Tag Archives: chlamydia trachomatis

“The Swedish Variant: Selection Pressure by Diagnosis”

The Science of Microbiology, , ,

When we think about selection pressure the first thing that comes to mind are antibiotics that selectively kill susceptible bacteria and thus allow more resistant bacteria to fill the ecological niche.

But fewer people realise that selection pressure can also be caused (indirectly) by laboratory diagnosis. Microbes which are diagnosed in the laboratory often end up getting treated and eradicated. However a microbe which mutates sufficiently to avoid diagnosis will have a selection advantage over its diagnosable counterpart. This concept is particularly applicable to microbes which are diagnosed by molecular techniques such as PCR where only a minor mutation or deletion can potentially create sufficient change in the base sequence to make the microbe undetectable by the original molecular test.

The most classic example of this is the “Swedish Variant”.

In 2006, a drop in Chlamydia trachomatis diagnoses was noticed on a particular molecular platform X, but not on others in use within Sweden. Further analysis revealed that a mutant strain of Chlamydia trachomatis (nvCT) containing a 377 base pair deletion was circulating. This was undetectable on platform X, but detectable on other molecular platforms.

Interestingly the nvCT strain had a much higher prevalence in geographical areas where platform X was used. In areas where other platforms were utilised, it wasn’t so successful as it didn’t have any selection advantage. But this makes perfect sense when you realise that a strain that avoids laboratory detection and consequently destruction is bound to do better than a strain that is easily diagnosed.

So what implications does all this have for laboratory practice?

Centralisation, tendering, and “packaged” contracts means that we are increasingly relying on just the one molecular assay to diagnose a particular pathogen within a large geographical area.

Laboratories or regions, or even countries which just rely on just one molecular test to diagnose a pathogen are always vulnerable to “escape mutants” such as nvCT emerging which escape detection and thus thrive in the population.

Testing a cohort of samples on alternative molecular platforms to validate the results and to look for these escape mutants is an important quality assurance measure.

The story of the Swedish variant also demonstrates the importance of using the percentage positivity rate of a molecular test over time as a Quality Control measure.

Even though the Swedish variant was diagnosed over 10 years ago, the lessons that can be learned from this episode are probably even more important in the large volume, centralised laboratory landscape that we have today.

In summary, one must be careful not to put all their eggs in one basket…

Michael

Check out this article for a more detailed overview of the Swedish variant. (about a 10 minute read)

“Antimicrobial Susceptibility Testing for Chlamydia: Out of Sight, out of mind…”

The Science of Microbiology, ,

We are fortunate with Chlamydia trachomatis, in that the organism so far, retains almost universal susceptibity to a range of oral antimicrobials, including tetracyclines, erythromycin, azithromycin and even amoxycillin.

This is just as well really as Chlamydia trachomatis is almost exclusively diagnosed by molecular means and antimicrobial susceptibility testing is both difficult and non-standardised.

What we don’t really know about Chlamydia trachomatis is whether continued heavy usage of tetracyclines and azithromycin are leading to “MIC creep” to these antimicrobials. It may be that we only start worrying about this when we start to see treatment failures in significant numbers.

The worry would be that as now Neisseria gonorrhoeae moves towards molecular diagnosis, we will apply the same “out of sight, out of mind” philosophy to this micro-organism. However we definitely cannot afford to go down this route for Neisseria gonorrhoeae as there are already significant resistance problems with this particular bacterium.

We need to remember for both C. trachomatis and N.gonorrhoeae, that just because we aren’t doing susceptibility testing, it doesn’t mean these micro-organisms have suddenly stopped selecting out resistant mutants under antimicrobial pressure….

Michael

p.s. While on the subject of GU microbiology, here is a really nice article on the conditions of cytolytic vagnosis and lactobacillosis, well worth a read.