Category Archives: The Science of Microbiology

“Dead Certs and Long Shots”

The more uncertain the result will be, the more useful the laboratory test generally is…

Sounds a little paradoxical, but it is absolutely true.

If we are looking to confirm something that is almost certain before the lab test is performed, then we need a “super-sensitive” test to fulfil this task. Otherwise we run the risk of giving false negative results.

For example, if we have a teenager with a sore throat and lymphadenopathy, a lymphocytosis and atypical lymphocytes on blood film, then the probability of this being EBV infection is about 90%. There is little point then in doing a confirmatory Monospot test with a sensitivity of 80-85%. This will only lead to giving negative results on patients who actually have EBV infection.

And if we are looking to diagnose a long shot (aka a very unlikely diagnosis) then we had better be sure our laboratory test is “super-specific”, otherwise we will run the risk of giving false positive results.

For example if we want to diagnose dengue fever in a patient with “flu like” symptoms returning from Mexico (an area of relatively low Dengue endemicity), then we need to think twice about performing Dengue serology testing which has a specificity rate of about 95%. You are just as likely to report a positive test in someone who doesn’t actually have Dengue.

What we are doing in actual practice here is taking our pre-test probability, and using it to give a prevalence rate (by proxy) in our tested population. Once we know this, then we can use our test sensitivity and specificity to calculate positive and negative predictive values, not always with the results we would like…

Laboratory specialists tend to be more aware of testing limitations such as these. Clinicians, in general,  tend to just take the laboratory results as gospel.

But I believe it is ultimately the laboratory’s responsibility to stress the limitations of using laboratory testing for “Dead Certs or Long Shots”, and either prevent such testing taking place, or put big disclaimers on the results.



“Reinventing yourself”

In the next generation (20-25 years), the diagnostic microbiology laboratory workforce will be decimated worldwide.

If you are a student, they don’t tell you that at the careers fair…

“You sound like exactly the sort of person we are looking for. Come and “train” for four years in a lecture theatre, and then work in a clinical microbiology laboratory, that is if you are lucky enough to get a job. Unless your Mum and Dad are well off, you will accrue a hefty debt which will likely take you a couple of decades to pay off. However in 20 years time your job will probably not even exist…”

Am I being too harsh?

In terms of general culture based bacteriology, most of it will have gone molecular. Whatever is left of it will be automated, not just partially automated as with the current Kiestra TLA system, but completely automated to include plate interpretation, colony picking, identification, antibiotic susceptibility testing and rule based signout. The whole works…

Most microbiology samples will never touch a laboratory worker’s hands.

Molecular testing will have increased, but on highly automated platforms, processing high volumes of work, with minimum manual input.

Our work will be reduced to oddities and troubleshooting. I would even chance to say that there will be just as many engineers as microbiologists on the laboratory floor.

And then I look at the core components of my own job as a clinical microbiologist…

  • Authorising important results:- This will be done automatically using sophisticated rules based computer algorithms. And they will do it much better than I can.
  • Giving antibiotic advice:- Decision support apps downloaded on clinicians’ smartphones will do this more sensibly than me.
  • Laboratory Management:- I fear there will be nobody left in the lab to manage…
  • Demand management:- Although the process of demand management will be performed by software algorithms, there might still be a little work left for me regarding the initiation and governance of such projects.
  • Anti-microbial stewardship:- Anti-microbial resistance is not going away anytime soon so there may be a continuing role in the governance of such programmes. But the nuts and bolts will be highly automated and app-based.

So I am not overly optimistic about my own long term future. No one is immune…

It is no accident that during conferences I heavily focus  on presentations in molecular diagnostics and demand management. That should help in the short term at least in securing my usefulness. However it is entirely possible I will need to retrain in something completely different before I am done.

I know my job description as a clinical microbiologist will change out of all recognition before I retire. It is not impossible that clinical microbiology as a career entity will cease to exist altogether.

We need to be constantly looking at what we do today, then imagining what we will potentially be doing tomorrow, and preparing for it as best we can…


“Reflex Testing: A Hot Potato”

A reflex test in the laboratory setting is most simply defined as a test that the laboratory automatically adds on based on the result of the initial requested test, in order to optimise the diagnostic process.

Sounds like a no-brainer…

For example one might add a Hepatitis C viral load test to a sample which is positive for antibodies to Hepatitis C. Or one could add cytomegalovirus (CMV) serology to a sample which is negative for Epstein Barr virus (EBV), but with clinical and blood count parameters consistent with infectious mononucleosis. Within molecular testing, an example might be reflex testing for trichomonas in a patient who tests positive for either chlamydia or gonorrhoea. There is not so much potential for reflex testing in classical culture based bacteriology, unless of course you consider antibiotic susceptibility testing to be a reflex test, which of course it is to a certain extent. And once you delve into the field of immunology, the potential for reflex testing is massive…

The potential list of reflex tests for a clinical laboratory is actually extremely long.

So what reflex testing should be performed by the laboratory? This is actually a bit of a political hot potato.

Because everyone has their different agendas on reflex testing:

The laboratory’s view of reflex testing will depend to an extent on how they are funded. If they are funded on a fee per service/test model, they will welcome reflex testing with open arms, and utilise every opportunity to implement and encourage it. More tests equals more revenue.

If however the laboratory is funded on a “capped budget”, they will shy away from reflex testing. Extra tests in this setting means extra expenditure.

With regards to the laboratory funders, occasionally they will see that reflex testing might save them money in the long run through decreased hospital care etc. In general however, funders aren’t big fans of reflex testing, as it essentially means extra tests to fund (see idealism and realism below)

Requestors generally like the idea of reflex testing. It prevents a further consultation, further sampling etc. Anything to make the system run smoother. Occasionally though requestors get annoyed at getting a result on a test which they have not requested.

For patients also, reflex testing is generally a good thing. One must always be wary however of the consent process. Will the reflex test be included in the initial consent for laboratory testing? Personally I think that consent for laboratory testing should be on the premise that the laboratory will do “whatever it takes” to diagnose the cause of the patient’s symptoms. We don’t do test consenting very well as a rule…

Reflex testing demonstrates the difference between idealism and realism. For example 100 patients have a positive test X necessitating test Y. If test Y was reflexed by the laboratory then all 100 patients  would receive test Y. If the undertaking of test Y depended on the requestor reviewing the result of test X and actively requesting test Y, only a proportion of the 100 patients would end up getting test Y done. This is the real world.

The clinical value of reflex testing is also a continuous spectrum. For some reflex tests, the clinical value of adding on the test automatically is unequivocally high. For others the clinical value (and cost-effectiveness) is much more debatable.

Because it is such a political area, I think it is important that none of the groups above have undue influence in what reflex testing is done. Ideally a completely independent panel should set the criteria for reflex testing, and preferably on a national basis.

“No science is immune to the infection of politics and the corruption of power.”  (Jacob Bronowski)