A discussion of syndromic molecular testing for clinical care

Abstract

Current molecular detection methods for single or multiplex pathogens by real-time PCR generally offer great sensitivity and specificity. However, many infectious pathogens often result in very similar clinical presentations, complicating the test-order for physicians who have to narrow down the causative agent prior to in-house PCR testing. As a consequence, the intuitive response is to start empirical therapy to treat a broad spectrum of possible pathogens. Syndromic molecular testing has been increasingly integrated into routine clinical care, either to provide diagnostic, epidemiological or patient management information. These multiplex panels can be used to screen for predefined infectious disease pathogens simultaneously within a 1 h timeframe, creating opportunities for rapid diagnostics. Conversely, syndromic panels have their own challenges and must be adaptable to the evolving demands of the clinical setting. Firstly, questions have been raised regarding the clinical relevance of some of the targets included in the panels and secondly, there is the added expense of integration into the clinical laboratory. Here, we aim to discuss some of the factors that should be considered before performing syndromic testing rather than traditional low-plex in-house PCR.

Respiratory virus infections after allogeneic stem cell transplantation: Current understanding, knowledge gaps, and recent advances

“…These assays display exquisite sensitivities and specificities 26 and can be used for to point‐of‐care testing. Also marketed and approved for clinical use by the FDA and CE are a large number of multiplex panel assays (syndromic) mainly using RT‐PCR (i.e., real‐time, nested, conventional coupled to microarray hybridization), PCR or TMA that allow for simultaneous testing of a variable number of CARVs including IFV A/B, RSV (A/B), HCoV (CoV229E, HKU1, NL63, OC43), SARS‐CoV‐2, HMPV, hPIV 1–4, HRV, hBoV and Adv 24,27–30 . Distinguishing between viable and nonviable virus in RT specimens was central during the various waves of the SARS‐CoV‐2 pandemic.…”

Enteric Pathogen Testing Importance for Children with Acute Gastroenteritis: a Modified Delphi Study

“…Such pan-pathogen testing raises several concerns, as the unrestricted use of multiplex panels has been associated with low-value care due to increased costs and laboratory utilization with few benefits ( 33 ). Testing for a high number of pathogens can additionally complicate reimbursement for patients and providers if payment is based on the number of targets or positive findings ( 34 ). However, targeted use in children with symptoms and history that potentially match several pathogens could improve their utility and reduce the likelihood of incidental findings ( 35 ).…”

Respiratory Tract Infections and Laboratory Diagnostic Methods: A Review with A Focus on Syndromic Panel-Based Assays

“…Table 2 reports a list of the most relevant FDA-approved syndromic panels for the diagnosis of respiratory illnesses both for the URT and LRT. Many studies [81][82][83][85][86][87][88][89] have been conducted to evaluate the accuracy of different syndromic panels in specific samples and various patient populations; however, finding enough clinical cases to test could take a long time and more research is needed [79]. As reported, the performances in terms of sensitivity and specificity of these panels are very similar [79], and the greatest number of reported discrepancies between these multiplex panels and reference methods is for ADV and FLU B [79,80].…”

“…Many studies [81][82][83][85][86][87][88][89] have been conducted to evaluate the accuracy of different syndromic panels in specific samples and various patient populations; however, finding enough clinical cases to test could take a long time and more research is needed [79]. As reported, the performances in terms of sensitivity and specificity of these panels are very similar [79], and the greatest number of reported discrepancies between these multiplex panels and reference methods is for ADV and FLU B [79,80]. The formulation of respiratory panels (RPs) not only allows the detection of a broad range of targets, some of which are not detectable otherwise, but also to teaches us about the prevalence and clinical significance of them, such as the demonstration of RV ubiquity and of h-MPV involvement in severe disease [72].…”

“…In any case, analysis of the results should be performed in the context of clinical manifestations, and physicians should interpret both the multiplex PCR result and the final culture results together when establishing antimicrobial therapy plans. Furthermore, it is important to consider inconsistencies with resistance gene detection, especially in cases of co-infections or when the sample is obtained from an anatomical site with low prevalence of resistant pathogens [79]. For example, the CTX-Mtype extended-spectrum beta-lactamases gene was reported for any member of the families Enterobacteriaceae, Acinetobacter spp., or P. aeruginosa, and for this reason, when a resistance phenomenon is common to different bacteria, the conventional culture and the phenotypic AST are required to confirm the indication of the resistance marker [82].…”