My name is Matt Binnicker, and I’m the Director of Clinical Virology and Vice Chair of Practice
in the Department of Lab 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.
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 of 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 four 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 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 15-20 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 1 or 2 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 4 hours, but the health
care provider must select the appropriate tests to order, which can be difficult since
respiratory pathogens can cause clinically-indistinguishable disease.
Over the past 5 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 all in one test.
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 7-year-old, otherwise healthy male presents in November to his primary
care provider with a 3-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 3
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 may
inform management decisions, including Infection Prevention and Control measures, and whether
the patient should be treated with certain antimicrobials.
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 that are critically ill.
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 5-7 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 are they 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.
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.