Old Drug Gets A Second Look For TB Fight
A small study offers a bit of cautious optimism about the prospects for treatment of tuberculosis, one of humankind's most ancient scourges.
This week's New England Journal of Medicine has a report showing that adding a 12-year-old antibiotic called linezolid, brand name Zyvox, to existing treatments cured nearly 90 percent of patients with a form of tuberculosis resistant to both first- and second-line antibiotics.
This kind of TB, called XDR-TB because it's extensively drug-resistant, is a lot harder to treat than multiple drug-resistant TB, or MDR-TB, a type that's unfazed by first-line drugs. A recent report from the World Health Organization estimates that 310,000 people have MDR-TB, most of them in India, China and the Russian Federation.
While XDR-TB is worse, MDR-TB is bad enough, says Dr. Kenneth Castro of the U.S. Centers for Disease Control and Prevention. "All of a sudden you switch from being able to cure someone in 6 months to requiring 2 years of treatment and lowering your ability to cure, using lousy and toxic drugs," he says.
About 1 in 10 people with drug-resistant TB have the more severe XDR type. Eighty-four countries have seen cases of XDR-TB, although most of them have counted fewer than 10 cases so far. There are nearly 9 million new cases of all types of TB globally each year, and 1.4 million deaths.
Drug-resistant TB is a growing problem and a flashing neon sign of what happens when people don't get prompt and proper treatment for ordinary TB.
"One of the major reasons for MDR-TB is inadequate treatment of plain old TB," say Dr. Anthony Fauci of the National Institute of Allergy and Infectious Diseases. "And one of the drivers of XDR-TB is inadequate treatment of MDR-TB."
Fauci and Castro spoke at a Washington press conference on Wednesday to mark the WHO's annual TB update.
The linezolid study, conducted in South Korea, suggests that even the most-difficult-to-treat form of TB may be curable most of the time. Patients have to take the drug along with others for 6 months and health workers have to make sure they're complying. That, of course, is no foregone conclusion in places with the worst XDR-TB problem, countries such as Tajikistan, Azerabijan and Belarus.
And, as with everything TB-related, the good news about linezolid comes with a dark side. There's a high incidence of serious side effects such as nerve toxicity and bone marrow suppression, which caused several patients to drop out of the study. And a few patients developed resistance to this antibiotic, too, though fewer than feared.
The linezolid report isn't the only encouraging news. The TB drug pipeline contains 10 other new or repurposed drugs, and two or three may get U.S. market approval in the coming year, says Dr. Mario Raviglione of the WHO's Stop TB program.
"Initial trials are showing that the capacity to kill bacteria resistant to the most important drugs is dramatically increased," Raviglione says.
The new drugs have been tested so far only in patients with MDR-TB, but Raviglione hopes they might ultimately be used as first-line treatment for TB that could shave months of the standard six-month regimen.
Millions of TB patients wouldn't progress to the MDR or XDR stages if they got treated promptly and correctly in the first place. And that's where another recent advance comes in.
It's called GeneXpert, a rapid diagnostic test that can tell in under 2 hours if someone has TB and if it's a drug-resistant form. Standard tests rely on growing the TB bacteria in the lab, which can take up to 8 weeks for results.
Castro says prompt diagnosis of TB is a big boon. "In the same day, you should be able to identify TB and start the patient on treatment," he says. "That is a game-changer."
Sixty-seven low- and middle-income countries have adopted GenXpert, and experts hope its use will expand rapidly due to a recent price cut for lower-income countries from around $17 per test to under $10.
In the future, Fauci is confident there will be an effective vaccine against TB. More than a dozen are in development.
But for all progress, the fight against TB remains a long slog. Patients have to be diagnosed, started on treatment, monitored and retained in treatment. Drugs have to be procured and distributed. Labs have to be built and their quality maintained.
It can be done. Over the past 17 years, 51 million people around the world have been successfully treated for TB. Consequently, the TB death rate has gone down by 41 percent. The world as a whole is on track to cut TB deaths by half the 1990 rate by 2015 – although Africa and Europe will miss that target.
But even though new cases of TB are falling at a rate of 2.2 percent annually, Raviglione says "that's far too slow to see elimination in this century."
He fears the campaign to stop TB will stagnate "if additional resources are not urgently mobilized."
The WHO says $8 billion a year is needed over the next three years for TB care and control. That's $3 billion more than donors have promised. Research and development has a $1.4 billion funding gap.
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