Category Archives: The Science of Microbiology

“The uncertainty of certainty”

There is one thing certain in the microbiology laboratory, that the results will be uncertain. This has nothing to do of course with laboratory systems or the competency of staff members. Just an acceptance that there is no such thing as a certain result…

The other thing to note is that the degree of certainty of results will vary between different tests, not only for separate tests but even for multiple tests contained in the one assay, e.g. any multiplex PCR.

Take for example a multiplex respiratory PCR, containing 24 or so different targets. (Most labs will “demand manage” such expensive assays, allowing them only for immunocompromised patients or the seriously ill. Nevertheless, such assays are becoming increasingly popular.)

In a multiplex respiratory assay, a positive result for rhinovirus is almost certainly going to have a greater chance of being “the genuine article” than a positive result for bocavirus.

This is because each individual target pathogen has a different positive predictive value (PPV), based on both its specificity and its relative prevalence in the tested population. As a result, positive predictive values for individual pathogens within a multiplex can, and do, vary greatly.

But how do we relate such information to the clinicians? Quoting the calculated PPV for each target in a multiplex would make for a long and complex laboratory report. I would not go there… It is probably best to use an appropriate comment for certain results. I.e. “Bocavirus is uncommonly seen in population x, therefore the positive predictive value of this result may be sub-optimal. Close clinical correlation is required.”

Of course, clinicians can increase the degree of certainty by clarifying the “pre-test probability”. I.e. A positive bocavirus result in a 6 month old during the winter season is much more likely to represent a true result than a positive bocavirus result in an adult during the summer season.

With multiplex PCRs, sometimes you are “forced” to perform a test, when it would be better not to know…

Clinicians, in general,  tend to believe that all laboratory results are certain, until we produce one that is very clearly wrong! After that, they will believe all results are uncertain until that trust is rebuilt over time.

To understand certainty of testing, you first of all need to understand the laws of probability. All a laboratory result ever does is convert pre-test probability of disease X into post-test probability. 

It neither confirms nor excludes…

Michael

 

“The Great Imitator”

There are many causes of a lymphocytic CSF, both microbiological and non-microbiological. Here is a quick and non-exhaustive summary:

  • Enteroviruses- probably the most common cause, in most parts of the world.
  • Herpes Simplex Virus (HSV)- one of the most important to diagnose/exclude as HSV encephalitis is associated with a high mortality rate.
  • “Lots of other viruses…”- There are many viruses which can cause a lymphocytic CSF, too many to list really. How many you test for depends on how much money your lab has, and how sick the patient is.
  • TB- Look for the classical risk factors and a more sub-acute presentation.
  • Cryptococcus- Usually in immunocompromised, particularly HIV. Remember cryptococcal antigen has essentially replaced Indian Ink stain as a diagnostic test.
  • Leptospirosis- Other systems (i.e. renal, respiratory) usually involved.
  • Non-infectious- Autoimmune, malignancies, drugs can all be causes of a lymphocytic CSF.

and the list goes on…

But one cause of a lymphocytic CSF that I have not mentioned is one that is often forgotten about.

Syphilis.

Syphilis is sometimes called “The Great Imitator” because of the diversity of clinical syndromes it can cause. In the words of William Osler “Those who know syphilis, know medicine.”


William Osler

And with the massive increase in syphilis over the past few years in New Zealand (and many other parts of the world), that syndrome diversity is starting to reveal itself…

In the past two years, I have personally seen 5 cases of lymphocytic CSF due to neurosyphilis. Sometimes it has been anticipated, in others it has been completely unexpected.

So all cases of unexplained lymphocytic CSFs should really be getting treponemal serology performed on serum. A lymphocytic CSF and positive syphilis serology is neurosyphilis until proven otherwise. On those with positive syphilis serology, neurosyphilis can be confirmed by looking for VDRL and FTA in the CSF.

Neurosyphilis does not just present with an acute/subacute meningitis picture. Tertiary neurosyphilis can present with psychiatric or dementia symptoms (I have seen one case of neurosyphilis presenting as dementia). Again these cohorts of patients should all be screened for syphilis. 

Syphilis can affect the neurovasculature and present as a CVA (stroke). In the same manner as above, all patients who present clinically with stroke should get syphilis serology.

Yes, syphilis is indeed the great imitator.

We do about 25000 syphilis serology tests a year at my lab. When I started at my current position 12 years ago, we would maybe see 1 case of syphilis every month. Now we see 5 or 6 cases a week…

Syphilis is a fascinating disease, one of my favourites. But because it imitates so many other conditions, it is important to always think about it, so it isn’t missed. Missing cases of syphilis can have catastrophic consequences down the line…

Michael

 

“Choosing Wisely Bacteriology: Ear swabs for otitis externa”

There is plenty of scope for choosing wisely in the microbiology laboratory. The most obvious targets are actually within infectious serology, a department now essentially in the process of being superseded by molecular methods. However there are lots of opportunities within culture based bacteriology also, with an impressive proportion of superficial swabs being of low clinical value… I will try and review some of these sample types over the next few weeks.

Otitis externa is a common condition, especially in the summer when people go and bathe in rivers and lakes and get their ear canals repeatedly wet with non-sterile water…

The microbiology laboratory receives lots of ear swabs from patients with otitis externa. But in the vast majority of cases, the swab result is absolutely meaningless in terms of managing the infection.

But it is very tempting to take an ear swab nevertheless. Who wouldn’t want to take a swab to a discharging ear!

Bacteria and fungi are usually bit part players only in otitis externa. The actual condition is a vicious circle of infection of ear debris- inflammation- swelling, blockage, leading to more infection and so the cycle goes on.

Releasing the blockage by clearing the debris, along with drying the ear canal are just as effective as antimicrobial drops, if not more so.

Most otitis externa swabs grow Pseudomonas aeruginosa or Staphylococcus aureus. A few grow Candida or Aspergillus species. Others simply grow a bacterial soup! (Our lab doesn’t report more than two organisms from an ear swab)

It actually doesn’t matter that much…

And antimicrobial susceptibilities are essentially useless as well. The treatment of otitis externa is with topical agents and it is well documented that the clinical response to topical antimicrobials is poorly correlated with their in-vitro susceptibility patterns.

Mild cases of otitis externa can often be managed with acetic acid drops alone (a drying agent with some anti-bacterial activity).

More severe cases usually get drops which often contain a bit of everything; a broad spectrum anti-bacterial, an anti-fungal, and a bit of steroid to reduce the inflammation.

So ear swabs should be reserved for recalcitrant cases of otitis externa, where the clinician is at the stage of discussing the case with an ENT specialist.

For the remainder, who cares that much what the swab grows…

From a choosing wisely perspective, how do we approach this? One option is to reject all ear swabs from otitis externa patients unless the clinical details suggested recalcitrant infection. Alternatively a comment could be added to every ear swab result saying that ear swabs are not indicated for otitis externa, except in special circumstances.

Time to act…

Michael