Are Culture-Independent Diagnostic Techniques Too Independent?

Saturday, July 09th, 2022

By: Drew Barkley

Let’s start by taking a quick trip down memory lane. The year is 2010, and after spending your evening watching highlights from the Vancouver Winter Olympics, you begin to feel sick. Your stomach starts to churn, and you realize that this might be something serious. You visit your doctor and they suggest taking a stool sample. Your sample gets sent off to a lab to be cultured, and after a few days you hear back that your culture came back positive for Salmonella Montevideo. Further, the lab submitted the Salmonella Montevideo strain isolated from your stool to PulseNet at the Centers for Disease Control and Prevention (CDC). PulseNet is a foodborne disease outbreak surveillance system here in the U.S. that uses whole genome sequence data taken from clinical isolates to find common strains between different cases. The isolate from your stool ends up matching isolates from other cases of Salmonella Montevideo around the country. As a result, the health department questions you about the food you ate over the last month to identify any common exposures with the other cases and identify a potential source of the emerging outbreak. 

Fast-forward to today. It’s 2022, and while watching replays from the Beijing Winter Olympics, your stomach begins to ache again. You feel the same illness coming on. However, when you go to visit the doctor this time, they do not send a stool sample off to the lab to be cultured. Instead, they use a small molecular array that looks like a chip to test your stool. Within a few hours, you receive the results that you are positive for Salmonella and are sent home to rest and recover. Because no culture was completed this time, unfortunately there is no way of knowing whether your illness is a sporadic case or part of a larger outbreak. 

The scenario described above highlights both the strengths and weaknesses of culture-independent diagnostic techniques, or CIDTs. CIDTs, like the small molecular array used to diagnose a foodborne illness in the paragraph above, are a relatively new method for detecting enteric or foodborne pathogens from stool. Unlike traditional culture methods that are labor-, resource-, and time-intensive, CIDTs are quick and easy, and can test for up to 20 or more different pathogens on a single test. Because CIDTs are so fast and test for several pathogens, they help physicians diagnose patients more quickly and allow for appropriate treatment to begin more rapidly as well. Within the last 5 to 10 years, because they are so easy and efficient, CIDT use has greatly increased. For example, the proportion of Campylobacter cases in FoodNet sites diagnosed with CIDTs increased from 13% in 2012-2014 to 38% in 2018.1 You can also see in the graphs below the increase in CIDT usage to diagnose various foodborne pathogens between 2015 and 2020.2 

Chart, bar chartDescription automatically generated 

ChartDescription automatically generated 

So if CIDTs are easier, more efficient, and test for more pathogens, what is the problem with increasing their usage? If you remember back to the scenario at the beginning of this post, when the molecular array CIDT is used today to diagnose a foodborne illness, there is no isolate or culture to send to PulseNet at CDC. This means there is no way to determine if your illness is a sporadic case, or part of a larger outbreak when using just CIDTs. That is because PulseNet needs bacterial isolates so that the exact strain causing an illness can be determined. By identifying the exact strain, if the strain for one ill person matches the strain of another ill person, outbreaks and linked cases can be more easily identified. As CIDT use increases, the effectiveness of the PulseNet surveillance system in identifying ongoing foodborne disease outbreaks becomes more jeopardized.  

So what can be done? While more research is needed to fully understand the impact of CIDTs on foodborne disease surveillance, the CDC has launched a pilot study for how to adapt PulseNet to CIDT data. CIDTs typically rely on genetic material of the pathogens present in the stool. The CDC is currently investigating using metagenomic approaches to match the genetic material from CIDTs to common, known outbreak strains for specific pathogens.3 This “shotgun” approach to seeing if CIDT results match any previous outbreak strains is not the most efficient way to identify outbreak strains, but may prove a useful tool as we move further from culture and more towards CIDT use. 


Drew BarkleyDrew Barkley

Graduate Research Associate

barkley.50@buckeyemail.osu.edu

 

 

 

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July 9, 2022 - 1:46pm -- onianwa.2@osu.edu

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