    In the other study, a team of US researchers supported by the National Institutes of Health (NIH) was essentially exploring the same question?whether gene expression could be used to determine the type of infection in very young (60 days or younger) febrile infants.
    To do so, they tested blood samples from 279 infants who had fevers (89 with bacterial infections, and 190 without), along with 19 healthy infants. From these samples they were then able to identify a biosignature of 66 genes that could distinguish infants with and without a bacterial infection.
    In the validation test set, the sensitivity of the biosignature was 87% and the specificity was 89%. A smaller biosignature of 10 genes was able to identify infants with bacteremia 94% of the time.
    A 'holy grail' for ER physicians

    The two studies are significant because they provide a glimpse of hope that detecting bacterial infections in young febrile children can be done more quickly, and painlessly than the current diagnostic method, which requires doctors to obtain a culture and wait 24 to 48 hours for a result. While they wait for those results, they may have to admit the child to the hospital and administer antibiotics. And in most cases the infection turns out to be viral.
    The scenario is even more difficult with extremely young children, because obtaining a culture can involve invasive and painful procedures like urinary catheterization or spinal taps. In addition, the false-positive rate in infant cultures can be as high as 10%.
    "Finding an accurate but less invasive method to determine if babies with fevers have bacterial infections is a 'holy grail' for emergency department physicians," Nathan Kuppermann, MD, MPH, co-author of the NIH-funded study and professor and chair of the Department of Emergency Medicine at the University of California Davis School of Medicine, said in a press release.
    "This proof-of-concept study demonstrates that the evaluation of RNA biosignatures could one day be that tool."
    And it's a tool that could potentially reduce unnecessary antibiotic treatment. As JAMA Editor-in-Chief Howard Bauchner, MD, notes in an accompanying editorial, while only 5% to 8% of infants younger than 30 days presenting with fever to an emergency department have serious bacterial infections, the vast majority are hospitalized and receive antibiotics.
    The authors of both studies say further research is needed on larger and more diverse populations to assess the accuracy and clinical utility of these tests.
    See also:
    Aug 23 JAMA study: "Diagnostic test accuracy of a 2-transcript host RNA signature for discriminating bacterial vs viral infection in febrile children"
    Aug 23 JAMA study: "Association of RNA biosignatures with bacterial infections in febrile infants aged 60 days or younger"
    Aug 23 JAMA editorial
    Aug 23 Nationwide Children's Hospital press release



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