Category Archives: The Science of Microbiology

“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

“Ageing methodology”

The laboratory detection of verotoxin/shigatoxin producing E. coli (sometimes called enterohaemorrhagic E. coli) has caused much grief for diagnostic microbiology laboratories over the decades. It is a relatively nasty infection, and it can cause bloody diarrhoea in a good proportion of patients. In a small minority it can cause severe complications such as Haemolytic Uraemic Syndrome (HUS) or Thrombotic Thrombocytopenic Purpura (TTP).

Diagnosis was initially centred on the culture of E. coli 0157 which can produce verotoxin/shiga toxin.

SMAC (Sorbitol MacConkey) agar plates were all the rage in the 1990s, taking advantage of the fact that E. coli 0157 does not ferment sorbitol. 

How lucky is that?

These were soon replaced by the more selective CTSMAC (Cefixime Tellurite Sorbitol MacConkey), with the cefixime and tellurite inhibiting other annoying non-sorbitol fermenters such as Proteus Spp.

The only problem is that E. coli 0157 is not the only E. coli serotype that can produce verotoxins. Lots of other E. coli serotypes are capable of doing this as well, e.g. 0111, 026, 045, 0145, etc.. As time passed, and our understanding of the infection improved, it became very apparent that a very significant proportion of VTEC induced diarrhoea was actually not due to E. coli 0157.

How inconvenient…

Nevertheless, CTSMAC plates were now entrenched in laboratories. And it was better than nothing.

As the years passed,  alternative methods came onto the scene.

ELISAs used for “direct” VTEC toxin detection in stool were employed in some labs in the early 2000s. At least they detected non-0157 associated disease, but sensitivity remained an issue when used directly on samples. They were not widely adopted by diagnostic laboratories.

Chromagar plates have also been developed to pick up the main VTEC serotypes. A little pricey however, and still need follow-up work for confirmation.

Then came PCR, and more recently multi-plex PCR, not only detecting (the toxins of) VTEC, but all the other common gastrointestinal pathogens as well.

In the molecular age, CTSMAC plates are starting to look a bit dated. What was seen as  modern methodology a generation ago no longer cuts the mustard.

As we move through this transition period for VTEC detection there is a real mish-mash of different VTEC methodologies used in laboratories worldwide. I don’t think this messy situation will last. In a decade or so I suspect 90% or more of microbiology laboratories will be using molecular methods for VTEC detection (and everything else stool related).

However at the moment, there are still plenty of CTSMAC plates being manufactured worldiwde. We still (guiltily) use them at our lab, as we continue to work out how to afford molecular testing for enteric pathogens…

But now they are used in the knowledge that they will clearly not pick up all VTEC strains in the patient samples, or anywhere close.

CTSMAC plates are getting old, and I for one can’t wait to see the back of them…

Michael

Note that the Infectious Diseases Society of America has just brought out updated guidelines on Infectious Diarrhoea, including quite a bit of detail on VTEC/STEC. Apart from the incorrect spelling of diarrhoea, they are very good!

I will add them to the guidelines section of this website also.