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Tuberculosis Evades Detection by Hiding in Bone Marrow


A man (L) is x-rayed to detect tuberculosis during a medical examination, Jan. 29, 2013.
A man (L) is x-rayed to detect tuberculosis during a medical examination, Jan. 29, 2013.
It's been a long-standing medical mystery: how tuberculosis (TB), a potentially fatal respiratory infection, can spring to life in a patient after lying dormant for many years. Scientists have discovered that the bacterium which causes TB hides in cells in the bone marrow, making it hard to treat with antibiotics.

Unlike other bacterial infections, tuberculosis is notoriously difficult to treat. Despite the availability of antibiotics for 50 years, treatment for TB involves a rigorous multi-drug regimen of up to six months' duration.

That’s led researchers to conclude that Mycobacterium tuberculosis, the pathogen that causes the deadly lung ailment, is lurking in tissue, where neither antibiotics nor the body’s protective immune system can kill it.

One potential hiding place is bone marrow, a spongy tissue inside bones containing stem cells responsible for manufacturing a variety of blood cells. Marrow has mechanisms for keeping out foreign substances, including antibiotics.

Researcher Antonio Campos-Neto, director of the Forsyth Center for Global Infectious Diseases in Cambridge, Massachusetts, and his colleagues at Stanford University School of Medicine in California conducted test tube, or in vitro, experiments to see what happened when bone marrow cells and the TB bacterium were mixed together.

“And sure enough, you know, in vitro experiments show the microorganism could be internalized very easily inside the stem cells,” said Campos-Neto.

That finding, according to Campos-Neto, may explain why the lung disease exists in two forms -- a latent phase in which individuals can be infected for decades without symptoms, and an active phase, characterized by extreme illness and, without treatment, death.

And it may have implications for the treatment of TB, explaining why antibiotics do not always rid patients of the disease.

“Many, many [TB] patients who have been successfully treated, later on in their life they can come back with tuberculosis again. And nobody ever understood why this was so difficult, and now we start to have this firsthand [knowledge] that it’s because the TB is hiding itself in some protective niche that drugs cannot reach,” explained Campos-Neto.

An estimated 2.2 billion people around the world live symptom-free with latent tuberculosis. Once active, the illness kills upwards of 1.7 million people every year.

Campos-Neto says researchers need to learn more about this complex disease so new diagnostic tests and effective treatments can be developed.

An article by Antonio Campos-Neto and colleagues on latent tuberculosis is published in the journal Science Translational Medicine.
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