Science Diction Podcast | Tuberculosis

Transcript – Tuberculosis: Hope in the Face of a Global Infectious Disease

Dr. Amy Manning-Boğ
Believe it or not, there is an infectious disease that is contracted by more than 10 million people globally each year with a mortality rate of approximately 15%. And though it’s curable and even preventable, we don’t hear much about it in the Western world. Do you know what it is? Erin Merritt is a principal scientist who heads a team of infectious disease specialist in collaboration with the National Institutes of Health and their support of the Mycobacterium Tuberculosis Quality Assessment Program at MRIGlobal, also known as TBQA. Erin and her team are leading efforts to eradicate this disease. Today on the show, tuberculosis. What it is, why it’s so difficult to treat, and the devastating impact that COVID-19 had on its diagnosis, treatment, and research. I’m Amy Manning-Bog and this is Science Diction from MRIGlobal.

Erin Merritt
Mycobacterium tuberculosis is a bacterium primarily transmitted by aerosol or droplet, just like COVID-19. It can be transmitted when a person has active TB infection and it can be transmitted through cough, sneezes, laughs or even when a person talks like we are right now. The disease exists in two forms an active form which is capable of being transmitted to others, and the latent form in which the patient is asymptomatic and cannot spread TB. Between the two forms, it’s estimated that nearly a quarter of the world’s population is actually infected with TB.

Dr. Amy Manning-Boğ
Wow.

Erin Merritt
Following infection, the bacteria most often attacks in the lungs. But the bacteria can also attack the kidneys, the spine, and the brain. Symptoms include cough, fever, fatigue, night sweats and weight loss.

Dr. Amy Manning-Boğ
I understand that prior to COVID, tuberculosis was the leading infectious disease killer in the world. Why is it so deadly?

Erin Merritt
It’s deadly because of the way it spreads. The aerosol contacts with family and friends. So it spreads through prolonged exposure with everyday contacts like your family and your coworkers. It also affects some of society’s most vulnerable populations. So conditions of poverty, such as malnutrition and crowded, poorly ventilated living spaces, create ideal settings where TB can spread. Along with the inability to access health care readily. Much like we experienced with COVID-19, it’s hard to avoid your friends and family when they are infected. You want to be there for them and that’s a comfort for them. But that puts you at risk of getting infected. So in addition to that, today’s treatments for tuberculosis are threatened by the emergence of drug resistant TB, which makes it even more deadly and more concerning.

Dr. Amy Manning-Boğ
So are there certain health conditions that put people at greater risk for TB infection?

Erin Merritt
Tuberculosis is actually pretty unbiased when it comes to who can be infected. It can be the very young, the very old, and it can be in any country around the world. However, there are certain medical conditions that put people at greater risk, both for the initial contact with the disease and how deadly it will become. For instance, TB is strongly influenced by health-related risk factors such as undernourishment, diabetes, HIV infection, alcohol use disorders, and smoking.

Dr. Amy Manning-Boğ
Why is that so? All of those different risk factors. Is there some sort of common link? Is it reduced immunity?

Erin Merritt
It is. And so particularly if you think about people with HIV infection, they’re 20 times more likely to develop active TB. And I think it’s more shocking that TB is actually the leading killer of people with HIV. And that’s where the TBQA program comes in. It’s situated under the Division of AIDS within NIH’s Institute of Allergy and Infectious Diseases. And the goal of TBQA is to enhance patient safety and data reliability for TB clinical trials within the AIDS Clinical Trial Group or ACTG through efforts such as training, longitudinal data analysis, TB repository, maintenance, and scientific evaluations of new commercial assays.

Dr. Amy Manning-Boğ
So once an individual is infected, what does a treatment protocol look like, Erin?

Erin Merritt
Unfortunately, it’s a pretty lengthy treatment. Even in the best-case scenario when the infection is from drug susceptible TB, it’s quite lengthy. The standard regimen for treating susceptible TB disease consists of a two-month intensive phase of four drugs: isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB), taken daily followed by a four-month continuation phase of isoniazid and rifampin. On the other hand, unfortunately, if a patient has drug resistant TB, it’s even more of a rigorous regimen that they have to go through. The guideline was recently updated by the World Health Organization. It’s now a six-month regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin, which is BPaLM.

Dr. Amy Manning-Boğ
Are there side effects associated with some of these antibiotics?

Erin Merritt
There are. In particular, one of the drugs, clofazimine, is known to cause skin discoloration. It’s very red. It’s got a lot of red dye in the drug itself. And so one of the side effects is skin discoloration for the patients and it can take six months to a year for those patients to have that skin color discoloration go away post treatment.

Dr. Amy Manning-Boğ
So this clearly sounds like an extensive process. It’s probably also an expensive process.

Erin Merritt
It is so it’s extremely expensive, particularly in the United States, where antibiotics, testing and health care aren’t subsidized to provide support. According to the CDC and a 2020 analysis, treatment in the U.S. alone for drug susceptible TB cost over $20,000 and then if you were dealing with extremely drug resistant TB over $550,000.

Dr. Amy Manning-Boğ
That’s shocking.

Erin Merritt
Internationally, it varies by country to country, but there’s more than just monetary costs to TB that I think should be talked about. Patients are in quarantine for a large portion of their treatment and that can negatively impact household incomes and also the mental health of the patient themselves. Often when we go to conferences to discuss clinical and epidemiological finer points, some of the most impactful moments come from listening to the survivor stories and how those impacts of the societal stigma of having TB, financial burden of having it, and the isolation and how that impacts them throughout their diagnosis and treatment, it makes the overall recovery that much more difficult.

Dr. Amy Manning-Boğ
Can you tell me how many lives have been saved as a result of diagnosis and treatment?

Erin Merritt
Yeah, the W.H.O. estimates that about 74 million lives have been saved as a result of diagnosis and treatment from 2000 to 2021.

Dr. Amy Manning-Boğ
And despite that progress, when the COVID-19 pandemic upended daily life around the world, it also impacted all aspects of tuberculosis diagnosis, treatment, and research.

Erin Merritt
There were a lot of supply chain issues, much like people experienced with groceries and other things that they used day to day. This also impacted lab supplies, diagnostic tests, even down to the most basic plastics that we use in the lab day to day. So the disruptions of supply chains and the diversion of healthcare resources to the COVID-19 response made the detection and diagnosis of TB much more difficult. Similarly, COVID-19 has hampered the monthslong treatment regimen for tuberculosis patients while causing pauses and disruptions to the critical clinical trials and research that was taking place around TB.

Dr. Amy Manning-Boğ
Are conditions improving now that we’re not in the middle of the pandemic?

Erin Merritt
During the pandemic, the reported numbers for TB cases actually declined, and I think there was some level of optimism about that. But there was also speculation that this was a false dip in the numbers due to the pandemic. And that’s exactly what we’re seeing. Unfortunately, now, the case numbers are starting to surge to pre-pandemic numbers. So we’ve actually taken a few steps backwards in the efforts to end TB.

Clinical trials are back underway, but it’s not incidental to get all of these moving again, to get patients enrolled into the trials. And so with that, I think we’re even further away from really seeing results that are positively impacting TB diagnosis and treatment at this point. Diagnostic instrumentation and resources are pivoting back to analysis other than COVID-19 and the resource supply chain issues have been much less frequent, so it does feel like things are improving on that front, which will inevitably, positively impact TB, research, diagnosis and treatment going forward. My hope is that we can use some of these lessons learned from COVID-19 to positively impact our handling of TB going forward, whether that’s supply chain efficiencies or up to and including mRNA vaccine technology.

Dr. Amy Manning-Boğ
Thinking about that dip that was seen in TB reporting during the pandemic. Do you think it was just that reporting, meaning fewer people showing up, getting diagnosed, or was it the fact that we were in isolation so there was a chance for less spread?

Erin Merritt
I think it’s a little of both. I mean, if you have families that are all together, then there’s TB there and it is going to spread, but it’s probably gonna spread even in non-pandemic times. So definitely isolation helped. Also, wearing the masks is going to help much in the way it did for COVID-19.

Dr. Amy Manning-Boğ
Good point.

Erin Merritt
But also people weren’t going to get tested for TB during that time where those numbers would get reported because either they couldn’t get into the hospitals or the hospitals were diverting all the resources to COVID-19. So it’s really a number of factors, I think, that led to that false dip that we saw during the pandemic.

Dr. Amy Manning-Boğ
So in your lab, did you see issues as a consequence of the supply chain difficulties that were faced?

Erin Merritt
We did actually. We had a lot of trouble getting certain media in that are TB specific. One of our speculations was that companies who make media were diverting to other media that was needed for COVID-19. So the specialty medias weren’t getting made. We also had issues with plastics and for a while, even just getting basic pipette tips was a challenge for all of our programs so to include TBQA.

Dr. Amy Manning-Boğ
I understand there was a TB outbreak in Kansas City, Kansas, just a few miles from our Kansas City, Missouri headquarters, and this was in 2021 and 2022. Why don’t we hear more about this disease?

Erin Merritt
Yeah, I think it’s interesting that the CDC recently mentioned this case study in its Morbidity and Mortality Weekly Report. The case involved 13 people. It was six children and seven adults from four different households in our community that were infected with a multi-drug resistant TB. So that means that their particular TB bacteria was resistant to our standard first line antibiotics, rifampin and isoniazid.

Because of this, their treatment needed a wider variety of antibiotics and took longer to resolve than the standard treatment. I think this case highlights that tuberculosis is still affecting people in the country. We just don’t hear much about it. And I think it’s notable that the infection was multidrug resistant, which is why it got some of the coverage. But it’s also worth mentioning that this case only highlights 13 of the 7,882 TB cases that were in the U.S. in 2021.

Dr. Amy Manning-Boğ
In the U.S.

Erin Merritt
Yes. And I think we just don’t often hear about this disease because it affects underserved urban communities in this country. And there’s a tendency to think of TB as a disease from antiquity or the 19th century. And that doesn’t affect people anymore, however TB is very much still present in the world, and the United Nations still lists ending TB by 2030 as one of its top goals.

Dr. Amy Manning-Boğ
Erin, can you tell me what you and your team are doing to contribute to this fight?

Erin Merritt
Our work involves supporting the AIDS Clinical Trial Group, or ACTG. We refer to them as a consortia of labs that are sponsored by NIH to participate in these clinical trials. None of the labs are U.S. based. They’re all international. And it’s largely in countries where there is a high burden of TB. We have a repository that we manage. We can use this to create validation panels for new technologies or new technologies that they’re bringing on to their labs.

We also do training. So we can do training again on those new technologies, but we also can go in and provide training if for instance, the lab is having interpretation issues or issues on any of their quality assessment testing panels, we can come in and provide some supplemental training to help get them on the right track.

Dr. Amy Manning-Boğ
So what are the barriers to reaching that 2030 goal?

Erin Merritt
Unfortunately, geopolitical instability, natural disasters, or a new pandemic could all derail our fight against TB. Consideration of TB and really other infectious diseases as well should always be included in our future crisis preparedness planning. For instance, take the current war in Ukraine, which is a country of high burden drug resistant TB. It highlights a serious challenge posed to the global community as citizens are forced to leave their country to seek asylum elsewhere. This is how transmission begins to move across countries more readily. Learning from COVID-19 responses in a coordinated and global way should be our top priority to attain a more common goal of ending tuberculosis.

It’s a big challenge, but my team and I are still hopeful that will defeat this disease.

National Institutes of Health, NIH-NIAID, DAIDS, Mycobacterium Tuberculosis Quality Assessment Program, Contract: HHSN272201700001C