Guy Thwaites: Tuberculosis meningitis
Tuberculosis meningitis affects a fractions of TB patients but causes high levels of mortality and morbidity. A recent trial at OUCRU showed that aspirin can greatly improve outcomes. Such trial is typical of the work done in our Vietnam units, where all the research is focussed on improving the outcome for patients directly.
My name is Guy Thwaites, I’m the director of Oxford University Clinical Research Unit here in Vietnam, in Ho Chi Minh City.
TB meningitis is a disease caused by a very common and very important bacteria called Mycobacterium tuberculosis; it’s a bacteria that kills more people than any other single infectious disease in the world. There are more than 100,000 cases each year and there’s somewhere around 18-19,000 deaths. Most of the disease affects the lung but about 1-5% affects the brain, and when it infects the brain this causes tuberculosis meningitis. That means an inflammation of the meninges, which is the surrounding of the brain, caused by the bacteria. It’s a severe disease, it kills around 20-30% of people and leaves another 20-30% severely disabled.
The earlier you treat TB meningitis the more likely you won’t die from it. For a doctor the greatest thing you can do to save someone’s life when you are confronted with this disease is give early treatment. The big problem is that it’s really difficult to detect this disease or diagnose this, so doctors are often delayed. With every day, every passing hour really, the risk of death or disability increases.
The problem with TB meningitis is that it involves the brain, and the brain is encapsulated within the body with something that divides it from the rest of the body called the blood-brain barrier. This is a good thing because it stops toxins, for example that you might ingest, getting to the brain and causing the brain to dysfunction. The bad thing is that it also stops some drugs from getting into the brain and killing the bacteria. So we’ve been doing quite a lot of research trying to work out how we can improve the concentrations of these drugs, antibiotics, into the brain.
Most recently however we’ve flipped to the other way of looking at trying to improve outcomes, by using other anti-inflammatories. We have had a really interesting trial result using aspirin. Aspirin is a drug that has been available since Hippocrates discovered that extracts of the plants that contain salicylic acid actually control fever, it’s an anti-inflammatory agent. One of the problems with TB meningitis is that it causes strokes: the blood vessels get blocked and areas of the brain die. We figured that we know aspirin in other strokes can prevent other strokes, and it does that by preventing clots forming, but it also has this anti-inflammatory effect as well. So we did a small trial we’ve just published that showed the addition of aspirin could also have a major impact on outcome: it can prevent strokes and might prevent death. We need to do a larger trial because it was quite small. We just wanted to test to make sure it could be effective and was going to be safe, and it looks to be both, so we’re going to go ahead and do a bigger trial; that’s one of the really exciting findings of the last year or so.
We have direct impact on clinical care, and by that outcome, lives. It’s difficult to quantify how many lives have been saved but you could look at the first trials for example that were done in Vietnam, on what were then new in the 1990s, the artemisinin derivative drugs, they have saved countless of thousands of lives. Those initial trials were instrumental in changing the way malaria was treated, and we try and do that with every infectious disease that we approach. We try and do work that changes the way that people think, doctors treat and diagnose patients, and I think that is worthy of funding – there’s not very many centres around the world that take that approach.
Everything we do in OUCRU is pretty translational. We place the patient at the centre of all of our research and we ask the question “what can we do to improve the outcome of people with severe infectious disease?” The TB meningitis work is absolutely no exception. We say “what are the techniques that we can use to develop, to diagnose the disease better?” “How can we improve treatment?” It’s all translational, it’s all aimed at improving the outcome of patients directly. If we’re not doing that within a reasonable timeframe, say 5 years, then I don’t think we should be working here. We’ve got to be doing things that impact on health almost directly, and that’s what we do.