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The majority of people infected with the dengue virus experience a flu-like febrile illness, but in a small proportion of patients, particularly children, the virus causes the blood vessels to become leaky which can induce shock and lead to death. Improved diagnosis and understanding of the disease process enable better outcomes for patients with severe dengue, as explained by Professor Bridget Wills.

Q: Can you tell us a bit about where you work and what your research interests are?

Bridget Wills: I am based in Ho Chi Minh City in Vietnam, at the Oxford University Cinical Research Unit. I have been there for a very long time, nearly 18 years now, and I am a paediatrician by background training. I focus on research related to a lot of different diseases that are common or pose a particular problem for children in South East Asia. Over the years my major interest has honed down on dengue, which is a viral infection transmitted between people by mosquitoes. The majority of people who get bitten by an infected mosquito can experience an unpleasant febrile illness that is a bit like flu, but in a very small proportion of cases, certainly less than 2 or 3%, there can be complications which can be very serious and occasionally result in death. A lot of my work is trying to understand how, or who, is likely to be in that very small percentage, who will develop that very severe disease, and then in that group to see if we can improve management. At the moment, there aren't any specific therapies available so management is primarily supportive but there are a number of different options we are considering.

Q: What are the mechanisms which underline the severe dengue?

BW: Unfortunately we don't know. We know a lot about the virus: we know about its structure and how it interacts with the human immune system, how it is passed between mosquitoes and humans, we know a lot about the lifecycle. What we don't know and what we would really like to know is how, in that small proportion of people, the virus ends up causing severe disease. The major problem that happens in people with severe disease, particularly in children, is that the blood vessels do not work very well and become leaky, so people can develop a type of shock which can be very rapid and unfortunately in a small number of children leads to death. What we are trying to understand is how the virus interacts with blood vessels to make them dysfunctional, to make them leaky.

Q: How does the management of dengue differ in children versus adults?

BW: Children are very similar to adults in many ways but their physiology is different: they are in the developing phase of their physiological systems. Children are much more likely to develop leaky blood vessels than adults are. If they do, then they are much more likely to develop shock. We are focused on trying to understand the interaction between the virus and the blood vessels, particularly in children, so we can look at developing novel treatments to interfere with whatever is happening at that level.

Q: What are the most important lines of research that have emerged in the last 5-10 years?

BW: As a clinician I think that the areas of research that are really important are the areas that focus on diagnosing and trying to improve management in people who suffer from dengue but there are also a number of other areas that have become very important in the last 5-10 years. One is the development of a vaccine. There are a number of vaccines that are in process of development and at various different stages of research but there is one whih has recently gone through phase 3 trials and is in fact just been licensed in one country. Unfortunately, it is not as good as we would like but it is still a step in the right direction. The other area of research that is of important public health interest is to try and interrupt transmission between humans and mosquitoes. There is a particular bacteria that mosquitoes can be infected with. There is a theory - that there is now quite a lot of evidence to support - that if you infect wild mosquitoes with these bacteria, you can limit the capacity of the mosquito to transmit dengue on to another individual.

Q: Why is this line of research important and why should we fund it?

BW: It is a huge problem worldwide. There are many people who suffer from dengue. Admittedly most of them do not get seriously ill from the disease, but when you have millions of people who experience the infection and even a small proportion get serious disease then I think trying to understand how that happens and trying to prevent and treat it is a very important area of research. Not maybe locally here but globally very important.

Q: How does your research fit into translational medicine within the department?

BW: All the work I am involved with is translational: aiming to improve understanding how disease process works, diagnosing an infection and then improving the outcome of people who are suffering from that infection. In Vietnam, all the doctors that I know in the centre where I work are actually very good at diagnosing and treating dengue, but they have huge amounts of experience because it is one the countries which really has a massive problem. As dengue has spread around the world, and there are now estimates of 50-100million symptomatic cases of dengue a year globally, doctors and nurses who have not previously come into contact with this as a common and potentially serious infectious, are faced with managing patients. Experience really counts. In a collaboration with World Health Organisation we are aiming to try and improve guidelines for diagnosis and management, particularly for staff who are being faced with managing this disease that they may be unfamiliar with.

By Professor Bridget Wills

Bridget Wills

Dengue

With 390 million infections occuring each year, dengue is the most important mosquito-borne viral infection, and no vaccine is currently available. Researchers at OUCRU try and target both the virus with antivirals, and the immune response to the virus. The Dengue Group aims to improve diagnosis and clinical management of patients; one notable achievement has been the revision of the WHO Dengue Guidelines.

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