Stuart Blacksell: Microbiology in Thailand

From his research group in Thailand, Professor Stuart Blacksell discusses improving the accuracy and the rapidity of tropical infection diagnosis in the field.

Q: How good is the diagnosis of tropical infections in rural South-East Asia?

SB: Unfortunately it is not so good; where we can actually demonstrate the infectious agent such as a bacteria, a virus or a fungus, it’s not too bad. However, it can be quite time consuming and expensive. The normal requirement is to grow the agent on something like a bacterial agar, or to use some sort of molecular method such as a polymerase chain reaction to indirectly demonstrate the presence of the infectious agent. Unfortunately many of the diseases that we encounter can’t be grown on agar plates (or we don’t have the technology in the field to do so), because of this we have to rely on antibody based tests using serum, which is just a surrogate marker of infection. Unfortunately the antibody based tests are not very accurate because they're not very sensitive (that is, the limit of detection is not very good) or specific (that is, providing the correct diagnosis). We can improve the situation by taking two approaches; the first is using a more direct method such as an antigen based test and combine it with the antibody based test. Secondly we can use a rapid test format such as a pregnancy style test, which we call a lateral flow device, to detect the antigen or the antibody.

Q: Can you give us an example?

SB: Probably the best example I can give is that of the Dengue rapid test, which uses the combination of an antigen based test and an antibody based test using the lateral flow test. The use of the antibody or antigen based tests alone only gives us 60 – 70% accuracy, however, combining the two increases the accuracy enormously. This is due to there being a complimentary dynamic between the Dengue antigen and the antibody during the course of the infection.

Q: What are the most important lines of research that have developed over the past five to ten years?

SB: From my point of view the most important lines of research have been in the comparison of commercial diagnostics for acute tropical fevers such as Dengue, scrub typhus, leptospirosis and others, to evaluate whether they are truly accurate. Many of the manufacturers claim that their tests are 100% accurate, but this is simply not the case. By performing comparisons with reference assays we can determine that the majority of the tests perform well below the manufacturers claims. Importantly, this means that the manufacturers have either improved their tests, or they have gone out of the market all together due to the poor performance or the lack of willingness to prepare new tests.

Q: Why does you line of research matter why should we put money into it?

SB: Put simply, if we can’t diagnose a disease then we can’t treat it and that is why an accurate diagnosis is very important. Unfortunately acute tropical fevers have a number of causes such as: Dengue, typhus, leptospirosis, malaria and typhoid, just to name a few. Each of these diseases requires a different treatment and without treatment there can be complications with serious and detrimental outcomes for the patients. Improved diagnostics save lives.

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

SB: Certainly by improving the accuracy and the rapidity of the diagnosis in the field we can improve the patient outcome. This is most relevant when speaking with regard to accuracy improvement in rapid diagnosis of Dengue virus infections. There are opportunities to measure the impact of improved diagnosis with relation to patient outcomes and this is something that our members in the MORU team are pursuing over a number of clinical sites.

The biggest challenge with being the safety officer for the programme is that we are quite spread out - in fact, we have seven sites and these are sometimes quite diverse in nature. This means that at all of the sites we have to perform risk assessments to determine the nature of the risks, and then to put in place interventions to ensure that staff members are not at risk of illness or accident. This requires a great deal of staff training as well as risk and intervention awareness. The safety office here at MORU also has to keep up with local and international administrative requirements, which keeps us very busy.

Of course, there are unique challenges faced when working in an overseas environment. However, the benefits outweigh the negatives. Some of the challenges can be language and cultural differences. However patience, listening and flexibility can solve most problems. The upsides are working with the people that you get to meet along the way, the cultural experiences and the opportunity to do things that you would not normally get to do in a western working environment.

This interview was recorded in April 2013.