Apocalypse? Not yet!

March 21, 2020

ANY sc2 2020.jpg

It’s hard to pick the fact from fiction and half-truth in media reports on COVID-19.

Social and mass media have combined to create an information overload, and may have difficulty explaining the more extreme predictions they’re making about an epidemic disease whose individual clinical impact and community impact seem grossly out of proportion.  This blog will do nothing to add to the mountain of alarmist reportage.

Rather, this is a place to celebrate the quiet professionalism of specimen collectors and clinical laboratory workers who doggedly push though an unprecedented mountain of clinical specimens to identify people with the virus. Note “with the virus”. Just for once, the phrase ‘diagnosed with’ may be an accurate assessment. As ‘with’ does not always equate to causation, detection of SARS-CoV-2 does not necessarily mean infection or verifiable disease. When a team from the University of Padua who tested everyone in the town of Vo, they found positive test results in asymptomatic individuals. All test-positive people were quarantined. The results have been impressive, in contrast with other locations nearby where infection continues to circulate.

In Australia, the crude mortality rate appears lower than the initial estimates and may even be falling, thanks to an enormous national effort by public health laboratories. Once again, accurate test capability is at the heart of control and containment measures.

So, we have to recognise the backroom team of lab staff that are stretched beyond their normal limits by the current workload. While it is great to have the WHO’s Director General insisting on widespread testing, we have to ask how the labs doing the testing are going to keep this level of output going for several months on end. And that’s in G20 nations that are able to cover the cost. How are middle and low income countries going to achieve this kind of intensive laboratory-grounded public health response?


μGnostics 101

January 11, 2010

μGnostics: the contribution microbiology makes to Diagnosis

The dust is settling after a busy weekend on call, dealing out decisions on a variety of infectious diseases. So much weight is placed on the results of lab tests, yet all too often they only form a part of a much bigger diagnostic picture. Knowledge of how microbes behave during the course of infection, and how they play their part in the process is not the same as the diagnosis. In fact, the personal responsible for the diagnosis is not usually the same as the person driving back office functions such as the clinical lab.

If you drill down into the etymology of diagnosis, it becomes clear that this is a process linked to a special kind of knowledge, recognised in the specifics of the relationship a physician has with their patient. To speak of a ‘laboratory diagnosis’ is to truncate a complex process that begins and ends with a poorly patient. It would be more correct to see the clinical laboratory as a toolbox full of clinical decision support gear.

Thinking aloud, this begins to explain the difficulty we have with the unrealistic expectations generated by terms like ‘diagnostic tests’. Neither the tests nor the tester make a diagnosis. They may, however, support a diagnosis or another critical decision process.

ætiology; a core issue for μGnostics

First generation μGnomes realised that they needed a method to establish a causal relationship between a microorganism and an infectious disease. They came up with a short list of rules against which any such linkage could be judged. The most famous of these is often known as Koch’s Postulates. Since then a series of improvements have been proposed, most recently including our own (see tag below). The full set of rules has only rarely been applied to support a specific microbe-disease pairing. Nevertheless, a short form of this method has been used to identify the likely cause of infection in day-to-day clinical practice, combining Koch’s Postulates with Occam’s razor, where the fewest types of microbe that explain the entire disease process are used to determine what course of action should then be taken.

The cartoon version of this managed process is One bug-One disease-One drug. Of course, that is a gross oversimplification. The devil, as they say, is in the details and must have a particularly wicked sense of humour.

So that brings us back to μGnostics. The root cause we so often look for, using a short form of the Priobe Argument, is what we then use to guide our choice of treatments, and on a larger scale, our preventive measures. These are the things that occupy most of my waking hours, and some of my dreams as well.


Crazy bug hunters #3

January 10, 2010

Ignaz Semmelweis (1818-1865)

Ignaz Semmelweis (born Semmelweis Ignác Fülöp in Buda, Hungary on 1st July, 1818) lived and worked before germ theory was popularised by Louis Pasteur. Things might have been a little easier for him if he had been born 10-20 years later.While employed as a senior assistant to the professor of obstetrics in the Vienna General Hospital, he  Mortality was significantly higher in the clinic where he taught medical students, compared to the second clinic where only midwives trained. So obvious was the difference that women preferred to be delivered in the second clinic. Semmelweis realised that the explanation had something to do with the movement of medical students between autopsies and the obstetric clinic, proposing “cadaverous particles” as the likely cause of infection. The final straw was the death of his friend and colleague Jakob Kolletschka who died from septicaemia after being pricked by a student’s scalpel. Semmelweis introduced removal of his proposed cadaverous particles with chloride of lime solution between the autopsy room and the delivery bed and documented an almost ten-fold reduction in mortality.

You would have thought that an improvement of care of this magnitude would have met with widespread acclaim. Unfortunately it was not. His discovery was greeted with indifference, disbelief, opposition and ridicule. Semmelweis’ increasingly angry protests did not help his position. When an opportunity for promotion arose, he was passed over in favour of colleague. He returned to Pest, Hungary and was able to show once again an impressive reduction in mortality from childbed fever on the introduction of his method. Rather late in the day Semmelweis began to publish his findings papers, monographs and books. These stirred up further opposition from prominent authorities such as Simpson in the UK, and Virchow in Germany. His key work, Etiology, Concept and Prophylaxis of Childbed Fever, was finally published only four years before he died.

Faced with the opposition of some of the leading specialists of his day, is is not surprising that Semmelweiss slipped into a rapid decline. After a period of erratic and increasingly irritable behaviour, he finally had a nervous breakdown in 1865. Speculation includes causes such as Alzheimer’s Disease and neurosyphilis (an occupational hazard of obstetricians in those days). He was committed to an asylum and, in a final twist of fate, died from septicaemia following injuries probably incurred during or shortly after his admission.

In retrospect it is easy to understand his frustration that a purely empiric demonstration of efficacy was not enough to win over his medical colleagues. It would take another generation to build a firmer foundation for a mechanistic understanding of the disease process Semmelweiss sought to prevent. Yet you have to admire his ability to make that leap of imagination that enabled him to understand the basis of a causal relationship between something he couldn’t see and its disease-causing effects. His use of the term “Etiology” in the title of his book shows his colours as a forerunner of the hygiene movement. His intuitive grasp of disease causation makes you wonder what he might have achieved if he had within his reach the laboratory tools we now command.

The house where Ignaz Semmelweiss was born is now a museum of  the history of medicine. It aims to put him in his rightful place as one  of   those  who developed methods we use today. It can be found underneath the  southern ramparts of Buda Castle, overlooking the Danube. A tram will  get  you close to the museum, but the walk along the west bank of the river is  a  pleasant alternative.

μGnome, January, 2010

μGnome’s first communication with the μGnom-i-nation

January 9, 2010

Welcome, fellow μGnomes; you who share a fascination in very small things that pack a punch well above their weight.

This posting introduces μGnomics, μGnosis and other topics gnominated by the μGnomination.

A few early musings were introduced previously under the title of Fascinella and Crazy Bug Hunters (Learning in the Fast Lane). Rest assured; there will be more of these. But first, we need to dwell a little on the derivation of μGnome, μGnosis and μGnominate.

μGnomes are a bit like the little guys that stand guard in your garden. They’re quite small, fare better in colder climates and like to be at the pointy end of things. You know that from the shape of their red hats. Just as the gnomes of Zurich are famed for their wisdom on financial matters – econ-gnomics, μGnomes have special wisdom in μGnomics; the behaviour of microscopic life.

Their wisdom allows the μGnomes special insight into the implications of microscopic forms of life for human infection; μGnosis. This is similar to diagnosis and prognosis, but with a focus on microbes.

So the term μGnomination, logically, is the process of naming and identification critical to the use of that special knowlege of microscopic life and its role in human disease.

We could have a lot of fun playing with words, generating neologisms and digressing into unexplored permutations of scientific English, but for starters we’ve got a bit of catching up to do. There are plenty of new words and phrases coming into wider use these days; so many that it can cause confusion. It certainly doesn’t help smooth & efficient communication.

So we’re in for quite a bit of fun.

Are you ready to μGnominate?