New Imaging Technologies Will Help Combat TB

To develop new strategies to control tuberculosis (TB), a contagious disease that infects one-third of the world's population and kills nearly two million people every year, U.S. researchers have received a US$11.4 million grant that will enable them to use new imaging technologies to evaluate TB to shorten and simplify its course of treatment, potentially improving survival and curtailing the global TB epidemic.

The researchers, from the University of Pittsburgh Center for Vaccine Research (PA, USA), received the grant from the Bill & Melinda Gates Foundation (Seattle, WA, USA). "One of the most challenging issues in treating TB and stopping its spread is the length of time it takes to adequately stem the infection,” said JoAnne Flynn, Ph.D., lead investigator of the grant and professor of microbiology and molecular genetics, University of Pittsburgh School of Medicine. "Current drugs are available, but we don't fully understand how or why they work. TB treatment must be continued for at least six months to be effective, placing an undue burden on those who are infected--often from the poorest and most disadvantaged countries.”

According to Dr. Flynn, TB is difficult to control because the germs that cause the infection hide from the immune system in small tissue nodules called granulomas, enabling the infection to reactivate years, and even decades, later. Although for the most part TB is a curable disease, patients must adhere to treatment long after symptoms have diminished. This proves challenging in many regions of the world where medication is not easily accessible. Indeed, an inadequate or incomplete course of treatment is the key factor that causes drug-resistant TB strains to develop. These strains are disturbingly high in many countries worldwide.

"Current medications for TB were developed more than three decades ago,” said Dr. Flynn. "To create significantly shorter and simplified approaches to treatment, we must improve our understanding of this disease and how current drugs are localized at the site of infection.”

To understand more about the basic biology of TB, Dr. Flynn and colleagues are using the grant to develop positron emission tomography (PET) and computed tomography (CT) imaging studies in nonhuman primates. By using combined PET/CT, the researchers will be able to follow the progression of the disease in animals over time and analyze alterations in tissue and responses to specific drugs. They will be utilizing three imaging technologies--radionuclides, fluorescence, and mass spectrometry--in combination to develop imaging probes and techniques to precisely locate bacteria associated with TB and to explore the underlying factors responsible for slow drug metabolism.

"By applying the tools of modern medicine to TB, we hope to lay the groundwork for real-time measurements of TB drug efficacy in clinical trials and develop new targeted therapies that will considerably shorten the length of treatment,” said Dr. Flynn.

Tuberculosis is a bacterial disease typically affecting the lungs. Called pulmonary TB, the disease is distinguished by a persistent cough, shortness of breath, weight loss, and chest pain. Left untreated, one person with active pulmonary TB will infect on average between 10 and 15 other people every year. The bacteria associated with the disease also can infect nearly any area of the body, such as the lymph nodes, spine, or bones. TB is deadly if left untreated.


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University of Pittsburgh Center for Vaccine Research