Webinar: Advancing early TB detection & care

This transcript is the automated English captions in the recordings. The text may not align with the audio and there may be errors the transcript.

Tom Lee: Okay. Hi everyone. My name is Tom Lee. Thank you for joining the Public Health Agency of Canada's Communicable Diseases and Infection Control webinar series. 

We're pleased to have you join us today for today's webinar titled Advancing Early TB Detection and Care: Public Health and Clinical Insights. A short disclaimer, today's webinar includes presentations from those external to the agency which may not reflect the views of the Public Health Agency of Canada. This webinar will be conducted in English. Simultaneous interpretation in French can be accessed through this selecting the interpretation button in the menu at the bottom of your screen. 

Feel free to take a moment to locate that. Following today's webinar, a copy of the presentation deck and a recording as well as a feedback form will be sent to you. Your feedback would be appreciated. A few technical notes. 

Your audio has been muted to reduce noise and video is disabled for this webinar. If you're having any technical problems and need help, you can reach us through the chat function. Please feel free to communicate in either English or French. If you have questions for the presenter, please submit your questions using the Q&A function and we will look to answer them during the pan question and answer period at the end of the webinar. 

Note, you may check send anonymously if you do not want your name attached to the question in the Q&A. Now I will now welcome Dr. Maureen Carew, Director of the Infection Prevention and Surveillance Division at the Public Health Agency of Canada, who will be today’s moderator. 

Maureen Carew: Welcome everyone. 

While we meet today on a virtual platform, I want to acknowledge the lands on which we each find ourselves. From coast to coast to coast, we recognize the ancestral and unceded territories of the Inuit, Métis, and First Nations peoples. I am speaking to you from the traditional and unceded territory of the Algonquin Anishinaabe Peoples in Ottawa. These lands have been home to the Algonquin Nation since time immemorial, and we recognize their enduring presence, stewardship, and cultural contributions. 

Today, as we discuss tuberculosis, I also wanted to acknowledge that Indigenous Peoples in Canada experience disproportionately high incidence of TB due to social inequities that are rooted in colonial policies and recognizing this history calls on us to work toward equitable health solutions and reconciliation in action. 

World TB Day is officially commemorated on March 24, and this year’s WHO theme “Yes! We can end TB: Commit, Invest, Deliver” is a message of hope, taking accountability, and taking action to reach TB elimination both globally and domestically in Canada.  

This year, the Public Health Agency of Canada is excited to share the recently released Government of Canada’s Tuberculosis Response which lays the foundation for the ongoing collaborative work being done with communities, with partners, Indigenous rights-holders towards our shared goals for TB elimination. And we’ll be putting a link to that document in the chat. 

World TB Day is also an opportunity to bring together awareness of TB prevention and care efforts and all the hard work being done to control this disease across this country 24/7. 

Today, we are excited to be joined by Dr. Tiffany Locke and Dr. Ryan Cooper. Dr. Tiffany Locke is a Public Health Physician who works as a Medical Advisor at the Public Health Agency of Canada. She works in the Infectious Disease and Vaccination Programs Branch on tuberculosis, as well as other infectious diseases. Her other areas of interest include risk assessment, global health, Indigenous health, and epidemiology. Today, she will start off our webinar by walking through the public health approaches to screening for TB infection and disease, including some lessons learned and considerations for their use. 

Following Dr Locke’s presentation we’ll be joined by Dr. Ryan Cooper who is an Infectious Diseases Physician with Alberta Health Services, a TB consultant for the Alberta TB Program, and an Associate Professor in the Faculty of Medicine at the University of Alberta. His expertise and interests also extend to HIV, viral hepatitis, and refugee health. Dr. Cooper will be giving a presentation on the clinical diagnosis, treatment, and management of TB infection, a pathway that is increasingly crucial to preventing the development of TB disease.   

Please join me in welcoming both Dr. Locke and Dr. Cooper. 

and I'm going to turn it over to Tiffany to start off the presentations.  

Thank you.  

Tiffany Locke: Thank you, Dr. Carew. 

All right, so today I'll be covering public health approaches to screening for tuberculosis. First of all, we're going to start off with a poll question. I'd like to ask the audience, are you familiar with the definition of asymptomatic TB? And I'll just give people a minute to respond. 

Right. Okay. So, it looks like the majority of people are familiar or have at least heard of it and are unsure of what it is. So I will proceed with the presentation and we will touch on this topic. 

First of all I'm just going to give a quick overview of TB infection versus TB disease. So TB is an airborne infectious disease caused by Mycobacterium tuberculosis. It is now increasingly recognized that it exists on a spectrum. TB infection also known as TBI or formerly known as latent TB does not have symptoms and does not spread from person to person. 

It is treated with antibiotics and is detected using the tuberculin skin test, TST, or interferon gamma release assay, IGRA. It can also sometimes be detected on chest X-ray. TB infection can progress to TB disease at any point anywhere from months to years or even decades later although most commonly progresses within the first 2 years after infection. TB disease is the form of the disease where there are clinical manifestations. 

It can be asymptomatic or symptomatic and it is infectious from person to person. It is treated with antibiotics as well. The detection is done through chest X-ray or other imaging modalities, microbiological samples, or sometimes is based off of clinical presentation. It is pulmonary TB and laryngeal TB that are the infectious forms that can spread from person to person. 

So not all individuals with TB disease present to health services with symptoms or declare that they are sick. The form of TB disease known as asymptomatic TB has more recently been defined by the WHO as a person with TB disease who did not report symptoms suggestive of TB during screening. It can be bacteriologically confirmed or bacteriologically unconfirmed on microbiological testing. Or it may be detected on clinical presentation or imaging. 

Evidence is mounting that suggests it's most likely infectious from person to person. Even in this asymptomatic phase, it can therefore be missed on some prevalence surveys or on screening methods that rely on symptoms. The understanding of asymptomatic TB is an in evolution and including factors such as the most appropriate treatment are still incompletely studied. So for more information on asymptomatic TB, you can refer to the WHO's resources and those will continue to be updated.  

Just a quick overview of the recent epidemiology of TB in Canada and the at risk populations. On the slide you will see here the data from 2023. Nunavut is the territory that has the highest incidence rate in Canada followed by Saskatchewan. 

In terms of TB disease cases that were reported, 79% were born outside of Canada. Among the 21% that were born in Canada, 37% were identified as Inuit, 37% were identified as First Nations, 24% as non-Indigenous born in Canada, and 3% were Metis. In terms of some of the sub populations with higher risk for TB, in 2023, Inuit had a rate of 204.2 per 100,000 people, which is significantly higher than the overall Canadian rate. this was followed by First Nations with 18.5, people born outside of Canada with 15.5. 

Correctional services also had a higher rate than the overall Canadian rate, although this data is a little bit out of date. And the most recent rate was 7.4 per 100,000 per year. Metis and non-Indigenous Canadian born were below the overall Canadian rate at 2.7 and 0.4. Now, I'll touch on an overview of screening approaches currently used in Canada, including contact tracing, communitywide screening, pop-up clinics, modified community screening, or opportunistic screening, and then some population-based universal screening programs. 

Contact tracing is one of the more traditional methods used for identifying contacts of an infectious case of TB and being a close contact of a person with infectious TB disease is one of the biggest risk factors for exposure and development of infection. So again infectious TB refers to TB of the lungs or throat. and one of the main screening approaches is to identify contacts with the highest risk of exposure as well as the highest risk of progression to disease or severe disease. For example, children under the age of five. 

There are general guidelines that recommend the timelines that are ideal for contact tracing. So within 48 hours of diagnosis ideally case notification occurs and within 24 hours the case investigation is initiated ,1 to 3 days for contact tracing interviews, 1 to 7 days to begin screening high priority contacts that's those who are at highest risk of exposure and highest risk of TB disease and then 30 days to complete the screening of all higher risk priority contacts. The next approach is the communitywide screening. So this is a resource intensive approach that is used in certain settings to identify and treat cases of TB disease and to identify and treat as many people as possible with TB infection typically in an outbreak setting or a high incidence setting. 

The decision to implement a communitywide screening is complex and requires factoring in the resources required, the community's investment in undergoing this intensive process. and it is a decision that is made jointly with the affected community. Some of the factors that might favor doing a communitywide screening include an ongoing outbreak that's not being controlled with contact tracing and other traditional methods of identifying cases. An urgent need for case finding. 

For example, if there's a high fatality rate or in communities where there's a high TB incident. In terms of what's required, it's very intensive for logistics coordination planning. it's very important to have community engagement ahead of a communitywide screening. transport and housing for staff, lab equipment, and clinic equipment, the IT infrastructure and computer systems, a multi-disciplinary team of staff, including specialists in healthcare, and outside of healthcare workers, and then a clinic site that doesn't detract from other ongoing health initiatives or community health sites. 

Some recent examples of communitywide screening that occurred in northern communities have highlighted some of the challenges and lessons learned with these approaches. So while they have been shown to help control outbreaks, identify active cases of disease and have high success in treating TB infection, there are a number of challenges and limitations particularly in the north. The remoteness of some of the communities, harsh weather and high costs were limitations. The legacy of colonialism and mistrust of the health care system can limit the uptake of screening. 

And then strained resources to staff the clinics as well as continue health care initiatives within the community. and challenges with accessing lab and x-ray can also be a challenge. In terms of some of the lessons learned that have been shared by some of these communities, it has been found to be essential to build trust with community leaders and the community ahead of the communitywide screening including health promotion initiatives and culturally appropriate and language appropriate initiatives to inform people of the communitywide screening happening. Tt's been critical to have self-determined and community-led solutions. 

The use of TB champions or community workers who are non-healthcare workers was found to be key to the success of these initiatives. These are people who are not traditionally trained in healthcare work but play an essential role in these screenings anywhere from social supports to helping with medication taking and as well. Conducting screening locally was highly valued by participants in the communitywide screening and incentives were helpful to have a high reach within the community. Typically these screenings aim to target around 80% of the community although that's variable and follow up and ongoing efforts are required. 

It's essential to have trained staff who are in the community and are able to continue to follow up with TB. It has also been recognized that some high incidence communities may require future communitywide screenings or other screening initiatives in years later. So given the limitations of the communitywide screenings and that they are not always feasible from a resource and logistics perspectives, other modified less resource intensive approaches have been considered. So these include pop-up clinics or modified screening. 

For example, clinics that do sputum collection only or chest X-ray only or a combination of sputum and chest X-ray have been trialed. Some smaller scale clinics on a more regular basis. For example, some initiatives in Alaska have gone into clinic or gone into communities and done smaller scale communitywide screens where they are there for typically 2 to three days and only reach a smaller proportion of the population. and then these are also targeted to communities who have the highest needs. 

There are also some targeted screening approaches or sometimes referred to as pop-up clinics. For example, having a schoolwide screening for certain age groups in high incidence communities or having a pop-up clinic in a high-risk setting like at a shelter. Opportunistic screening refers to screening offered to those attending a health clinic for other reasons. For example, in a high incidence setting, you may offer TB screening when people present for health care for other reasons. 

Some of the key takeaways were that trust and relationship building was really key to success of these initiatives. A number of these modified or less intensive approaches are still under study and still trying to look at the optimal approach. There were some approaches that looked at longer term strategies that were led by the community and did find that those were able to reduce the rates of TB along or similarly to what were found with more intensive approaches that they may just take longer to achieve those decreases in the TB rates and repeat screening and ongoing efforts seem to be required. I'll now touch on a couple of the population based or universal screening programs. 

So, migrants to Canada are one of the groups that receive universal screening and this is done through the immigration medical exam or IME. So, this is a mandatory medical exam that is required typically before entry to Canada. Although there are some select groups where this is done after entry for example asylum claimants in which case the IME is done within the first 30 days of arrival. The IME screens for a number of health conditions including tuberculosis. 

Currently the IME requires a chest X-ray for anyone over the age of 11 years along with a symptom screen and a physical exam. Children under the age of 11 have a chest X-ray if they had a past TB infection or in a high-risk group. This screening approach screens primarily for TB disease. However, it does include TB infection screening for high-risk groups. 

So that's done either through IGRA or TST. And the high-risk groups include close contacts of a TB case, those who have HIV, people with recent head or neck cancer, severe kidney disease, or solid organ or bone marrow transplants who are on immune suppressants. So some of the lessons learned from this are that the TB screening or the lack of TBI screening for some groups does leave a population at risk to develop TB disease later. Some studies have shown that universal screening for TB infection is not necessarily cost effective. 

So the priority should really be on identifying those who are at increased risk for developing TB disease and coming from a higher incident setting. There remains an ongoing need for better data sharing and needs to be some consideration of the risk of re-exposure as people may return to visit countries from where they may have come from. in terms of the approaches in congregate living settings, the general approach is to reserve routine screening for TBI for those who are at higher risk. So in terms of long-term care facility and treatment programs, universal TBI testing is discouraged. 

Although there are still some guidelines that exist recommending TST at admission for those under the age of 60 years and even some guidelines recommending universal screening through chest X-ray and symptom screening. In terms of correctional facilities, this is one of a one of the higher risk congregate settings. in the provincial systems, there are different screening recommendations based on the sentence whether it's less than two years or greater than two years. So typically less than two years TST is recommended only for individuals with high risk. 

Whereas sentences over two years TST screening is recommended for all. In the federal system, symptom screening is used and a two-step TST. So there are some inconsistent practices and guidelines around the use of screening in these settings but generally speaking the recommendation is to reserve TBI screening for those who are at highest risk or who are at an ongoing risk of exposure in a high-risk setting. In terms of employment screening, screening for people living with HIV and other populations, again the recommendation is to really prioritize those who are at highest risk of exposure and ongoing exposure. 

And prioritize screening for people who have underlying medical conditions like HIV that will increase their risk of developing TB disease. In the health care worker setting, healthcare workers are recommended to have baseline TB screening. However it's recommended against routine annual TB testing for all health care workers and rather to prioritize those at highest risk for example those who participate in aerosol generating procedures. For people who are at higher risk of developing TB like people living with HIV it or people who inject drugs it's recommended to have regular screening for TB using TST or IGRA or chest X-ray as appropriate. 

And people with a high risk of ongoing exposure, for example, staff working corrections facilities, serial testing or repeat testing is recommended to be done preferentially with TST. Again, there exists some challenges around inconsistent practices, some issues with IGRA not being covered in all jurisdictions. And there continue to be some use of tests like TST which is not recommended serially or annually for people who are of low risk. So now that I've covered some of the general screening approaches used in Canada and screening recommendations, we'll briefly touch on the recommendations for screening TBI on an individual assessment level. 

So we recommend that everyone remembers to consider TB when working in a high-risk setting or working with individuals who have high risk for TB infection. Generally the approach is to screen those who are most likely to experience favorable risk benefit ratio. That is to say screen those where the risk of progressing to TB disease outweighs the risk of TBI treatment. Consider whether you would think about treating the person if they were positive for TBI. 

And based on the evidence there are a number of risk factors that you can consider whether a person infected with TBI is at higher risk for developing TB disease. Some of the highest risk factors included people living with HIV with a relative risk in the range of 50 to 100. Those who are a recent contact of an infectious case of TB had a relative risk of 50. And then some of the other risk factors included underlying medical conditions that affect the immune response like solid organ transplant recipients. 

People with end stage renal disease and other hematological cancers and other cancers in general as well as diabetes, corticosteroid use. And then of course people who had fibronodular scarring on imaging had a higher risk of progressing. So when you're considering whether to screen someone, consider their risk of progressing to TB disease based on some of these risk factors. In terms of who should be tested for TBI, so the top box here, you can see some of the recommendations that we've discussed in the overall screening recommendations. 

However, you should also consider on an individual level those who are at risk of progression to TB disease. So those with medical risk, anything that impacts the immune response. Ideally, if someone is going to be going on an immunosuppressing medication, wherever possible, things like TNF inhibitors and other biologics, it's ideal to test for TBI prior to starting those therapies and treating the TBI if they are positive before they start on something that will affect their immune response. So just a reminder test for TBI if you plan to treat for it. 

And then lastly, this is just an example of a recent tool that can be used to help guide your decision. So this is a screening or a tool that will provide an estimate of the risk of TB disease at 2 years and 5 years for people coming to Canada from a higher risk setting. So you can input individual risk factors and it gives an estimate of the risk and that can be considered along with the individual risk factors to help guide whether you would consider testing and then treating for TBI. So for more information on TB you can go to canada.ca/tuberculosis. 

And I will now hand it over to Dr. Cooper who will walk us through the treatment for TB infection.  

Ryan Cooper: Right. Thanks. 

I hope people can see my slides. I think they're being shared. Thanks for the introduction and also thank you for having me here today. I also appreciate PHAC for hosting this and also helping to ensure my slides are bilingual which I'm grateful for. 

I'm speaking to you from Treaty 6. I'm going to focus on TB preventative therapy. So my objectives today is well mostly I want to talk to you guys about where the concept of TB preventive therapy TPT where that how that originated. Then we'll spend five minutes in the middle teaching you everything I do in my day-to-day job. 

Once you've mastered that then we'll talk about where we might take TB preventive therapy going forward. This is an obligatory poll question, and I do mean obligatory. You must all answer. Have you ever used the TST-in-3D web-based calculator in managing TB infection? 

Yes or no?  

And while you contemplate or while you listen to my talk today, I'd like you to maybe reflect on how you use this tool and what value it provides to you. And perhaps we could talk about that in the discussion. It looks like most people have not and so I'm grateful that in addition to my objectives stated earlier that I might also be able to to share new knowledge with lots of people. 

So that's great.  

Okay so TB is a big problem globally. It's the leading infectious disease killer globally. We think that about two billion people in the world are infected with TB in a latent fashion or inactive fashion and that's if we use a positive tuberculin skin test or a positive IGRA as a definition for that. 

Of these two billion only a small fraction will ever progress to active disease but because this reservoir if you will is so large every year we see about 11 million people develop TB disease and fall sick and that results in about 1.25 or resulted in more than a million deaths last year. When we talk about TB preventive therapy, what we're talking about is trying to address this this group of people with latent infection, trying to treat them before they develop TB disease. Where did this concept arise from? Well, it dates back probably to the 1950s. 

In 1952, INH and found to be extremely effective for the treatment of TB disease. It helped bring people back to health and restore health and it and it was cheap and widely available and well tolerated. Lots of people probably thought about using INH as preventative therapy. But Dr. Edith Lincoln, a pediatrician from New York City was the is sort of the most famous and had published on her experience. She'd observed that in children with recent TB infection, if they received a TB treatment regimen that contained INH, they did not progress to severe disease.  

So she hypothesized that maybe INH could be given early to prevent people developing disease. This hypothesis was then tested by Sheila Ferebee who is an OG TB giant a woman who was an operational lead at the US public health service and she conducted this massive placebo controlled randomized control trial of INH in over 25,000 contacts of people with TB and she found a 60% protection of TB in people who received their INH prescription. 

Her findings.  

She was the first to demonstrate the effectiveness of TB preventative therapy. But her findings were extended and confirmed by Dr. Comstock out of Baltimore, another giant in the history of TB. 

Instead of looking at contacts, Dr. Comstock went to communities with high incidence of TBT and did mass testing and mass preventative therapy in these communities. And he also demonstrated 60% protection for individuals. And we're going to touch on this later, but he also demonstrated that in communities where TB preventive therapy was introduced that the rates in those communities started to fall in a sustainable fashion and it's felt that TB preventive therapy contributed to the fall of TB in these communities. 

So we're going to come back to that later, but for now it's enough to know that there was individual protection from the INH. And then over the ensuing four decades, multiple randomized control trials of INH preventive therapy were conducted in a variety of different types of settings and people including contacts, immunosuppressed individuals, people with remote infection. We learned lots from those many TB preventative therapy studies. Perhaps the most important and want to celebrate on in advance of world TB day is that INH prevents TB. 

and that's amazing but one thing we learned from these studies is that the benefit the direct benefit is occurs only to those who are TB test reactors so this set up that paradigm that we use now where we first have to find people who at risk of TB test them and then offer treatment we don't just that test everyone or sorry we don't just treat everyone in the community we have to use the tuberculin skin test or the IGRA to guide that treatment and that that paradigm is still around today and that adds logistical challenges that we have to surmount. The other thing we learned from these TB prevention trials is that completion of treatment matters. We have to support people on treatment to finish treatment to get the optimal benefit. In the intention to treat analysis in these RCTs, we found a 60% reduction in benefit. 

But in but if you limited the analysis to those who completed the therapy, protection was more than 90%. So that's an important concept. And then we also learned that TB therapy was well tolerated. So this was an important public health tool. 

And I'm going to tell you a story from 1968. I wasn't around to this time, but of course, but I learned about the story from these references, which I quote down there. but I gather this was a big deal if you were around to this time, but in 1968 there was an outbreak of TB on the Capitol in Washington DC, and public health said, "Well, we have a new tool, a TB preventative therapy. We're on it." and TB public health took center stage and they provided they did TST testing on essentially everyone who worked at the capital and in the associated buildings regardless of whether they had direct contact with the cases and then anyone who reacted they gave TB preventive therapy as per the contemporary guidance. 

But unfortunately what they found is that unlike those original clinical trials they noticed that there was a pretty significant rate of INH hepatotoxicity or liver injury from the drug about 1% of the recipients of TB preventive therapy developed jaundice, some had to be hospitalized and some people died and this was a shock and was unfortunate because I think it sowed some skepticism of public health and it reduced the enthusiasm for TB preventive therapy at this time here in the 70s. But I guess in hopes of rehabilitating the reputation of TB preventative therapy another giant in the field of TB prevention  

Dr. Menzies developed a tool called the TST-in-3D. This is an online risk calculator. 

You can find it at the website below. And this tool developed in the early 2000s was based on all data from all of those clinical trials I described 70,000 people and using that data allowed clinicians to enter in data about their patient some of the characteristics that they're dealing with and that would help and then it would print out for you that clinician the likelihood of your patient benefiting from TB preventive therapy and the risk of certain adverse effects. So this tool would help you navigate that that you know that that minefield of trying to get benefit to your patient without hurting them.  

But Dr. Menzies was not content to navigate that risk or limit that risk but rather wanted to try and change things so that we had safer therapy. And so in the early 21st century large he led a large multi-site randomized control trial at multiple sites across Canada and globally testing a new drug Rifampin which is known to be effective against TB but also less liver toxic than INH. He said let's try four months of Rifampin versus a standard 9 months and found that it was indeed better tolerated, safer and just as effective. Around the same time, the US CDC ran performed a similar trial using a slightly different Rifampin called Rifapentine, which has a longer half-life and allows it to be administered weekly rather than daily. 

And they showed that 3 months of 12 or 12 weekly doses of INH and Rifapentine was just as effective as nine months of INH at preventing TB and people at risk of TB reactivation and that it was better tolerated and let and safer. So these landmark trials inform the current TB standards on world TB day in 2022 the latest edition of the TB standards were released and they indicate that the preferred regimens for us clinicians is are these Rifampin regimens. These are what our go-to is in the clinic. 

I should point out though that INH is still kicking around. Sometimes people cannot are not eligible for Rifapentine. Rifapentine can interact with other medications particularly some antiretroviral therapy, opiate agonist therapy, blood pressure medication, anti-coagulation. And so we are still using in some patients where drug interactions cannot be managed, we still use INH more than 75 years old and it's still joining the fight against TB.  

We should all be so lucky. So, how do we administer these drugs safely in 2025? Well, I was recently at the TB conference in Vancouver in 2025 where I got to see a presentation with Dr. Bastos. She's currently in Manitoba, but I've been in Montreal for her work in updating the TST-in-3D calculator to become the TST-in-4D calculator.  

And the fourth dimension is really the patient. This tool allows not only the provider to navigate the risks and benefits of TB preventative therapy but also helps center the person with TB infection in that decision and helps them get involved in seeing the risks and benefits. 

So just to take you through this tool you'll see on the one side that you input your personal or your patients information. So age, the reaction of their test results, TST, and/or IGRA there's much more comprehensive lists of TB risk factors, including recent exposure, habits, immunosuppression, and then and I just click TNF inhibitors here just for funsies.  

And then in the middle, you can see what the risk what your or your person or your patient's risk of TB is if nothing is done over the next 20 years. And then it's presented in this visually I guess easy to read format where you get these sad faces. 

It's not just your risk of TB, but it also gives you information about your risk of TB death and long-term disability from TB. And then you can also on the third section enter in the treatment that you want to give. And then it flips these faces to green. So that's kind of fun. 

There's no reason this can't be fun, you guys. Treating TB. You can see how the red faces turn to green, but this also gives you and your patient some information about the risk of side effects based on your age or other risk factors for drug side effects. And then you can print out the information and involve the patient in the decision. 

So I think this is really exciting tool even though part of me worries that AI is going to take my job.  hey Siri, can you please take my job and I guess I'll then retire. So, I wanted to move a little bit on what in looking at it's funny when I said, "Hey Siri, my own phone started talking to me." we know that TB preventive therapy is very effective for individuals at risk of TB. There's no doubt about that. 

I'm an ID physician and I don't think I don't have any other treatment I give people that is as well studied as TB preventive therapy that is so clearly beneficial. So that check that works. It's also pretty self-evident that using TB preventative therapy for contacts or in the setting of an outbreak is good for public health. It's good for the community as well. 

There's no doubt about that. But I think a remaining question, one that I think the TB community is working on right now is whether TB preventive therapy can be used as a tool for TB elimination by screening much more broadly just as Dr. Locke was describing. We do have observational studies that show that such widescale TPT when combined with active case finding can reduce TB incidents. 

The first time this was shown was in that George Comstock study in Alaska that I alluded to earlier in this presentation. In those remote communities, largely Native American communities, large-scale TBT and active case finding did result in sustainable reduction in TB incidents in those communities. And I really draw your attention to this study in the Lancet public health by Menzies and colleagues sort of describing the impact of TB preventive therapy. This has also been shown in a few Pacific island nations where the entire nation was screened for active TB and latent TB infection and treatment was provided and it seemed to result in reductions in the community incidents. 

One thing we learned from those studies is this is a massive undertaking. It's massive for the program. It's multi-year intervention often requires lots of providers, lots of resources and a big commitment but it's also a massive undertaking for the community. For this to be effective, the community has needs to be involved. 

People with living with TB also it's a massive undertaking for them. Sorry, people living with TB infection they have to they're the ones who are going to take the burden of TB preventative therapy. And so whether this is going to be useful, I think we're still working on that. I know that there's currently a randomized control trial called the ACT 5 study enrolling in Vietnam that's going to test whether this these observational studies whether the hypothesis they've generated is true whether large-scale TPT in communities when provided along with active case finding will have an impact and what impact and at what cost. 

Another question that comes up all the time and I actually saw it in the chat box during this talk was whether we should be offering TB preventative therapy, TB test, TB infection testing and treatment to people who are born or spent significant time in highly TB endemic countries. So for example, migrants and whether this might help eliminate TB in Canada. I draw your attention to some more Canadian studies. Jonathan Campbell currently in McGill and Dr Kevin Schwarzman. 

Dr. Jonathan Campbell, Dr. Kevin Schwarzman have done a lot of mathematical modeling around and continue to do this and things we've learned from that mathematical modeling is that this is going to be a very challenging exercise of scale up. If we are going to try and use TPT to end TB or eliminate TB in Canada and we are we're going to have to scale up TB a lot and we're going to have to do it safely. 

And so to do that, I don't think I'm not sure we're going to be able to do that with our current tools. I think we're going to need some improvements and I've listed some ideas here. One, I think we have to be better at identifying people who will actually benefit. It's true. 

If you have a positive skin test or a positive IGRA, you're at risk of TB and you will benefit from TB preventive therapy for the most part.  However, most people with a positive test never get TB. Most people will live their whole life without getting TB even if they have a positive TST and IGRA. So, we need a tool that can better figure out which of those individuals will go on, whether that's a new test or whether that's risk calculators as Dr. Locke alluded to, for example, the TB migrate tool. We also need to monitor our cascade of care. We know that we need to test some identify someone as eligible for testing. We need to test them. 

We need to get the test result. We need to get them connected with the TB provider, start on treatment, and then finish treatment. That's a whole cascade of care. And we can lose people at each of those steps if we're not supporting them and don't have a good system in place. 

And so the ACT 4 study also involving multiple Canadian centers looked at how the impact of monitoring the cascade of care, troubleshooting the gaps that are identified, can result in better uptake of TB preventive therapy. And I want to draw your attention to Dr. Nancy Bedingfeld’s study out of Calgary where she showed that monitoring the cascade of care, developing interventions, can improve the reach of TPT. We also know from other studies that paying people to take TB preventive therapy works or at least supporting their cost, not making them pay. 

We recall that, you know, that people do benefit from TB preventive therapy. But if we're going to do mass screening, we're going to end up finding people where the risk benefit ratio is narrow and those people will be taking preventive therapy for the benefit of their community. And so they deserve support at the very least and possibly cash incentives. I think we're probably also going to need shorter, simpler, and safer drugs. 

We're in luck.  there are new drugs coming down the pipeline. I'm from Alberta where we think pipelines are mostly about oil, but they also sometimes are about drugs. We do have a active TB drug pipeline and several drugs looking at TB preventative therapy. 

For example, a one-month regimen containing daily INH and Rifapentine is being currently studied. A six-week regimen of Rifapentine. We're conducting a trial at multiple sites in Canada. Canada at multiple sites and globally is studying double dose Rifampin given for only two months. 

So again shorter the safety data is already out. This proves to be safe. We're now waiting for the ongoing study to see if it'll be effective. There's a new drug for TB called Bedaquiline with a very long half-life and people are trying to study whether it'll work for one month. 

If the USAID funding is not renewed, I worry this study will be at risk. But and then I've heard rumors of pre-clinical data of using a drug depo. Sort of like I guess depo birth control or depo opiate agonist therapy where you give one shot and that would last long enough to prevent therapy, but that is in the pre-clinical phases just yet. Okay. 

So, by way of epilogue and wrapping up, I just kind of wanted to change gear from the biomedical and remind us that TB is a social disease and there are other things besides medicine we can do to prevent TB. This is a new study published just under two years ago in Lancet called the ration study. It was a large randomized control trial in India in a state in India where there are high rates of combined TB and malnourishment. And they had a large they don't do a lot of TPT in this region. 

They don't have the ability to provide that. But they had they randomized 9,000 household contacts where some the one half would receive usual care and the other half would get food baskets every day of about 700 calories. And they found that that provision of food resulted in a 50% reduction in TB amongst the contacts. Now although I titled this is new, it's not new. 

This is old news. We know that the social determinants of health are important for preventing TB. And I just want to draw your attention to a famous study back in 1918 conducted before we had any medications. This is a TB rehabilitation village in Papworth, England. 

And what happened here is a public health officer, Sir Varrier-Jones, Dr. Varrier-Jones. I guess he must have been independently wealthy because he set up a village in England where people with TB and their families could live and he ensured that they had employment if they're able and provided adequate food and housing for the people with TB and their families. And then he monitored rates of TB disease in contacts in those who lived in the village and those who couldn't come to the village or weren't in the village. 

And he showed it a more than 90% reduction in TB rates. And so I guess there's lots of ways that we can eliminate TB and TB preventative therapy. That's a big part of what I do until Siri takes over and takes my job. And that's really important. 

That's what we've talked about today. Giving INH preventive or giving some type of biomedical preventive therapy to try and address this large reservoir of people infected with TB to prevent them from developing disease. But we have other tools that we have to use in combination like case finding people who are sick with TB and getting them treated promptly, ensuring that we have adequate housing as well as nutrition.  

And with that, I'll just say thank you so much for your attention and for letting me come chat today and remind you that World TB Day is on March 24th. 

The theme this year is yes, we can end TB. And so we'll celebrate not TB disease, but the people fighting it and the people who survived it and the people who take preventative therapy.  

Thank you so much.  

Maureen: Thanks very much Dr. Locke and Dr. Cooper. Very informative presentations and it was particularly interesting to hear about some of the tools that have been developed as well to help with decision-making for clinicians around TB infection and also even with their patients. And also thanks Ryan for that reminder about the fact that you know social determinants of health are such a core part of this disease and some of the studies that have been done on nutrition like the ration studies. 

So that's always really helpful to bring it back to some of the nonclinical pieces here in terms of preventing TB. So thanks those were really helpful presentations. So, we're going to move into the question and answer part of this webinar. And just a reminder for those to please put your questions in the Q&A. 

And we'll try to get through as many as we can in the next 10 minutes or so.  

So, the first question I'm going to just read it out, which is from Raza. Perhaps Tiffany might want to take this one, but so the question is what strategies would be recommended for community-based TB screening in a way that reduce the risk of stigma and ensure a supportive environment for those being screened.  

Tiffany: Thank you. 

That's a great question. So there are a number of strategies that have been reported to have an effect on reducing stigma. In a number of the communitywide screenings that have taken place, it was found that having community engagement and health promotion or education programs ahead of the screening initiatives really did reduce the stigma and really made people open up to engaging in screening. So hiring health promoters who spoke the language and were familiar with the culture, providing culturally appropriate information sessions and going to places where they were well received like in important places in the community. 

So in some places that was the grocery store in the community. Sometimes it was at a community feast or at a community center, a pop-up health promotion booth at a community event. And as well hiring TB champions. So these are people who are from the community, not necessarily healthcare workers, but they can do some of this health promotion work. 

They have a good relationship with people in the community and really help to address those fears around stigma. And I think a final approach that's been used in other places as well is integrating TB screening with other health care so that it wasn't so identifying for people showing up for example to a TB clinic, you didn't know why they were going there. so it's not always possible like if you're doing a communitywide screen. 

which is why the engagement beforehand is really important. But in other settings it might be helpful to integrate it with other types of healthcare.  

Maureen: All right. That's great answer. 

Thanks Tiffany. this one I think Ryan maybe if you want to respond to it first but Tiffany's welcome to join in as well. so are there potential risks of administering Rifampin to TB patients who have cannabis use particularly in terms of mental health issues. So some of the side effects dizziness, confusion, headache and treatment adherence. 

So anything in particular around treatment especially for these types of patients who may have substance use and cannabis in particular.  

Ryan: You know, that's a great question and I cannot recall to mind right now a study that would specifically address that question. My own experience, personal experience is that there doesn't seem to be an interaction there. And so I don't frankly I hope nobody's listening, but I don't discourage cannabis use if they're using TB preventative therapy. 

Maybe their other doctors might care about that, but I don't. But one thing I do emphasize is that Rifampin and other Rifapentine can interact with opiate agonist therapy such as methadone and buprenorphine and so that that can present a challenge.  

Maureen: Great.   

So the next question's on BCG vaccine and its efficacy. 

I can see if Tiffany wants to take this one first, but again, Ryan, you're welcome to jump in as well. So we know that BCG is cost effective. Do you think that those who are eligible should receive BCG vaccine in infancy? Can you elaborate on the overview of BCG vaccine as a preventative intervention? 

Tiffany: That's a great question. So BCG vaccine is a bit of an older vaccine. It doesn't have as high of an efficacy against preventing TB infection as we would like. So it's been found to be most effective to prevent severe TB disease if it's given in infancy. 

So it prevents things like TB  meningitis. So it is generally reserved for high-risk communities in Canada. So it is based on incidence and that's actually been reviewed more recently. So it was scaled back a while ago where only really reserved for high incidence communities. 

But there's now been consideration with outbreaks that seem to continue to occur of a bit more universal use in some Indigenous communities for example where there's a higher risk of infection. It can be used if an infant were to be traveling for a more prolonged period. For example, if parents are visiting maybe friends and relatives in a higher incidence setting, then they may consider getting vaccinated for their infant. but it's typically reserved for infants. 

So those would be the main considerations.  

Maureen: All right, great. There's another question here. I'll ask Ryan to to take this one, but it is about whether the size of the reaction to the tuberculin skin test matters. 

Ryan: Yeah, that that's a great question. And thanks for that. I have to say when I trained, I was taught that the size did not matter. That we would it was an on off phenomenon but I think cohort data particularly in migrants some data out of Vancouver’s cohort have shown that the size of the TST reaction and the QuantiFERON may convey an elevated risk of subsequent TB down the road. 

So I guess like joining the football team size might matter with TST and IGRA when it comes to preventing TB. There is a useful TB risk calculator that I did not show in my presentation in the interest of time but it is called the TB Periskope and periscope is spelled weird as I recall but it it's a study of a risk calculator which takes into size account the size of the tuberculin skin test reaction and the and the strength of the IGRA response in calculating the subsequent downstream risk of TB.  

So I guess watch this space.  

Maureen: Okay. Some questions I'm seeing on portable chest X-rays and screening. So, I maybe I'll just put that up to whoever wanted to answer it. But, have they been found to be useful?  In particular, I guess in communitywide screenings, but maybe I'll just open it up to either of you to jump in. 

Tiffany: I'll take a first go in. Ryan's welcome to add. So globally there's been a lot of increased use in portable X-rays I would say in screening approaches. So with technological advances there are these new ultra portable machines that can almost fit in a backpack. 

So they've they're used a lot in high incidence countries and they are they have software that can be used with them that uses AI. And it does tend to be used more in high incidence low health resource settings with that AI. In higher incidence or higher income lower incidence countries like Canada and some other countries that are similar that AI software is used less because we have pretty good access to remote radiology. But it does seem like they are able to produce quite good quality films. 

It just with the recognition that you do need someone who's trained and able to get those good images so that they're useful. But yes, they they seem to be developing that technology and I know it's being used in some remote communities in Canada, so it's pretty exciting.  

Maureen: Okay. we might have time for like two more quick questions. 

This one perhaps Ryan just wondering there was a question about in particular some of the pros and cons for TBI treatment the weekly 3HP. So is there things that clinicians can look at in terms of the Rifampin versus 3HP and that they should be thinking about for patients?  

Ryan: Yeah. No, that's a very good question and one we spend deliberating. 

So Rifapentine is not actually licensed in Canada. However, we can get access through a specialized program through Health Canada for prevention of TB. So I guess it is essentially available to people. But it's access to special the TB standards from 2022 do recommend that 3HP the 12 weekly doses be given with direct subserve therapy. 

The clinical trial used 3HP as direct observed therapy whereas Rifampin was used as self- administered therapy and that in Alberta that's how we tend to use 3HP is we use it with DOT so we I we tend to favor the 3HP in people who we feel and who've told us that they need support to complete their TB preventative therapy and where the nursing visit once a week and that sort of fulsome support will be useful.  For some people the need for DOT can paradoxically be bit of a barrier to care. They they don't want to knock off work to have to take their preventive therapy and so they might prefer just to take the meds home with them with Rifampin. The side effect profile of the drugs is slightly different as well. 

There is a rare but noticed hypersensitivity reaction with rifapentine and that's another reason we administer DOT is because you need to be somewhat vigilant for that reaction and stop the drug should it occur.  

Maureen: Okay. Well, we're right at 2:00. So I think we'll wrap up today's webinar. 

I did really want to thank our speakers again Dr. Cooper and Dr. Locke for sharing your expertise and your insights and your presentations and the responses during the Q&A have been really helpful in deepening our understanding about screening approaches for TB. Also just wanted to thank all those who attended today. 

We had a great turnout. So glad to see so many people interested in this subject. I think it speaks to the importance of it across all spectrum of public health, clinical and community efforts towards TB elimination. So, thanks everyone for joining us today. 

And hopefully you'll be able to join some of the upcoming activities for World TB Day for March 24th. But thanks, thanks again to everyone for joining.