CAMBRIDGE, Mass. — A year and a half ago, I attended the seventh birthday party of a young boy named Fanyana, who was quarantined at the Sizwe Hospital in Johannesburg, South Africa due to his extensively drug-resistant tuberculosis. Fanyana's tuberculosis is virtually untreatable, and when I returned to Johannesburg this past fall, he remained in quarantine. He was as charismatic as ever, but slower and more tired than when I had first met him, evidence of a gradual decline that will end with his death.
One hundred and twenty-eight years after Robert Koch discovered the bacteria that cause tuberculosis, the disease continues to thrive throughout the world. It kills nearly 2 million people a year and infects almost 9 million annually. One third of the world's population is estimated to be infected with the latent form of the disease.
“The global tuberculosis situation remains a huge concern,” says Dr. Mario Raviglione, head of the World Health Organization's Stop TB Department.
After a flood of antibiotics came on the market in the middle of the 20th century, research in the field of TB has been marked by a lack of funding and complacency, as the disease faded from high-income countries. The last new tuberculosis drug was introduced 40 years ago, and the disease has found a foothold in lower and middle-income countries, with China, India, and South Africa leading the world in new infections.
“There continues to be an attitude of having to make do when it comes to TB that does a disservice to patients,” says Carole Mitnick, an assistant professor in Harvard Medical School's Social and Global Health program, who works on drug-resistant tuberculosis in Peru.
Drug-resistant forms of tuberculosis have made the battle against the disease that much harder. Whereas a regular TB infection can cost $20 to treat, multi-drug resistant TB (MDR-TB), which is resistant to those cheap first line drugs, can cost $5,000 to treat, and extensively drug-resistant TB (XDR-TB), which is resistant to first and second line drug treatments, can be far more.
In a recent report on drug-resistant tuberculosis in the world, the WHO found that in some places, one in four people newly infected with TB is infected with an MDR-TB strain, the highest rate ever reported. The WHO reports that 440,000 people were estimated to have MDR-TB in 2009, and a third of them died. While there are no official numbers on XDR-TB, the agency puts those infections at “around 25,000” cases, nearly all of which were fatal. The most resistant form of the disease has been found in 58 countries so far, and there are reports of XDR strains that are resistant to every single TB drug.
Only 7 percent of those infected with MDR-TB are ever diagnosed, increasing the potential for transmission. Of those, Dr. Raviglione notes, only 3 percent are treated under good programs. The WHO reports that treating MDR/XDR-TB infections over the next five years in the 27 high-burden countries will require more than $16 billion in funding. Only $280 million is available for 2010.
If those funding patterns do not change, Mitnick expects the global TB situation will worsen. “The burden of drug-resistant tuberculosis in people who are HIV-positive is going to keep increasing globally. In places where it's bad, it's going to get worse. In places where it's just starting to develop, it's going to get bad.”
In South Africa, for example, tuberculosis prevalence has increased threefold in the last ten years and is now the number one killer of South Africans. The country made headlines in 2006 when reports emerged of a highly lethal strain of XDR-TB in a rural village called Tugela Ferry. South Africa instituted a controversial policy of detaining drug-resistant tuberculosis patients in quarantine hospitals, like the Sizwe Hospital in Johannesburg where Fanyana is quarantined.
In 2008, I rode along with community health workers in a pilot program studying the use of community-based treatment of drug-resistant tuberculosis in the rural area surrounding Tugela Ferry. Because MDR-TB takes two years to treat, the study is only now seeing the results. Approximately fifteen people who completed their MDR-TB treatment in the community-based program are cured. There have been no cases of household transmission and, while the numbers are preliminary, mortality rates seem to be well below the 67 percent rate seen in other programs. In part because of the success of this study, South Africa has since announced plans to decentralize treatment and institute more community-based treatment programs.
Despite research and funding woes, there are a handful of new drugs in the development pipeline. “Things are more encouraging now than they have been anytime since I started doing this work in 1996,” says Mitnick. Still, these drugs will have to be deployed carefully and in combination with other drugs to avoid the same patterns of resistance that have occurred with older drugs.
Because of the need for combination therapy, the Critical Path Institute, the Gates Foundation and the Global Alliance for TB Drug Development have launched a new initiative aimed at speeding up the development of new TB drug therapies. Working with pharmaceutical companies and the FDA, the initiative seeks to lessen the regulatory hurdles for TB drug regimens, by testing out promising new drugs in combination with others in early-stage drug development and pushing forward with promising regimens.
At Sizwe Hospital, one young girl bounced in her seat as she told me that she was going home soon. She was nearing the end of her successful treatment for MDR-TB. Another little girl, whom I had seen on my last trip, had gone from an emaciated, lethargic child who was too sick to walk or attend class to a bright-eyed little girl who ran after a crowd of kids as they played in the hallways. She was still deaf, a side effect from the medicine that may always be with her.
For these two girls, 128 years of research on tuberculosis has succeeded in giving them a chance to live. The question will be whether South Africa, and other countries hit hardest by the tuberculosis epidemic, will have the money and resources to treat the millions of other TB patients who will need it going forward.
Elizabeth Chiles Shelburne reports on issues including HIV/AIDS, tuberculosis, malaria, access to water and how high food prices affect the health of populations in the developing world.