Incurable Tuberculosis Is Making a Comeback

It's been nearly a decade since U2 frontman Bono turned the entire continent of Africa into a pet cause, drawing attention to the problems of -developing-world health like never before. By some accounts, that publicity has started to pay off: since 2000, malaria incidence is down 50 percent in some of the hardest-hit regions, and in the past five years, the number of people with access to life-saving HIV medications has increased 10-fold. But while First World philanthropists and rock-star do-gooders were out to conquer AIDS and malaria, they left a far more ancient killer to fester. Tuberculosis has been traced back as far as the Egyptian mummies. It still kills 5,000 people every day—more people than swine flu has killed in the past year. And right now, natural selection and human fallibility are conspiring to make the germ indestructible.

Since the first effective medications were made available in 1944, Mycobacterium tuberculosis has routinely developed resistance to one drug after another. But in the late 1990s a more disturbing trend emerged: strains of tuberculosis called multidrug-resistant, or MDR-TB, that were resistant to not one but several of the most effective medications (called first-line drugs), began popping up in Africa, Asia, and Eastern Europe. Now those strains have evolved into something even more deadly: extensively drug-resistant, or XDR-TB, which is impervious to first-, second-, and third-line drugs—virtually all the antibiotics in existence. It's the kind of bug that gives epidemiologists nightmares. And in the past two years, while the world was distracted by the financial crisis, it has emerged in nearly every country on the planet. Experts say it's time to start worrying. In a 2009 speech delivered to the U.N., World Health Organization director Margaret Chan warned that without swift, decisive action, we might soon find ourselves back in "an era that predates the development of antibiotics," when tuberculosis was completely incurable. In country after country, drug-resistant strains will start to replace drug-susceptible strains, spreading from the inner cities to the suburbs and from the slums to the countryside. And as scientists start from scratch in a hunt for effective antibiotics, the death toll will steadily rise in rich countries as well as poor.

The global health community is scrambling. In April 2009, at an emergency meeting in Beijing, experts acknowledged the situation was a disaster in the making, but said that reversing course would be impossible without a huge influx of cash. It's true that new medications, modern diagnostics, and more and better-trained doctors and nurses are urgently needed, and that those things will cost money. But a small contingent of TB specialists has begun to argue that money will not be enough. What's really needed, they say, is a whole new way of doing business—a way that apportions funding based on need, not just Western interests. Western dollars have skewed global health priorities in favor of diseases with young victims, obvious solutions, or a good "Nobel Prize–-worthy" challenge. Tuberculosis has thrived by sidestepping any such attention--capturing snags. It's old. It preys on societies' most disenfranchised members. And having made an ally of the very air we breathe, it won't be deterred by anything as simple as a condom or a bed net. In fact, experts say that more than any other disease, this 19th-century relic is exposing all the cracks in our -multibillion-dollar global health system.

Roughly one third of humanity carries a latent form of tuberculosis: thick, encrusted capsules deep within the lungs that were formed when the immune system first encountered the bacteria and fought them to a stalemate. In healthy people, those capsules can remain dormant for decades; most people go their entire lives without ever knowing they're infected. But when the immune system is compromised—as it is with HIV—the capsules burst open and the bacteria begin a slow, consumptive feast of lung, kidney, bone, and neuron known as active TB. Someone with HIV is 20 to 30 times more likely to develop active TB, so when this unknown retrovirus reached epidemic proportions in the late 1980s, the ancient bacteria were not far behind.

At the time, global health experts were focused on improving primary care around the world, convinced that would be the key to eliminating disease. People with clean water, nutritious food, and functioning clinics, they reasoned, would be less likely to spread illness in the first place and better able to withstand the outbreaks that did occur. The approach held particular promise for combating tuberculosis, a disease that was thriving in places with poor sanitation and rampant malnutrition. But as the AIDS epidemic swelled, wealthy nations began flooding the developing world with their cash, expertise, and good intentions. Before long, priorities shifted. Food, water, and basic infrastructure fell by the wayside; vaccine development, drug discovery, and the eradication of individual diseases became paramount. By accident, a new global health system was born, one in which every parasite was a cause unto itself, and some causes—namely those that captured the Western imagination—were bigger than others.

In this new paradigm, TB experts and HIV experts found themselves pitted against one another in a quest for attention, funding, and intellectual capital. Thanks largely to activism in wealthy countries, the HIV team won out: by the early 1990s, HIV funding was five times greater than TB funding. But even as it became clear that the epidemics were linked, the AIDS boon did not lead to progress on TB. HIV workers were trained in TB control only as an afterthought; labs built with HIV money were not equipped to diagnose or treat TB. And as the arsenal of anti-HIV medications grew 10-fold, the number of tuberculosis drugs remained abysmal. Before long, tuberculosis had emerged as the single biggest killer of people with HIV-AIDS, and HIV--positive populations in Africa and Asia had become hotbeds of drug-resistant TB.

As these newer, deadlier strains began to emerge in disparate regions—from Africa and Asia to Eastern Europe and the United States—experts found themselves divided over how to proceed. Some wanted to treat the problem aggressively—using available funds to treat as many drug-resistant cases as possible so that XDR-TB would not spread. But second-line drugs are far more expensive than first-line drugs, and many scientists believed that the drug-resistance problem would eventually take care of itself. Any mutation that rendered a given strain of the microbe drug--resistant would also make that strain more virulent, they thought. The more virulent a strain became, the faster it would kill its host and the less time it would have to spread through the population. "The hope was that the resistant strains would just fizzle out over time," says Salmaan Keshavjee, a Harvard Medical School physician who works on TB control in Africa and Eastern Europe with the nonprofit Partners in Health. "But that didn't happen." As Keshavjee and his colleagues discovered, even XDR-TB patients who face mortality rates as high as 90 percent usually live for several months—more than enough time to pass the bug along.

Because XDR-TB patients live to infect others, ignoring the problem now will most certainly cost us more later. Reversing course will require an aggressive offense, and that will mean spending more money upfront on developing drugs and diagnostics and making them available to the people who need them. But money is only part of the problem, and it may not even be the biggest part. Fighting XDR-TB will require wholesale changes in the global health system: TB and HIV specialists will have to work together. More resources will have to be devoted to primary care. And wealthy countries will have to pay attention to tuberculosis.

We are headed for a tipping point. In some pockets of the world, XDR strains are on track to replace drug--susceptible strains in the coming years. This is already happening in parts of Russia—the number of drug-resistant cases has doubled even as the number of drug-susceptible cases remains flat. "It means we really could end up in a situation where tuberculosis is completely incurable," says Mario Raviglione, director of the WHO's Stop TB program. When that happens, it may truly be too late.