Michigan is taking center stage in the nation’s fight against drug-resistant tuberculosis with the creation of the National Tuberculosis Molecular Surveillance Center at Michigan’s state laboratory in Lansing.

Funded by the federal Centers for Disease Control and Prevention, the tuberculosis surveillance center was opened in August and will identify the genetic footprint of each new TB case in the nation so scientists can better track the disease and prevent its spread.

Isolates, or bacterial cultures, from all confirmed tuberculosis cases across the United States will be sent to the State of Michigan Laboratory for whole genome sequencing. Scientists will use special equipment to determine the exact sequence of millions of bits of genetic material contained in the tuberculosis bacterium that made each patient sick.

The aggregated data will provide a better picture of tuberculosis across the country, said James Posey, an applied research team leader within the CDC’s Division of Tuberculosis Elimination.

“This is going to allow us to do a level of surveillance on drug resistance which we’ve never been able to do in the United States on a national level,” Posey said.

Whole genome sequencing will allow CDC scientists to track TB strains by their genetic signatures and keep an eye out for tiny variations or mutations that can result in new drug-resistant strains. They couldn’t do so with the current genotypic susceptibility testing, which wasn’t 100 percent accurate for some drugs, Posey said.

“Now we’re going to have a molecular surveillance to determine what (strains) are circulating in the communities to predict what drug resistance is there,” he said. “In some of the (previous) cases, some tests missed what is called low-level, drug-resistance strains whereas molecular tests can actually detect those.”

The CDC hopes to use the genetic information gathered in Michigan to detect or even predict the emergence of new drug-resistant TB strains. And it’s likely that research technologies developed here will someday be used to combat other drug-resistant diseases.

Scientists worldwide are worried about antibiotic resistance, which occurs when bacteria change their genetic identity to reduce the effectiveness of antibiotic medications. Salmonella, gonorrhea, step throat and the intestinal disease called shigellosis are among the long list of organisms that have developed drug-resistant strains.

“We’re going to build a body of knowledge and new tools moving forward and an even faster ability to detect resistance and have an impact on the next clinical case,” said Dr. Jean Patel, science lead for Antibiotic Resistance and the CDC’s Antibiotic Resistance Laboratory Network.

“The whole genome sequencing that we’re doing here for TB is also being applied to other pathogens that are antibiotic resistant.”

24-month treatment

Tuberculosis has been declining nationwide, and multidrug-resistant cases are relatively rare. But the severity of the disease and its infectious nature mean TB requires constant vigilance, experts said.

About 9,287 U.S. tuberculosis cases were diagnosed in 2016, a 2.7 percent decrease, according to preliminary CDC numbers. About 8 percent of TB cases nationally are resistant to at least one commonly used antibiotic, and roughly 1 percent of the cases are considered multidrug-resistant.

Michigan last year had 133 patients diagnosed with TB, a slight increase over the 131 cases in 2015. It’s been several years since a case of multidrug-resistant tuberculosis was diagnosed in the state, but it’s fairly common to find a specimen that’s resistant to at least one commonly used antibiotic, said Marty Soehnlen, microbiology section manager with the infectious diseases division at the Michigan Department of Health and Human Services.

“It’s one of those things that people think that it’s gone, but it’s not,” Soehnlen said.

TB is spread through the air when an infected person coughs, sneezes, speaks or sings. It’s harder to catch than colds or the flu because it doesn’t spread through casual contact like shaking hands or sharing food. But it’s a life-threatening disease that takes time and resources to treat.

Tuberculosis usually attacks the lungs, but can spread to the bones, the spine or even the brain. Even a normal case takes about nine months to treat, and it can take as long as 24 months to treat multidrug-resistant TB. Patients are quarantined until they are no longer contagious, often in hospitals.

“It’s difficult because they are put in isolation, so they feel very out of touch with what’s happening in society,” Soehnlen said. “Because of that it’s very important that the treatment is correct the first time. We want to treat them effectively and quickly.”

Solving a puzzle

The state laboratory, run by the Michigan health department, was selected to house the National Tuberculosis Molecular Surveillance Center following a competitive evaluation of proposals submitted to the CDC. Michigan received an initial $1.5 million grant to launch the center.

“Michigan ... had more than 20 years of experience with genotyping micro-bacterial tuberculosis using various methods and working with CDC over those years, and demonstrated a record of success with the evolution of the genotyping method,” the CDC’s Posey said. “For the last two years, Michigan’s also been performing whole genome sequencing for CDC in support of outbreak detection.”

At the state laboratory in Lansing, microbiologists extract strands of DNA from cultures of a tuberculosis bacterium collected from TB patients across the country. They break the strands into tiny pieces and tag each piece with an identifier. Then the sample is placed in a DNA Sequencer, an instrument that breaks DNA down into four basic “building blocks” called nucleotides.

“At the end of this process, it’s like a puzzle, and the scientists will put it back together to identify the sequence,” the state lab’s Soehnlen said. “It’s from that sequence that we can determine where something came from and if there’s antimicrobial resistance. It’s really an amazing process.”

At the CDC in Atlanta, scientists will do further analysis and add the results to libraries of data used for research.

“Any time you do a test, you want to think about the person that’s behind it,” Soehnlen noted. “There’s always a patient that needs help.

“The U.S. has put a lot of work into the reducing the number of tuberculosis cases across the country, and we want to continue to push forward on reducing the (number of) cases every year.”

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