STEC stx2f: An overlooked subtype?

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I catch what some don't look for: STEC stx2f
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Clinical case

STEC subtype went undetected, delaying diagnosis

Based on a published clinical case (1)

A two-year-old boy arrived at the ER struggling to pass urine. He'd recently had an episode of non-bloody diarrhea and vomiting but seemed to recover.

The initial lab results showed worrying signs of hemolytic uremic syndrome (HUS) – anemia, low platelets, kidney failure and hemolysis – which quickly led the team to suspect a Shiga-like toxin-producing E. coli (STEC) infection.

While the team worked to stabilize the child's symptoms, they sent a stool sample for multiplex PCR testing.

The results were unexpected: The test picked up the eae and ehxA genes, which pointed to STEC, but didn't find the expected stx toxin genes. The lab scientists knew the stx assay they used couldn't detect the stx2f toxin gene subtype – could that explain the unusual results?

The team pursued further stx-subtype PCR, which finally uncovered the presence of the stx2f subtype, indicating a true STEC infection.

Some GI panels can't detect stx2f. In the clinic, this can lead to the need for additional testing. Modern syndromic panels like QIAstat-Dx are designed to avoid this pitfall by including stx2f coverage.

Many routine tests can't detect stx2f

Some multiplex PCR tests can't detect stx2f, and return false negative results for STEC strains carrying this toxin (1,3–5).

In some cases, these tests also misclassify STEC stx2f. One study found that an alternative syndromic panel misclassified a STEC strain carrying both stx2f and eae (1).

  • The eae gene is a key marker for EPEC but is also commonly found in STEC.
  • If only eae is detected, the result is reported as EPEC. If stx is also detected, it's reported as STEC.
  • However, if the assay fails to detect stx2f, a STEC strain may be mistakenly reported as EPEC instead of STEC.

This kind of error can have significant consequences for patient management and could contribute to underreporting of the stx2f subtype.

QIAstat-Dx Gastrointestinal Panel 2 is proven to effectively detect stx2f (1,5), supporting comprehensive diagnostic coverage for GI illness.
Isolates of stx2f-positive E. coli in the UKHSA archives, adapted from (4).

Caution around detecting the STEC stx2f subtype

Public health organizations, including the ECDC and the UK Health Security Agency, recently highlighted a notable increase in GI illnesses linked to the stx2f subtype. It's now considered an emerging threat (3,4).

But not all syndromic tests can detect it (9,13).

That's because stx2f is genetically divergent from other subtypes, and standard PCR primers can fail to pick it up (1,3,4).

STEC detection is important for patient management

STEC gastrointestinal (GI) infections can result in a wide range of symptoms, from diarrhea to hemorrhagic colitis. STEC's pathogenicity depends on the expression of shiga toxins, encoded by the stx1 and stx2 genes and their subtypes.

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References

1. Cointe A, Birgy A, Pascault A, et al. Be aware of Shiga-toxin 2f-producing Escherichia coli: case report and false-negative results with certain rapid molecular panels. Diagn Microbiol Infect Dis.. 2020;98(4):115177. doi:10.1016/j.diagmicrobio.2020.115177

2. Kakoullis L, Papachristodoulou E, Chra P, Panos G. Shiga toxin-induced haemolytic uraemic syndrome and the role of antibiotics: a global overview. J Infect. 2019;79(2):75-94. doi:10.1016/j.jinf.2019.05.018

3. European Centre for Disease Prevention and Control Annual Epidemiological Report 2021 – STEC Accessed February 7, 2024

4. Den Ouden A, Greig DR, Rodwell EV, et al. Escherichia coli encoding Shiga toxin subtype Stx2f causing human infections in England, 2015-2022. J Med Microbiol.

5. Engberg J, Vejrum LK, Madsen TV, Nielsen XC. Verification of analytical bacterial spectrum of QIAstat-Dx® GI V2 and Novodiag® Bacterial GE+ V2-0 diagnostic panels. J Antimicrob Chemother. 2021;76(Suppl 3):iii50-iii57. doi:10.1093/jac/dkab242


In some cases, data cited pertains to the use of a device from another manufacturer.

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