Diagnosing tuberculosis has always been a complex affair, as much of the science on the TB bacillus still escapes us - and many of the tools are either antiquated and unreliable, or modern and too high-tech for use where they're needed most. Now that drug-resistant strains of the disease are rapidly spreading, and that HIV is pouring oil onto the fire of the TB pandemic, there is an urgent need for tests that can deliver accurate results, in the remotest settings, and fast.

We ask Martine Usdin, biologist with the MSF Access Campaign, what needs to be done for better TB diagnostics, and how IGWG can change the picture.

What are the biggest challenges today in diagnosing TB?
Diagnosing standard tuberculosis has always been difficult, and this is one of the reasons why TB is making such a comeback, because many people that needed treatment have been missed, and have gone on to infect others.

But the emergence of drug-resistant strains, when the TB bacteria have become resistant to some of the medications which are then no longer effective, has considerably complicated the challenges.

For patients with drug-resistant strains, you need to know which drugs work and which don't through drug sensitivity testing or DST. Otherwise you run the risk of giving patients drugs that simply won't do anything to treat them. Evidence shows that patients with drug-resistant TB who are treated inadequately with first-line drugs do very much worse than if you treat them with the correct drugs from the start.
Also, TB is the number one killer of HIV patients. But they are often too sick to produce a sputum sample for testing, or have the very severe extra-pulmonary forms of TB, which are also harder to diagnose. But these people are often the sickest ones, precisely the ones for whom we need a result quickly if we can hope to save their lives.

Are today's tests suited to these challenges?
No, in fact they are woefully unsuited. Existing tools, such as sputum smear microscopy, are very insensitive, which in practical terms means that fewer than half of the patients that have the pulmonary form of TB disease will be diagnosed, and none of the patients with other forms of the disease. But smear microscopy is the tool in widest use today, which is quite incredible given that it's a technique that misses more patients than it detects, and hasn't improved much since its development in the late 1880s.

Another technique to detect TB is culture, when you 'grow' a sample of bacteria. Culture is more sensitive than microscopy and can also tell you if the bacteria is sensitive to the drugs, but in its current form it's complicated to perform, requiring expensive equipment that is hard to maintain. Plus culture is slow - it can take weeks to months to get an answer. For patients with HIV and that are infected with resistant TB strains, most of them die before their DST results are available. Modified culture methods are being developed that are simpler and faster. But they are still not simple enough to make them useful in the most remote areas.

What are the critical characteristics needed for a test to be useful in remote settings?
We urgently need a test that identifies active TB disease. We also need to know the drug sensitivity pattern in that patient, at the time of diagnosis or very soon thereafter.

Ideally the test shouldn't require electricity or refrigeration. It must give an answer rapidly, preferably the same day, and that answer should be easy to interpret in a way that can then be used to directly influence the management of patients, for example a positive test means treat or refer to the clinic, and a negative test means no action. It needs to handle large numbers of patients per day. Of course, it must also be affordable.

The need for a test to detect active TB - when the person has the disease and is sick- is urgent. Much of the research into new tests is focused on tests that detect latent TB - when the person is infected but the bacteria are dormant. Detecting latent TB is only a priority for countries with few cases of active TB, which is the case of many Western countries. There is a potential wealthy market for such TB tests, so current commercial incentives are more likely to stimulate development of a new test to detect latent TB infection, when what we really need, what is far far more urgent, is a better test for active TB.

What are the main obstacles that are holding up the development of new tools?
We need more money, and that money should go to different sources. Today, funding for TB diagnostics development is mostly channelled through the product development partnership FIND, which has gathered a powerful team of accomplished minds to help develop products. But many more groups need to work on this. Also, FIND has chosen to focus on tests that can be commercialised – a model that has its merits but should not be the only one.

But it doesn't stop at money. TB is a hard organism to work with, making progress slow, and is not viewed as an important area of research, so scientists find it hard to find funding to tackle some of the fundamental research questions. There are enormous gaps in our knowledge of many aspects of TB such as interactions between the host and the TB organism, how the bacteria survive in the body, what makes some people fall ill while others do not, and so on. 

We need improved tools now, not in ten or twenty years. So we need to explore how we can optimise our current knowledge, for example by systematically evaluating combinations of antigens to develop a point-of-care test that works better than current tests.

What needs to happen now? What's your message for the IGWG?
We need to dare more, to ask for more. Things move so painfully slowly in the TB world, and we don't have the luxury of time any longer. If we had acted boldly 60 years ago, we would be in a very different place now.

I'd like to see the IGWG finally break this cycle of neglect and hesitation. We need more money, for a start, as TB diagnostics only gets about 7% of what little money is allocated to TB research. Academics need more grant funding to push their research forward more sustainably.

The IGWG should also come up with solutions that encourage open access to results and sharing of knowledge, as a lot of work is duplicated by different groups, or is not done systematically because everybody works in their own corner.

But there is also a need to create rewards for groups that come up with a new point-of-care test. A prize might be an effective pull mechanism because you can define the specifications of a test, and ‘reward’ multiple steps along the way, and it can help ensure that the test will be affordable and accessible. It's critical that any financial rewards do not result in higher prices for the test.

Acting now is an ethical requirement so that we can better treat our patients. There is no time to waste.