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March 27, 2017

Test outperforms all others on market and takes just hours to complete, key in fighting disease that remains major worldwide risk

Tuberculosis, once better known as consumption for the way its victims wasted away, has a long and deadly history, with estimates indicating it may have killed more people than any other bacterial pathogen.

Consumption played a role in many of our stories of the Old West, but even today — despite $6.6 billion spent for international TB care and prevention efforts — it remains a major risk to human health.

A group of maverick scientists from Arizona, Texas and Washington, D.C., has teamed up to develop the first rapid blood test to diagnose and quantitate the severity of active TB cases.

Led by Tony Hu, a researcher at Arizona State University’s Biodesign Institute, eight research groups, including the Houston Methodist Research Institute and scientists at the National Institutes of Health, are harnessing the new field of nanomedicine to improve worldwide TB control.

“In the current frontlines of TB testing, coughed-up sputum, blood culture tests, invasive lung and lymph biopsies, or spinal taps are the only way to diagnose TB,” said Hu, an associate professor at the ASU's School of Biological and Health Systems Engineering, part of the Ira A. Fulton Schools of Engineering. “The results can give false negatives, and these tests are further constrained because they can take days to weeks to get the results.”

The team’s newly developed blood-based TB test not only outperforms all others on the market but also takes just hours to complete. This is critical since effective TB control requires that patients start treatment as soon as possible to reduce the risk of spreading it.

This test also holds promise for rapid assessment of TB treatment, an important factor in reducing the development and spread of drug-resistant strains.

And in a fitting twist of fate, Hu’s laboratory in the Biodesign Institute's Virginia G. Piper Center for Personalized Diagnostics is only about a mile away from the original Arizona State Tuberculosis Sanatorium, a Moorish-influenced structure that opened in Tempe, Arizona, in 1934 and had 60 beds available to treat patients.

A history of affliction

Estimates suggest that TB has killed a billion people over the past two centuries.

Locally, TB deeply influenced the early history of Arizona, since the warm, dry climate spurred the growth of sanatoriums and a medical tourism industry that helped give rise to Phoenix’s original population boom in the late 1800s.

Perhaps the most notorious TB victim in Arizona’s rich history was the Old West's John Henry “Doc” Holliday, a dentist, gambler and gunfighter, whose role at the OK Corral shootout is still re-enacted daily in Tombstone. After the gun smoke cleared, Holliday survived but died just a few years later, finally succumbing to the disease he seems to have contracted a decade earlier.

TB appears to have played a major role in his life, first influencing his migration west for a healthier climate, but also branding him with a prevailing social stigma. In the hit movie “Tombstone,” Doc Holliday’s enemies taunted him by calling him “lunger,” a derogatory term for those afflicted with consumption, who were stigmatized and often removed from society and placed in sanatoriums, such as the one near Hu’s modern-day lab. 

Worldwide scourge

Thankfully, TB now has a greatly reduced impact on Arizona, but it remains a major risk, particularly for the developing world and people with HIV infections.

Making matters worse, TB bacteria, such as in Holliday's case, can lurk dormant in a person’s lung tissue, often for decades, before spontaneously producing full-blown TB disease that can then spread to others. Currently, the World Health Organization (WHO) estimates that up to one-third of the world’s population may have such dormant TB infections.

In 2016, an estimated 10 million people worldwide still develop TB each year, according to the WHO’s most recent report, resulting in almost 2 million deaths. TB treatment has prevented almost 50 million deaths between 2000 and 2015, but TB remains a worldwide epidemic due to the lack of an effective vaccine, the rise in drug-resistant strains and the relatively poor performance of available diagnostics.

A new and easy way to rapidly screen those susceptible to TB infections was recognized by WHO and other public health officials as the major technological hurdle needed to overcome the disease.

Enter Hu and the research team.

Nanomedicine to the rescue

The research team’s newly developed NanoDisk-MS assay (see image below), could significantly improve TB diagnosis and management because it is the first test that can measure the severity of active TB infections. It does so by accurately detecting minute blood levels of two proteins (CFP-10 and ESAT-6) that TB bacteria release only during active infections.

The research team’s newly developed NanoDisk-MS assay could significantly improve TB diagnosis and management because it is the first test that can measure the severity of active TB infections. It does so by accurately detecting minute blood levels of two proteins (CFP-10 and ESAT-6) that TB bacteria release only during active infections.

“We are particularly excited about the ability of our high-throughput assay to provide rapid quantitative results that can be used to monitor treatment effects, which will give physicians the ability to better treat worldwide TB infections,” said Hu. “Furthermore, our technology can be used with standard clinical instruments found in hospitals worldwide.”

Current TB assays often demonstrate reduced performance with HIV-positive TB patients or those with TB infections in non-lung tissues, and these patients can require tissue biopsies for diagnosis. The NanoDisk-MS assay, however, detected lung- and non-lung-resident TB cases with similar sensitivity (about 92 percent) regardless of patient HIV status, and revealed good specificity to distinguish patients with related disease cases (latent TB and nontuberculous mycobacterial infections; 87 and 91 percent, respectively) and healthy subjects (100 percent).

The strategy used to generate this assay may also be adaptable to other infectious diseases. Hu is now developing the current TB assay for clinical approval and hopes to make it available for clinical use as soon as possible to re-establish the role of Arizona and ASU as central players in the fight against TB.  

The study, “Quantification of circulating M. tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring,” was published in the Early Edition of the journal Proceedings of the National Academy of Sciences.

 

Top image: An illustration depicting an active TB infection targeting the lungs. Courtesy of the ASU Biodesign Institute

Joe Caspermeyer

Managing editor , Biodesign Institute

480-258-8972

 
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ASU study shows effect of climate change on food, energy and water across Southwest

President Donald Trump's executive order on climate change is expected any day.
Arizona supplies live animals, other agricultural products across the region.
ASU study shows connection between food, energy and water.
March 27, 2017

Disruptions in Arizona would have ripple effects throughout the supply chain for several major US cities

With the world waiting for President Donald Trump’s executive order on climate change, an Arizona State University study on Arizona agriculture shows the potential effect of a warming planet on the state and the region by examining the food-energy-water nexus.

Disruptions from temperature increases could drop crop yields, require more irrigation and cause ripples, including increased food prices, throughout the Southwest, according to the paper from Andrew Berardy and Mikhail Chester of the Julie Ann Wrigley Global Institute of Sustainability at ASU.

“One of the main things to take away from this is there’s a connection between energy and water in agriculture, and that connection is vulnerable to climate change,” said Berardy, who focuses on sustainable food systems.

“As temperatures increase,” he said, “as there’s more variability in rainfall, and less rainfall overall, these things are going to have cascading impacts, not only impacting farms and agriculture and our food system in general, but the energy and water systems that supply the necessities to grow food.”

Trump’s upcoming order could include changes to power-plant emissions standards that he has said are excessive. Opponents worry that without such protections in place, the U.S. would not reduce its carbon footprint.

For major Arizona crops, according to Berardy and Chester’s research, yields could drop more than 12 percent per 1 degree Celsius. It also could require increased irrigation of about 2 percent per degree, according to the study.

Disruptions would be felt locally and across the Southwest, including California, Nevada and Texas, affecting food supply chains to several major U.S. cities, the research shows.

Tucson gets all of its live animals and fish from within the state. It also gets the overwhelming majority of its “other agricultural products” and foodstuffs from Arizona. Phoenix, meanwhile, gets nearly 90 percent of “other agricultural products,” nearly three-quarters of its animal feed, and more than half of its cereal grains, foodstuffs and live animals from within the state.

Los Angeles receives nearly a quarter of its live animals from Arizona.

San Diego gets 14 percent of its animal feed from the Grand Canyon State.

El Paso takes 25 percent of foods other than animal products, feed and milled grains from Arizona.

But more than anything else, Arizona ships food — mostly lettuce — to states as far-flung as Washington state and Massachusetts.

Shocks and strains on energy and water production and their delivery systems could result in failures that cascade down to food systems. Failures in one system could easily spread to another.

“That’s one of the things we wanted to capture: what the actual consequences of any reduction in Arizona agriculture would be,” Berardy said.

Berardy and Chester analyzed public data that show different modes of freight and what types of goods are going across state lines. They also studied the threshold temperatures of crops, U.S. Department of Agriculture and U.S. Geological Survey data, Arizona crop budgets and region-specific literature.

“We definitely were surprised at how much California and Texas and some other states depend on Arizona’s agricultural output,” Berardy said.

It’s going to be more complicated than just the price of food skyrocketing. Land used for fodder production, like alfalfa, might be shifted to other crops.

“The shifts are going to be felt first in livestock, in the price of meat and dairy, because the effect of the temperature increase will be felt there first,” Berardy said. “If these impacts are happening in Arizona, they’re going to be found in other states, too. That will have a compounding effect.”

Other studies have looked at one crop, or the effect of temperature increase on its own. This study came from a holistic approach to get a more realistic look at what might happen.

The paper recommended farmers switch to more efficient irrigation methods, like drip irrigation.

Smaller farms might not be able to afford a switch to drip irrigation. Larger farms might already have a pricey sprinkler system in place they don’t want to replace. Only about half of Arizona farms with flood-irrigation systems engage in any kind of water conservation, according to the study.

“You can change any one component of it, and it has cascading effects downstream,” Berardy said. “No matter what you change, it’s going to change something else too.”

 To read the study, please visit this link: http://iopscience.iop.org/article/10.1088/1748-9326/aa5e6d

Top photo: Arizona ships food — mostly lettuce — to states as far flung as Washington state and Massachusetts. ASU Now file photo. 

Scott Seckel

Reporter , ASU Now

480-727-4502