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South Africa: TB research does not have enough funds, but new medicines are on the way

In this second article in a three-part series on TB, we look at what is being done about new drugs and tests.

"TB has been largely neglected," said Dr. Helen Cox, an epidemiologist at the Institute of Infectious Diseases and Molecular Medicine at UCT.

"When you think about HIV and the amount of drugs and tests you get and how much work you have moved in that area, it has to do with funding," Cox said. The funds allocated in the past to tuberculosis are "regrettable compared to HIV".

The United States treatment action group estimates that $ 358 million in research and development of tuberculosis was spent worldwide in 2005. Uncorrected by inflation, this figure rose to 726 million dollars in 2016, but with some faults along the way (financing fell between 2014 and 2015). However, taking into account inflation shows that spending has stagnated in recent years.

TB research and development funding is stagnating in real terms. Graph taken from The Ascent Begins: Tuberculosis Research Funding Trends, 2005-2016 by Treatment Action Group.

This is not a large amount of money for the size of the problem. In comparison, a single US research institution. UU., The National Institutes of Health, spends more than one billion dollars a year on diabetes and almost three times more on HIV.

Current research looks at new drugs that have fewer side effects and shorter durations. of treatment and different combinations of drugs. The hope is that by giving patients a medication regimen that is shorter and easier to take, they can complete their treatment.

There are different types of drug-resistant TB. Multidrug-resistant TB (MDR) is when the standard drugs used to treat TB do not work for a patient. Tuberculosis that is extensively drug resistant (XDR) is even worse: MDR-TB is more resistant to two of the most effective medications to treat MDR-TB. Before the introduction of new anti-TB drugs, three quarters of people with XDR TB died in five years.

Despite this bleak picture, there is progress.

TB Alliance, a non-profit organization that develops new anti-TB drugs, has had good preliminary results with its Nix-TB trial. The trial tests a combination of three drugs for XDR TB: bedaquiline, linezolid and pretomanid.

The objective of the trial is to cure patients with XDR TB within six to nine months, compared to the standard treatment for XDR TB, which can be taken up to two years.

Pretomanid has not yet been approved in South Africa for use outside of clinical trials, but bedaquiline and linezolid are increasingly used to treat drug-resistant tuberculosis.

Dr. Sean Wasserman, an infectious disease The UCT doctor said the results of Nix-TB are "very exciting", but there is still concern about how many people will relapse (they will get tuberculosis again) and linezolid toxicity .

Another trial called STREAM-2 is comparing a regimen with bedaquiline against one of the common ways of treating MDR-TB. Their results are expected by 2021.

TB Alliance has also started a new trial called ZeNix that tests a lower dose and a shorter duration of the drug linezolid, which has a very high toxicity.

Another trial that is bringing renewed hope is the endTB trial that also has sites in South Africa, and is testing different drug regimens for patients with drug-resistant TB. In addition to bedaquiline, you also use a new medication called delamanid.

Bedaquiline has been approved for use in South Africa, but delamanid is only available under strict conditions in very few places throughout the country.

"It is imperative that drug control The Council takes urgent measures to help expand access to delamanid," said Dr. Anja Reuter of Medécins Sans Frontières last year. "When products are registered, access improves."

What about a vaccine for tuberculosis?

The current tuberculosis vaccine, the BCG vaccine, does not work very well.

Cox explains: "We know that people who have had TB and are cured are still at very high risk of getting TB again, so if a previous illness does not even prevent you from getting TB again, it is very difficult. find a vaccine that does it. "

the vaccine is useful to prevent severe TB in children, it does not work well in adults.

"Vaccines are such a complex area and we certainly need to encourage much more money for research because clearly if we could find a vaccine that would be the holy grail of TB," said Cox.

Are the tests good enough?

TB tests are not always easy, especially if you are HIV positive. But a machine called GeneXpert that allows rapid testing of both TB and whether it could have drug-resistant TB has improved the way we find TB cases. South Africa is also launching an even better version: the GeneXpert Ultra. But the tests are far from perfect and do not work well in all settings or for all patients.

The use of X-rays could also be reappearing, both Cox and Wasserman mentioning their importance in TB tests.

"We are not doing enough systematic X-ray tests," Wasserman said. He explained that this is how tuberculosis was tested in Europe after the Second World War. "They came out with these mobile chest x-rays and found people with TB and put them in treatment, we're just not doing that enough," Wasserman said.

Cox said that although X-rays are labor-intensive, there are new programs for reading X-rays with digital help so you do not need a qualified radiologist to read each x-ray.

Another useful test detects TB in the urine of people who are sick with HIV (ie, people with low CD4 counts). It's called TB-LAM test and it's cheap.

But to really make a dent in TB, Cox said we need "much better tools" and "much more funding is needed for research and development."

"We have to do what we know works [and do this] much better and we have to focus on researching new tools and new ways of doing things," said Cox.

More on the role of tuberculosis May 2018

Why do it? many South Africans die of tuberculosis? May 16, 2018


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