TB experts have come a step closer to solving one of the great mysteries in
global public health: why the BCG vaccine often fails to protect against the
disease in developing countries.
BCG is a weakened, live bacterium known as Bacille Calmette-Guérin, a
relative of Mycobacterium tuberculosis, the organism that causes
is supposed to stimulate immune responses that protect against M.
tuberculosis. Numerous different strains of BCG are used around the world.
In trials in developed countries, the vaccine has been shown to protect more
than two-thirds of those who receive it.
For years, researchers have puzzled over why BCG fails in developing
countries. Some argue that the vaccines used are of poor quality. Others say
that children in tropical countries are exposed to numerous other
mycobacteria—relatives of both TB and BCG—and that these somehow
interfere with the BCG vaccine’s ability to stimulate immunity to TB.
Now, in the biggest vaccine trial ever undertaken in Africa,
the London School of Hygiene and Tropical Medicine and colleagues in
ruled out the first explanation, and found strong support for the second.
In a trial involving 120 000 children, they found that the strain of BCG
vaccine that protects 70 per cent of British children offered absolutely no
protection in Malawi against the lung form of TB, which is responsible for most
deaths (The Lancet, vol 348, p 17). This crushes the idea that
vaccines are to blame, says Paul Fine, who led the trial.
“This result is really interesting,” says Mark Carrington, a molecular
biologist at the University of Cambridge. “It shows that the vaccine we use in
the UK simply does not work there.” Now, says Fine, the finger points to the
effects of other mycobacteria.
Scientists have long speculated that the presence of other
mycobacteria—such as M. avium and M.
block the effect of the BCG vaccine. These mycobacteria are ubiquitous in soil
and even tapwater, not only in the tropics but also in temperate countries such
as Britain. But in hotter, damper climates these bacteria are much more
Fine says there are several possible ways in which the bacteria could
interfere with the vaccine. If a child’s immune system has already been exposed
to numerous infections with mycobacteria, it may hardly react to BCG
antigens on the surface of the bacterium are similar to those of the other
mycobacteria. As a result, the child’s immune system is not primed to
Another possibility, says Fine, is that the child’s immune responses to
mycobacteria may offer some natural protection against M.
This would mean that the vaccine’s effect in trials would be masked: since even
the unvaccinated children have some protection against TB, the relative
difference between vaccinated and unvaccinated children would be smaller
countries with fewer mycobacteria.