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Gastrointestinal Pathogen Panel

Gastrointestinal pathogens include a variety of bacteria, parasites, and viruses all of which may cause serious, and sometimes life-threatening, diarrhea. Conventional testing for diarrhea-causing pathogens is a mishmash of bacterial culture, viral culture, microscopy, special stains, antigen detection, toxin immunoassay, and single target PCR. This testing is expensive, time-consuming, labor-intense, generally of very low yield, requires multiple samples to improve detection, and has variable sensitivity and specificity. Diagnostic algorithms designed to provide test-ordering guidance for clinicians are of limited usefulness due to the similarity of symptoms caused by these organisms.

Multiplex PCR/array panels are optimal for diagnosis of infectious diarrhea, due to improved sensitivity for common pathogens and detection of more unusual pathogens that are not identified by conventional means.  

In 2014, BioFire Diagnostics received FDA approval for their FilmArray Gastrointestinal Pathogen panel that detects 22 targets from a single stool specimen including bacteria, viruses, parasites, and toxins. Targets detected by this assay include:

 

Shiga toxin production, currently detected by immunoassay, is associated with post-diarrheal hemolytic uremic syndrome (HUS). Although E. coli O157:H7 is the most common cause of HUS in the U.S., several other bacteria may produce shiga toxin, including other enterohemorrhagic E. coli (EHEC). In addition, Campylobacter, Shigella, Salmonella, and Yersinia can produce shiga toxin and subsequent HUS.

A recently published comparative evaluation of 500 diarrheal stool specimens performed at Mayo Medical Laboratories (J. Clin. Microbiol. 2014, 52(10):3667) found this Panel’s sensitivity >90%, and specificity  >97% for 243 previously characterized positive samples. Another 230 specimens not previously tested yielded 19 positives (8.3%) from conventional testing and 65 positives (28%) from the GI Pathogen Panel, which were confirmed by alternate methods. The Panel identified mixed infections in 27% of confirmed positive samples, compared to 8% tested by conventional means. 

A major advantage of the GI Pathogen Panel is identification of organisms not detected by conventional testing. Key characteristics of these pathogens are as follows:

• Diarrheagenic E. coli/Shigella, 5 major types:
  • Enteroaggregative E. coli (EAEC). Inflammatory diarrhea, sometimes bloody.  May have low-grade fever and/or vomiting. Common in the U.S., second most common cause of travelers’ diarrhea and causes large outbreaks worldwide.
  • Enteropathogenic E. coli (EPEC). Non-bloody diarrhea. Mostly children. Seasonal peaks in summer/early fall. No toxin production.
  • Enterotoxigenic E. coli (ETEC). Watery diarrhea due to toxins that bind to epithelial cells. Most common cause of travelers’ diarrhea.
  • Shiga-like toxin-producing E. coli (STEC). Bloody diarrhea. Can progress to hemolytic-uremic syndrome. Foodborne (ground beef), contaminated water, peron-to-person or animal contact. In addition to E. coli, shiga toxin is also produced by Campylobacter, Shigella, Salmonella, and Yersinia.
  • Shigella/Enteroinvasive E. coli (EIEC). Bloody or non-bloody watery diarrhea. Highly contagious, low infectious dose. EIEC believed rare in US but molecular target is indistinguishable from Shigella.
• Viruses
  • Adenovirus F 40/41. Common in children under 2, and can cause outbreaks. Resistant to disinfectants. Mild illness of several days duration with prolonged shedding of virus in feces.
  • Astrovirus. Mild symptoms lasting ~72 hours. High seroprevalence in school-age children, therefore very common.
  • Norovirus. Highly contagious, low infectious dose. Moderate to severe vomiting and diarrhea with fever. Outbreaks common. Most common cause of foodborne GI illness in US. Peaks in winter.
  • Similar to norovirus but infects children more than adults. Fever & vomiting with diarrhea. Also very contagious, causes outbreaks, peaks in winter.

Due to the enhanced sensitivity & specificity provided by this technology, conventional diarrheal stool testing with suboptimal performance characteristics (including ova/parasite stains, bacterial stool culture, and viral stool culture) should be considered obsolete. Single-target PCR testing for Clostridium difficile toxin, as well as Giardia/Cryptosporidium and Rotavirus antigen testing will continue to have clinical relevance.

Specimen requirement is a fresh diarrheal stool sample. Outpatient samples should be submitted in Cary-Blair transport media. The panel should not be available on inpatients that have been hospitalized for more than three days, for whom Clostridium difficile toxin PCR is still the most appropriate initial test. Time to result from initiation of testing in the laboratory is approximately one hour.