Detection of Influenza A and B Viruses and Respiratory Syncytial Virus by Use of Clinical Laboratory Improvement Amendments of 1988 (CLIA)-Waived Point-of-Care Assays: a Paradigm Shift to Molecular Tests

Abstract

An accurate laboratory diagnosis of influenza, respiratory syncytial virus (RSV), and other respiratory viruses can help to guide patient management, antiviral therapy, infection prevention strategies, and epidemiologic monitoring. Influenza has been the primary driver of rapid laboratory testing due to its morbidity and mortality across all ages, the availability of antiviral therapy, which must be given early to have an effect, and the constant threat of new pandemic strains. Over the past 30 years, there has been an evolution in viral diagnostic testing, from viral culture to rapid antigen detection, and more recently, to highly sensitive nucleic acid amplification tests (NAAT), as well as a trend to testing at the point of care (POC). Simple rapid antigen immunoassays have long been the mainstay for POC testing for influenza A and B viruses and respiratory syncytial virus (RSV) but have been faulted for low sensitivity. In 2015, the first POC NAAT for the detection of influenza was approved by the Food and Drug Administration (FDA), ushering in a new era. In 2017, the FDA reclassified rapid influenza diagnostic tests (RIDTs) from class I to class II devices with new minimum performance standards and a requirement for annual reactivity testing. Consequently, many previously available RIDTs can no longer be purchased in the United States. In this review, recent developments in Clinical Laboratory Improvement Amendments of 1988 (CLIA)-waived testing for respiratory virus infections will be presented, with the focus on currently available FDA-cleared rapid antigen and molecular tests primarily for influenza A and B viruses and RSV.

Appropriate Use and Future Directions of Molecular Diagnostic Testing

“…Without question, the future of rapid, random-access molecular testing is moving closer and closer to the bedside or clinic room. Currently, there are a number of Clinical Laboratory Improvement Amendments (CLIA)-waived molecular tests for Influenza virus, some paired with respiratory syncytial virus, group A Streptococcal pharyngitis and for Chlamydia trachomatis and Neisseria gonorrhoeae (CT/NG) with excellent analytical sensitivity and specificity [51,52]. CLIAwaived means that these tests can be performed outside of a laboratory and by non-laboratory staff such as nurses.…”

Recent advances in the detection of respiratory virus infection in humans

“…The major viral pathogens include influenza virus, respiratory syncytial virus (RSV), coronavirus, adenovirus, and rhinovirus. In children below the age of five, the combined global mortality of only influenza and RSV reaches 300 000 deaths each year 2 . Other respiratory viruses, such as adenovirus and rhinovirus, are associated with lower mortality, but significant morbidity, causing a huge economic burden 3 .…”

“…Over the past decades, an evolution in viral diagnostic testing has been seen, all the way from conventional approaches to rapid antigen detection. More recently, highly sensitive nucleic acid amplification tests (NAAT) and point‐of‐care tests (POCT) have been developed 2 …”

Point of care influenza testing using Alere-i Influenza A & B assay: a practical assessment

“…Young et al found Ai-POCIT less sensitive than the Cobas Liat POCIT, using stored UTM samples (5). There has also been an excellent review of rapid tests for influenza recently published (6).…”