TB forecast: Scattered trouble ahead with resistance, reactivation, money
Sequencing of TB genome inspires more sophisticated research
The good news from last year’s TB case totals — an 8% decrease from 1997 and a 31% drop from 1992, the high-water mark of the resurgence — inspired TB Monitor to ask experts from around the country to dust off their crystal balls and talk about trends in TB cases in the United States within the next five or six years. (See story, p. 99, for all the numbers from the Centers for Disease Control and Prevention’s latest TB report.)
They generously obliged and spoke of worries about drug resistance, problems with immigrant screening, and the perennial threat of funding cutbacks. Research inspired by the sequencing of the TB genome makes them hopeful; the steady decline in cases gives them cause for cautious optimism. Points many of them (though not all) touched on included the following:
• Yes, Virginia, the days of steeply declining rates are past, and now it’s time for the gritty work of screening and treating high-risk populations at risk for reactivation to begin.
• Watch for lawmakers to feel strong temptations to shrink TB funding and privatize public health. In areas of low incidence and low numbers, the addition of a little private-sector expertise might not be unwelcome — given all the young docs who’ll be tending the foreign-born.
• That black cloud on the horizon is global drug resistance. Here at home, expect increased rates of resistance among the foreign-born, because what’s happening elsewhere can’t fail to touch the United States as well.
• Get ready to spend more time and money on immigration screening programs and policies. The same goes for high-burden countries that send lots of immigrants here.
• The forecast from the bench-science front is sunny, with lots of new developments in the pipeline. But will anything really big pan out in the next five or six years? A tough call.
Experts who spoke with TB Monitor were the following:
• Charles A. Daley, MD, assistant professor in the department of pulmonary and critical care medicine at the University of California — San Francisco General Hospital;
• Barry Kreiswirth, PhD, director of the TB Center at the Public Health Research Institute in New York City, which specializes in using molecular genotyping and other high-tech methods to isolate, identify, and track strains of resistance;
• Jeff Starke, MD, the nation’s foremost expert in pediatric TB and chief of pediatrics at Ben Taub General Hospital in Houston;
• John Sbarbaro, MD, professor of medicine at the University of Colorado Health Sciences Center in Denver;
• Clifton Barry III, PhD, chief of the mycobacterial research unit at the National Institute for Allergy and Infectious Diseases;
• Sally Blower, PhD, associate professor in department of medicine at the University of California — San Francisco and a specialist in mathematical models;
• Carole Mitnick, director of Partners in Health in Cambridge, MA, and a contributing author of an upcoming report on global trends in TB drug resistance commissioned by financier and philanthropist George Soros.
Here’s what the experts had to say:
Kreiswirth: "This is not the time to celebrate! Since the numbers are down, we’ll cycle right back to where we just came from. We’re like a fat guy trying to lose weight who’s gotten back down to where he was. What kills me is that this is a reactive disease; it hasn’t gone away! Here in New York, immigration numbers are sky-high.
"The number of drug-resistant strains outside the U.S. is growing, and a lot of those strains are going to end up on our shores. Then there’s HIV — as soon as that rolls in, it’ll increase the numbers, which are already huge, in India, China, Russia, and of course South Africa. That means you lose all these people of working age, and you devastate the economies of all these countries.
"Of course, more TB abroad means more drug resistance because people will start putting Band-Aids on the problem and throwing good money after bad, just like they always do. This is such a hard disease to work on; even if you have lots of money and good intentions, it’s really hard to get things done."
Daley: "San Francisco reflects the rest of urban America. We’ve had a rapid drop-off in cases since 1993, and now our numbers are falling more slowly. In California, 70% of our cases are now foreign-born. So the shut-off of transmission in high-risk populations has left us with a lot of TB remaining among foreign-born and among older individuals. New guidelines will get rid of the age 35 cut-off, but I don’t know how the TB community will react to that.
"What happens outside our borders will be more important than ever. We ought to spend more money on international work; unfortunately, there’s not a lot available. What money there is should be tied to specific countries. Russia is fairly insignificant to the U.S., but we have a big problem with Latin America and Asia. And the money shouldn’t go without any strings attached; it should be tied to educational and TB control projects that will improve things here in the U.S."
Mitnick: "In major cities, if resources are maintained or improved, we’ll see more cases detected upon arrival. You’ll probably see more drug resistance detected among arrivals, too.
"Here in Massachusetts, the problem isn’t with the screening process; it’s that so few of the foreign-born go through screening. They come mostly as students or visitors, not refugees and immigrants. So what happens depends on who this country lets in and what circumstances led to their arrival.
"With growing immigration from the former Soviet Union, you’re likely to see more primary resistant disease; but since they may not be coming from refugee camps, they may not break down as soon after they arrive as, say, we saw in immigrants from Southeast Asia."
Blower: "Overall, the picture looks good, but there’s incredible heterogeneity. Five years hence, it will probably look better here, and worse globally. So a lot of what happens will depend on migration and immigration patterns."
Barry: "The TB genome is forcing us to think about the biology of the TB organism in a whole new way. It’s making us ask better questions that are much more sophisticated. We’re on the brink of being able to monitor simultaneously every gene in the cell at one time; a lot will spin off from that.
"I’d watch two agents in pre-clinical development: KRM-1648, a derivative of rifamycin, may let us do once-a-week therapy; and PA-824. They’re both languishing at Pathogenesis, but the public sector is trying to pick them up. We’ll see more immunomodulatory vaccine strategies as well; the researcher to watch there is Gilla Kaplan, [PhD, associate professor at the Laboratory of Cellular Physiology and Immunology at Rocke feller University in New York City], who’s modulating tumor necrosis factor with thalidomide treatment."
Starke: "We all know kids are the yellow canaries of TB; the fact that pediatric cases are down reflects the fact that current transmission is way down, and that means health departments, especially those in big cities, are once again getting the money they need to do their jobs. The decline in pediatric rates occurred at the same time that the CDC discouraged mass testing of kids; that reinforces the wisdom of the decision.
"Will we sustain this level of decrease? I doubt it. What gains we’ve made have been resource-bound; taking away some of those resources could make the gains go away. In the foreign-born, not just the proportion but the actual numbers are up; clearly, our current immigration policies aren’t doing enough. That’s the next big thing the federal government needs to work on."
Sbarbaro: "If we focus on those who immigrate and encourage them to take get appropriate preventive care, that’ll speed up the decrease. The trouble is you’ve got a group of new young docs and foreign-trained docs who provide most of the care to foreign-born groups, and they have so much other stuff to deal with. So they need to be linked to the health department. If we do that, great!
"But let’s not declare victory prematurely. We still have pockets of resistance at home, and we know resistance abroad is going to soar. If we have people in this country who know how to treat resistance, great; if not, we’ll have a new-wave epidemic, and it’ll be scarier than anything we’ve seen."
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