Benefit of BCG outweighs risk in AIDS patients

New BCG strain may protect against resistant TB

A study of more than 500 HIV-infected adults who were vaccinated at childhood with BCG has found that the protective benefit of the vaccine outweighs the relatively small risk of developing disseminated BCG infection.

The study, published in the journal AIDS, helps put to rest concerns that vaccinating populations at high risk for HIV makes them vulnerable to developing BCG infection once they become immunocompromised.1 Although BCG (mycobacterium bovis bacille Calmette-Guerin) is not offered in the United States, populations in developing countries and parts of Europe are routinely immunized with the vaccine, which is believed to have a 50% effectiveness against developing tubercular meningitis and miliary TB.

"People have been wondering if we should stop BCG vaccinations in populations with high HIV prevalence," says lead author Bryan Meyers, MD, assistant professor of medicine at Dartmouth Hitchcock Medical Center in Dartmouth, NH. "The main implication of the study is that there is no reason to consider not immunizing with BCG that population given that we didn’t see much disseminated BCG infection."

Cases of disseminated BCG infection in AIDS patients have been seen most frequently soon after HIV-positive children have been immunized. However, some cases have been reported in HIV-positive adults who were immunized as children, the authors note.

The study followed HIV-positive patients with CD4 counts of less than 200, enrolled at sites in New Hampshire, Boston, Finland, Trinidad, and Kenya. Of the 566 patients enrolled, 155 had childhood BCG vaccine. Of the 21 patients who tested positive for tuberculosis, none were positive for M. Bovis BCG.

Moreover, the researchers found an association between childhood BCG immunization and protection against TB in adult patients with AIDS. The two results taken together support the current recommendations from the World Health Organization that children should be vaccinated with BCG in areas with a high prevalence of both HIV infection and TB.

Recently, researchers have found a weakened BCG strain that can completely eliminate the risk of disseminated BCG in immunocompromised people. (See TB Monitor, May 1996, pp. 54-55.)

And in Brazil, two researchers have discovered that vaccination with BCG appears to confer a degree of protection upon the contacts of patients who are infected with multidrug-resistant TB.

The study that turned up the tantalizing finding was conducted by Lee Riley, MD, professor of infectious diseases and epidemiology at the University of California at Berkeley, and Afranio Kritski, MD, MPH, a research associate with the Federal University of Rio de Janeiro. The two discovered the protective effects of BCG by accident, Riley says.

"Basically, what we were doing was a long-term study looking at the epidemiology of TB," says Riley. "We were trying to answer another question that everyone was interested in answering, namely, what is the risk for contracting MDR among contacts?" Among a host of other factors the two looked at — including ethnicity, age, income level, and whether subject had had a BCG vaccination — the last factor was the only one that stood out as significant, Riley says.

The finding is one Brazilian officials have begun to weigh as they debate a change in the national policy regarding BCG vaccinations, Riley says.

In Brazil, citizens are now vaccinated with BCG only once, at birth, Riley says. Based partly on the evidence of the protective effect Riley and Kritski discovered, the ministry of health is now contemplating a stepped-up program of vaccinations, whereby boosters will be given once, or perhaps twice, to teens, school-aged children, or young adults.

Russia and China are examples of two nations that have already adopted such policies, Riley says. Because the vaccines would be given to everyone, there would be no need to give an additional vaccination to household contacts of someone suffering from MDR-TB, Riley says.

How long the protective effect of BCG lasts is not known, he adds. "It depends on the type and the batch," he says. "Some are longer lasting than others; but generally, the effect lasts about 10 years."

In Brazil, added protection against MDR-TB could have profound consequences for public health. Many second-generation drugs that fight MDR are available, at least in some areas, Riley says. Kritski has found that both there and in the United States, in large urban centers, those infected with HIV are more likely to develop MDR-TB, Riley says.

Yet it is difficult to detect when a patient suffers from resistant TB because, as in many third-world countries, specimens are rarely cultured for sensitivity, says Riley. The diagnosis of MDR usually rests on clinical features, he says, with sensitivities performed only when patients are lucky enough to become part of a research project.

Pending the more widespread use of BCG, Riley and Kritski have developed a system, based on the clinical history of a case, physicians can use to reliably estimate the likelihood that a patient suffers from MDR. Patients who have previously abandoned treatment have a 6% chance of having MDR; those who have completed treatment but have relapsed have a 33% chance; and those who have been on both primary and secondary drug regimens but failed, have a 55% chance of having MDR, Riley says.

Reference

1. Marsh B, Reyn C, Edwards J, et al The risks and benefits of childhood bacille Calmette-Guerin immunization among adults with AIDS. AIDS 1997; 11:669-672.