“We need to break the cycle of neglect”
Martine Usdin, Biologist with the MSF Campaign for Access to Essential Medicines, is organising a seminar on tuberculosis diagnostics R&D at the start of the Cape Town Conference on TB. We ask her what needs to be done for better TB diagnostics, now and in the future.
What are the biggest challenges today in diagnosing TB?
Diagnosing standard TB has always been difficult. But the emergence of drug-resistant strains has considerably complicated the challenges: for patients with drug-resistant strains, it is crucial to identify which drugs work and which don't through drug sensitivity testing or DST. 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 or have the very severe extra-pulmonary forms of TB, which are also harder to diagnose.
Are today's tests suited to these challenges?
No, they are woefully unsuited. Existing tools are very insensitive. Out in the field, smear microscopy will identify less than half the patients that have the pulmonary form of TB disease. Culture, which is more sensitive and can also give DST information, is complicated to perform, requiring expensive equipment that is hard to maintain, and is also 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?
Ideally it shouldn't require electricity or refrigeration. It must give an answer rapidly, within a few days at most. It should give an answer that is easy to interpret, and 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.
What are the main obstacles that 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 has also chosen to focus methods 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. We need more research into the fundamental scientific questions that need to be addressed. TB is a hard organism to work with, and scientists find it hard to have some of the fundamental research questions funded. Also, although they're not great, some helpful improvements in the tools available today are possible. We need more studies to demonstrate whether these tools can make a difference and more implementation in the field of existing and emerging innovative tools.
What needs to happen now?
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. We need to break this cycle of neglect and hesitation. This is an ethical requirement for our patients. We don't have any time to waste.