A dangerous form of tuberculosis that resists treatment with both first-line and second-line drugs is spreading around the world, spurring an urgent search for new ways to stop the ancient scourge.
Extensively drug-resistant TB (XDR-TB) has been found in 28 countries, including, rarely, the USA, the World Health Organization says.
Multi-drug-resistant TB (MDR-TB), which is immune to the two most powerful anti-TB drugs, has been reported for years and is now in 90 countries. But it was not until March 2006 that WHO and the Centers for Disease Control and Prevention recognized XDR-TB, a form of the disease that has developed further immunity, which makes some of the second-tier drugs ineffective. It is still sometimes curable, but only with expensive drugs and intensive treatment.
Last August, an outbreak in South Africa was reported in which 52 of 53 patients with XDR-TB died. Most also had HIV. Now, XDR-TB is in every province of South Africa. At last week's Conference on Retroviruses and Opportunistic Infections in Los Angeles, Karin Weyer of the South Africa Medical Research Council estimated 600 XDR- TB cases in the country with a fatality rate of 84%. More than 80% of those infected are HIV patients.
WHO says $650 million is needed each year to control drug- resistant TB.
"We were fairly complacent with the sense that we had drugs that work, and we do," says Maria Freire, CEO of The Global Alliance for TB Drug Development, a non-profit devoted to finding new TB drugs.
But when those drugs are given inappropriately or stopped too soon, drug resistance emerges, requiring more expensive and toxic alternatives. Regular TB can be cured with a combination of drugs taken for six months. MDR-TB requires a different combination, taken for 18 months to two years. If that regimen isn't followed carefully, XDR-TB can emerge.
"It doesn't mean you're totally untreatable, it means ... they're giving you everything they have," Freire says. And in some cases, "we've simply run out of ammunition. We no longer have the drugs we need to fight this."
The TB Alliance is working with pharmaceutical companies, academic researchers and institutes to find new drugs, Freire says, and there are promising candidates in the pipeline. She says the goal is to develop drug combinations that attack different parts of TB bacteria to reduce resistance; that can be taken along with the anti-retroviral therapy needed by HIV/AIDS patients; and that are effective when taken for two months or less.
"That's a huge leap," she says, "but not an impossible goal." Ultimately, she says, the hope is to be able to "treat TB as you would any normal infection, with a 10-day treatment," but that may require a decade or more of biological research.