Tuberculosis can hide in peoples’ bone marrow, lying dormant after aggressive drug therapy and emerging years later to re-infect, according to a finding that may help explain why the disease is difficult to eradicate.
One third of the world’s population, more than 2.2 billion people, are infected with the deadly bacteria that causes TB. A four-drug cocktail of antibiotics and other drugs are typically prescribed for a minimum of six months in an effort to wipe out the disease. Still, most remain vulnerable even after treatment.
Investigators writing today in Science Translational Medicine said they have uncovered the first evidence of tuberculosis nestled in mesenchymal stem cells in the bone marrow of people treated for the disease. The bacteria’s hideout in the self-renewing cells, where they capitalize on protection from the body’s own immune system, may explain how the germs survive. The next step is to find out how a re-infection is triggered, and then how to stop it, researchers said.
“Tuberculosis has remained a terrible health threat despite the proliferation of knowledge, diagnostics and treatment,” said lead researcher Antonio Campos-Neto, director of the Center for Global Infectious Diseases at the Forsyth Institute in Boston, in a statement. “By gaining a greater understanding of latent TB, we can potentially save hundreds of thousands of lives each year.”
More than 1.4 million people die from tuberculosis every year, according to the U.S. Centers for Disease and Prevention.
The findings build on similar discoveries with other ailments, including cancer, said Dean Felsher, a professor of oncology at Stanford University School of Medicine and a senior author of the paper. Oncologists have long known that self-replicating bone marrow stem cells have other properties that make them hard to eradicate, such as natural resistance to drugs, infrequent division and protection in the immune system.
“Now it turns out that this ancient organism, Mycobacterium tuberculosis, figured out a longtime ago that, for the same reasons, these cells are ideal hosts to invade and in which to hide,” he said in a statement.
The researchers started looking into bone marrow in the hunt for tuberculosis after Bikul Das, now a postdoctoral scholar at Stanford, found the bacteria in bone marrow biopsies conducted on his patients in India for other conditions. Work using mice showed the bacteria survived even when the cells weren’t dividing, and it could subsequently spur infections in other mice that were exposed to the infected stem cells.
A study of nine patients in India who completed a full course of therapy for tuberculosis and had no detectable bacteria in their systems confirmed the pathogen could conceal itself in the mesenchymal stem cells. The adult cells normally are able to develop into bone, fat or cartilage. In eight of the nine patients, the cells also contained tuberculosis DNA. Living bacteria was detected in two of the patients.
“Not only is this strong evidence that the tuberculosis can remain dormant in stem cells, but it shows that the living bacteria could be recovered from these cells after a long period of time,” Das said. “We now need to learn how the bacteria find and infect this tiny population of stem cells, and what triggers it to reactivate years or decades after successful treatment of the disease.”
The study was funded by the Bill & Melinda Gates Foundation, the U.S. National Institutes of Health, the Canadian Cancer Society and other philanthropic institutions.