Turning the Corner
by Sarah Stone Wunder
July 2008
After decades of neglect, leading to a rapid increase in incidence, tuberculosis started gaining attention from industrialized nations over the past 10 years. With this new focus, TB’s incidence has started to decrease—but barely.
Photography by A.B. Dowsett/Photo Researchers, Inc
In many parts of the world, tuberculosis is thought to be a disease of the past. And in these places, that belief is somewhat understandable: Overall, only 4 percent of all global TB cases occur in the Americas; only 6 percent occur in the eastern Mediterranean and only 5 percent occur in Europe, according to the World Health Organization (WHO).
Worldwide, however, the statistics are more startling—one-third of the world’s population is currently infected with TB bacillus, and many might not even know they have it. As the world becomes increasingly globalized, the prevalence of TB may grow exponentially. In fact, in Eastern Europe, after 40 years of decline, TB deaths are increasing.
Recognizing this threat, groups such as the Bill and Melinda Gates Foundation, the Stop TB Partnership and the Global Fund to Fight AIDS, Tuberculosis and Malaria are all working to prevent, treat and contain TB worldwide.
The Global Situation
One of the United Nation’s Millennium Development Goals (MDGs) is to halt and reverse the incidence of major diseases such as TB, HIV/AIDS and malaria by 2015. Specifically, the MDGs outline that by 2015, the prevalence and death rates of TB should be reduced by 50 percent, relative to 1990. And by 2050, TB should be eliminated as a public health problem.
Since the MDGs were established, there has been significant progress made toward these targets. According to WHO, in 2005, an estimated 60 percent of new sputum smear-positive cases were treated, just short of the 70 percent target. Treatment success of those detected was 84 percent on average, close to the 85 percent target. However, cure rates in the African and European regions were only 74 percent.
Overall, the global TB incidence rate probably peaked in 2005, WHO reports, and if the current progress continues, the resulting improvements in TB control should halve prevalence and death rates in all regions except Africa and Eastern Europe by 2015.
According to Dr. Mario Raviglione, director of WHO’s Stop TB Department, until about 2003 or 2004, the rate of TB incidence was increasing by about 1 percent every year. In 2005, the rate started to level off, while over the past two years there has been a decrease in the incidence of TB by 0.6 percent per year.
Raviglione says the incidence started to come down specifically due to the decreasing prevalence of HIV, which began to decline around 2000. Africa, he says, is responsible for about one-third of the world’s TB cases. Over the past few decades, the incidence of TB in Africa increased steeply, while it was stable or declined slowly in the rest of the world. However, this increase stopped in Africa three to four years ago because the HIV/AIDS epidemic also reached a peak in Africa, a few years before, Raviglione says.
“So, as a consequence, TB, which is strongly associated with HIV/AIDS in Africa, stopped increasing. That also resulted in the start of the slow global decline we are seeing now,” he says. “It is a great result, however, it’s far from being something we can be happy about for the simple reason that if it keeps coming down at 0.6 percent per year, it will take millennia after millennia before we get rid of TB.”
Ultimately, Africa needs to see rates decrease at 5 percent to 10 percent per year, as it did in Europe and North America in the 1940s and ’50s, he says. “That’s the ideal situation, but we are far from that kind of level,” Raviglione says.
In addition, because the rate of TB cases continued to increase after 1990 in Africa and Eastern Europe until the mid-2000s, while it leveled off or decreased elsewhere, it will be difficult to meet the MDG to halve the prevalence and mortality of TB relative to 1990, Raviglione says. “So now we have reached a peak [in Africa and Eastern Europe], but to get down to half of what it was in 1990, after it increased so much after 1990, is going to be very difficult, and we only have 7 years to go,” he says. “So that’s why we believe these two targets in these two regions will not be achieved.”
Industry Action
One of the main barriers to TB control is a lack of new tools for prevention, diagnosis and treatment. And until recently, the pharmaceutical industry hadn’t made many significant investments in TB research. According to Raviglione, many in the world feel that TB has been eliminated. The four drugs used to treat TB were developed between the 1950s and 1970s. During the ’70s, the combination cocktail of these four drugs was fine-tuned, resulting in a regimen that treats TB in six months, which is still used today. However, many argue that the six-month treatment timeline is too long. In fact, it is because of this long timeline—which requires regular daily treatment over six months—that multidrug-resistant TB (MDR-TB) began to emerge. MDR-TB is caused by inconsistent or partial treatment, when patients do not take all their medicines regularly for the required period because they start to feel better, because doctors and health workers prescribe the wrong treatment regimens or because the drug supply is unreliable.
Although it became clear to many observers in the 1990s that TB was still a problem, and was getting worse, many in the industry still needed to be convinced to invest in TB research, Raviglione says. “It was obvious industry was not really for it because they discovered that, after all, the cases of TB in the north of the world were fairly limited,” he says. “The majority of the cases were in the south of the world. And so one can easily understand the hesitation because the drug industry has to recover money out of their investments in research. So they say, ‘Why should we invest in TB research when there are very few cases we can benefit from in the northern countries where there is money to pay for the drugs to recover the investments?’
Meanwhile the majority of new cases, 8.5 out of 9 million cases, were in the south of the world, and where they will have to give lower prices, so they will never recover what they spend or invest on research. So that turned the industry to a situation of complete neglect of the problem of TB.”
But, Raviglione says, this situation shifted in the late 1990s and early part of this century as the three big diseases—TB, malaria and HIV/AIDS—began receiving increased attention as human rights issues. This push has led industry and not-for-profit groups to raise money and start to invest in TB research again. Yet, these efforts have raised only a fraction of what’s needed to develop the tools the world needs, Raviglione says. “Although far from what is necessary to face a global tragedy like TB, it’s still better than it was 10 years ago, which was nearly zero,” he says. “So as long as we manage to still convince the industry and also the public sector that funds research—those branches of the government that are international agencies and research entities within governments that can pay for these things—as long as we manage to keep convincing them that it is of advantage to everyone in the globalized world to control a disease like TB, then it will be OK. If people forget, then we go back another 5 or 10 years.”
Recent Developments
Vaccine development for TB is still a long way on the horizon. According to Raviglione, about a dozen vaccine candidates are in the pipeline to be developed in the next decade. “What the vaccine industry is telling us is that by 2015 we might have something that is really promising. But we’ll see,” he says. “Right now there is no hope for any new vaccine to be used in the field before 2015.”
Instead, Raviglione says that diagnosis and treatment development might be more feasible. Ideally, drugs that shorten the length of treatment from six months to a few weeks would go a long way toward combating TB, he says. However, currently no such treatment appears to be in the works.
“There are studies being conducted now to reduce treatment from 6 to 4 months, but the trials are ongoing, and we won’t have result until 2010, 2011,” he says. “That is not going to be a revolution, frankly, because 4 months is still too long. A revolution would be to shorten the treatment to two weeks. So I think we are far from it.”
The one place where there is a promising development is in diagnostics, specifically for MDR-TB. Within the next month, Raviglione says a new type of molecular test should be announced, which would be able to detect MDR-TB in 24 hours. Currently, in most developing countries, it takes two to three months to detect the presence of MDR-TB. “This will allow us to do the proper treatment right from the beginning,” he says. “So that is promising.”
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