TB elimination possible with BCG, targeted prophylaxis
Critics take issue with Harvard assessment of vaccine
By broadening preventive strategies to include mass BCG vaccination for high-risk populations and prophylaxis for HIV-positive patients, TB can be eliminated in this country, say Harvard researchers. But TB experts take exception to the academicians’ strategy, saying vaccination would be costly, poorly accepted, and possibly less effective than they have estimated.
Discussions of eliminating TB, published in a recent issue of the Journal of the American Medical Association, come after four years of declining TB cases in the United States.1 Prior to 1986, when TB rates rebounded, the Centers for Disease Control and Prevention had established the elimination of TB as a reasonable goal achievable by the year 2010. Indeed, its confidence in eradicating the disease was reflected in the naming of its TB branch the "Division of TB Elimination."
Then came AIDS, increased immigration, growing poverty, and, most significantly, the delayed response from years of government cutbacks in TB funding. Suddenly, the goal of "TB elimination" was replaced with "TB control."
With control of TB firmly established and cases decreasing at about 5% a year, the CDC commissioned Harvard researchers to evaluate the agency’s TB control and prevention strategies developed in the past decade and to assess whether they can meet the goal of completely removing TB from the American scene.
Using a computerized mathematical model, the researchers divided the U.S. population into three age groups and 18 clinical conditions based on disease status and the risk for TB and HIV. They then measured the effects of major changes in TB policy that have been introduced in recent years: increased coverage and improved efficacy of preventive therapy; increased coverage and improved efficacy of treatment, primarily through directly observed therapy; and introduction of the BCG vaccine, whose widespread use in developing countries has never been recommended here.
What they found was that current strategies won’t lead to elimination of TB, says lead author Timothy Brewer, MD, an instructor of medicine at the Harvard School of Medicine in Boston.
"The message is that the United States is focusing on treatment alone, primarily as a control strategy," he tells TB Monitor. "Treatment strategies are good for control, but they aren’t sufficient for elimination."
Ultimately, TB can be eliminated if the CDC broadens its prevention efforts to include a BCG vaccine program and a preventive therapy program targeting HIV-positive patients who have positive PPD tests. Although many HIV-infected patients who test positive for TB are given preventive TB therapy, the practice has not become a standard of care.
Using their computerized model, the researchers estimate that the proposed strategies would reduce TB cases by 47% and TB deaths by 50% during the next 10 years. The authors did not calculate how long it would take to eradicate TB, Brewer adds.
For the BCG strategy alone, a program targeted to 10% of eligible children and 1% of eligible adults each year would result in a 17% decrease in cases and an 11% decline in deaths over 10 years, the authors say.
Value of BCG challenged
The implementation of a BCG vaccination program is by far the more controversial of the two strategies. In a commentary published in the same issue, Kenneth Castro, MD, director of the division of TB elimination, agrees that TB won’t be eliminated without more focus on prevention tools, but he provides four reasons against widespread BCG vaccination: The 10 to 15 million already infected with TB would not benefit; many foreign-born residents already have been vaccinated with BCG; vaccine candidates would have to be screened for HIV prior to vaccination because of BCG’s adverse reaction to HIV infection; and tuberculin skin tests would have to be administered before vaccination because BCG compromises the test.
When TB rates were on the rise, the CDC’s Advisory Committee for the Elimination of TB considered recommending BCG for high-risk children and adults, particularly after Brewer and colleagues at Harvard concluded in a meta-analysis that BCG was 50% effective. (See TB Monitor, January 1994, p. 1.) The committee, however, discouraged vaccination, and its use has been limited primarily to health care workers in high-risk settings.
"The CDC went as far as they could to say don’t give it without actually saying don’t give it," says Brewer, who is a proponent of the vaccine. "But we need to be creative if we want to eliminate TB, and the data clearly show that BCG works."
Don’t tell that to George Comstock, MD, retired professor of medicine at Johns Hopkins University and the country’s leading expert on BCG.
"There is no evidence whatsoever that the BCGs we have are even 50% effective," he says. "Where the Harvard people are completely wrong is assuming that all BCGs are the same, and they completely ignored three studies that showed quite clearly it is not effective with respect to TB in people."
Cultural obstacles to vaccine
In addition to the concerns raised by Castro, Comstock also points out the difficulty in this country of people accepting a vaccine that leaves them with a chronic ulcer. "In countries where it is accepted as a part of life, that is different, but we aren’t used to that sort of thing," he says.
While Castro says that TB elimination may hinge on developing a better vaccine and more tolerable anti-TB drugs, Comstock says the recent reversal in TB rates proves that funding is the key determinant.
"For the past four years, we have had a remarkable decline, so when they blame [the rise in rates] on resurgence of AIDS, poverty, homelessness, and immigration those things weren’t any better in the past four years then they were 10 years ago," he notes. "The only thing that has changed is we finally put some money back into it."
The best alternative to an effective vaccine and drugs is to develop better methods for identifying people who harbor tubercle bacilli, Comstock says. In the meantime, TB control must continue to focus primarily on identifying cases and treating them adequately and completely.
Targeting preventive therapy for HIV-positive patients also is a sound strategy, he says. Although HIV-positive patients are often in late-stage AIDS by the time they develop active TB, new anti-HIV drugs are extending their lives and, consequently, their risk of spreading TB.
"Both for their own good and the good of society, they should be offered preventive therapy because they have a terrible risk and can spread it, and there is some evidence that the presence of TB can aggravate HIV infection," he says.
The Harvard model estimates that targeting HIV-infected patients for preventive therapy would reduce HIV-associated TB cases and deaths by 14% to 20%.
Reference
1. Brewer T, Heymann J, Colditz G, et al. Evaluation of tuberculosis control policies using computer simulation. JAMA 1996; 276:1,898-1,903.
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