Peter M. Small, MD, who runs the tuberculosis program at the Bill & Melinda Gates Foundation and is a member of the Stop TB Partnership’s Coordinating Board, has done extensive research in the genetic variability of tuberculosis. He’s a global expert in TB epidemiology, biology and control. He spoke to Science Speaks about recent developments in the field of TB control and treatment. This is the second in a two-part series with Gates Foundation leaders on recent developments in HIV and TB. Small talked particularly about the promise of the Gene Xpert, which will be able to detect TB and drug resistance in 90 minutes, whereas current methods can take up to three months.
What do you see as important developments in TB in the last year and what does that mean going forward?
It’s been a really exciting year. Undiagnosed and untreated TB is what drives the TB epidemic. This past year has seen significant progress in new diagnostics and new drugs, so we are really in a great spot. Global scale up of DOTS (directly observed treatment, short course) has averted 6 million deaths in the last decade. Yet the number of cases of TB will be greater than last year, which was more than the year before that. The core problem is quickly diagnosing the number of cases. We need better diagnostic tests and shorter treatment delivery.
On those two fronts, what’s important?
The headline grabber has been the Gene Xpert machine, but I’m also very excited over the whole pipeline of drugs now underway. It’s easy to forget how desperate we were five years ago, and how drastically things have changed.
What is happening in this pipeline of drugs?
The major transformation in TB drugs is the global recognition that we don’t need a TB drug. We need a TB drug regimen. We now have eight drugs in TB trials, and they can be mixed and matched in ways that will accelerate new ways to fight TB and lead to a cure. Toward the end of last year, the Global Alliance for TB Drug Development and its partners started the first human trial in which two experimental drugs were brought together at the same time. It’s a phenomenal transformation in thinking, and it provides us with major new opportunities.
But even with these technological developments through research, you still must have major worries. What are they?
These technologies are exciting but they have no impact if they don’t get to the people who need them, and the challenges are significant. The issues for diagnostics are the relatively high cost and some challenges in how systems have to be modified to take advantage of these new technologies. On the positive side of this, it’s really been invigorating for the field to take on these challenges. I am particularly excited to see that China, India, South Africa – all countries with the largest number of cases – are putting together coherent and very strategic plans to implement these technologies while assessing where and how they can have the most impact. It’s really a challenge for a field that has relied too long on old technologies.
But what about concerns whether there will be enough funding to make these technologies widely available?
That’s a huge challenge. For example, people talk about the cost of the Gene Xpert. Frankly, it’s jaw dropping for two very different reasons. Some people look at price and compare it to the 125-year-old smear test and say how could we afford it? Others look at the cost-savings at promptly diagnosing TB patients and how many will benefit from $14 in treatment costs of the drugs. And they are shocked that it is so affordable. It’s going to take some hard-nosed technical assessment on how to use these most effectively and make the best use of scarce resources.
Is the Gene Xpert a worthwhile investment for countries?
The World Health Organization announced the price of $16.86 per test. With that test, you empower a relatively untrained health care worker to test whether a patient has TB and then get that patient on treatment. This has a huge benefit to a patient. In the current paradigm, many patients now spend an enormous amount of money out of pocket while waiting for results, often driving them into poverty. This has a huge benefit to the health system. This has a huge societal benefit. This test has the potential of interrupting the transmission of TB in such a way as to change the future of the epidemic.
Why should Americans care about this, other than for humanitarian reasons?
There are two basic and very compelling reasons. First, Americans are individually, intrinsically generous people who want to make the world a better place. Never in my professional career in tuberculosis could the U.S. be prouder with the development of this Gene Xpert machine, which was largely funded by the Department of Defense and the National Institutes of Health. The leaders of the Centers for Disease Control and Prevention, the President’s Emergency Plan for AIDS Relief (PEPFAR), and the U.S. Agency for International Development have rallied around it and are working on scaling it up, toward the goal of saving lives. The second reason has to do with the simple fact that TB anywhere is TB everywhere. It’s in our best interests that TB is controlled globally because we as individuals travel and there is a high degree of travel within the U.S. There is a self-centered reason and a humanitarian reason.
Where have you traveled recently and what lessons have you learned about TB efforts from those trips?
I was in India in December of last year, and I came away extremely excited about the renewed ambition the Indian government is taking on TB. India has the highest number of TB cases in the world – 21 percent of the world’s TB. They recognize a significant problem in their economy because of it, so they are revising their program for the next five years. They are looking at an ambitious program that not only would be doing basic DOTS, but would also use new diagnostics and start to integrate with the private sector, which can make a huge difference in that country.
And I was in South Africa a few weeks ago and went down in the deepest mine in the world – 1200 feet underground. The morning started off as a carnival ride, but shortly into it I was struck by the fact that 2000 people were underground with us, chipping away at work while being at a great risk of contracting TB. They will be helped by this new diagnostic.
I think these large emerging economies of India, China, South Africa, and Brazil can define a new paradigm in global health, a difference from one in which the rich world is solving problems for the rest of the world. This paradigm has emerging economies themselves solving their own problems and in so doing will develop approaches for the entire world.
What will the Gates Foundation be supporting in the years ahead in the TB fight?
About 75 percent of our effort and resources has been on the development of better drugs, diagnostics and vaccines. But as we’re starting to see progress out of those pipelines, we are partnering closely with governments and asking them how we can be of help to them as they solve their problems, and how the technology can best fit into TB control as they see it.
What about your assistance in the scale-up of Gene Xpert?
I think for implementation that PEPFAR, UNITAID, and the Global Fund to Fight AIDS, Tuberculosis and Malaria have the potential to play a critical and catalytic role in accelerating the uptake of innovation that is critical for the future of TB control. We are always interested in discussions and partnership with them and others to understand exactly how to best make that happen.
With the Gene Xpert, we are one of many players trying to understand how the next five years will play out, so we can look back and say that the TB community was challenged with a transformational technology that we needed to scale up. I hope we can look back on these questions five years from now and answer that we were able to save millions of lives.
Many people have been skeptical of public-private partnerships, or private development projects (PDPs). Is the success of the Foundation for Innovative New Diagnostics (FIND) with the Gene Xpert machine in putting together a public-private partnership an aberration or a sign that these kinds of groups can make a difference?
Yes, there has been skepticism from the start of the PDP model and yet I think now we can look at the data. I find the data quite compelling. Gene Xpert simply would not have happened were it not for FIND. Personally, I find that answers much of the skepticism. How that model evolves moving forward is now the question. But it’s so easy to forget how desperate the TB product development was five or 10 years ago, and how PDPs have played a critical role.