Matthew Binnicker, Ph.D., is the Director of Clinical Virology and Vice Chair of Practice in the Department of Laboratory Medicine and Pathology at Mayo Clinic. He holds the academic rank of Associate Professor of Laboratory Medicine and Pathology.
Contact us: MMLHotTopics@mayo.edu.
Transcript and References
Hi, I’m Bobbi Pritt, the Director of the Clinical Parasitology Laboratory and Vice Chair of Education in the Department of Laboratory Medicine and Pathology at Mayo Clinic. Did you know that upper respiratory tract infections are one of the leading causes of morbidity and mortality? In this month’s "Hot Topic," my colleague Dr. Matt Binnicker explains how syndromic testing can be used to diagnose viral and bacterial respiratory infections. He will share the advantages of using this method and advise when a syndromic respiratory panel should be ordered. I hope you enjoy this month’s "Hot Topic," and I want to personally thank you for allowing Mayo Clinic the opportunity to be a partner in your patients’ health care.
Thanks for joining me for this video "Hot Topic," which is part one of a four-part series on syndromic testing for infectious diseases. My name is Matt Binnicker, and I’m the Director of Clinical Virology and Vice Chair of Practice in the Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, Minnesota. In this presentation, we’re going to discuss the use of multiplex panels for the diagnosis of respiratory infections, and specifically, we’ll focus on the clinical utility of these tests in the setting of upper respiratory tract infections.
Before we begin, I should mention that I don’t have any financial conflicts of interest to disclose related to this topic.
Also, as you view this presentation, I encourage you to consider the following important points regarding test utilization. First, how would syndromic testing for respiratory infections best be used in your practice? Second, when should the test be used? And finally, how would results impact patient management? So, with that, let's get started.
Upper Respiratory Tract Infections
Upper respiratory infections are one of the leading causes of morbidity and mortality worldwide, and may result in a range of symptoms, from mild clinical manifestations, such as a cough, pharyngitis, or runny nose to life-threatening disease that may involve respiratory distress. Infections of the upper respiratory tract are extremely common with an estimated 17.2 billion cases worldwide in 2015. As you’re probably well aware from personal experience, individuals can have multiple upper respiratory infections each year, with children less than 5 years old experiencing a mean of 6.1 episodes per year, and adults older than 40 suffering from about 4 upper respiratory infections each year.
We now have an appreciation that these infections can be caused by a variety of pathogens. Viruses account for the majority of upper respiratory infections, and they frequently involve coronaviruses and rhinoviruses, which are causes of the common cold. In addition, influenza is an important cause of respiratory infections and demonstrates a pronounced seasonality with the vast majority of cases occurring between the months of November and March each year in the United States. Bacteria can also cause upper respiratory tract infections with Streptococcus pyogenes being the etiologic agent for strep throat and Bordetella pertussis causing pertussis ( or whooping cough). Other bacteria, such as Mycoplasma pneumoniae can also be associated with upper respiratory illness.
In the vast majority of cases, patients with an upper respiratory infection do not require laboratory testing or treatment, since the illness is generally mild and self-limiting. However, when lab testing is needed, it’s historically been performed using a "mixed bag" approach. This has included routine bacterial and viral cultures, which are limited by prolonged turnaround time, sometimes requiring days to weeks for the organism to be recovered and identified. Antigen testing (specifically for influenza, respiratory syncytial virus, and group A strep) is also fairly common. This approach provides a rapid result, typically in 15 to 20 minutes; however, the sensitivity of these tests is often low, requiring follow-up testing if the result of the antigen test is negative. In the last 10 years or so, molecular tests, usually targeting one or two organisms per assay, have revolutionized our ability to diagnose infectious diseases. A growing number of targeted, commercial assays directed against causes of respiratory infection, such as influenza and RSV, are available. These tests are sensitive and typically generate results in less than four hours, but the health care provider must select the appropriate tests to order, which can be difficult, since respiratory pathogens can cause clinically indistinguishable diseases.
Over the past five years, syndromic testing has come to the forefront and potentially represents the next frontier in diagnostic testing for respiratory infections. In this approach, multiplex molecular panels are used to test for a broad array of pathogens that are associated with a particular syndrome, for example, respiratory disease, rather than ordering specific tests that target one or two pathogens. A number of commercial, FDA-cleared multiplex respiratory panels are now available, and some of the instruments and platforms used to test these panels are shown on the right-hand side of your screen. These systems offer several advantages over conventional testing, including a relatively easy, sample-to-answer workflow with a rapid turnaround time. In addition, some of these respiratory panels offer broad coverage, including up to 20 viral and bacterial targets in an all-in-one test.
Syndromic Panels: Broad Coverage
This slide summarizes the targets that are commonly included on commercial respiratory multiplex panels. As you can see, the coverage is quite broad and includes both viral and bacterial causes of respiratory infection, including some pathogens, such as metapneumovirus and coronaviruses that were not routinely detected by conventional testing.
So, at this point, you may be saying to yourself, “These multiplex panels are faster than routine tests, and they’re bigger in terms of coverage, so they must be better, right?"
Well, unfortunately, it’s not that simple, and to help illustrate when these respiratory panels may be clinically indicated, I’d like to review two "case vignettes."
In the first case, a seven-year-old, otherwise healthy male presents in November to his primary care provider with a three-day history of fever, cough, headache, and muscle pain. This patient definitely appears to have a respiratory illness, but the question arises, “Should a syndromic respiratory panel be considered in this case?”
Although there’s no definitive answer, in an otherwise healthy individual without severe disease, I feel that targeted testing would be most appropriate in this case. Given the patient's symptoms and the time of year in which he is presenting, one might consider first testing using a targeted influenza PCR assay or a molecular test for group A strep.
In our second case, a 35-year-old female undergoes an allogeneic stem-cell transplant, and three weeks following her transplant, she develops a cough and fever. She is admitted to the ICU due to respiratory distress, and the team is interested in diagnostic testing. Again, the question of, “Should a syndromic respiratory panel be performed?” is raised by the clinical team.
I think that in this instance, a respiratory multiplex panel could definitely be considered as a first-line test. Due to the patient’s immunosuppressed status and development of respiratory distress, a diagnostic approach that is both rapid and broad in coverage would be warranted, and it may inform management decisions, including infection prevention and control measures and whether the patient should be treated with certain antimicrobials.
Syndromic Panels: Advantages
As we’ve discussed, multiplex respiratory panels offer a number of advantages over conventional tests, including the potential for rapid results with some systems being able to provide a report in less than 60 minutes. Several commercial assays also allow for the detection and identification of certain viruses, such as human metapneumovirus and the coronaviruses that were not routinely tested for in most clinical labs. Due to these benefits, multiplex respiratory panels should be considered in immunosuppressed patients or those who are critically ill.
Syndromic Panels: Limitations
Despite these advantages, syndromic panels have a number of limitations that you should keep in mind. First, these assays often have a higher cost, both to the lab and to the patient, compared to conventional laboratory methods. However, they may be cost-effective, especially if the provider was planning to order multiple routine tests, such as cultures and a number of targeted molecular assays. In addition, use of multiplex panels may reduce downstream costs. For example, providing a rapid result for a broad range of pathogens may allow the health care team to modify isolation precautions, adjust antimicrobial therapy, and potentially, make informed decisions regarding the need for hospitalization.
Another issue to keep in mind with multiplex panels is that getting more information does not always equate to improved patient management or patient outcomes. One common example is the detection of viruses, such as rhinovirus or coronavirus in certain patients, such as an immunosuppressed host. For some of the targets on commercial respiratory panels, there are no specific therapies available, so it is sometimes difficult to determine how to best manage a positive result.
In summary, respiratory infections are extremely common and can be associated with high morbidity and mortality. Over the past five to seven years, syndromic panels have become commercially available, and these assays offer a rapid and broad approach to testing for causes of respiratory infection. It’s important to keep in mind that the cost of syndromic panels is typically higher than conventional methods, but their use may impact downstream costs associated with patient management.
And finally, there are several important issues to consider prior to ordering a syndromic respiratory panel. First, is the patient otherwise healthy, or is he or she immunosuppressed or critically ill? Second, will I manage my patient differently based on the results of the multiplex panel? Specifically, what will I do if I get a positive result for any one of the targets represented on this panel? And finally, would targeted testing be prudent due to the patient’s clinical presentation or the time of year that the patient is ill?
I think considering these issues will be helpful when deciding whether a multiplex respiratory panel may be of clinical benefit.
On this slide, I’ve listed the references that were used in the preparation of this talk, and I’d encourage you to review these for additional information on this topic:
- GBD 2015 Disease and Injury Incidence and Prevalence, Collaborators. 2016. Global, regional and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 388:1545-1602.
- Byington CL, et al. 2015. Community surveillance of respiratory viruses among families in the Utah Better Identification of Germs-Longitudinal Viral Epidemiology (BIG-LoVE) Study. Clin Infect Dis. 61(8):1217-1224.
- Manuel O, Estabrook M, et al. 2013. RNA respiratory viruses in solid organ transplantation. Am J Transpl. 13:212-219.
In conclusion, I’d like to thank you for joining me for this update on syndromic testing for respiratory infections, and please let us know if you have any questions related to this topic.