The Eijkman-Oxford Clinical Research Unit (EOCRU) develops clinical trial models for clinical interventions for preventing and treating malaria. Prof Kevin Baird speaks about the challenges of delivering healthcare in Indonesia.
Treatment and prevention of P. vivax in Indonesia
Q: Which infectious diseases are a big problem in Indonesia?
Kevin Baird: I think it is the same infections that affect tropical countries that struggle with getting healthcare services out to their peripheries, where people have difficulty accessing healthcare. It is the same three infections in most tropical countries: HIV, tuberculosis and malaria - the Global Fund's big three, those are good investments. There are also many other important infections that are not typically addressed in Indonesia: lymphatic filariasis, dengue fever, Japanese encephalitis, leptospirosis and others, that I can't tick off.
It is important to realise that Indonesia is a very large country. It has 250 million people, 14,000 islands and over 5000 kilometres in length. To give you a perspective, that's like from London to Kabul, Afghanistan. It is a massive piece of real estate and the Indonesian government struggles to provide adequate health care services all across that and on every island. They struggle and I think that is one of their key challenges.
Q: How can the burden of those diseases be reduced?
KB: I look at that question through the same lense as the challenges and limitations imposed by geography and economics. Because of my experience in Indonesia I have become a strong advocate for very simple and affordable point of care diagnostics. If we can’t diagnose infections, we can't treat them, we can't beat them back. The people most affected by these infections do not have access to laboratories. Therefore, if we make progress in point of care diagnostics we are going to make significant progress against many of these infections.
Q: Can you talk about the treatment and prevention of Plasmodium vivax?
KB: That actually is a poster child of the issue of having access to diagnostics. To understand that I have to explain a bit about the biology of that parasite. Plasmodium vivax malaria is actually two infections. On the one hand it causes an acute attack and disease that must be treated, and we have drugs to treat it. On the other hand, it also has a stage that goes dormant, then awakens in the months to follow and causes more clinical attacks. That stage is called hypnozoite and we need a separate treatment for that stage, a 'hypnozoidocide'. The only drug that we have is called primaquine, and that drug happens to be haemolitically toxic to patients who have an inborn abnormality called G6PD deficiency. Unfortunately, this deficiency is quite common where there is malaria, about 8%. If patients receive treatment against that latent stage of Plasmodium vivax and we don't know their G6PD status, their life is at risk. It is so toxic, it can end in death and has ended in death. There is a terrible therapeutic dilemma that we face with every P. vivax patient. Do we give the treatment and risk harm because of G6PD, or do we withhold treatment and allow the parasite to do its harm? A point of care diagnostic that allows us to sort out who is G6PD normal and who is not, allows us to treat people for Plasmodium vivaxwhere today in truth that rarely happens. It is a serious problem and it is a diagnostic problem.
Q: What are the most important lines of research that have developed in the last 5-10 years in this area?
KB: With respect to Plasmodium vivax, we have made great strides in the past decade or so. The malaria research community has sorted out some very important dogma, discredited dogma now. The first is that for decades we were all taught in school that Plasmodium vivax was relatively harmless, it rarely caused death, it was kind of a mild infection. When we go into hospitals and survey patients with the infection, actually we find the opposite is true. Very often, almost as often as with P. falciparum, they develop severe disease syndromes that are associated with the fatal outcome. We now appreciate that Plasmodium vivax threatens life; this gives us a perspective to take it more seriously and perhaps more aggressively.
The second discovery was the importance of that latent hypnozoite stage in terms of the epidemiology of this infection. It turns out that in endemic areas, more than 80% of the acute attacks that we see in patients come from the liver, not the mosquito, and this is very important in terms of understanding how to control the infection. The third important advance, and this is simply connecting those two dots, has informed us of the necessity of addressing this G6PD diagnostic problem and ensuring that every patient that is diagnosed with Plasmodium vivax is treated against those relapses, safely.
Q: Why is your research so important and why should we fund it?
KB: I think there is a simple way to put that: we just need to look back over the past 65 years. Primaquine has been available for 65 years, but the people most in need of it have had no access to it. All we ned to do is think about those decades, the untreated infections and the clinical attacks that have occurred. These are uncountable numbers of infections. Now that we understand this problem, we can take steps - and we are - to resolve it and get Plasmodium vivax treated every time.
Q: How does your research fit into translational medicine within the department?
KB: Looking at translational research is simply research aimed more directly at better health outcomes. I think a lot of research laboratories typically advance the front of some technology and move it forward, pushing that envelope of technology. They then try to translate that to a better health outcome, looking for an illness that is relevant. In Indonesia, and this has a lot to do with the geography where very often the sick patient is right in front of us, we take the inverse approach. Our starting point for translational research is a sick patient, and then to shop the available technology to see how we can improve this patient’s health outcome.
That approach largely explains the emphasis of clinical trials at the unit in Jakarta. We mostly do clinical trials and I view that as a technology: doing randomised controlled trials is not simple, it is a technology and it is a skill set that has to be acquired by practise and learning, and that is what we try to do in Indonesia. We develop a team that can do randomised clinical trials that can be applied not just to malaria but to other infections. In fact, my team will be undertaking a randomised controlled trial for TB meningitis at two hospitals in Jakarta this year. It is the same people and the same skill sets, but it is a different disease and that is the business of translational medicine. I might add that our Indonesian friends and partners embrace this very much. This is what they want and expect from us: better health outcomes for their patients, and that is what we strive to deliver.
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