Syndromic Testing for Infectious Diseases, Part 2: Gastrointestinal Infections

Expires November 2020

 

 

Presenter

Bobbi Pritt, M.D., is the Director of the Clinical Parasitology Laboratory and Vice Chair of Education in the Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, Minnesota.

Questions?

Contact us: MMLHotTopics@mayo.edu.

Transcript and References

Introduction

Hi, I’m Matt Binnicker, the Director of Clinical Virology and Vice Chair of Practice in the Department of Laboratory Medicine and Pathology at Mayo Clinic. We’ve all experienced a gastrointestinal ailment, like vomiting or diarrhea, but did you know that there are close to 200 million cases of gastroenteritis each year in the United States and that these infections can be caused by viruses, bacteria, or parasites? In this month’s "Hot Topic," my colleague Dr. Bobbi Pritt will discuss a powerful new technology called "multiplex molecular testing" that can assist in the diagnosis of gastrointestinal infections. 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.

Thank you for that introduction, Dr. Binnicker.

As Dr. Binnicker mentioned, this is the second part of a “Hot Topic” series on syndromic testing for infectious diseases. Today, I will be discussing testing for gastrointestinal infections.

Disclosures

Before I begin, I’d like to state that I have no disclosures.

Utilization Message

I’d also like to deliver a message on test utilization. As you view this presentation today, consider the following important points regarding testing:

  • First, consider how a multiplex molecular test for gastrointestinal pathogens could be used in your practice.
  • When should the test be used?
  • How will results impact patient management?

With these questions in mind, let’s begin with an overview of gastrointestinal infections.

Gastrointestinal Infections

These infections primarily manifest with vomiting and diarrhea. Infectious diarrhea, specifically, is a significant source of morbidity and mortality worldwide. The World Health Organization (WHO) estimates that infectious diarrhea is responsible for 1.7 billion cases and 2.2 million deaths each year globally.1 In the United States, the Centers for Disease Control and Prevention (CDC) estimates that there are nearly 48 million cases of infectious diarrhea each year and more than 3,000 associated deaths.2 This results in an estimated cost of $150 million dollars per year to the U.S. economy. Therefore, infectious diarrhea is an important health problem to be considered.

Gastrointestinal Pathogens

Now, let’s discuss what causes infectious diarrhea.

There are a number of bacteria, viruses, and parasites that can cause gastrointestinal infections. This includes preformed toxins that are formed by certain bacteria. Many of these pathogens are acquired through consumption of contaminated food, so we will discuss common food-borne illnesses on the next slide. Also, I should note the prevalence of the pathogens varies with the host’s age, their immune status, and their travel or exposure history.

Common Pathogens Causing Diarrheal Illness

Because consumption of contaminated food is an important source of infection, let’s look at the data we have on causes of foodborne illnesses. In 2011, the CDC reported that norovirus was the most common cause of food-borne illness, followed by nontyphoidal salmonella species, Clostridium perfringens, and Campylobacter species. These data were obtained from both passive and active collections, including outbreak investigations. Of course, these are just the most common food-borne infections. The following slides list other important pathogens that should be considered.

Viral Pathogens

This slide shows the most important viral pathogens that can cause infectious diarrhea.

Bacterial Pathogens

Similarly, this slide shows a list of important bacterial pathogens that cause infectious diarrhea. Note that there are a significant number of organisms in this category.

Parasitic Pathogens

Finally, there are a number of important parasitic pathogens that must be considered in patients with infectious diarrhea as shown on this slide.

Evaluation and Diagnosis of Infectious Diarrhea

So, how do we evaluate a patient for all of these pathogens and diagnose the cause of infectious diarrhea?

First, it is important to note that most cases of infectious diarrhea are self-limited and do not require treatment or testing. Therefore, finding out the specific cause of the patient’s symptoms may not be necessary because the patient will get better on his or her own. However, some pathogens can cause severe, life-threatening infections, especially in immunocompromised hosts. And in these patients, clinical evaluation alone cannot identify the causative agent. Also, definitive identification is necessary to guide therapy and implement adequate infection prevention and control measures.

Gastrointestinal Pathogens: Testing

Given these caveats, the approach to laboratory testing may vary and should be based on a careful evaluation of the patient and an assessment of disease severity and risk factors. This includes the patient’s immune status; evaluation for signs and symptoms of severe disease such as fever, bloody diarrhea, dysentery, abdominal pain, dehydration, and the need for hospitalization; and specific risk factors for severe disease, including a compromised immune system and advanced age. Testing should also be considered for select populations such as international travelers, food handlers, patients with persistent or relapsing disease, and in certain outbreak settings.

Now, let’s discuss our testing options.

Traditional laboratory testing for gastrointestinal pathogens consists of exams performed on stool specimens, commonly including bacterial stool culture, the classic “ova and parasite exam,” antigen detection methods for Cryptosporidium, Giardia, and rotavirus, and sometimes PCR tests for norovirus and adenovirus types 40 and 41. These tests range in price and can take several days until a result is produced.

Multiplex Molecular Gastrointestinal (GI) Panels

This is where the use of multiplex molecular gastrointestinal panels can be helpful.

Ordering is simplified when a clinician only needs to order a single panel rather than multiple individual tests. Also, there are now several FDA-cleared tests available, making it easier for labs to perform panel testing. Some of these commercial multiplex panels detect bacterial, viral, and protozoal pathogens, and the test results are commonly available in one laboratory shift.

The benefits of these panels are recognized by the American College of Gastroenterology, which states that “molecular diagnostic tests can provide a more comprehensive assessment of disease etiology by increasing the diagnostic yield compared with conventional diagnostic tests.”4

Comparison of FDA-Approved/Cleared GI Panels for Bacteria and Viral Pathogens, +/- Parasites

This next slide shows a comparison of the three FDA-cleared multiplex GI panels that include at least two classes of organisms. At Mayo Clinic, we use the BioFire gastrointestinal panel, which detects the presence of 22 targets in just one hour.

Advantages of Molecular Panels

The advances of using multiplex molecular panels include

  • Their rapid nature.
  • A similar or increased sensitivity compared to conventional methods.
  • The fact that they can detect viruses and bacteria for which testing isn’t routinely available such as sapovirus, astrovirus, and enteroaggregative Escherichia coli.
  • And that they detect more potential pathogens than conventional methods.

Studies: Increased Detection

A couple of studies that show this increased detection are listed on this slide.

The first study listed is by Spina, et al., 2015. They conducted a multicenter study across 10 European countries using the BioFire GI panel. This study included results from 709 patient samples. Their positivity rates for at least one pathogen are shown here, with the BioFire gastrointestinal panel having a 54% positivity rate, while conventional methods yielded only an 18% positivity rate.

At Mayo Clinic, we conducted a similar study in 2014 and found that the BioFire gastrointestinal panel had a 33% positivity rate, the Luminex gastrointestinal pathogens panel had a 30% positivity rate, and conventional methods yielded only an 8% positivity rate. So clearly, more potential pathogens are detected using multiplex molecular panels.

Potential Disadvantages

Unfortunately, use of these panels is not without disadvantages. For one thing, they are relatively expensive. With patients potentially charged more than $1,000 for a single test. However, this may be cost-effective if multiple tests would have otherwise been ordered.

Another potential disadvantage is that the results may be difficult to interpret. For example, panels allow for detection of multiple potential pathogens, and some targeted organisms may be commensal in some individuals and not actually causing disease. This requires careful clinical correlation, and it is not always clear when some potential pathogens are actually playing a role in a patient’s illness.

Finally, bacterial isolates may not available for public health testing when specimens are only tested by molecular panels and not grown in bacterial culture. Therefore, when labs are only using molecular testing, they should consider saving an aliquot of the unfixed specimen for potential additional testing at a reference or public health laboratory.

These disadvantages drive home my previous point of why a targeted testing approach is indicated.

Algorithm

In order to help guide testing, we have created the algorithm shown on this slide, which is based on widely accepted national and international guidelines. Note that testing is driven by patient factors, in which patients can be placed into three categories.

The first category is patients with community-acquired diarrhea, less than seven days’ duration, without warning signs or risk factors for severe disease. Testing is not generally indicated in these patients.

However, if the diarrhea persists, or if warning signs and risk factors for severe disease are present, this brings you to the middle category where testing with a molecular gastrointestinal pathogens panel is recommended. This provides a rapid result and simultaneously tests for important bacterial, viral, and parasitic pathogens.

The third and final category is when patients have health care-associated diarrhea or a history of recent antibiotic use. In this case, targeted testing using our Clostridium difficile toxin PCR is recommended, rather than an entire molecular pathogens panel.

The algorithm shown here is freely available online at this link.

Main Points

So, in summary, a variety of pathogens can cause infectious diarrhea, and most infections are self-limited and do not require treatment or testing. However, a subset of patients is at risk for severe disease. As clinical symptoms overlap, specific testing is needed to identify the causative agent. Identification is needed for treatment decisions and prevention and control efforts. Finally, syndromic testing using multiplex molecular panels provides a rapid and potentially cost-effective method for detecting the causative pathogens in settings where testing is indicated.

References

This last slide provides references for future reading. Thank you for joining me today in this discussion of syndromic testing for gastrointestinal pathogens.

  1. World Health Organization.
  2. Centers for Disease Control and Prevention (CDC).
  3. Scallan E, Hoekstra RM, Angulo FJ, et al. Food-borne illness acquired in the United States: major pathogens. Emerg Infect Dis. 2011;17:7-15.
  4. Riddle MS, DuPont HL, and Connor BA. ACG clinical guideline: diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016;111:602-622. doi: 10.1038.
  5. Spina A, Kerr KG, Cormican M, et al. Spectrum of enteropathogens detected by the FilmArray GI panel in a multicentre study of community-acquired gastroenteritis. Clin Microbiol Infect. 2015 Aug;21(8):719-728.
  6. Khare R, Espy MJ, Cebelinski E, et al. Comparative evaluation of two commercial multiplex panels for detection of gastrointestinal pathogens by use of clinical stool specimens. J Clin Microbiol. October 2014;52(10):3667-3673.
  7. Halligan E, Edgeworth J, Bisnauthsing K, et al. Multiplex molecular testing for management of infectious gastroenteritis in a hospital setting: A comparative diagnostic and clinical utility study. Clin Microbiol Infect. 2014 Aug;20(8):0460-0467. doi: 10.1111/1469-0691.12476.
  8. Rand KH, Tremblay EE, Hoidal M, et al. Multiplex gastrointestinal pathogen panels: implications for infection control. Diagn Microbiol Infect Dis. 2015 Jun;82(2):154-157. doi: 10.1016/j.diagmicrobio.2015.01.007.
Bobbi Pritt, M.D.

Bobbi Pritt, M.D.

Bobbi Pritt, M.D., is Director of the Clinical Parasitology Laboratory in Mayo Clinic's Department of Laboratory Medicine and Pathology. Her research interests are in clinical parasitology, vector-borne diseases, trainee education, and appropriate test utilization.