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Rickettsial diseases such as scrub typhus are important causes of fever in southeast Asia especially in rural communities. Discovered quite recently and not big killers, these diseases are among the most under-reported and under-diagnosed illnesses that are both treatable and preventable. Rickettsial studies at he Mahidol Oxford Tropical Medicine Research Unit (MORU) focus on the epidemiology and incidence of the disease using hospital-based fever studies in Thailand and Laos. Our research unit has developed highly improved acute diagnosis of rickettsial illness. MORU also has ongoing studies to determine the pathophysiological mechanisms of scrub typhus infection.

From his research centre in Bangkok, Professor Daniel Paris tells us about the challenges posed by Rickettsia to rural populations in South East Asia.

Q: What are Rickettsia?

DP: Rickettsia are gram-negative obligate intra-cellular bacteria; they live within cells, they can’t live outside cells, and they cause a disease called typhus. There are many different forms of Rickettsia, but the interesting thing about these bacteria is that they are transmitted by different vectors: they are transmitted by ticks, lice, fleas, chigger mites, all these small little etymological creatures. This makes it extremely interesting.

Q: Can you give us an example?

DP: Well one example, and probably the most important one for us here in the tropics, is scrub typhus. Scrub typhus is transmitted by bacteria called Orientia tsutsugamushi, which is a Japanese name – very difficult to pronounce the first time! It’s extremely common and extremely interesting. It makes a disease which affects your whole blood vessel system but particularly the brain and the lungs. It causes a great burden of disease in the region here. It is transmitted my mites, the smallest vectors of all the Rickettsia.

Q: What challenges do Rickettsia pose to rural populations in South East Asia?

DP: Rickettsial illness has only been discovered quite recently; it took over ten years to be recognised as an extremely important cause of fever and disease here in Asia. Almost 30% of all fevers diagnosed here are attributable to Rickettsial illness; that’s a huge number – three out of ten. It’s probably the most under-diagnosed, under-reported febrile illness which is treatable and preventable in the world at present. That makes it a huge challenge. It’s not necessarily a big killer; the death rates are about 5 – 10 % and they are largely due to problems with diagnosis, where doctors can’t make the actual diagnosis and know that they are dealing with typhus.

Q: What are the most important lines of research that have developed here in the last five to ten years in this disease?

DP: Definitely diagnostics. Diagnostics are always based on the immune response of a person; so you look for antibodies against the Rickettsia in the blood of people. This is the gold standard way of making this diagnosis, but it is quite difficult, costs a lot of money, and a lot of expertise is needed. You need a good lab and you also need microscopes and reagents for this diagnosis. So we have been trying to focus on making rapid diagnosis cheap and easy using small rapid tests, and also increasingly using DNA detection tests which enable us to make the diagnosis earlier. The second really important thing is to design a vaccine or any sort of preventive measure to control the disease. The disease is endemic, which means it has been here for a long time, and people keep getting ill with typhus; they don’t build up a memory immune response and they keep getting ill. We need to understand these issues before we can move on to design a vaccine.

Q: Why is your research important? Why should we put money into it?

DP: Firstly it is probably the most common cause of illness and fever in Asia, in this region, at the moment. That, together with it being treatable and as such preventable, makes a huge case. Investing in training doctors, study nurses, and making better diagnostics will reduce the disease burden enormously and have a huge impact, including on economics and all the country associated political issues as well.

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

DP: All the research I have been involved in so far, and I say this as a clinical doctor – I am actually a physician I did my PhD just a couple of years ago – all this work comes from the patients. It comes from the day to day clinical setting in the hospital, and all the research questions we address are derived from problems which we encounter while treating patients. These problems obviously focus on diagnostics, preventive measures like developing a vaccine, but also, and this is really important, on describing the variety of different strains of Rickettsia in the area. We need to know and characterise these Rickettsia so that we can adapt the diagnostic measures and the future vaccine candidates to cover all these organisms.

Q: Are there any specific challenges of working in an overseas environment?

DP: Yes, there are actually quite a few. Obviously working here, in an area where the language is totally different means that the language barrier is a big issue. It is very important to show respect; even if other people have made a mistake it is important to not point fingers at them and to maintain a low profile oneself. But then there are other issues like temperature – it is extremely warm here. Right now it is the warmest time of the year, we had 42 degrees Celsius just a couple of days ago. All of these many little setbacks add up, but it's all part of the game and its fun.

This interview was recorded in April 2013.

Translational Medicine

From bench to bedside

Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.