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In conversation: infectious disease

Dr Peter English, an infectious disease expert, discusses how genomics informs his speciality.
So it’s a great pleasure to have Dr. Peter English here, who is a consultant in communicable disease control as part of the Health Protection Team for Surrey and Sussex and the outgoing chair of the BMA Public Health Medicines Committee. Peter, thank you so much for joining us. And I’d just like to kick off by just asking you, how you– or what your interest is in genomics and how relevant it might be to your day-to-day work in infectious diseases? Genomics has become increasingly part of what we do in the communicable disease control. Increasingly, we’ve been looking at the genetic makeup of the organisms that cause outbreaks, rather than just their phenotypic characteristics.
We’ve been using, really, 19th century microbiology techniques for a long time– Gram stains and the like. But the genomics tell us a lot more about the real nature of the organisms we’re looking at. So that’s been becoming more and more part of what we use as our arsenal of trying to work out whether organisms are related to each other and so forth. I’ve also become involved with my BMA role. The BMA’s board of science organised a seminar a while back, which I attended, on genomics where I learned a lot more. And I’ve– since then I’ve had a role in genomics in our local team, keeping an eye on what’s developing– developments there and so forth.
So it’s not my core interest, but it’s something I’ve been interested in for some time. So Peter, how do you see new genomics techniques impacting on infectious diseases, particularly, as you’d expect, in the context of COVID, but perhaps other diseases such as multidrug resistant TB, for example? Well, this has become a huge thing with COVID-19. But we’ve been using method– this sort of method for some time. We’ve been using PCR testing– polymerase chain reaction testing– to look at bacteria and viruses for quite a long time. The kit to do a PCR is quite expensive and tricky.
But once you’ve got it, it’s much quicker to run a PCR screen looking for bits of DNA– or bits of RNA– in a wide range of organisms. So you can run a panel looking for a whole range of respiratory viruses, for example, and identify those viruses if they’re there. That’s not using the whole of the genome. It’s just looking for particular bits of RNA or DNA. But that has become much cheaper than doing the old fashioned microbiology– and relatively quick.
We use it specifically looking– we use more whole genome sequencing, where we look at all of the DNA in things like tuberculosis, where by comparing the genomes of different strains of tuberculosis– which of course is a bacteria– we can see how closely different organisms are related– different people’s organisms are related. The organism does mutate slowly, but it means we can look at particular strains or variants and see how the outbreak that’s been running in Brighton, for example for some years, seems to have been seeded from an outbreak that was happening in the Midlands, because it’s a very closely related strain.
When we’re doing another outbreak investigations, it can be very useful to see how closely related the organisms that two people have. If they’re almost identical or exactly identical, then it’s very likely that that one infected the other or they have a common source, so– there seems to be an outbreak going on. And if they’re very different we can relax and think, oh, this isn’t an outbreak. It’s just an unfortunate coincidence. You’ve seen this, for example, with Clostridium difficile, which is an organism which lives in the guts and generally does no harm. But if you take antibiotics, it doesn’t– it isn’t killed off by the antibiotics.
So when all the other bacteria in the gut are killed off by antibiotics, the Clostridium difficile can grow unimpeded by these other bacteria. And it can produce a toxin which can cause diarrhoea. And we always used to think when we had several cases of Clostridium difficile infection on a ward that it indicated a problem with the infection control systems, that it was cross infection. But actually, when you look at the genomics of the bacteria, you very often find that it’s just that you’ve got people taking antibiotics and they have completely different strains of the bacterium. So we know that they’re not– it’s not caused by poor infection control mechanisms.
It’s just one of those things that happens when you give lots of people antibiotics. That’s very interesting. So would you say genomics, in terms of tracking outbreaks, is a much more powerful tool? Or is it just a complement to existing tools that you have in outbreak management analysis? It can be a very effective way of saying that cases are unrelated and therefore not part of an outbreak. So it is very powerful in that. So where we can get that level of data– and increasingly we can– that can shut down an outbreak investigation, because we know it’s not an outbreak. It’s just unrelated coincidences. Coming back to it– you asked me another question about antimicrobial resistance.
We can look for the DNA which encodes for the resistance to various antibiotics. You mentioned TB, and that’s a good example. It used to take a very long time. TB grows slowly in culture. I think it’s one of the organisms that we do actually– they used, actually, to grow in Guinea pigs– are one of the animals it would grow in. But it does grow very slowly in culture. So when you’re looking to culture the organism you got from somebody’s sputum, it can take a very long time. And until you’ve cultured it, you can’t tell which antibiotics it’s susceptible to in the traditional way.
But using the genomics approaches that we use these days– and the PCR approaches– you can quite rapidly tell if it’s producing the–
if it’s got the coding for the antimicrobial resistance So you know which antibiotics it’s likely to be immune to. Similarly, with– we look with E coli– which causes this– E coli 157 was the one that got most famous. We tend to call– refer to STEC these days– toxigenic E coli. You can look for the toxigenicity genes. And so these days, rather than growing the organism, we tend to do a PCR test. And there are PCR probes that specifically look for the toxigenicity genes. So you can tell whether it’s just an ordinary E coli– like you get in lots of urinary tract infections– or one that has the potential to cause quite serious disease.

The second part of our Week 3 course delves a little into the increasingly important ways that genomics is used within the field of infectious disease.

Many of these are of particular interest and relevance currently due to the global COVID-19 pandemic and as a Doctor, your friends and colleagues may expect you to understand and comment on the genetics involved.

In the video above and the following step, Dr Rafi interviews Dr Peter English, a consultant in communicable diseases control, about his experiences with genomics in infectious disease.

Some examples of how genomics is used include:

  • Helping to track outbreaks, sequencing genomes and watching mutations arise in real time to aid tracking of spread across the world
  • Identifying treatment targets – the sequence of a pathogenic organism can be analysed to identify possible treatment targets – these would be conserved domains across evolution that are important for the pathogen to function
  • Looking for pathogen mutations which confer drug resistance, allowing tailored treatment strategies for each individual
  • Identifying vaccine targets and new delivery models to produce an immune reaction to protect against the pathogen

Next we will discuss these areas in a little more detail with examples from the COVID-19 pandemic and TB pharmacogenomics.

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Genomic Scenarios in Primary Care

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