Researchers tackling deadly TB discuss the way forward in treatment and prevention

Nov 29 2017

Researchers from across the world who are tacking the deadly bacterial disease tuberculosis (TB) attended a symposium at St George's, University of London to discuss the way forward in treatment and prevention.

TB is one of the top 10 causes of death worldwide and in 2016, 10.4 million people fell ill with the disease and another 1.7 million died. Many of the deaths - 95% according to the World Health Organization - are among people have immune systems damaged by HIV.

The International Consortium for Trials of Chemotherapeutic Agents in Tuberculosis (INTERTB) group of experts meeting at St George's was organized by Dr Amina Jindani, an Honorary Senior Lecturer.

So INTERTB is a consortium of all the groups in the world who carry out trials to improve treatment for drug-sensitive TB, and they have met annually at St George's since 2009.

Dr Jindani was involved in some of the first TB drugs trials 50 years ago.

She explained: "When I started working in TB, the treatment was 18 months, and although the regimen was very effective, 18 months was just too long, and very few people completed the treatment.

"When two new drugs became available in the 1960s, rifampicin and pyrazinamide, from preclinical studies, it was thought that they would be able to shorten the treatment duration. The very first short course study that was ever done using these two drugs was done by the MRC, and I coordinated it in 42 centers in Kenya, Tanzania, Uganda and Zambia."

Dr Jindani explained: "In spite of having a very effective six month treatment, the annual incidence is not decreasing; and the annual mortality remains at nearly 2 million in this is a curable disease. Why should 5000 people globally a day die of a curable disease? In any other situation it would be an outrage."

"We have a safe, well-tolerated, highly effective treatment regimen but six months is still too long. After the first two months they feel well again, and so they stop taking their treatment.

"Then they relapse - if they relapse with drug-sensitive organisms that's fine, but sometimes they relapse with drug-resistant organisms.  What we need is an effective vaccine, but in the absence of that, the only thing we can do to encourage compliance and completion of treatment, and increase the cure rates, is to reduce treatment duration."

Rather than use new drugs, Dr Jindani's main efforts are going into making one of the existing drugs - rifampicin - more effective by increasing its dose in the hope that treatment can come down to four months.

She is leading a new trial, RIFASHORT, to test using higher doses of rifampicin, and to have just four months of treatment.

She said: "In one arm we're doubling the dose of rifampicin, in another we're tripling the dose of rifampicin for four months", she said, "because we have some pre-clinical evidence that that might kill off the persisting bacteria, and that's the aim now, to eliminate the persistent bacteria".

Another St George's expert, Professor Julia Critchley is Professor of Epidemiology in the Population Health Research Institute, spoke to the delegates at the INTERTB meeting about her concerns regarding the concern that people with diabetes are three-times more likely to get TB than people without diabetes, possibly because their immune system is less effective in a way that the TB bacteria exploit.

Genetic factors and diet changes are considered the most probable causes of the rise in diabetes in Africa and Asia.

Dr Jindani said, "So Indians have a genetic disposition to developing diabetes. In the other countries, diets are changing. For example in the past I never saw a fat person in Africa, and now I do, because they're all eating junk food. There again the levels of diabetes are going up exponentially, and they risk getting TB."