2022 Western Medical Research Conference

Therapy Shows Promise To Help Clear Tuberculosis

Texas Biomedical Research Institute scientists have identified a promising way to help fight tuberculosis (TB), a disease that still kills nearly 2 million people annually. The research focuses on a potential host-directed therapy targeting the immune system to bolster the body's ability to control the infection, a method shown to improve cancer treatments.

Specifically, the team found that inhibiting a particular enzyme, known as IDO—short for Indoleamine 2,3 dioxygenase—helped nonhuman primates completely eliminate active TB infection. Blocking IDO for four weeks in conjunction with antibiotics led to improved health metrics compared with antibiotics alone. The findings were reported in JCI Insight.

"This is exciting," says Texas Biomed Professor Smriti Mehra, Ph.D., who led the study. "We have promising results suggesting an IDO inhibitor could be a host-directed therapy that reduces the length of time and amount of antibiotics that TB patients have to take, especially those with multi-drug resistance."

Tuberculosis is still one of the leading causes of death worldwide and among the top two global infectious diseases. Current treatments require patients to take dozens of pills every day for months, sometimes up to a year, to control the bacterial infection. Many of those with TB have a more mild, latent form that reactivates years later after exposure to another illness, such as HIV. The dual infection often proves to be a deadly combination.

Physicians and patients need better treatment options. Professor Mehra and her collaborators have been interested in IDO for many years. IDO is an immune system protein known to suppress other immune responses. Cancer researchers have explored blocking it to improve cancer treatment, while Professor Mehra and her collaborators were the first to document its role in TB in 2018.

In that paper, they found IDO prevents critical immune cells from killing Mycobacterium tuberculosis (M.Tb), the bacteria that causes TB. The bacteria are usually found inside circular structures, called granulomas, in the lung. Granulomas are a congregation of immune cells that surround the bacteria.

The team detected a large amount of IDO present in the granuloma's intermediate myeloid layer. When they blocked IDO production, it reduced IDO levels in the granuloma and the body was able to kill more bacteria. They hypothesize more immune cells are able to enter the granuloma to do their jobs when there is less IDO present.

The JCI Insight paper took that research a step further to determine whether inhibiting IDO enhances TB treatment. The team, which included researchers, veterinarians and pathologists from Texas Biomed and Southwest National Primate Research Center, compared how groups of macaques with active TB infection fared without treatment, with antibiotic treatment, and with antibiotic treatment plus the IDO inhibitor. The inhibitor was given for four weeks, while a lower-than-usual dose of antibiotics was given for 12 weeks.

The results showed that the animals given the IDO inhibitor did better than those just with the antibiotic treatment.

"The animals given the IDO inhibitor cleared TB completely from the lungs, granulomas and other organs," says Bindu Singh, Ph.D., a postdoctoral research fellow at Texas Biomed and first author of the paper. "Most animals given just antibiotics also controlled the infection well, but still had some bacteria in there."

The research team notes the data were not statistically significant, but it does show potential benefits for clearing infection faster than with antibiotics alone, and could be especially helpful for patients with antibiotic-resistant bacteria.

"Taking antibiotics for months isn't great for the body, so this is something we are hoping we can advance to reduce the time and high dosage currently required to treat TB," Dr. Singh says.

There is still much research to be done before moving to human clinical trials, such as clarifying exactly how the IDO inhibitor helps battle TB, how much IDO blocker to give and for how long. The team is also investigating whether inhibiting IDO prevents latent TB reactivation in the presence of SIV, the nonhuman primate equivalent of HIV.

"The leading killer of people with HIV is reactivated TB, so if we could reduce TB reactivation levels, that would be a very important avenue to explore further," Professor Mehra says.

More information: Bindu Singh et al, Inhibition of indoleamine dioxygenase leads to better control of tuberculosis adjunctive to chemotherapy, JCI Insight (2023). DOI: 10.1172/jci.Insight.163101

Citation: Therapy shows promise to help clear tuberculosis (2023, April 5) retrieved 30 April 2023 from https://medicalxpress.Com/news/2023-04-therapy-tuberculosis.Html

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Tuberculosis-Infectious Woman Refuses To Get Treatment And Isolate, Putting Public At Risk

A women in Tacoma, Washington, who has tuberculosis (TB), has been refusing treatment and was ... [+] spotted taking public transit and going to a casino. (Photo: Getty)

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When you have a contagious disease like tuberculosis (TB), refusing treatment and refusing to isolate are not personal choices. Such choices affect not only you but also everyone around you, at least those with nostrils or mouths. That's why there is now a warrant for the arrest of a woman in Tacoma, Washington, as reported by KOMO News. She has TB yet for over a year now has refused to be treated or to be isolated. That's two not-to-be's that be bad for preventing the spread of TB. Although Pierce County judge Philip Sorenson signed off on that arrest warrant last month, that TB move doesn't appear to be having much effect as the woman was recently spotted taking public transit and going to a casino.

This has been an "If at first you don't succeed, try, try again fifteen times" situation. So far, there have been 16 court orders for this woman to submit to the Tacoma-Pierce County Health Department (TPCHD) for involuntary detention, testing, and treatment. This has meant that a whole lot of taxpayer money has gone into getting one person to take steps to protect not only her own health but also the health of those around her. This would mean taking a medication called isoniazid (INH) in combination with three other drugs: rifampin, pyrazinamide and ethambutol. While treatment would last three to nine months, she would have to stay isolated no longer than 45 days or until testing has shown that she is no longer contagious.

TB can result when you breathe in Mycobacterium tuberculosis bacteria that's exhaled by someone who is infected. So if you are infected, you can spread Mycobacterium tuberculosis into the air by coughing, speaking, or singing the Doors song, "Break on Through to the Other Side" or any song for that matter. When you air such infectious grievances, they can hang in the air for others to breath into their lungs. This is why those with active TB are often kept in negative pressure rooms. In this case, negative pressure doesn't mean being in a room with someone who is telling you to do something because you suck. Instead, it's a room where the air pressure inside is lower than the air pressure outside the room. As a result, whenever the door is opened, this pressure difference effectively sucks air into the room so that any dangerous airborne pathogens don't leave the room.

This chest X-ray shows pulmonary tuberculosis, interstitial infiltration in the left upper lung due ... [+] to Mycobacterium Tuberculosis infection (Photo: Getty)

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Getting TB is not to be a fun thing. The infection can ravage your lungs as well as other parts of your body such as your kidneys, spine, and brain. Typical symptoms include a chronic cough, coughing up sputum or blood, and chest pain. You may become weak and fatigued, suffer fever, chills, and night sweats, and lose your appetite and weight. You may have any combination of these symptoms. Of course, these symptoms aren't always specific to TB. For example, just because you lose your appetite after watching that vomiting scene in the 2011 movie Bridesmaids doesn't necessarily mean that you have TB.

You can be infected with Mycobacterium tuberculosis without having symptoms. This is called latent TB. When you have latent TB, you aren't infectious. However, you should still get treatment because latent TB could always become active TB.

Now, TB treatment is not like eating a hot dog. Once you start, you had better finish the entire course. Ending treatment early could end up selecting for and promoting Mycobacterium tuberculosis that's resistant to antibiotics. Taking the full course of treatment makes it more likely that you will wipe out all the Mycobacterium tuberculosis in your body and not just the weaker ones.

Speaking of hot dogs, not too many people relish getting TB. It can be a killer, and not in a positive sense of the word. The World Health Organization (WHO) indicates that "A total of 1.6 million people died from TB in 2021," and that "Worldwide, TB is the 13th leading cause of death and the second leading infectious killer after COVID-19." While TB in its early stages is very treatable, those who go untreated may have a 50% probability of dying.

So it would totally make sense to get treated if you are infected with Mycobacterium tuberculosis. And it would totally make sense for others to want you to get treated if you are infected with Mycobacterium tuberculosis. After all, no one should say, "It would be great for there to be more TB."

As they say, it's all fun and games until someone gets TB. You can cry freedom all you want, but that doesn't mean that you have the freedom to put others in danger.

Woman With Tuberculosis Faces Jail And Forced Treatment After She Refused Isolation And Visited A Casino

A woman in Washington state who was diagnosed with tuberculosis was found in contempt of court Friday after she allegedly refused to pursue treatment and took a public bus to a casino rather than isolate while under surveillance.

Judge Philip Sorenson authorized law enforcement to detain the unidentified woman following a civil arrest warrant issued March 3, according to local King 5.

The warrant permits the woman's involuntary detention, testing and treatment at the Pierce County jail.

The woman has reportedly refused to take medication and follow protective guidelines despite the efforts of her own family members and the Tacoma-Pierce County Health Department.

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The unidentified woman has reportedly refused to take medication and protect herself and the community despite the efforts of her own family members and the health department. (Spencer Platt/Getty Images)

An officer with the Pierce County Corrections Bureau surveilled the woman's home last month and saw a city bus drop her off at a casino, according to court documents.

She reportedly has not been seen at her home since, and members of her family have not responded to inquiries from the police.

"We have worked with family and community members for more than a year to do everything we can to persuade this woman to take her medication to protect herself and our community," the Tacoma-Pierce County Health Department said in a statement.

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The case marks the third instance in the past 20 years when the Tacoma-Pierce County Health Department has sought a court order to detain an individual with tuberculosis. (iStock)

Pierce County Corrections Bureau Chief Patricia Jackson stated in a court declaration that she believed the woman with tuberculosis was actively evading arrest.

The Tacoma-Pierce County Health Department sees about 20 cases of active tuberculosis every year, which health care providers are required to report under state law. 

"We are always hopeful a patient will choose to comply voluntarily," the department said in a statement. "Seeking to enforce a court order through a civil arrest warrant is always our last resort."

This case marks the third time in the past 20 years that the health department has sought a court order to detain an individual who is potentially contagious with tuberculosis and refusing treatment.

Common symptoms of tuberculosis include cough, fever, night sweats and weight loss, according to the World Health Organization. (Reuters/Denis Balibouse)

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Tuberculosis is an airborne disease caused by bacteria that primarily affect the lungs. Common symptoms include cough, fever, night sweats and weight loss, according to the World Health Organization.

Jon Brown is a writer for Fox News Digital. Story tips can be sent to jon.Brown@fox.Com.

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