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Molecular diagnostics for infectious disease at the point of care

Sponsored by Alere

Breakthroughs in technology have now brought amplified DNA or RNA measurement for infectious disease detection to the point of care

Molecular diagnostics is a broad term that refers to laboratory measurement of nucleic acid (DNA or RNA) or protein biomarkers.  As applied to detecting infectious disease, the term ‘molecular’ is used when measuring DNA or RNA sequences unique to the infectious organisms, typically viruses or bacteria.

Real advances in molecular technology emerged with the ability to amplify DNA or RNA.  With such techniques it became possible to measure a vanishingly small quantity of an infectious organism.  This led to significant improvement in the sensitivity for detecting disease-causing organisms.  The DNA or RNA sequences are very specific for the target organism, and hence amplified nucleic acid measurement represented a dramatic improvement in infectious disease detection.

Achieving such advances has historically meant complex, expensive, laboratory equipment and highly trained laboratorians in hospital or large commercial laboratory environments.  But breakthroughs in technology have now brought amplified DNA or RNA measurement for infectious disease detection to the point of care (POC).  One such breakthrough has been to eliminate the repeated cycle of heating and then cooling again (called thermocycling) that is part of the traditional polymerase chain reaction (PCR) technique, and to instead conduct the amplification at a constant temperature (isothermal).

A POC platform that uses such isothermal amplification technology for detecting various infectious organisms was the first molecular POC platform to receive a CLIA waiver from the FDA for any type of nucleic acid-based test.  Specifically, this was a rapid, POC molecular test for influenza A & B.1  As the FDA noted, CLIA waiver for this platform allows this technology to be used in a greater variety of healthcare settings; these include physician offices and outpatient clinics.  In fact, this platform, the Alere™ i Instrument and its menu of tests (Influenza A & B, Strep A, and RSV2) was designed and engineered to meet the FDA’s CLIA waiver requirements rather than being a scaled-down, repurposed laboratory analyzer.

Rapid, CLIA waived, immunoassay tests (sometimes called ‘lateral flow’ tests) that detect infectious organism antigens for influenza, Group A Streptococcus (GAS), and respiratory syncytial virus (RSV) are widely available and used routinely by clinicians in hospital EDs, physician offices, and clinics.  While such tests have been proven to be useful in managing patients when test results are positive, lack of sensitivity creates a clinical challenge when results are negative.  Confirming negatives with centralized laboratory molecular tests can take hours and culturing the infectious organism can take days.  Such delays in obtaining test results do not enable timely treatment decision making.

The value POC molecular technology brings to infectious disease testing is in combining speed with accuracy which delivers actionable information for the patient encounter.  As an example, rapid immunoassay tests for detecting GAS infection are the most commonly used respiratory infection test.  A meta-analysis of 105 clinical studies evaluating such tests compared with culture in 58,244 children found a summary sensitivity of 85.4%.3  Compared to this, a rapid, POC molecular GAS test yielded a sensitivity of 95.9% compared to culture.4  This increase in sensitivity obtained with a rapid, molecular POC test translates to a 72% reduction in the number of false negative results.  Similar improvements in sensitivity can be achieved when employing a rapid POC molecular test for influenza5 compared to rapid immunoassays.6

The ability to amplify DNA or RNA sequences from infectious organisms enabled improvements in test accuracy over older technologies by increasing the sensitivity of detection while maintaining or improving specificity for the target organism.  And now, POC molecular technology that can deliver results in minutes advances patient care to the next level as actionable information enables clinicians to make faster decisions with greater confidence.

References

  1. FDA News Release, January 6, 2015. FDA grants first CLIA waiver for nucleic acid-based flu diagnostic test. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm429127.htm, accessed 8/29/16
  2. Alere™ i RSV is 510(k)-cleared as a CLIA moderate complexity test; CLIA waiver application pending
  3. Cohen JF et al. Rapid antigen detection test for group A streptococcus in children with pharyngitis. Cochrane Database of Systematic Reviews 2016, Issue 7.
  4. Cohen DM et al. Multicenter clinical evaluation of the novel Alere i Strep A isothermal nucleic acid amplification test. Journal of Clinical Microbiology. 2015;53(7):2258-61.
  5. Bell J et al. Multicenter clinical evaluation of the novel Alere™ i Influenza A&B isothermal nucleic acid amplification test. J Clin Virol. 2014 Sep;61(1):81-6.
  6. Chartrand C et al. Accuracy of rapid influenza diagnostic tests: a meta-analysis. Ann Intern Med. 2012;156(7):500-11.

 

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