What Niger's AMR outbreak means for the world

What do we need to know about the threat posed by AMR? Brad Spiller is head of medical microbiology at Cardiff University…

Brad - I like to think about bacteria as a supervillain. In the theatres it was the Avengers, where you had Thanos. Thanos is the giant purple bacteria and he's running around collecting the infinity stones. And the infinity stones are the equivalent of the resistance genes, right? So as he gets each individual stone, he gains a new power and he becomes less and less killable. The O'Neill report that was commissioned by the UK government said that by the year 2050, more people are going to die from antibiotic or antimicrobial-resistant bacteria than die from cancer and diabetes combined. And I mean, that's a scary number - that's like 10 million people a year.

Chris - How does this arise? When I was first a doctor, for example, the card that the microbiologist in my hospital gave me for what drug to use for which infection - when I looked at that the other day, none of those drugs work anymore. When we look at those sorts of infections, I couldn't use those drugs today. Why have we ended up in that position and how?
Brad - When penicillin was discovered in 1928 by Alexander Fleming, there were already a few bacteria in the wild that carried natural resistance. The resistance has always been there - it was just sort of at low levels. What antimicrobial resistance is, is actually that selection process. So when we use an antibiotic, it kills the sensitive bacteria and it selects the tough ones. So those survivors multiply and pass that resistance on. That resistance can be a DNA mutation. Often it's actually on a small extra DNA loop called a plasmid that the bacteria can share between them. Antibiotic overuse and misuse, plus heavy antibiotic use in things like agriculture, accelerate that selection. The real danger is when you get a single strain that collects resistances to multiple drug classes. Penicillin is the oldest one, and the reason that we have probably more penicillin resistance than anything else is because we've been using it longer. Tetracyclines came along in the '60s. And there are some, like Group B Streptococcus, for instance, greater than 95% of them are resistant because in the 1960s they used tetracycline for everything. To some degree, that's part of the problem we have now. People try to use antibiotics to cure a cold - which has no effect whatsoever on a virus. And all you're doing is basically giving that selection process and getting rid of the bacteria that we could have an effect on.

Chris - In other words, if you go out into the environment, your chances of running into a microbe that now has resistance against the antibiotic shoots up because we've used a lot of that antibiotic. So that if you're going to get that bacterium, you're going to get one that's resistant just because there’s so many of them around now, because we've killed all the ones that were sensitive.

Brad - Yes, it's that pressure - the overuse and misuse. The other thing is taking the antibiotics through the whole course. You might start to feel better and stop taking the antibiotics, but that's exactly the sort of thing that drives mutation. If you take the pressure off, then all of a sudden they want to survive. They're going to start making mutations. Some of those mutations will make them resistant to the antibiotic. They'll also start trading little bits of DNA that carry resistance genes. And those resistance genes have always been there - they're just not highly prevalent. So it's just a case of stopping them from sharing and concentrating those resistance genes into the bacteria that we have left that cause pathological infections.

Chris - What can we do about the problem?

Brad - Number one, I would say, is targeted treatment. You diagnose the bug and its susceptibilities before or soon after you start therapy. Number two is stewardship - you use the right antibiotic at the right dose for the right duration. Number three is prevention. There are things outside of antibiotics that we can do, like vaccination, hygiene, safe food, and safe water. Surveillance, number four, track what's happening locally. Because if you have an idea of what is already highly resistant or which antibiotics don't work in a local situation, you can change and perhaps treat them more appropriately. And then number five, I’d say, is something we call One Health. And that is outside of just human patients. You probably don’t realise that non-essential antibiotic use in agriculture and treating animals is equally driving bacterial resistance, because the bacteria are in the soil, it’s in the water, it’s in the environment. It’s not just going from one person to another. Some of this pressure isn’t just what we’re doing - it’s also what’s happening around us. Some places in these developing countries, you end up with issues where they’ve got poor sanitation. So a lot of times the bacteria will go through our digestive systems and end up in the sewers. But you’ve also got knock-off pharmaceutical companies that aren't getting rid of their intermediates appropriately. So that’s feeding into the same sewage. And all of this is happening at an ambient temperature of around 37 - 35°C - which is almost the perfect storm for these bacteria to mutate, to evolve, and to exchange these pieces of DNA. That’s where you end up with high concentrations of antibiotic resistance, and that’s why we see this in particular parts of the world. But like COVID, we know it isn’t going to stay there. All these resistant bacteria are going to move across borders. And the rate at which they move will largely depend on what we do here to try and make our antibiotics work better and longer.

Chris - Presumably there are also some practices - despite the fact that the risk exists in the environment and these microbes are out there - we can put in place to minimise the risk.

Brad - Definitely. Crowded wards help the germs spread. So we have to develop safe habits and make those habits the easy habits. For instance, things like putting hand gel at the end of every bed and near the door - use it on the way in, use it on the way out. Move patients as little as possible, because obviously it can spread from one patient to another. Keep people known to carry the same resistant germs together and away from others, or in single rooms - though that’s not always possible in low-resource settings. Dedicate the kit - thermometers, blood pressure cuffs, etc. - to those patients. But always things like clean water and working toilets. I suppose for the antibiotics we have, ideally you want to use quick, cheap tests to check if they're really needed. And then, probably after 48 hours, review that, and make sure that if they don’t need antibiotics, you don’t continue to use them. Or if it’s the wrong antibiotic, you change immediately to something that’s more effective. That way, you can sort of stop the process of concentrating these resistant bacteria and getting them to gain multiple resistances.

In 2015, the UK government set up the Fleming Fund, committing £250 million to fight antimicrobial resistance across Asia and Africa. It was an enlightened move because, as we keep saying, what goes around comes around, and so we need to keep an ear to the ground, microbiologically speaking. But, in July, the shock announcement came that funding would be withdrawn and the initiative would be closing down. This move echoes a worrying trend set by the US in cutting foreign aid spending. Jeremy Knox is head of policy for infectious diseases at the research charity The Wellcome Trust…

Jeremy - Turning off the funding, removing the funding that had been available through the Fleming Fund, is undoubtedly going to have a very significant impact in terms of their ability to actually do the type of monitoring, the type of disease surveillance they've been doing. In terms of how we quantify that impact, that's very hard to say, but clearly if the laboratory capacity that's been built, if the capabilities that have been developed using Fleming Fund money, is lost, then that really is going to impact those health systems and national governments, in terms of being able to understand the problem in their country, to make sure they're treating patients effectively, to make sure they're mounting an effective national response to AMR. The other element is the global element, and I guess there’s two sides of it. I think firstly, the Fleming Fund has been supporting a great deal of work, including some that Wellcome had co-funded.

When the fund was set up back in 2015, we didn't have a single estimate, or a credible estimate, of what the overall global burden of AMR looked like. The Fleming Fund has helped fund research which has given us a much better understanding now of what that global picture looks like, what the country-level estimates look like, and then what the trajectory is of the patterns of drug resistance. Then in terms of the wider global picture, as we lose that understanding and we lose the capabilities to deal with drug-resistant infections in poorer countries in Africa and Southeast Asia, like so many infectious disease problems, a problem anywhere can very quickly become a problem everywhere. Drug-resistant bacteria, like any infection, don't respect borders. So it was a very sound investment. It was a real win-win to be supporting efforts to improve surveillance, to improve the response to AMR in low- and middle-income countries, because that improves global health security and makes sure that we don't have problems of AMR developing and spreading around the world before we can effectively control them.

Chris - The Wellcome Trust is a pretty powerful entity, and you have the ear of some pretty
powerful other entities. Is this a void that you can step into, to try to offset some of those difficulties that you've just outlined?

Jeremy - AMR is not unique at the moment in terms of facing real funding challenges. Of course, we've seen in the last six months or so what's been going on with the US making significant funding cuts to its investments in all sorts of different areas, and that having a very profound impact. Of course, we - as a major global funder of AMR, but of other issues as well - we will try and address issues that arise because of this where we can, but we don't have the capacity to close the gap that's left by the US government or by the likes of the UK government.

Chris - Who actually killed off the Fleming Fund though? Because one journalist - from one of our major radio networks - phoned me up and asked me for my opinion on it. She said, this seems to have flown under the radar. People don't seem to have realised this is going on. And she wanted to make a particular thing of it on one of our flagship news radio programmes. So who is responsible for pulling the plug? And is this an irreversible decision? Can we not point out to them the error that is intrinsic to this decision and try to get it reversed?

Jeremy - It's hard to say exactly where the decision was taken. But I think clearly it's in the context of the UK government having to make, unfortunately, cuts to its overseas development spend. We're seeing a lot of reductions across the piece in global health that we're very concerned about. For instance, we're seeing significant cuts in the amount of R&D spending that comes from ODA - Official Development Assistance, to use its technical term.

In terms of a question of whether the Fleming Fund decision is reversible, that's hard to say. But what we have heard from ministers is that they are committing to working very hard to make sure that there isn't simply a loss of the capabilities, or the networks, and learning that have been built by the Fleming Fund over 10 years of excellent work. They have said they will think about how they can try to mainstream it within things that the FCDO - the Foreign, Commonwealth and Development Office - do, or by asking countries to build work on AMR into what they do on pandemic preparedness.

So I think we've heard the right noises in terms of making sure we don't have a total loss of what the fund has been doing. But I think we will need to keep a very close eye on that and make sure there is follow-through, and that AMR is still seen and championed as a priority. And, as I said, that AMR becomes more of a mainstream issue alongside other country-level health imperatives, and that the UK continues to support and champion that.