World Tuberculosis Day 2015

On March 24th 1882, Dr Robert Koch announced that he had discovered the cause of tuberculosis (TB). 24^th March is 'World Tuberculosis Day' - an opportunity to raise awareness about the burden of TB worldwide.

Although not that common in the UK (there were 7,892 recorded cases in the UK in 2013), TB is still a big problem in other parts of the world. NDM spoke to Professor Guy Thwaites, Director of the Oxford Clinical Research Unit in Vietnam, about the situation in South-east Asia and the ongoing research at OUCRU in to eradicating the disease and improving patient outcomes.

Q: How common is tuberculosis in South-east Asia compared with the rest of the world?

Guy Thwaites: TB is very common in South-east Asia, especially in Myanmar, Cambodia and Vietnam. However, although the incidence of new TB cases is lower than in many parts of sub-Saharan Africa, the very large populations in the region means that moderately high incidence rates translate to very large numbers of people with the disease. For example, in Vietnam each year (with a population of 90 million) there are more than 100,000 cases notified and treated.

Q: What challenges need to be overcome to improve patient outcomes?

GT: There are three major challenges and they are not unique to South-east Asia. The first challenge is drug resistance. We have estimated that there are probably around 5000 new cases of multi-drug resistant TB in Vietnam each year. Only around 1000 of these are currently being detected and treated.  Treating these cases is difficult and the outcomes for people with drug-resistant TB are much worse than for people who have drug susceptible disease. This is a major problem, especially when these missed cases will be responsible for on-going transmission of multi-drug resistant TB to other people.

The second challenge is organisational. Detecting patients quickly and getting them to take 6 months of treatment (or in cases of multi-drug resistant TB at least 18 months of treatment) is difficult and requires considerable co-ordination and support on behalf of the healthcare services. In resource-limited countries this is very challenging. The situation is not helped in Vietnam by increasing numbers of patients opting to start treatment in the private healthcare system, where drug regimens are unregulated and often inadequate, exposing the patient to greater risks of treatment failures and the development of drug resistance.

The third major challenge is a scientific one: how can we shorten TB treatment to 2 months or less such that adherence would be improved and the organisational strain on TB treatment programmes alleviated? Why TB takes such a long time to cure is still a mystery, especially when we know that 90% of the bacteria are killed within the first 14 days of treatment. If we knew why the last 10% of bacteria took another 5.5 months to kill we would probably be very much closer to developing very much shorter treatment regimens.

Q: What research is OUCRU doing to try and combat tuberculosis?

GT: OUCRU has worked for 15 years in trying to improve outcomes from some of the most severe forms of tuberculosis and, in particular, tuberculous meningitis. We have performed a series of clinical trials, addressing the role of adjunctive dexamethasone, the timing of anti-retroviral drugs, and most recently whether the use of higher doses of TB drugs improves outcomes. We will continue to work on tuberculous meningitis because it kills or disables around 50% of sufferers, but it has also allowed us to make some important observations of the pathophysiology of the disease which may have implications for the clinical management of all forms of TB. In the light of some of our recent findings in TB meningitis – in particular the genetic control of the inflammatory response to the infection - we will extend our work into pulmonary tuberculosis. We want to better understand the determinants of treatment failure and, with the Mahidol-Oxford Research Unit in Thailand, we want to set up a network of sites across SE Asia that would be capable of performing large, pragmatic randomised controlled trials. There has been an increase in clinical tuberculosis research worldwide over the last decade, but most of the clinical trial data comes from Africa.  Trials networks are required in Asia and we look to lead the development of these through the Oxford-linked centres in the region.

Q: Do you think that tuberculosis will ever be eradicated in our lifetime?

GT: I am an almost pathological optimist, but no - I do not think we will eradicate the disease in my lifetime. In might be possible in my children's lifetime (my youngest daughter is 12) but I wouldn’t put more than 30,000 Vietnamese Dong (~£1) on it. The reason for my pessimism? The ability of the bacteria to lie ‘latent’ in our bodies without causing any disease for many years. It is estimated that around 1/3^rd of all the world is ‘latently’ infected with TB. However, only around 10% of these people will actually get symptoms and disease and it is not yet possible to predict who these will be with any accuracy. So, if we were going to eradicate TB by the end of my lifetime we would not only need to successfully treat every case of active TB on the planet, but also the more than 2 billion people with latent infection too - to ensure that the bacteria won’t just spring back into life in someone when it is least expected!  A good vaccine would help, but we are still a long way off having one. Therefore, I think TB clinicians and researchers will still be very busy for many decades to come.