Tag Archives: molecular platforms

“The impact of COVID on the molecular department of microbiology laboratories”

COVID has had a profound, and ongoing impact on microbiology laboratories and everyone who works in them. But today I want to write about molecular departments in particular. This department and the staff that work in them have had some momentous experiences and unexpected changes over the last couple of years.

Prior to COVID, we just had a few staff working in the molecular department at the microbiology laboratory where I work. We had a limited after-hours and weekend service. Pre-COVID, we were working hard to expand our molecular menu and staffing but as with all such changes, it was a slow process.

COVID changed all that…

When COVID first arrived in NZ in early 2020, it took a few weeks for the first diagnostic tests to be set up in the reference centres, and another couple of months for such assays to arrive at our (regional) lab. When we were finally able to offer diagnostic testing in-house, we could not initially keep up with demand so testing had to be prioritised to hospital inpatients.

Pooling of samples and the arrival of new testing platforms allowed our test capacity to quickly increase, but that brought other issues. New staff had to be recruited & after-hours and weekend molecular rosters had to be dramatically extended. As these SARS-CoV-2 assays were all new, they had to undergo test validations, which then needed to be written up for accreditation purposes. This validation work put extra pressure on staff that were already processing far more samples than they would normally. In addition, worldwide demand for test consumables, along with border restrictions created supply issues, which meant maintaining an effective service could be extremely difficult at times.

Several of our non-molecular microbiology staff were periodically drafted into the molecular department to help with sample pooling and to process all the COVID PCRs. This allowed us to offer 24/7 COVID PCR testing. It was all hands on deck!

Other molecular (& culture based) tests were “rationed” in order to allow for the avalanche of COVID testing. Clinical microbiologists like myself tightened up the clinical acceptance criteria for molecular assays such as enteric PCRs & STI multiplex PCRs in order to free up both testing platforms and staff for COVID testing. We also clamped down on relatively low value culture-based testing such as sputum culture and skin and nail mycology from the community setting.  The other main role for clinical microbiologists was to approve out of hours “rapid SARS-Co-V testing” on rapid testing platforms such as GeneXpert. This led to several disrupted nights’ sleep, but we know we got off lightly from the pandemic compared with the staff who were actually doing the tests!

During the peak of the SARS-CoV-2 PCR testing surge, we were processing in excess of 3000 SARS-CoV-2 PCR tests per day. Normally we would do 1000-1500 microbiology and molecular tests in total per day, so the increase in tests was completely unprecedented.

Then COVID Rapid Antigen Tests (RATs) arrived in the community, and things changed dramatically… For various reasons, the introduction of RATs into NZ for COVID diagnosis arrived relatively late and it also occurred very suddenly.  Our COVID-19 test volumes went from 3000 per day to 200 per day, literally overnight.

Once this happened, the staff could take a breather, catch up on other tasks & projects that had been put on the backburner, take some well-deserved downtime, take some leave, and recharge the batteries.

Despite the trials and tribulations, I have no doubt whatsoever that our molecular department has been left in a better place as a result of the COVID pandemic. The increased resourcing has allowed us to offer more molecular tests after hours and at weekends, thus improving our clinical service. It has also given us the staff resource to validate and implement new molecular assays, further extending our diagnostic menu. The increase in testing platforms within the department have also given us more testing options. The molecular staff, battle-hardened by COVID, are now a resilient bunch and well prepared for future challenges!

We continue to work hard to position ourselves as one of the leading molecular departments in the country. COVID has undoubtedly helped that process along.

How has COVID impacted on your molecular department?



“The Molecular Revolution”

Time to get back to some writing “post” COVID!

When I started at the laboratory I currently work at in New Zealand in 2007, we only did one molecular assay, a chlamydia PCR, and we did this with separate extraction and amplification platforms on an open bench, with all sorts of potential for contamination. And we were/are not a small lab, a sizeable regional centre, processing well over 1000 microbiology samples a day.

2007, it’s actually not that long ago…

Fast forward 15 years and everything has changed. We now have a very sizeable menu of molecular assays performed on a range of different platforms. CSF, respiratory virus and GI panels, gonorrhoea, trichomonas, HSV/VZV,  HIV, HBV &HCV viral loads, Legionella spp., Mycoplasma pneumoniae, C. pneumoniae, C. difficile to name just a few. We even have a Mpox PCR!

A lot of these assays are now on commercial platforms that perform both the extraction and amplification steps in an automated fashion in a closed environment, essentially allowing placement of the platform anywhere, and can be run by most of our staff. The results are often available within a few hours of the sample being received in the laboratory.

In summary, the clinical service we can now offer is vastly improved from 15 years ago. I suspect it is much the same in many diagnostic labs throughout the world.

The big question is what will happen in the next 15 years? Will high volume sample types such as throat swabs, vaginal swabs, sputum samples, all still culture based at my lab, succumb to the revolution and go molecular? It is entirely possible that this will be the case. It will probably come down to cost first and foremost. Personally I see throat swabs switching to molecular very soon.

And what place will there be for whole genome sequencing in the diagnostic lab? That is a whole other question in itself but there are quite a few labs now in NZ who have acquired Nanopore Minions and are now “playing” with them in the areas of Infection Control and metagenomics.

My prediction is by 2030, for most diagnostic microbiology labs, their molecular department will be bigger than their traditional culture-based bacteriology department…

What do you think?


“The Swedish Variant: Selection Pressure by Diagnosis”

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…


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