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Advances and New Technologies in Syndromic Testing

Test tubes of blood.
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Syndromic testing combines tests for multiple pathogens capable of causing overlapping signs and symptoms into a single panel. As a result, patients can be tested for multiple different conditions simultaneously, rather than testing for the possible causes individually, reducing the time taken to make a medical diagnosis.


Technology Networks spoke with Arvind Kothandaraman, managing director of specialty diagnostics at PerkinElmer, to find out more about the technologies underpinning syndromic testing, recent advances in the field and its possible role in pandemic prevention.


Anna MacDonald (AM): What is syndromic testing? Is it another term for multiplexing? Does multiplexing compromise the detection accuracy of individual genetic/infectious factors?

Arvind Kothandaraman (AK): Syndromic testing uses multiplex molecular panels to test for a broad array of pathogens that are associated with a particular syndrome. The primers and probes for different viruses are carefully selected. Specific regions are labeled with unique fluorescent dyes to generate target-specific signals and optimized such that multiplexing does not compromise the accurate detection of individual targets.

One common example and category of syndromic tests are those that enable the simultaneous qualitative detection and differentiation of SARS-CoV-2, influenza A, influenza B and respiratory syncytial virus (RSV). Symptoms presented by influenza and COVID-19 are often the same, and individuals can be infected with none or multiple of these viruses at once.

AM: Besides the convenience of a single test that detects multiple pathogens, are there any other diagnostic/practical advantages for syndromic testing in the clinical lab setting?

AK: The convenience of using a single test has more downstream benefits than one might initially expect. Beyond the test itself, many more resources go into a clinical laboratory workflow (i.e., collection media, extraction kits, reagents, etc.), which all come at a cost. Then there are the human resources necessary to keep a lab running, which managers must thoughtfully account and plan for too. When testing needs surge during times such as peak flu season, or as we saw in the early days of the COVID-19 pandemic, the lab is exposed to significant financial and operational strain. Rather than running multiple panels, a single combined test for the flu and other conditions with similar symptoms can lessen that strain.

Additionally, the importance of saving time by using syndromic testing cannot be understated. Examining Australia’s 2022 flu season data, the possibility of a more severe flu season is real. If clinical labs help identify active infections as soon as possible, those individuals can seek treatment if needed, isolate and help stop the virus from spreading further. The relatively short turnaround time also makes syndromic testing more appealing.

AM: Can you tell us about some recent advances in syndromic testing for infectious diseases?

AK: The emergence of new viruses like the one that causes monkeypox has caused many to revisit talks about broader syndromic tests in clinical labs. We can expect to see other additions to syndromic test panels moving forward that will help achieve broader coverage and identify viruses that are not routinely screened for by most clinical labs. The question often revolves around the health economics of testing for uncommon pathogens and the willingness to pay for these tests.

AM: How are combination/syndromic tests developed?

AK: The first step in designing a multiplex assay is target identification. Scientific publications, databases like NCBI and GISAID, as well as agencies like the World Health Organization offer reliable information that test developers leverage in this step of the development process. Developers are also careful to avoid genes that are prone to mutations in choosing targets to identify. Subsequent stages of development include:

  • Primer design using bioinformatics algorithms
  • Wet lab testing to ensure the primer/probe designs work well
  • Optimization of cycling and other conditions to increase specificity and sensitivity
  • Design iterations as needed
  • Assay validation with commercially available reference materials and/or patient samples

AM: Are certain technologies more amenable to syndromic testing than others e.g., polymerase chain reaction, ELISAs etc.?

AK: Preferred methods will vary from lab to lab, but over the last several years, polymerase chain reaction (PCR) technology has earned a reputation as being the gold standard in diagnostics this includes syndromic testing applications. PCR tests may use blood, saliva, mucus or tissue samples, which allow for greater flexibility in lab workflow. PCR tests also tend to allow for greater sensitivity and specificity, which are two very important elements in tests designed to detect highly infectious diseases like those we’re discussing.

AM: How scalable are such combination tests?

AK: Laboratory automation can also make a big difference in the scalability of syndromic tests. FDA and emergency use authorization (EUA) tests such as PKamp™ Respiratory SARS-CoV-2 RT-PCR Panel 1 allow laboratories to scale their testing up or down as the workflow remains largely the same. With automation flexibility, the assay can be coupled with modular, scalable extraction and liquid handling options suitable to process a broad range of samples every day (from a few hundred to over one hundred thousand).

AM: Can you tell us about the role of syndromic testing in pandemic surveillance and prevention?

AK: Syndromic testing is especially valuable in building a robust global pandemic surveillance system. It can help avoid confusion that may arise from similar symptoms caused by different infections and reduce cost and resource strain on healthcare providers as well as labs. With proper differentiation, public health organizations will be in a better position to take appropriate measures to prevent further transmissions of existing and emerging contagious pathogens.

Arvind Kothandaraman was speaking to Anna MacDonald, Science Writer for Technology Networks.