When it Comes to Tuberculosis, Seconds Matter

When it Comes to Tuberculosis, Seconds Matter

When it Comes to Tuberculosis, Seconds Matter

TGen North stands guard against this worldwide threat

Each year across the globe, nearly 2 million people die of tuberculosis (TB) — that’s one death every 17 seconds.

“TB is still one of the great health threats in the world,” said Dr. David Engelthaler, Co-Director of TGen’s Pathogen and Microbiome Division, or TGen North, in Flagstaff, Arizona.

TB is an infectious disease caused by Mycobacterium tuberculosis (Mtb) bacteria, which attacks the lungs and is spread through tiny droplets released into the air from coughs and sneezes.

The leading infectious disease worldwide, TB infects nearly 1 in 3 people on the planet, more than 2.5 billion human beings. And while most develop no symptoms, more than 10 million cases occur annually, more than the second- and third-leading infectious health threats — HIV and malaria — combined.

Through the advent of modern medicine, TB infections are rare in the U.S. and other developed nations. But for those living in underdeveloped regions in countries such as India and South Africa and the eastern part of Europe, TB afflicts greater than half of the population. With an increasingly mobile world population, the need to protect the health of Americans is ever more dependent on protecting the health of all humanity.

“TB is a chronic condition that is part of the daily life of much of the world’s population,” Dr. Engelthaler said. “Here in the U.S., hardly anyone is infected with TB. In other parts of the world, almost everyone knows someone who is infected with TB. That’s really tragic.”

And researchers are working against the clock. TB is continually mutating, creating drug-resistant varieties as fast as science’s ability to create effective new antibiotic counteragents.


The Power of Partnership

In May, Tucson’s Critical Path Institute (C-Path) forged a partnership with TGen North as part of their $1.1 million grant from the Bill & Melinda Gates Foundation to significantly enrich its TB data platform developed to better understand the genetic basis of drug resistance in Mycobacterium tuberculosis. Over the next three years, TGen North will sequence more than 12,000 TB samples, or isolates, from more than 35 countries around the world.

This project will help track and map the ever-changing genomic signatures of this disease, as it continues to mutate and evolve. By exactly mapping different types of TB isolates, TGen North will help guide a global precision-medicine response to this elusive health threat.

“This effort will provide us with a complete view of the DNA of TB from across the globe,” said Dr. Engelthaler, adding that the primary goal of the effort is to make all the sequencing information publicly available. “By bringing all of this data together, it will essentially benefit the world’s researchers and clinicians working on TB. It’s about building a global resource. The abilities of all these researchers will be brought to bear.”


Creating a Precise Genetic Test for TB

TGen North is also working to develop a Rapid Drug Sensitivity Test (RDST), a diagnostic kit that is both compact and economical for use in the world’s most remote locations, providing physicians with an exact identification of each patient’s strain of TB. Such a test would help ensure that doctors get the right drugs to treat each patient’s specific type of TB.

“We believe that new targeted sequencing technologies can help physicians care for patients with drug-resistant TB,” Dr. Engelthaler said. “Drug-resistance occurs when the wrong antibiotics are prescribed at the wrong time. This new approach is designed to not only help doctors better treat patients, but to help slow or stop the global threat of multi-drug resistant TB.”

Collaborating with researchers in California — University of California, San Francisco and University of San Diego — Cape Town, South Africa, and the eastern European country of Moldova, TGen North faculty proved the potential of such a
test using Single Molecule-Overlapping Reads (SMOR) technology developed at TGen, which precisely identifies variants of TB, even in cases where other technologies found no drug-resistant mutations.

‘It’s not quite the tricorder, but it could be’

Known as an amplicon sequencing tool, an RDST diagnostic includes molecules and compounds that quickly extract DNA from a sample of saliva and mucus and feed it into a desktop sequencer, where the billions of bits of data can be automatically analyzed and the type of TB quickly identified.

Currently, most samples must be grown in a petri dish before testing to identify which drugs might work. Because Mtb grows so slowly, this process often takes two to six weeks and leaves physicians guessing how to treat patients, which often leads to the wrong medication for a specific infection.

If successful, the TGen test would provide an exact analysis in as little as 24 hours. And on the horizon is an even newer generation of “nanopore” sequencers, which would be capable of delivering results in less than two hours.

Think of how fictional Star Trek physicians analyze patients by using a hand-held “tricorder” scanner to produce an instant diagnosis.

“We can see a day in the not-too-distant future when, with this kind of test, you could get results back in a couple of hours,” Dr. Engelthaler said. “You could get the results while the patient is still in the clinic. It’s not quite the tricorder, but it could be someday.”


TGen North strives to protect public health

Such exciting technological advances could someday put such devices in the hands of physicians everywhere, Dr. Engelthaler said.

“These tools give us so much more precision and accuracy so that, at the very beginning of an infection,” he said. “We could detect the very first resistant bacteria, and give doctors time to provide the precise drug treatment, and hopefully, allow their patients to be cured of TB.”

This effort is yet another example of how the translational efforts of TGen North are helping protect public health, working with local, state, national and international health agencies, non-governmental organizations and private industry.

“We’re able to use these next generation tools to advance the state of public health,” Dr. Engelthaler said, “to improve our ability to do disease tracking and surveillance; to identify outbreaks, and to chase down some of these long-time problems, like antibiotic resistance.”