September 7, 2016
A microscopic view of Mycobacterium tuberculosis, the microbe that causes TB. Shutterstock
Tuberculosis persists in many patients after they receive drug therapies, while others relapse after being successfully cured of symptoms, a study published in Nature Medicine finds.
Patients with pulmonary tuberculosis (TB) are typically treated with several medications for a period of six months, and some longer. Through PET and CT scans, and by looking for the presence of Mycobacterium tuberculosis mRNA in patients during treatment, researchers discovered that TB lesions and the infecting bacteria can remain in the lungs long after treatment – even if M. tuberculosis can no longer be cultured from a sputum sample.
“This is very surprising: When we treat people with TB drugs, we don’t seem to always cure the infection, even if patients appear to be clinically cured,” said David Alland, a co-author and director of the Division of Infectious Diseases at Rutgers New Jersey Medical School. “Therefore, the body must do the rest of the job. We need to find ways to stimulate the body’s immune system to find a faster way of killing TB.”
David Alland, associate dean of clinical research at New Jersey Medical School and director of the Division of Infectious Diseases, says the findings reveal researchers need to finds ways to stimulate immune systems to eradicate M. tuberculosis faster. John Emerson/Rutgers University.
TB remains one of the leading causes of death worldwide, despite TB mortality rates dropping 45 percent between 1990 and 2012. One third of the world’s population is infected with TB, with more than 9.5 million people a year becoming sick with the disease, according to the Centers for Disease Control.
As the World Health Organization and the Bill & Melinda Gates Foundation focus on developing shorter, simpler treatment regimens to increase the number of TB patients who complete treatments as prescribed, these findings will help researchers test how new therapies and different drug combinations are working, Alland said. PET/CT scans and mRNA analysis during treatment can measure inflammation, detect lesions and live bacteria in the lungs, and monitor how effectively the treatments are eradicating the disease.
Studying 99 non-HIV, nondiabetic adult patients with TB in Cape Town, South Africa, researchers found that after six months of treatment, PET/CT scans found lung lesions similar to those found in untreated pulmonary TB patients in 76 of them. A year after treatment ended, 50 patients continued to show lung abnormalities; researchers found that while most lesions decreased in severity and size, only 16 patients with these abnormalities were fully free of TB lesions. The remaining 34 had significant residual lesions and many had detectible M. tuberculosis mRNA in their sputum, indicating the persistent presence of live bacteria, even though these patients were considered cured of the clinical symptoms of TB.
“It’s kind of a mind-blowing study that tells us we need to refocus on how to kill this persistent-population TB,” Alland said. “There are a range of new drug combinations and new vaccines being worked on, including therapeutic vaccines to stimulate the immune system. With these markers that we’ve developed to look at outcomes, we should be able to get a better line on what works.”
Alland’s post-doctoral student Subhada Shenai was the second author on the study, to which Alland also contributed. Researchers from Stellenbosch University in Cape Town, South Africa, are the lead authors. Researchers from the National Institute of Allergy and Infectious Disease, National Institutes of Health; Stanford University; the International Tuberculosis Research Center in Seoul, South Korea; and the Catalysis Foundation for Health in California also participated.
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