What Research Can Do to Stop Tuberculosis

2015. The last year before we draw the final balance for the Millennium Goals. The target of halting and reversing the spread of tuberculosis (TB) throughout the world—not such an ambitious target really—was achieved years ago. Even so, that is not really much cause for satisfaction. According to the World Health Organisation, one of the world’s oldest known disease is still causing 9 million new cases and 1.5 million deaths a year. More people die worldwide from TB in less than 60 hours than have died from Ebola since the start of the latest outbreak in West Africa.

Wouldn’t it be wonderful to have a test that could rapidly confirm or rule out a diagnosis of tuberculosisOne solution to the problem is to invest in research, to invest in generating the knowledge that will give us new tools to fight TB on all fronts: in prevention, diagnosis and treatment, as well as in strengthening health systems and optimizing strategies that have already been shown to work. There is no other investment that can offer greater long term benefits. Can you imagine having a treatment that could cure TB in a week—the length of time it takes to treat most infections with antibiotics—instead of the 6 months currently required, or as much as 2 years in the case of multidrug-resistant disease? Wouldn’t it be wonderful to have a test that could rapidly confirm or rule out a diagnosis of tuberculosis, something like the one we use to detect high blood glucose? Better still, imagine having an effective vaccine to immunise children and provide lifelong protection against TB. It is possible that we may not be so far from achieving some of these dreams, but clearly the way forward is in research.

One huge breakthrough has been the development of GeneXpert, a molecular test that can identify bacterial DNA in sputum in less than two hoursGreat progress has been made in recent years in the field of new diagnostic methods. One huge breakthrough has been the development of GeneXpert, a molecular test that can identify bacterial DNA in sputum in less than two hours. This new test is important not only because of the short time needed to produce a result, but also because it detects the presence of the bacillus more effectively than classical microscopy, which is still the most widely used tool today even though it can only diagnose cases with a high bacterial load.  GeneXpert can also detect resistance to rifampicin—one of the best drugs we have to treat tuberculosis. This means that the physician can start the patient on appropriate therapy immediately rather than having to wait for the results of cultures that can take weeks to grow. The sooner we can diagnose patients, the sooner we can treat them and the lower transmission rates will be within the community. New molecular tools and biomarkers are being developed for use with different kinds of specimens. The ultimate aim is to optimize the methods so as to provide fast, cheap and accessible results, even in the poorest and most remote areas of the planet.

One huge breakthrough has been the development of GeneXpert, a molecular test that can identify bacterial DNA in sputum in less than two hoursFinding better ways to treat tuberculosis still presents a formidable challenge. Two new drugs (bedaquiline and delamanid) have received accelerated approval in the last two years for use in patients with TB caused by bacteria that are resistant to the usual therapies. However, the standard courses of treatment are still too long, extremely long in the case of multidrug-resistant TB (up to two years). Moreover, that regimen is toxic and very expensive for health care systems (the ones that can afford it). Evidence from ongoing studies investigating a regimen known as the Bangladesh regimen indicates that it will very soon be possible to reduce the treatment cycle from two years to nine months.  Another important study, currently in the evaluation phase, is the STAND trial, in which 50 centres in all the continents, with funding from the Bill & Melinda Gates Foundation, are testing a regimen that may shorten TB therapy to four months.

There are currently 16 vaccines in various stages of clinical research (two here in Spain) But if we really want to reduce the incidence of TB by 90% and cut the number of deaths by 95% by 2035—the targets set by the Stop TB Partnership and endorsed in 2014 by member countries at the World Health Assembly—the essential tool would appear to be an effective vaccine. The current TB vaccine, known as BCG in honour of the scientists Calmette and Guérin who developed it about 100 years ago, only protects children against serious forms of the disease. We have no effective vaccine to protect adults against pulmonary TB, the most common form. In the last 20 years, however, progress has been made in the preclinical and clinical development of TB vaccines. In fact, there are currently 16 vaccines in various stages of clinical research (two here in Spain). The problem is that only a few of these vaccines will reach the advanced stages of development in which their efficacy can be demonstrated in countries with a high incidence of TB. The studies involved can easily cost over 100 million euro, and they are the final phase of development before the vaccine can be put on the market. Very little funding is available for TB vaccine development (the United States spends three times more on researching HIV vaccines than it does on TB vaccines), and few dare to invest when the risk of failure is high. We need to create vaccine candidates that are innovative both in their design and in the type of immune response they induce. We need to innovate in the design of clinical trials in order to assess vaccines with fewer patients but without compromising scientific rigour. And we need to devise innovative financing strategies based on public and private funding.

The task facing the scientific community is challenging, but the time has come for the international community to recognise that if we continue in the same way, using the same tools, we will fail to make any real progress in the control of this disease. Investment in research can provide us with the tools and knowledge we need to reduce the unacceptable burden of TB everywhere. In the meantime, someone, somewhere in the world, will die from tuberculosis every 23 seconds. And the clock keeps ticking ...

Infographic: 7 Facts about Tuberculosis and a Reason for Hope

[Alberto García-Basteiro es investigador del Instituto de Salud Global de Barcelona (ISGlobal) y del Centro de Investigación en Salud de Manhiça (CISM), Mozambique.]