Harvard MDR-TB report calls for action, money
DOTS’ slow progress now impeded by resistance
One of the scariest points raised in a new report from Harvard University on the global multidrug-resistant TB (MDR-TB) epidemic is this: With only 12% of TB patients enrolled in a program of directly observed therapy, short-course (DOTS) as of 1998, the push to get rolling on the strategy hailed as a panacea for the TB pandemic appears to be in deep trouble.
The 407-page report, released to great fanfare in late October, was written by the Harvard Medical School’s program on infectious disease and social change and was commissioned by financier/philanthropist George Soros’ Open Society Institute.
As for the report’s main subject — MDR-TB — that phenomenon has now gotten so out of hand that it threatens to further undermine DOTS programs, asserts Paul Farmer, MD, assistant professor in the program of infectious disease and social change and lead author of the Soros report.
All this may explain the surprising spectacle of a report that touts the virtues of DOTS-Plus — a DOTS variation that includes effective treatment for patients sick with MDR-TB — and features a foreword signed by luminaries at the World Health Organization, which for years has been bashing the DOTS-Plus concept.
Just how much MDR-TB is out there? Though the 1997 WHO report on the subject pegged the proportion of MDR at less than 2% of the global total, the true answer to the question is something like "a lot more than we think," the report suggests. (The 1997 WHO survey only looked at 35 countries, which probably were not representative of problems in the real picture.) As for prevalence, a review of literature since the 1997 survey reveals that MDR-TB has been found virtually everywhere health officials have bothered to look, for a total of 104 countries so far.
When it comes to implementing DOTS-Plus, one big question has always been how to pay the bill. Here, the report makes an interesting point. Resources for TB treatment are not necessarily as static and finite as they’re often made out to be, the authors contend; far from diverting funds from regular TB programs, the specter of MDR-TB sometimes focuses a government’s attention and gets serious money flowing. (Just such a thing happened in New York City, a scattering of Russian provinces, and Peru.)
Plus, the biggest cost of DOTS-Plus — the drugs — may not be as steep as we’re led to believe, the report adds, because virtually all TB drugs are off-patent and in theory can be produced cheaply by the generic drug industry.
That means the biggest argument against treating MDR-TB comes down to whether letting loose a supply of second-line drugs will result in their abuse and mismanagement. If that happens, the world could find itself bereft of any useful drugs for treating MDR-TB at all.
In a chapter that’s the real heart of the report, the authors outline a strategy aimed at preventing just such an outcome. To begin with, they say, second-line anti-TB agents should be added immediately to the WHO’s "essential drugs" list. Doing so would encourage the robust generic industry (located chiefly in China, Korea, and India) to begin cranking out supplies of the drugs. The same dynamic would encourage competitive bidding, help ensure good quality and bioavailability, and allow the introduction of mechanisms for strict control of the use of the drugs.
As for the sophisticated laboratory services needed to diagnose and characterize resistance, the authors argue that supranational reference laboratories and others in a position to provide help should get on the ball; that’s not asking too much, they add, given that culture and sensitivity testing can be done for about $4 U.S. per person. (Since 1996, the Massachusetts state lab has provided free services for the DOTS-Plus program in Peru.)
Failing that, the authors concede the fallback remedy — one they clearly feel is inferior to therapy tailored to individual needs — is to use standardized, empiric regimens structured to account for local patterns of resistance.
The report devotes a chapter to each of several countries, using them as case studies of the various ways in which MDR-TB can emerge and how it can behave. In Russia, with its decimated public health infrastructure and utter absence of DOTS, a full-scale MDR-TB disaster is under way. In Peru, even with its model DOTS program, pockets of drug resistance nonetheless occur. In South Africa, the specter of HIV looms, waiting for the dry tinder of drug resistance to appear — so far, in mercifully short supply. That possibility raises an even more urgent question when it comes to Russia. If HIV flares up there and leaps into existing "hot zones" of MDR-TB, the results will be catastrophic.
"Instead of tens of thousands of cases of TB, we will have hundreds of thousands," says Alex Goldfarb, PhD, director of Soros’ Russian TB project. "Instead of 50,000 cases of MDR-TB, we’ll have 10 times that number." (See story, below.)
So far, he adds, this is mere conjecture and depends chiefly on how much HIV increases in the former Soviet Union. "I am one of those who believe this probably will come about," Goldfarb adds. "But of course, only history will tell."
(Editor’s note: To view or download the entire report, go to www.soros.org/tb.)
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