Mexico needs 4th drug; can it find the money?
Mexico needs 4th drug; can it find the money?
Resistance rates overwhelming TB programs
TB control in Mexico isn’t working, and not even widespread application of the World Health Organization’s sanctioned treatment approach will help, say two new studies. Conducted by binational teams of American and Mexican researchers, the studies provide groundbreaking new data that suggest rates of resistance in Mexico, which supplies the United States with 25% of its annual caseload, are so high they undermine TB control, no matter how well it’s performed.
To fix the problem, Mexico urgently needs to add another drug to its first-line, three-drug regimen, both studies suggest; retreatment patients may need five or even six drugs in all, they say.
But at least one veteran Mexico-watcher says he doesn’t think the country will shoulder the extra cost of adding a fourth drug, which would raise the price of therapy by an estimated 30%. "It’s not so much a question of documentation or of whether it makes sense to do this, but whether the resources are available," says Miguel Escobedo, MD, regional director of regions 9 and 10 of the Texas Department of Health. "The extra cost may not seem like much to us, but to Mexico, it’s a lot."
Drug resistance, and where to find money to deal with it, lies at the heart of one of the biggest problems facing global TB control today, says Peter Small, MD, an author of a recently published report on the subject,1 director of the Stanford Center for Tuberculosis Research, and assistant professor of medicine in the division of infectious diseases and geographic medicine at Stanford (CA) Medical Center.
"There’s no question that DOTS" — directly observed therapy, short-course, WHO’s directive for running TB control programs — "does work to keep resistance in check," says Small. "The trouble is that in Mexico and virtually every other country where we’ve looked, the horse is already out of the barn. Now the question is, how do we work cost-effectively in a situation where there’s already drug-resistant TB?"
In Small’s study, a binational team found that 28% of isolates from TB cases were resistant either to isoniazid (INH) or rifampin (RIF); and more than 10% of isolates were resistant to both drugs.
A second study found levels of resistance to at least one of three drugs — INH, RIF, or pyrazinamide (PZA) — stood at 12.9% among new patients and at 50.5% among retreatment patients. That study also found rates of multidrug-resistant TB stood at 2.4% in new patients and 22.4% in retreatment cases.2
TB is not priority, but there is hope
Even though the news from Mexico isn’t good, getting a more accurate picture of it is a good first step, adds Small. "It’s what you might call the thin silver lining to a very large gray cloud. Binational efforts are finally under way to look at this problem. USAID is finally paying attention. We’re all trying to come up with some answers."
The reports aren’t intended as criticism, he adds. In the site where his team was looking, the Mexican health authorities "are running one of the finest TB control programs in the country, and they’re doing a great job of observing therapy. But it’s an approach that has a high rate of treatment failure and death. So what Mexico needs to think about is whether they’re going to simply expand the present program, or whether they’re going to modify it."
The question facing Mexico and other countries fighting HIV or entrenched drug resistance is what to do next, says Small. "Do you add active case-finding or provide treatment for latent TB infection, or do you try doing individualized TB therapy?"
In a pilot study starting soon, he hopes to find out. The pilot, which Small says he hopes will supply an effective and "scalable" model for the rest of the country, includes standard four-drug therapy and a beefed-up regimen for retreatment patients. Instead of relying on expensive individualized susceptibility testing, the retreatment algorithm will be drawn from patient histories. Since the binational team has eight years of epidemiology and history to draw from, Small says he’s confident they’ll make choices that are data-driven.
One problem with getting Mexico to spend more money on TB is that the disease has never ranked high among the country’s priorities, says Escobedo. "Mexico performs lots of public health functions better than we do," he says, pointing to the country’s rates of childhood vaccination coverage, which exceed those in the United States. "But TB is so expensive to treat, you get more bang for the buck in something like immunizations," he explains.
"It’s not my role to tell Mexico what to do," Small says philosophically. "As an investigator, all I can do is focus on a site I understand well, and then give that information to the policy-makers."
References
1. Garcia-Garcia ML, Ponce-de-Leon A, Jimenez-Corona ME, et al. Clinical consequences and transmissibility of drug-resistant tuberculosis in southern Mexico. Arch Intern Med 2000; 160:630-636.
2. Granich RM, Balandrano S, Santaella AJ, et al. Survey of drug resistance of Mycobacterium tuberculosis in 3 Mexican states: 1997. Arch Intern Med 2000; 160:639-644.
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