Meningitis and Encephalitis PCR Testing – Targeted vs Panel Approaches
It is important to distinguish the causes of brain dysfunction and to identify a specific etiologic agent (e.g. viral or bacterial). Patient management is highly dependent on pathogen identification, with unfavorable outcomes directly correlating with delays of correct treatments and therapies.1 Rapid and accurate diagnosis of central nervous system (CNS) infections across a wide spectrum of presentations is paramount along with early initiation of aggressive treatment to help guide management and improve patient outcomes.
Currently, molecular testing for CNS infection has been rapidly growing due to fast turnaround times and improved sensitivity and specificity compared to culture.2 Timely diagnosis provided by molecular testing can confidently rule out the most common pathogens and can reduce length of stay, extended therapies, and numerous investigational procedures.2 Currently, diagnostic guidelines state that viral PCR testing should always be carried out as soon as possible in all suspected meningitis and encephalitis cases.3,4
The FDA has cleared a polymerase chain reaction (PCR) based panel test, which detects 14 targets including various bacterial, viral, and fungal etiologies. There are many conversations surrounding the usefulness and clinical utility of these types of panel tests. Although there are clear advantages to syndromic based panel testing, including the quick identification of a wide variety of CNS infectious pathologies, studies are showing that many targets included in the panel fail to reveal the etiology of the disease.2,5 Several studies have also reported both false-positive and false-negative results that lead to costly and ineffective treatments, which ultimately lead to poor patient outcomes.1,2 With so much at stake, it is crucial for laboratories to use tests that fit hospital algorithms, are fast, and provide accurate results.
In one case, a false-positive herpes simplex virus (HSV)-1 result caused a delay in treatment of an immunocompromised patient ultimately leading to his poor neurologic recovery and long-term disability.6 In another case, a kidney transplant patient developed cryptococcal meningitis that was reported as negative during two tests causing needless treatment.7 There are also concerns about contamination, which can lead to false positives, especially when testing for organisms that can be found as normal oral flora in laboratory staff.5 Healthcare providers must be familiar with the limitations of this type of test, especially false positive, which can lead to needless treatments and delay life-saving therapy.6
Extended hospital stays also increase the cost for the hospital. It is beneficial to both hospital and patient to decrease their length of stay through proper diagnosis and treatment. Recent studies show that the mean hospital stay for a meningitis or encephalitis patient can range from $15,000 per patient to over $40,000 depending on their length of stay and severity of disease.8 It is critical for hospitals to utilize the right tests to ensure proper diagnosis and patient management to improve patient care and reduce costs.
Dr. Kevin Alby from UNC School of Medicine, Chapel Hill, NC recently provided an overview of the testing options along with a discussion about his lab’s experience with panel testing. You can view the webinar below.
In a separate study of 363 patients that were tested with Simplexa™ HSV 1 & 2 Direct, clinicians were able to discontinue acyclovir faster than when tested using a laboratory developed test (29.2 hours versus 14.3).9 The mean turnaround time also decreased by 14.5 hours and the median hospital length of stay was reduced by 20% after implementing the Simplexa™ test (Table 1).9
Access to the test also increased as the laboratory was able to offer the Simplexa™ test 24 hours a day every day rather than only 9am-5pm for 6 days of the week.9 This is important because 45.3% of results using the Simplexa™ test were reported during the night shift, indicating a large patient population would have had to wait before receiving possible life-saving results.9 Lastly, STAT testing was able to be offered as tests could be run immediately upon receipt directly from the patient sample, using the Simplexa™ procedure (Table 1).9
Another study demonstrated that 6 months after implementing a targeted PCR assay there was a reduction in the length of stay for 12 pediatric patients.10 They projected a total decrease of about 55 hospital days for the first year of implementation, indicating up to $43,000 worth of savings (Table 1).10References
1. Cuomo, L., Trivedi, P., Cardillo, M.R., Gagliardi, F.M., Vecchione, A., Caruso, R., Calogero, A., Frati, L., Faggioni, A., & Ragona, G. (2001). Human herpesvirus 6 infection in neoplastic and normal brain tissue. J Med Virol. 63, 45-51.
2. Bard, J.D. & Alby, K. (2018). Point-counterpoint: Meningitis/encephalitis syndromic testing in the clinical laboratory. J Clin Microb. 56 (4), 1-10.
3. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the International Encephalitis Consortium. Clin Infect Dis 57, 1114–1128.
4. Polage, C.R. & Cohen, S.H. (2016). State-of-the-art microbiologic testing for community-acquired meningitis and encephalitis. Kraft, C.S., ed. Journal of Clinical Microbiology. 54(5), 1197-1202.
5. Paxton, A. (2019). ME multiplex panel: debating the tradeoffs. College of American Pathologists. Retrieved from https://www.captodayonline.com/me-multiplex-panel-debating-the-tradeoffs/
6. Gomez, C. A., Pinsky, B. A., Liu, A., & Banaei, N. (2016). Delayed diagnosis of tuberculous meningitis misdiagnosed as herpes simplex virus-1 encephalitis with FilmArray syndromic polymerase chain reaction panel. Open Forum Infectious Diseases,4(1), 245.
7. O’Halloran, J. A., Franklin, A., Lainhart, W., Burnham, C. A., Powderly, W., & Dubberke, E. (2017). Pitfalls associated with the use of molecular diagnostic panels in the diagnosis of cryptococcal meningitis. Open Forum Infectious Diseases, 4(4), 242.
8. Balasa-Llasat, J. M., Rosenthal, N., Hasbun, R., Zimmer, L., Ginocchio, C. G., Duff, S., Allison, J., Bozzette, S. (2018). Cost of managing meningitis and encephalitis among adult patients in the United States of America. International Journal of Infectious Diseases, 71, 117-121.
9. Van, T. T., Mongkolrattanothai, K., Arevalo, M., Lustestica, M., & Dien Bard, J. (2017). Impact of a rapid herpes simplex virus PCR assay on duration of acyclovir therapy. Journal of Clinical Microbiology, 55(5), 1557-1565.
10. Rand, K., Houck, H., & Lawrence, R. (2005). Real-time poly¬merase chain reaction detection of herpres simplex virus in cerebrospinal fluid and cost savings from earlier hospital dis¬charge. Journal of Molecular Diagnostics, 7(4), 511-516.