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We Have Bad News for TB
Published: Tuesday, 19 Mar 2013
We are taking on Drug Resistance
At Michigan State University, scientists are working to put down one of the biggest global health threats— tuberculosis. The World Health Organization estimates someone is infected with the organism that causes TB every second of every day. Although an infected person may not develop full-blown TB, the disease is still killing approximately 1.5 million people every year. “One-third of the world’s population are believed to be infected with TB, making it a top global health threat,” says University Distinguished Professor John Kaneene.
TB is a horrible disease causing untold suffering and distress. The bacteria can attack any part of the body, but most frequently attacks the lungs. When a person breathes in TB bacteria, it settles in the lungs and begins to grow. From there, it may move through the blood
to other parts of the body, such as lymph nodes, bones, reproductive organs, kidneys, and the spine.
The Complexity of TB
Researchers know the disease is curable. But the treatment to clear the immune system of tuberculosis is complex, involving a lengthy drug regimen that is dependent on patient compliance for 6 to 9 months. Another characteristic that contributes to its success as a disease is the fact that TB is a zoonotic disease—or an infectious disease that can be transmitted between species—from animals to humans or from humans to animals.
"We have a disease triad involving humans, livestock and wildlife," explains Dr. Kaneene. "To eradicate or control TB we need strategies to protect and treat humans, testing and management of livestock and we need education, and policies to address the spread of the disease in wildlife," he said.
Kaneene says TB is prevalent in many countries like India and Russia and throughout the African continent where people may have weakened immune systems. “Malnutrition and a higher prevalence of HIV are additional factors helping to drive the spread of tuberculosis in some of the poorer parts of the world,” says Dr. Kaneene.
“We have to be aware of places where the capacity to identify TB and control it are poor, and where high HIV rates continue to drive the epidemic,” he said. It is also under these conditions where scientists are seeing evidence of a new challenge related to TB: drug resistance.
Known as multi drug-resistant or MDR–TB, this form of the infection is not responsive to the first-line TB drugs, and the treatments that are available take longer and are more expensive than regular TB medications.
“Of a greater concern is a new, more dangerous MDR–TB strain known as extensively drug-resistant TB or XDR–TB, which is not only resistant to the first-line drugs, but also our second-line,” says Walter Esselman, chair of Microbiology and Molecular Genetics.
“Having the experience and expertise of a person like Dr. Kaneene is a great asset to solving the issues contributing to such a complex disease,” says Esselman. “As a doctor of veterinary medicine, with a Ph.D. in epidemiology, he is helping us understand the strains and infection patterns between animals and humans. His work in public health helps us think about human behavior and other points of infection such as food products.”
Controlling TB
Through his involvement with the global organization International Union Against Tuberculosis and Lung Diseases, Kaneene is making others aware of a model he helped develop for effective prevention and control of TB in Michigan. “This model can help lead the way to effective prevention and control systems,” says Dr. Kaneene.
In an effort to control the disease, the International Union Against TB and Lung Diseases has asked the World Health Organization and other bodies like the World Bank to focus on tuberculosis in developing countries.
As a result, Kaneene, in collaboration with Johns Hopkins University, is now working on a study based in Uganda that will use MSU’s experience with the Mycobacterium bovis strain of TB.
In this study Kaneene is looking at several important issues. The team will first look at what proportion of the human infections are caused by the M. bovis strain and then at the dynamics of co-infection between TB with HIV. “We want to know which specific subspecies of TB are more likely to co-infect with HIV and which disease do we need to treat first,” said Dr. Kaneene.
According to Esselman there haven’t been new TB antibiotics introduced to the market since the 1960s. “Microbiologists were the ones who discovered the antibacterials we use today. We believe that new antibiotics are discoverable but it takes a special lab and special skills to work with the organisms that cause TB.” As an air-born pathogen, researchers must work in a very controlled environment with an air filtration system that effectively removes microbial organisms.
This is where Assistant Professor Robert Abramovitch steps into the picture. In his biosafety lab Abramovitch and a team of scientists are studying several strains of Mycobacterium tuberculosis, the bacterium that causes TB.
“Tuberculosis can live inside humans for years, even decades,” says Abramovitch. “This ability to establish a chronic infection in humans is a key factor that makes it such a difficult disease to control. My approach is to basically find new drugs that stop the ability of TB to survive inside the human host.”
The process Abramovitch is trying to target is difficult to replicate inside a test tube. Mycobacterium tuberculosis physiology essential for establishing chronic disease is normally only activated during growth in immune cells.
So he has developed a synthetic biosensor that glows in response to conditions that mimic human tuberculosis infection. He will screen for compounds that target chronic TB infection and may help shorten therapy or treat multidrug-resistant TB.
“Using biosensors and florescent reporters is a very new and non-traditional approach in drug development,” says Abramovitch.
A Grand Challenge
Earlier in 2012, for his work on developing new treatments for tuberculosis, Abramovitch was named a Grand Challenges Explorations winner, an initiative funded by the Bill & Melinda Gates Foundation.
Grand Challenges Explorations funds individuals worldwide to explore ideas that can break the mold in solving persistent global health and development challenges. Abramovitch’s project is one of the outstanding winning proposals chosen by the Grand Challenges Explorations Round 8 grants recently announced by the Gates Foundation.
“Grand Challenges Explorations encourages individuals worldwide to expand the pipeline of ideas where creative, unorthodox thinking is most urgently needed,” said Chris Wilson, director of Global Health Discovery and Translational Sciences at the Bill & Melinda Gates Foundation. “We’re excited to provide additional funding for select grantees so that they can continue to advance their ideas toward global impact.”
To receive funding, Abramovitch and other Grand Challenges Explorations Round 8 winners demonstrated a bold idea to solve a critical global heath issue in development topic areas that included agriculture, development, immunization and nutrition.
“It would be very easy for drug resistant TB to spread around the world and come to Michigan,” says Abramovitch. “In fact it happened in New York back in the 90s. It’s extremely difficult to get control of a drug resistant epidemic.”
Abramovitch sees his work as a first step.
“We hope within the next couple of years to have identified new chemistries that might function as a new drug,” says Abramovitch. It would then take the work of the pharmaceutical industry to turn those discoveries into something that could be used to cure TB.
Abramovitch says there is a very small window to take control of drug-resistant TB. “Every person in the world has something at stake—we need to take control and find the new drugs to stop drug-resistant TB.”
Watch an interview with MSU’s TB team at www.isp.edu/multimedia
