Transcript for:
Understanding Mycobacterium Tuberculosis

This is the first of a series of videos I'm going to do on Mycobacterium tuberculosis. The Mycobacterium themselves, tuberculosis aside, are a huge group of organisms. And particularly with tuberculosis, the thing you need to understand about them is that these are complex disorders that can be seen on a spectrum. And really, the patients...

own immune response is so key to understanding basically the course of infection that a patient will have, diagnosing it, and what responses you would expect to see when trying to diagnose it. So I'm going to start basically just talking about the organism itself, and then in future videos, I'll talk about the diseases, I'll talk about the diagnosis, and then we'll have a separate video for the non-tuberculosis mycobacterium which would include things like mycobacterium leprae or leprosy and um mac so first off mycobacterium tuberculosis um i think just personally tuberculosis has to be the most feared organism of poets a lot of people have been diagnosed with mycobacterium historically and if you were a poet or a writer tb seems to have been a big problem Jean Mollier, John Keats, Anton Chekhov, Kafka, Emily Bronte, and her less-known sister, Anne Bronte, both died from tuberculosis. The third writing Bronte sister of five, Charlotte, actually died of epidemic typhus, which we learned about in a different case.

Eleanor Roosevelt, she died of TB. George Orwell. And most famously, and very seasonally appropriate for when we teach this, Edgar Allan Poe's wife died of tuberculosis, although at the time they called it consumption.

Just before her death, he published The Raven, and following her death, he was really inspired, I guess, by kind of what happened to him, because much of his work then tended to focus on the death of a beautiful woman and loss of beautiful women, including Virginia. who incidentally was 13 years younger and his cousin in addition to being his wife. So tuberculosis, not only an opportunity for me to provide you a history lesson, which you know I love to do, but also a significant global health concern in the past and remains to be in the present. It is a huge cause of disease throughout the world, and it has a lot of areas of drug resistance or multi-drug resistance. that are actually making it really difficult to control and treat.

And we also have patient populations that have increased susceptibility and increased disease. And particularly, tuberculosis is a huge concern for the HIV community, but it is also a concern for people who are older, people who are younger, or anyone with any sort of cell-mediated immunocompromised state. All right, so how do we distinguish Mycobacteria tuberculosis from other organisms?

What makes it different than strep pneumoniae or E. coli? So these bullet points kind of summarize the nuts and bolts of what makes up Mycobacterium.

If you look at them under a microscope, they have a distinctive slender curved kind of shape. And I'm actually going to draw one here, kind of like this. And they wouldn't be purple like this.

Purple would tend to indicate that we were looking at a gram negative or sorry a gram positive organism and these guys are not gram positive they actually have kind of the inability to be gram stained if you do you'll see what's known as ghost cells so basically like the shape where a cell should be but isn't and that's because they have kind of spotty uptake in some of the mycobacterium with like of a slight beaded appearance but most will just resist the gram stain altogether. The reason for this is that the cell wall is very unique and it has high content of mycolic acid. And that's kind of what makes it difficult to stain.

So it resists acid removal though, and that's why these organisms are referred to as acid fasts. So we use acid-based stains to actually stain these guys. So So any of the acid fast means that if you coat the stain in acid, some stains will wash out, but others will stay because the acid actually locks it into the cell membrane.

These are extremely, extremely, extremely fastidious organisms with very complex media requirements. They will not grow on blood auger. or chocolate auger. The main ones they grow on, and I don't think I have them listed here, are Lowenstein Jensen, and I know that that's in your course notes, and then Middlebrook, that's the other one. Those are kind of their main augers that we look at if we're trying to grow it in culture.

Both of them are egg-based or have albumin in them, and this is important because even on these... TB conducive media, it takes a really long time, two to six weeks to produce growth. So that means that culture can actually be a really difficult way to try to detect this pathogen. So during that six weeks, you're trying to grow it out and see if the patient actually has TB.

They are probably shedding TB via aerosols with all of the people they interact with. So it's a very long... duration for patients to spread. They are strictly aerobic organisms, so it makes sense. They require oxygen.

They like to hang out in the lung. And that makes sense intuitively because most of the time we find TB in the lung, it isn't the only place we can find them. It can actually grow in almost any body site, which I'll discuss a little bit later.

Most of what I have said here is true for all of the bacteria, not just TB, but avium, consace, fortuitum. Really, the only exception is M. leprae.

M. leprae is one of only two organisms in the entirety of medical microbiology that cannot be grown in culture, not with host cells, not in culture. You cannot isolate it in culture. The other one is actually syphilis or Treponema pallidum, which is the causative organism of syphilis. Neither M.

leprae nor T. pallidum can be grown in culture. So if I ask you, what media you would use to grow m lepre it's a trick question okay so how do we classify the micro the mycobacterium um there are about 70 different species of mycobacterium so we have a really simplified classification of mycobacterial species that we're going to work through over the course of you know the next several videos and i'll recap it again in other videos um so TB itself, Mycobacterium tuberculosis, is not actually a single organism.

It is a complex of organisms. And I've listed some of the common ones here. So like M.

bovis, M. kineti, M. microti, M. africanum, and then M. tuberculosis.

These are found kind of all over the place. Of note, M. bovis is largely associated with cattle. In Australia, New Zealand, if more than about five percent of the herd shows up positive for M.

bovis, it can lead to the entire herd being sacrificed because it's a highly infectious disease in cattle. And if humans ingest unpasteurized milk of infected cattle, it can lead to human gastrointestinal disease. Thankfully, this is not really common, and the most common organism is still Mycobacterium tuberculosis sensu stricto, and that's what we're largely going to deal with.

There are other mycobacterium that are referred to as mycobacterium other than tuberculosis or MOT. Another active acronym you might hear is non-tuberculoid mycobacterium or NTM. And those are broken down using something known as the Runyon classification, which basically just asks when you grow it in culture, how long does it take to grow and does it produce a color? And we're going to go into that in a separate video. But for now, we just need to ask one simple question.

Can the organism be cultured? If the answer is yes, the next thing you ask is, is it TB? If it is Mycobacterium tuberculosis sensu stricto or any of its closely related friends, then the answer is MTB complex. If the answer is no, it's one of these guys. If all the way up here, when I asked you, can the organism be cultured, you said no, it's M.

leprae. Okay, so we are largely going to talk mainly about M. tuberculosis as this is the prototypical disease we are dealing with. And then we'll extend from there. It is a huge cause of disease worldwide, second only to HIV.

All of you have heard about TB. Africa actually has the highest incidence of disease. However, the disease rate in Asia is actually a little bit higher because the population density in places like China and India. No big surprise there because China and India each have populations in the billions. So it kind of makes sense that we actually are seeing like more density there.

But currently, it infects about a third of the world's population. That is huge. third of the world in some way shape or form has TB and in the time we've been sitting here a new infection with TB has occurred every single second.

There's eight million new cases per year that we know of and over two million deaths per year. I mentioned earlier the huge list of famous people that have died with TB but it's not just historical it's happening now. Now, what about the U.S.?

We've had good control in the U.S. due to good public health initiatives. And you'll hear from your pharmacology directors and your case directors that we do have good drugs that help us combat TB. So that's good. That's really helped.

So from the 1950s to the 1980s, we enjoyed a steady decrease in the amount of cases reported each year. However, in about the early 1980s, we started to see a significant increase. And this was basically due to the HIV AIDS epidemic. When we had HIV peak, we created a huge amount of immunocompromised individuals. And when you have a huge pool of people who are basically immunologically defenseless, TB has a great place to take root.

There was another thing that happened in the late 80s and early 90s, and that was actually that we kind of dismantled our public health initiative that dealt with TB. So we were like, hey, we have TB under control. I guess we don't need to spend tax dollars there anymore. And then, whoops, we saw an increase in TB.

So there was that that was a problem. We also saw an increase in immigration from countries where TB is common. So we had an influx of people who might be carrying latent TB, and we also had an increased pool of people who were susceptible to TB, and we stopped looking for it. And altogether, that's just a recipe for a significant TB increase.

Since about 1993, we've started seeing a decline here again. This time also correlates with a couple of things. One, when we started getting anti-HIV.

drugs, so mainly AZT, which was kind of the first one. That was approved in 86, and it was the first treatment approved for HIV. And we didn't really start getting combined antiretroviral therapy, which has been kind of wildly successful until the 90s.

And so once we got kind of the immunocompromised population underhand, and we started paying attention to it again, then we saw declining cases again. So that's pretty much what this graph shows, if we kind of look at the U.S. population here, we can see over time that we had kind of this increase here, and this is kind of where we stopped looking, and HIV kind of ran rampant. So we saw this like increase in TB cases, and then once we got HIV a little bit more under control, and we started looking for it again and testing it, we saw this nice downward trend.

Um, the line down here that's actually kind of remaining stagnant. is for people that are born outside of the United States. This rate tends to stay pretty constant, potentially ticking up here a little bit more as we're seeing an increase in multidrug-resistant TB, so that makes it obviously more difficult to combat this worldwide. If you were born in the United States and particularly have never left the United States, your incidence of TB is actually fairly low.

So we seem to have a good... handle on it here, but we are unable to eradicate it from the earth. And if you're unable to eradicate it from the earth and it's highly infectious, then we're always going to see some contribution here.

All right. So how do we get TB? It's airborne.

It's in the air that we breathe. It's spread through aerosols or droplets. And it's generally expelled when a person with infectious TB coughs, sneezes, or speaks.

Infectious TB is the key here. As I'll talk about later, there's kind of, there's patients who have like actively replicating infectious TB and then there's patients with a latent TB. A patient with latent TB is not infectious, so even though they previously had TB and their body is currently controlling it, they're unlikely to spread it to others.

The person's at highest risk of becoming infected are anyone who lives in close proximity with somebody with active pulmonary TB infection. So immediate family, significant others. We tend to see it in places where people live closely, so prisons. And we see this as an issue where there's poor air circulation as well.

So that's where prisons would be a good idea. Also in places where patients have low access to health care, those are other high risk kind of living situations. So like I said, there's kind of two forms, latent and active.

There is also kind of a safety note that I want to give to all of you who are potentially involved in a career in medicine. You're going to want to use protective personal equipment when working with somebody who you think could potentially be high risk for TB. Think about it, you go in, you see your patient, you tell them to open up and say ah, and as they do that they cough right on your face.

I mean that's a potential TB exposure. So you can contract it, so make sure to use appropriate PE and other precautions.