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Syndromic Testing

A faster diagnostic option for meningitis and encephalitis

By QIAGEN Syndromic Testing

Despite advances in vaccines and other preventative measures, meningitis and encephalitis continue to claim lives across the globe. The expanded use of rapid, evidence-based diagnostic tools will be crucial for reducing the harm caused by these infections.

David M. had been dealing with a cluster of unusual symptoms, including a severe earache, headaches and vomiting, for 48 hours before his doctor conducted a lumbar puncture (1). From then, it was still a few days until his test results came back: David had bacterial meningitis. 

Unfortunately, five days had passed between the 51-year-old from Glasgow’s first symptoms and the positive diagnosis. When doctors finally learned that David was infected with Streptococcus pneumoniae, they admitted him to the hospital, where he stayed for ten days. David’s hearing suffered for a few weeks, and he felt tired for some time after returning home from the hospital.

Still, David was lucky. He survived and today has no lasting effects from battling bacterial meningitis.

Around the world, about 2.5 million people contract bacterial meningitis each year (2). One in five cases results in permanent complications, such as hearing loss, brain damage and seizures (3,4). And without treatment, about half of patients with bacterial meningitis will die (3).

Even just a six-hour delay in treating bacterial meningitis can lead to an increased risk of mortality or long-term severe complications (5).

Early pathogen detection is critical in treating bacterial meningitis, as well as another central nervous system (CNS) infection, encephalitis. For both meningitis and encephalitis, swift, accurate diagnosis and treatment is crucial to preventing long-term complications and, in some cases, saving a person’s life (6–8).

Unfortunately, the traditional approach for diagnosing these CNS infections often takes many lab tests spread across multiple days. These conventional practices leave doctors in the dark and patients at greater risk while awaiting test results.

But multiplex syndromic testing offers an easier, faster and more accurate way to supplement the diagnosis of meningitis and encephalitis.
Unlike traditional diagnostic methods, like bacterial culture and microscopy, syndromic testing uses multiplex PCR to test for several pathogens at once – and it only takes around an hour.

The problem with traditional meningitis/encephalitis testing

Doctors traditionally rely on several different tests to diagnose CNS infections (9,10). These methods include:
  • Computerized tomography (CT) or magnetic resonance imaging (MRI) scans
  • Blood draw, followed by blood chemistry and blood culture
  • Lumbar puncture, followed by cerebrospinal fluid (CSF) microbiology and chemistry, including CSF culture, Gram stain and latex agglutination assays
  • Traditional molecular diagnostics using single-target PCR and send out tests
Using these traditional methods alone presents a number of challenges to the diagnostic laboratorian, the clinician and the patient:

  • Time: While some of these traditional methods can provide results in a matter of hours, it can take up to two days or more for pathogen identification from CSF culture (9). And if send-out tests are required, results are typically delivered in days, not hours.
  • Labor and expertise: Most traditional methods for diagnosing CNS infections take time, effort and specific expertise to complete. Further, distinct assays – and distinct sets of expertise – are required to determine if the cause of the infection is viral or bacterial (9).
  • Low diagnostic yields: The rate of pathogen identification from CSF and blood culture varies between 62–97% and 40–90%, respectively, depending on a patient’s antibiotic status and the pathogen causing the infection (9). The efficacy of Gram stain and latex agglutination are also impacted if a patient has received prior antibiotic treatment. The sensitivity of bacterial meningitis Gram stain is around 60%, while the sensitivity for latex agglutination ranges from 7–100% (9).
  • Limited CSF sample volumes: For CSF-based assays, all of these methods must rely on the limited volume of CSF that is collected from patients during a lumbar puncture.
As clinicians wait on these tests for comprehensive results, they are unable to make targeted treatment decisions. But multiplex syndromic testing offers an additional molecular approach that can help detect a CNS infection in less time and with less effort than traditional tests alone.

What is multiplex syndromic testing?

The U.S. Food and Drug Administration cleared the first syndromic testing panel in 2008 (10). Since then, syndromic testing has become increasingly available to doctors for diagnosing various ailments, including CNS infections.

Syndromic testing uses multiplexed real-time polymerase chain reaction (PCR) to analyze multiple bacterial, viral and fungal pathogens simultaneously in a small patient sample. Doing so helps doctors accurately diagnose patients presenting with many overlapping symptoms. 

And syndromic testing is faster and easier to conduct than most traditional methods. For example, a single syndromic test can deliver results in about an hour. These tests provide two possible results: positive or negative. Syndromic testing’s binary results eliminate the subjective readings of traditional meningitis and encephalitis tests.

An example of a positive result, where two pathogens were detected in a patient sample.

Benefits of syndromic testing for CNS infections

Syndromic testing is an ideal supportive diagnostic technique for meningitis and encephalitis since time is critical when treating these infections. Syndromic testing has the potential to:

  • Significantly reduce the time to diagnosis, which could reduce the risk of death and long-term complications in patients with CNS infections (11,12).
  • Quickly distinguish between viral and bacterial meningitis pathogens, enabling targeted treatment decisions to be made (11,13).
  • Decrease a patient’s time in the hospital (11,12,14), lowering the risk of hospital-acquired infections and saving on overall healthcare costs (11,14,15).
  • Support antimicrobial stewardship efforts by increasing diagnostic certainty, which can help optimize antimicrobial use (including de-escalation) (16) and reduce the risk of antimicrobial resistance emerging.

Syndromic testing delivers these benefits by providing fast, evidence-based pathogen identification, which enables improved patient management and targeted treatment to be initiated sooner. 

A better way to diagnose CNS infections

Fast, reliable results are critical for diagnosing and treating meningitis and encephalitis. Fortunately, syndromic testing delivers fast, accurate results for pathogens most often associated with CNS infections. 
With syndromic testing, you can:
  • Run tests on-demand, 24/7, without needing many highly-trained lab staff with specific expertise
  • Get comprehensive results, including differentiating bacterial, viral and fungal pathogens, in about an hour
  • Provide improved, evidence-based care for your patients
When treating CNS infections, it’s a race against time. But syndromic testing can help doctors beat the clock.
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References
  1. Meningitis Now. https://www.meningitisnow.org/support-us/news-centre/meningitis-stories/david-ms-story/.
  2. Meningitis Research Foundation. https://www.meningitis.org/meningitis/the-global-burden-of-meningitis.
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  4. Rosenstein N.E. et al. (2001) N Engl J Med. 344, 1378–1388. doi: 10.1056/NEJM20010503344180.
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  12. O’Brien M, et al. (2018) J. Pediatr. Infect. Dis. 37, 868-71
  13. Leber A. et al. (2016) J Clin Microbiol. 59(4), 2251–2261. doi: https://doi.org/10.1128/JCM.00730-16.
  14. Moffa M.A., et al. (2020) Antibiotics (Basel). 9(6), 282 doi: 10.3390/antibiotics9060282.
  15. Posnakoglou L. et al. (2020) Eur J Clin Microbiol Infect Dis. 39, 2379–2386. doi:10.1007/s10096-020-03986-6.
  16. Hagen, A. et al. (2020) BMC. Pediatr. 20(1), 56.
  17. PATH. https://www.path.org/articles/toward-world-without-meningitis/.
  18. Dumkow. LED. Worden. LJW. Rao. SNR. 2021. Syndromic diagnostic testing: a new way to approach patient care in the treatment of infectious diseases. Journal of Antimicrobial Chemotherapy. Pages iii4–iii11.