Category Archives: History of Microbiology

“Modern Plague: Learning from the Past”

I have had a passing interest in the recent Plague outbreak in Madagascar. Living and working in provincial New Zealand, I don’t come across many cases of Plague. In fact I can safely say, I have never seen a case, and may well never do so. But as a microbiologist, I need to know something about the plague, just in case somebody asks…

The causative agent of Plague is Yersinia pestis. The other two main pathogenic bacteria in the Yersinia genus are Yersinia enterocolitica and Yersinia pseudotuberculosis

And I am bored to tears already… Rote learning is no way whatsoever to learn about bacteria, and especially ones like Y. pestis which most people will only encounter very rarely in real life.

When I think of plague, my mind turns to medieval London, Ring-a-ring-of-roses, Samuel Pepys, etc.

But most of all I think of the discoverer of the causative organism, Alexandre Yersin (picture above), a Swiss-French bacteriologist who has a fascinating life history. 

Born in Switzerland in 1863, he went to medical school in Lausanne, before ending up in Paris at Louis Pasteur’s research institute. There he was involved in the development of anti-rabies serum with Emile Roux. He joined the Pasteur Insitute in 1889 and again with Roux, discovered diptheria toxin.

He then worked as a doctor for a shipping company in South East Asia and it was during a secondment to Hong Kong in 1894 to investigate an outbreak of plague, that he discovered the pathogen responsible for causing plague. It was originally named Pasteurella pestis, but this has since been changed to Yersinia pestis in 1944.

As is often the case, there was a degree of controversy as to who was the first to make the discovery of Y. pestis. A fellow scientist, Kitasato Shibasaburo, made very similar findings to Yersin, but over the years, Yersin took most of the credit for the discovery due to the greater accuracy of his microbiological findings.

He then settled in and spent most of his life in Nha Trang, now in Vietnam.

He also directed a medical school in Hanoi, and was involved in establishing rubber trees and Cinchona trees (used for making quinine) in the region.

Alexandre Yersin died in Nha Trang in 1943, during World War II. A museum was set up in his former house and to this day, he is venerated by the Vietnamese people.

When you read about the history of a disease, it contextualises it, and thus the associated facts get remembered better.

So if you get asked to learn about Yersinia pestis, then go and read about Alexandre Yersin, go and read about The Great Plague of London, read about the living conditions, the rats, and the fleas… All you need to know about Yersinia pestis will be in such texts, and you will remember the stories.

And it is also far more interesting than reading a textbook

Michae

“Bacteriology Automation: Warts and all…”

Whether you are a microbiology student undertaking exams, a lab manager considering a business case, or a scientist wondering just what exactly the future holds, you need to know something about bacteriology automation.

We have now had the Kiestra TLA in place for 18 months at the lab where I work. It would be foolish to say it has all been plain sailing. Far from it. There have been breakdowns, computer malfunctions, and interfacing problems, particularly in the early days.

The learning curve is very steep.

But would I ever go back to traditional “manual” bacteriology processing? No way! In fact, I would go as far as to say that I would be very reluctant to ever work in a microbiology lab in the future that didn’t have automation of the bacterial culture process.

It would simply be a backward step…

With some great feedback from staff members (and expanding on a previous post), I have listed below an honest account as to what I think are the advantages and disadvantages of a bacterial automation system like Kiestra:

 

ADVANTAGES

  • Standardised incubation times: Personally I think this is one of the strongest advantages of the system. No matter when the plate was inoculated, the system will image the plate after a pre-set incubation time, and thus allow plate reading. This in turn will allow reduction in turnaround times for specimens. The old concept of Day 1, Day 2, etc. plate reading should disappear and be replaced by 1st reading, 2nd reading….
  • Plate Tracking: Each plate has a  comprehensive electronic audit trail attached to it, including when it was inoculated, incubated, imaged and read, and by whom. The audit trail is encyclopaedic, if not a little complex in nature.
  • Less menial tasks: Gets rid of finding appropriate plates for each sample, carrying the plates to and from the incubator, “putting up” of specimens, and other repetitive, manual tasks.
  • Better plate spreading: Automated spreading performed by machine will almost always succeed in better use of the whole agar plate and improved isolation of single colonies. It will also be a standardised procedure. Kiestra TLA uses the magnetic rolling bead method. It occasionally needs a bit of tweaking, but when it works, it is beautiful!
  • Less plate contamination: As the plate has less manual handling and less time spent with its lid off, the risk of plate contamination is almost certainly much reduced, which is very important for those “sterile site” specimens. A study in this area would make a nice research project for someone.
  • Storage of digital images of plates: Plates eventually deteriorate, images do not, and images can be stored to be viewed again at any stage in the future depending on how long you want to store them for. Great for presentations!
  • Less time out of the incubator: The plate goes straight into the incubator when it is inoculated, and essentially stays in the incubator whilst it is being examined. No hanging around and very little downtime. The advantage is twofold; shortened turnaround times, and a decreased chance of “losing” fastidious organisms.
  • Remote plate reading: The system should allow you to view the plate images from anywhere, including home. The possibility of microbiology scientists working from home in the near future is a real one.
  • Plate interpretation: This is still in the developmental stage but software is now available allowing rapid detection of plates with no growth, and (chromogenic)plates with colonies of a particular colour. Further development in such software will eventually lead to massive gains in efficiency.

 

DISADVANTAGES

  • Redundancy of staff: Whether staff members are made redundant or not due to the implementation of a system like Kiestra TLA, the simple fact is that this type of automation will get through (far) more specimens with less labour. Some (managers) might see this as an advantage, but from a people point of view it is a big downside. I personally find this aspect of automation very difficult to deal with.
  • Dependency on the automation: What happens if it breaks down? Because of the above, and because it is a complex operation, the consequences can be potentially serious if the system goes down. Fortunately as the Kiestra TLA is modular in nature, it is very unusual for the whole system to go down at once. We are also fortunate to have excellent engineering support at our lab.
  • Loss of ownership: Because the majority of the culture process is automated, staff members are less involved with the clinical sample from start to finish. This can lead to a loss of “ownership” of the sample.
  • Loss of continuity: Even with Kiestra TLA, there are still a few steps in the process that are still to be automated. Those steps are batched together in lists (e.g. MALDI-TOF spotting, susceptibility testing). Staff members are often only involved with one step in the whole culture process for any one patient sample. Continuity, which I regard as important, can therefore be lost…
  • More knowledge required: Not only do the staff now need to know about microbiology, they also need to know about Kiestra, how the system works, and how to troubleshoot any issues. Therefore a lot of new learning is required, as well as keeping up core knowledge in microbiology.

 

Change always comes with downsides as well as upsides.

But having said that, change is utterly inevitable, and I believe that Kiestra TLA or similar systems ( Biomeurieux, Copan Wasp) will be as ubiquitous as MALDI-TOFs in our clinical microbiology laboratories in 10 years time.

And if you understand both the pros and the cons of such systems before you start, it makes that change just a little bit easier…

Michael

A couple more posts coming on microbiology automation over the next week!

“Old rules for old tests”

800px-Mantoux_tuberculin_skin_test

I have been looking recently at the various merits of Mantoux testing versus the newer Interferon Gamma Release Assays (IGRAs) for the diagnosis of latent TB infection. Whilst the IGRAs (such as T -spot and Quantiferon Gold) are not perfect by any stretch of the imagination they still seem to have difficulty replacing the long entrenched Mantoux test.

The Mantoux test, which has been in existence for well over a hundred years suffers from various problems. False negatives due to immunocompromise, false positives after BCG, inter-observer variability in measuring the results, and the logistics of administration, just for starters.

One wonders if Mantoux were a new test invented today, whether a test with so many deficiencies and subjectivity would get anywhere near the commercial market. The validation requirements for new tests as stipulated by accreditation agencies are much stricter now than they were 100 years ago, 50 years ago, or even 20 years ago.

I think we are applying old rules for old tests to a certain extent. Mantoux testing is an institution, a tradition, and is what a lot of us are used to. However because it was acceptable testing in previous generations does not mean it is acceptable by today’s standards.

I don’t think IGRAs will need to improve too much more before Mantoux testing ends up as a historical test, and PPD is kept in museums and not laboratories….

Michael