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In Monday afternoon’s session, titled, “Serology in the time of molecular diagnostics,” Chen and fellow speaker Elitza Theel, PhD, ABMM, medical director of clinical microbiology at Mayo Clinic, presented a case-based approach to highlight important concepts for diagnosing infectious diseases using serologic methods. They emphasized how the application of serology testing depends on the specific infectious disease being investigated.
Derrick Chen, MD, medical director of clinical microbiology and point of care testing at the University of Wisconsin Health emphasized that “knowing the optimal approach and potential pitfalls is critical for any laboratorians or healthcare providers involved with serologic testing.”
There were discussions on both serologic and molecular testing options for infections such as Epstein Barr virus, parvovirus, and West Nile virus. Some diseases can be diagnosed with a single serologic test, while others may require a panel of serologic tests, multiple tiers of serologic testing, or additional non-serologic testing for confirmation. Chen presented cases that required “single tier,” while Theel dived into “multiple tier” cases.
Chen described a case of an elderly female who presented with meningoencephalitis. The initial workup for infectious diseases was negative, including a meningitis/encephalitis multiplex PCR panel. After consultation with infectious diseases, she was ultimately diagnosed with West Nile virus neuroinvasive disease after anti-WNV IgM antibodies were found in her serum and cerebrospinal fluid. “Although serologic testing doesn’t seem as glamorous as the newest tech in the market, like artificial intelligence, it’s nevertheless used daily and is a cornerstone to diagnosing many infectious diseases,” Chen said.
Theel then discussed the concept of “multiple tier” testing, using Lyme disease, syphilis, and HIV as examples of conditions requiring layered diagnostic approaches. She cleverly introduced two similar cases, one from Kansas and the other from New York, for her starting case of Lyme. This case underscored the importance of geographical context in disease management. She pointed out that an individual from New York, having a higher risk of Lyme infection, would prioritize prophylactic care compared to a patient from Kansas.
In her Lyme disease discussion, Theel differentiated between standard and modified two-tiered testing protocols, particularly highlighting their effectiveness in the diagnostic algorithm. She presented studies demonstrating how modified two-tiered testing offered significantly greater sensitivity, especially in the early stages of Lyme disease, although this sensitivity becomes comparable to standard two-tiered testing in later disease phases.
Transitioning to syphilis, Theel acknowledged the potential confusion arising from the two primary testing algorithms. To clarify this, she focused on the critical questions posed at each step of the algorithms. Her emphasis on distinguishing between true and false reactivity was key to helping the audience understand the underlying logic of each pathway.
For instance, in the reverse algorithm, initial screening uses an automated treponemal test. A reactive result at this stage does not conclude testing; instead, it prompts further investigation into whether the reactivity signifies a recent, past, or false positive infection.
This then leads to a second, non-treponemal test, typically a rapid plasma reagin (RPR). A reactive RPR indicates current syphilis. However, a non-reactive RPR raises questions about a false-positive initial screen, previously treated syphilis, or early/late syphilis. If a second treponemal test is then reactive, it confirms syphilis exposure but does not definitively differentiate between past treated infection and early or late stages. Theel’s presentation not only outlined these complex multi-tier serologic tests but also provided crucial insights into their methodology and proper interpretation.
The session was full of real clinical scenarios that engaged audience members to think through the cases as if each had arisen in their own practices. Both speakers presented relevant information that enhanced attendees’ problem-solving skills and knowledge retention. Attendees will think twice before ordering a PCR assay for infectious disease. The seminar resonated with understanding the importance of serologic methods and knowing that “newer is not always better.”
