Syndromic panels are a molecular test that detect more than one pathogen associated with similar and overlapping clinical symptomatology, enabling better patient management. Before the advent of syndromic panels, physicians would select individual tests based on the most likely culprit, relying on multiple lab tests and empiric therapy until definitive results were available. In addition, traditional culture-based methods limit the targets that can be tested for and can sometimes not detect slow-growing or difficult-to-culture pathogens, which is especially problematic for diseases with clinical symptoms potentially caused by a variety of pathogens. Syndromic panels offer a solution of simplicity, sensitivity, and specificity with panel size ranging from a few to dozens of pathogens that can be detected simultaneously. A range of commercial syndromic panels are available for some of today’s most significant infectious diseases, and custom syndromic arrays permit clinical laboratories to test for relevant molecular targets for specific patient populations. This article summarizes highlights learned from syndromic panels for Respiratory Tract Infections (RTIs), Gastrointestinal (GI) Infections, Urinary Tract Infections (UTIs), Vaginal and Sexually Transmitted Infections (STIs), and Antimicrobial Resistance (AMR) markers.
Respiratory Tract Infections (RTI)
According to the World Health Organization (WHO) RTIs are the leading cause of disease burden worldwide, measured by years lost through death or disability (1). Many respiratory infections have similar clinical presentations, and molecular testing makes it possible to quickly distinguish the causative agent. Viruses cause most RTIs, including common cold and influenza (1). Historically, routine respiratory viral testing was confined mostly to influenza and respiratory syncytial virus (RSV) (2). However, we have since learned with multiplex PCR that human metapneumovirus (hMPV) often causes severe illnesses, and that rhinoviruses are more ubiquitous than previously recognized (2). Not all RTIs are viral. In fact, bacterial pathogens tend to cause some of the most severe RTIs, namely pneumonia and tuberculosis. The WHO estimates that lower respiratory tract infections cause nearly 4 million deaths each year, 1.4 million of which can be attributed to tuberculosis (3). Furthermore, viral infections can predispose a patient to secondary bacterial co-infection, and immunocompromised individuals may be susceptible to fungal or parasitic RTIs (4). Syndromic panels for RTIs allow for more rapid identification of the causative organism, which may allow earlier definitive therapy, which may decrease antibiotic therapy duration, length of hospital stay, time in isolation, and the number of additional (often invasive) tests (5).
Gastrointestinal (GI) Infections
Gastrointestinal (GI) infections are the second most common infectious disease worldwide (6). A variety of bacterial, viral, and parasitic organisms can infect the intestinal tract, resulting in infectious gastroenteritis, also known as “stomach flu“ (7). Syndromic panels for GI are particularly useful as there is significant overlap in the clinical presentation of patients infected with the various disease-causing pathogens (2). Viruses (rotavirus, calicivirus, adenovirus, and astrovirus) and bacteria (Salmonella, Campylobacter, Shigella, and Yersina) are the main etiological agents of gastroenteritis (7). Syndromic panels for GI shed light on the prevalence of norovirus, one of the most common causes of acute gastroenteritis (2). One study found that using the results from a GI pathogen panel reduced overall hospital expenses associated with isolation despite the costs of introducing the new test (8). Another study found that 20% of the patients could have been removed from isolation based on negative molecular panel findings in retrospective samples (9). Custom-designed GI panels can be adapted to include prevalent local organisms, important resistance genes, and to guide treatment for immunocompromised populations. Currently, little outcome data is available to support widespread GI syndromic panel testing, and some of the targets in larger expanded panels do not have associated antimicrobial treatments (10) (9). Although promising, expanded GI panels will likely require additional research before being implemented into standard practice.
Urinary Tract Infections
Urinary Tract Infections (UTIs) affect approximately 250 million individuals and result in an estimated 150 million deaths annually (11). Each year, the US alone spends over $3.5 billion on UTI-related costs, and over half of the prescribed antibiotics for suspected UTIs may be unnecessary (11). To reduce antibiotic misuse, it is important to identify the causative pathogen(s) and understand antimicrobial susceptibility. Clinical practice has relied on urine culture for UTI diagnosis since the 1950’s, which commonly identifies Escherichia. coli, Klebsiella spp., Enterobacter spp., Pseudomonas aeruginosa, and/or Proteus mirabilis (12). In one study, a multiplex PCR urine panel detected pathogens that did not grow in culture in 22% of patients (13). Polymicrobial infections are not uncommon, and certain bacterial combinations are thought to increase the probability of antibiotic resistance (12) (14). The sensitivity, accuracy, and speed of syndromic panels to diagnose UTI may improve patient outcomes by enabling physicians to make faster, more accurate diagnoses by detecting significantly more pathogens than conventional methods (10).
Vaginal and Sexually Transmitted Infections
According to the WHO, more than 1 million STIs are acquired every day globally. In 2020, there were an estimated 374 million STIs from chlamydia, gonorrhea, syphilis, or trichomoniasis (15). Conventionally, diagnosis of vaginal and STIs relies on clinical assessment and labor-intensive microscopic staining and scoring of the pathogens. Molecular methods are particularly useful for identifying microorganisms that are difficult to culture, including Chlamydia species (16). Furthermore, Neisseria gonorrhoeae and Chlamydia trachomatis not only cause similar clinical syndromes, but also coexist in many patients, highlighting the need for panel testing (17).
Disruption of a healthy vaginal ecosystem contributes to the overgrowth of pathogens that could cause complicated vaginal infections such as bacterial vaginosis (BV), aerobic vaginitis (AV), vulvovaginal candidiasis, trichomoniasis, and other STIs (18). BV is the most common vaginitis among women of childbearing age, but AV is likely underreported because reliable tests are not available (19). The distinction between AV and BV is clinically important because BV treatments do not work for AV (20). One study found that a molecular profiling offered higher resolution of species identification than microscopy and Nugent score (20). Syndromic panels may offer a more comprehensive understanding of the vaginal microbiome, and with a faster time to result than culture, may help to improve women’s health and diagnosis of STIs.
Antimicrobial Resistance (AMR) Markers
Drug-resistant and multidrug-resistant pathogens are now recognized as among the top 10 global health threats facing humanity (21). Accurate and rapid diagnostic methods are the key to guiding antimicrobial therapy and infection control interventions. AMR occurs when bacteria, viruses, fungi and parasites adapt and evolve so that they no longer respond to the medicines that were discovered or designed to inhibit the pathogen’s essential cellular processes (22). Tremendous progress has been made in recent decades towards understanding the genetic alterations, or “resistance markers”, and the biochemical consequences of these mutations (23). Genetic approaches are useful for screening known resistance determinants quickly but detecting susceptibility using microbial culture is still the preferred guide for antimicrobial therapy. Phenotypic tests such as culture are still important but may be augmented with molecular-based panels to better characterize the antibiogram (24).
Diagnostic Stewardship and Looking Ahead
Molecular syndromic panels can benefit labs, patients, and clinicians with improved sensitivity, specificity, turnaround time, and potential for automation and simplified workflows compared to traditional methods. Probes sets can be tailored for specific disease areas, do not require live culture, can detect co-infection of multiple organisms, and even offer insight into multidrug resistance genes. As with any new application, it requires time to generate sufficient evidence-based data to incorporate syndromic panels into routine diagnostics (10). Indeed, there is still controversy within the medical community regarding how syndromic panels should be used: as an initial screening test, part of a testing algorithm, or not at all. There is no one size fits all “best” panel to fit the patient’s, clinicians’, and laboratory’s needs. Panels need to be carefully designed to incorporate the most appropriate targets to fit differences in patient populations, pathogen prevalence, and clinical management protocols. As more outcome data becomes available, clinicians will be better equipped to understand how to interpret and utilize results from syndromic panels. Laboratories and clinicians will need to implement strict measures to ensure that syndromic panels are used responsibly, and diagnostic stewardship is our best hope for maximizing the benefits of syndromic panels in the future (2).
To learn more, visit https://www.labroots.com/ms/webinar/influenza-underestimated-threat
- L. Avendano Carvajal and C. Perret Perez, "Epidemiology of Respiratory Infections," Pediatric Respiratory Diseases, 2020.
- J. D. Bard and E. McElvania, "Panels and Syndromic Testing in Clinical Microbiology," Clin Lab Med, 2020.
- WHO, "Fact Sheets: Tuberculosis," 14 10 2021. [Online]. Available: https://www.who.int/news-room/fact-sheets/detail/tuberculosis.
- Z. Li, G. Lu and G. Meng, "Pathogenic Fungal Infection of the Lung," 2019. [Online]. Available: https://doi.org/10.3389/fimmu.2019.01524.
- B. Rogers, P. Shankar, R. Jerris, D. Kotzebauer, E. Anderson, J. Watson, L. O'Brien, F. Uwindatwa and K. McNamara, "Impact of a rapid respiratory panel test on patient outcomes," Arch Pathol Lab Med, 2015.
- WHO, "Fact Sheet: Diarrhoeal disease," 2 May 2017. [Online]. Available: https://www.who.int/news-room/fact-sheets/detail/diarrhoeal-disease.
- C. M. Chow, A. K. Leung and K. L. Hon, "Acute gastroenteritis: from guidelines to real life," Clin Exp Gastroenterol, 2010.
- S. D. Goldenberg and M. e. a. Bacelar, "A cost benefit analysis of the Luminex xTAG Gastrointestinal Pathogen Panel for detection of infectious gastroenteritis in hospitalised patients," Journal of Infection, 2015.
- K. H. Rand, E. E. Tremblay and M. e. a. Hoidal, "Multiplex gastrointestinal pathogen panels: implications for infection control," Diagn Microbiol Infect Dis, 2015.
- CMS, "MolDX: Molecular Syndromic Panels for Infectious Disease Pathogen Identification Testing," 17 4 2022. [Online]. Available: https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdid=39001&ver=4.
- A. K. Mohiuddin and M. Nasirullah, "UTI Prevalence Among Population with Chronic Conditions," Journal of Medical Research and Case Reports, 2019.
- J. A. B. K. W. A. A. C. Gaston JR, "Polymicrobial interactions in the urinary tract: is the enemy of my enemy my friend?," Infect Immun., 2021.
- K. J. Wojno and D. e. a. Baunoch, "Multiplex PCR Based Urinary Tract Infection (UTI) Analysis Compared to Traditional Urine Culture in Identifying Significant Pathogens in Symptomatic Patients," Urology, 2020.
- V. W. S. J. G. M. P. C. A. M. Gemma Croxall, "Increased human pathogenic potential of Escherichia coli from polymicrobial urinary tract infections in comparison to isolates from monomicrobial culture samples," Journal of Medical Microbiology, vol. 60, no. 1, 2011.
- WHO, "Sexually transmitted infections (STIs)," 22 11 2021. [Online]. Available: https://www.who.int/news-room/fact-sheets/detail/sexually-transmitted-infections-(stis)#:~:text=STIs%20have%20a%20profound%20impact,and%20trichomoniasis%20(156%20million).
- S. Muralidhar, "Molecular methods in the laboratory diagnosis of sexually transmitted infections," Indian Journal of Sexually Transmitted Infections and AIDS, 2015.
- C. K. S. J. e. a. Ginocchio CC, "Prevalence of trichomonas vaginalis and coinfection with chlamydia trachomatis and neisseria gonorrhoeae in the United States as determined by the Aptima trichomonas vaginalis nucleic acid amplification assay.," J Clin Microbiol., vol. 50, no. 8, pp. 2601-2608, 2012.
- W. J. Y. Chee, S. Y. Chew and L. T. L. Than, "Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health," Microbial Cell Factories, 2020.
- K. Peebles and J. e. a. Velloza, "High Global Burden and Costs of Bacterial Vaginosis: A Systematic Review and Meta-Analysis," Sexually Transmitted Diseases, 2019.
- T. Lynch, G. Peirano and T. e. a. Lloyd, "Molecular Diagnosis of Vaginitis: Comparing Quantitative PCR and Microbiome Profiling Approaches to Current Microscopy Scoring," Journal of Clinical Microbiology, 2019.
- "Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis," The Lancet, 2022.
- WHO, "Fact Sheet: Antimicrobial resistance," 17 Nov 2021. [Online]. Available: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance.
- A. Sundsfjord, G. Simonsen and e. al, "Genetic methods for detection of antimicrobial resistance," Journal of Pathology, Microbiology and Immunology, 2008.
- N. Woodford and A. Sundsfjord, "Molecular detection of antibiotic resistance: when and where?," Journal of Antimicrobial Chemotherapy, 2005.