TB Honest

The Big 3: Tuberculosis Part 3

2017-09-12T08:35:00.000-07:00

It's time for our third and final post on TB, or at least for the time being. Part one and part two are here if you haven't read them yet.

In my last post, we talked about the course of a tuberculosis infection. Now let's dig into how we've treated TB over our history.

Treatment

Antiquity

A disease as old as tuberculosis has endured many treatment regimes over the centuries, some worse than others. Hippocrates prescribed milk, food, and exercise for his patients. The Roman physician Galen recommended fresh air and sea voyages in addition to the milk. It also appears that he and other doctors of his time advised that their patients eat wolf liver and drink elephant urine. Our ancestors treated their tuberculosis with bloodletting as well, which isn't a surprise because bloodletting is a terrible treatment that was used to treat everything back then. Other treatments included: inhaling smoke, licking limestone, consuming animal fat, and eating butter boiled with honey.(6)

In the Middle Ages, scrofula became known as "the King's Evil" because it was believed that it could be cured with the touch of a king.(6)

Sanatoriums

The sanatorium came into vogue in the 1800s. If you were rich, it was a luxury resort in the mountains and other pleasant, airy places believed to help people with their infection. There were also sanatoriums for the poor with less pleasant food and a greater resemblance to nursing homes or hospice centers. From a public health stand point, sanatoriums were a good way to remove your TB patients from the rest of society. There is some really interesting history behind these places, so sanatoriums will probably get a blog post at some point.

Pneumothorax

In the late 1800s, physicians noticed that tuberculosis patients whose lungs collapsed seemed to have a better prognosis. Some doctors began to wonder what if they collapse the lungs before TB could? An Italian physician came up with a procedure that did this and then filled the lungs with nitrogen. It seems to have been all the rage for a while, despite the risk of additional infections.(7)

Did collapsing someone's lungs work? The answer is that I don't know. I was unable to find modern commentary on it. But people did it until antibiotics became a thing.

Modern Antibiotics

Tuberculosis is a tough, resilient organism from the primal mists of time. It is hard to kill these bacteria because of that thick fat layer. Even when we have modern day antibiotics, you're still facing nine months of drugs to clear the infection. And these aren't fun drugs.

The four core drugs of choice when combatting tuberculosis are isoniazid, rifampin, ethambutol,
and pyrazinamide. These are our first-line drugs, which means that they're the first things we try. Those four drugs are not our only drugs. There are a few others we mix in, and sometimes when they don't work as well as hoped we turn to our second-line pharmaceuticals. This post is already too long to single out the mechanism of action for each of these agents, but together they work to neutralize tuberculosis. In cohort, these medications prevent TB bacteria from maintaining their membranes, stop their division, and impair their metabolism. However, these have substantially more side effects than popping an aspirin.(5,13,15,17)

While taking TB drugs, it is not uncommon to experience anorexia, nausea or vomiting, and weakness or fatigue. People taking rifampin will find their body fluids turned orange, including their urine and tears. This can lead to permanent staining of contact lenses. Patients may also feel tingling, numbness, or burning around their hands or feet. Their bodies will bruise more easily, and they may experience blurred vision.(2)

Compared to the past when we collapsed people's lungs, these drugs are a step up. However, getting people to follow through with the full course of treatment is a problem. Just making sure patients take all of their antibiotics when they have strep throat is difficult, and now they have to commit to a nine-month regimen of intense, powerful drugs with nasty side effects. And remember, if they have a latent infection, they are not showing symptoms so this is a step down in quality of life for about a year. Not taking the right dosage and all of your medication can lead to drug resistant TB, a nasty subject we'll talk about in a few sections below. Due to the public health threat of tuberculosis, it is understandable that countries have a vested interest in their citizens completing treatment.

Here in the United States, some communities have a system called Direct Observed Therapy. What this means is that a health care provider comes to your house with the medication and watches you swallow them. DOT became a thing when US public health officials looked around the world and realized to their embarrassment that some of the poorest nations in the world had better TB treatment completion than the wealthiest country in the world. So we adopted similar programs. Mozambique and Tanzania kept their tuberculosis under control with methods similar to DOT at low cost until the AIDS crisis overwhelmed their public health systems.(8)

Tuberculin skin test.
Image credit to Greg Knobloch. Content provided by CDC/ Gabrielle Benenson.

TB or not TB: Detection and Prevention

If you have ever worked or volunteered in a health care setting or served in the armed forces, you have received a purified protein derivative (PPD) test. There's a picture of it right above this section: they put a bubble in your arm, then they look at it a couple days later. The purpose of the test is not to see whether or not you have tuberculosis. What the test is actually doing is seeing if your immune system has ever been exposed to M. tuberculosis.

When they stick that needle in you, you are being injected with a protein called tuberculin. This is made by tuberculosis bacteria. If your immune system has ever been in contact with the bacteria, it will freak out and make the skin around the area swell and turn red. As soon as the health care provider sees this reaction, they will order a chest x-ray and a sputum test to confirm if you actually have TB. The chest x-ray is to see if you have any granulomas in your lungs, which would imply a latent infection. The sputum test is to see if you are producing live TB bacteria. If they find TB there, you are infectious.

In the United States and many other parts of the world, the tuberculin skin test is a major part of our detection system to find TB cases. I mentioned in my first post that there has been a vaccine for tuberculosis since the early 1900s. This is the BCG vaccine, which is made from Mycobacterium bovis, a cousin of M. tuberculosis that causes TB in cows. The vaccine is popular in other countries, particularly those with high rates of tuberculosis, but here in the US, we don't typically use it. Now I'm going to talk about why.

A vaccine primes your immune system to kill pathogens. If your immune system is ready to attack TB, it will also react with the tuberculin skin test. That means the test will give a false positive. From a public health stand point, we're left in a bit of an awkward either/or kind of situation. If everyone receives the BCG vaccine, the PPD test is useless.

So why doesn't everyone get the vaccine?

Well, the BCG vaccine provides about 80% protection against tuberculosis. That means that 20% of people who have received the vaccine will still be infected if they are exposed to the bacteria. That makes it just an okay vaccine. There are also different strains of the BCG vaccine because over time the cultures grown by different countries and manufacturing facilities have diverged. That makes efficacy variable. So from the viewpoint of the United States, the BCG vaccine is not worth it because our tuberculosis numbers are so low and PPD has been sufficient to detect cases. That doesn't mean we never use it though. The BCG vaccine is given to children in homes with endemic TB as well as healthcare workers working in high-risk facilities. Also, it appears that the BCG vaccine is a treatment for bladder cancer. Go figure.

Now, there is a new form of TB test which has been in use now for a couple years. This is called an interferon-gamma release assay (IGRA). Unlike PPD, this is a blood test which directly checks if your immune system has encountered tuberculosis before. The test has fewer mistakes, and most importantly, will not give a false positive to someone who has received the BCG vaccine. The downside is that IGRA is very expensive, so from a fiscal policy standpoint, PPD is where it's at.(2)

Drug Resistance

The mechanisms for why and how bacteria develop drug resistance deserve their own post, so I'm leaving the full discussion of that topic alone for now. When we talk about drug resistant TB, the CDC has some definitions for the different types of drug resistance. And they're all acronyms because science loves acronyms. If you have a strain of tuberculosis that is resistant to isoniazid and rifampin, then it is Multidrug-Resistant TB (MDR TB). Then there is Extensively Drug-Resistant TB (XDR TB), which is very concerning. This strain has resistance to isoniazid and rifampin as well as some second-line drugs and other antibiotics.(2)

Remember what I just said about how long you need to take drugs and their side effects? This is one of those cases where, in the mind of the unfortunate person subjected to that battery of drugs, the treatment may be worse than the disease. So people stop taking the antibiotics, or they take less than they're supposed to. They may not even have a choice for continuing their treatment. What if there's a civil war going on? What if there's a natural disaster like a hurricane or some other circumstance that prevents TB patients from finishing the therapy? The problem is that there may still be tuberculosis present in their bodies, and since the treatment regimen was not completed, it can come back with resistance to what was used before.

Drug resistance is one of the greatest threats to modern medicine because eventually, we will run out of viable antibiotics. What happens when we don't have the magic drugs anymore? Well, hopefully, we won't go back to sipping elephant urine.

TB and AIDS

Since AIDS is such a pressing health concern and changes the way other infectious diseases function, I'm hoping to have a little section like this in every disease post I make. HIV is actually going to be the next disease we talk about so we will delve into some of its nuances pretty soon. But for now, we can talk about the TB side of the AIDS crisis.

Tuberculosis is the number one killer of AIDS patients. Where before we saw a patient, methodical killer, when paired with HIV tuberculosis roars through the body. Remember, tuberculosis was on the decline until HIV became a major problem. This pair goes together like two pathogenic peas in a pod.

When you throw drug resistance into the mix, you have a rapid onset disease that is difficult to treat. If you have drug resistant tuberculosis, you need to figure out what that strain is resistant to. How do you do that? Take a sample, grow it in the lab, and run some tests. But tuberculosis is a slow growing bacteria. That means those lab tests take some time. And unfortunately, when it comes to AIDS patients, that might mean that by the time you figure out what drugs will work on the TB, the patient is dead.(8)

Closing Remarks

Tuberculosis has been one of the most persistent infectious diseases in our history. From the looks of things, it will continue to do so. Back in my first TB post, I talked about how many Western nations have negligible TB rates while other countries are being overwhelmed. The three nations with the greatest number of tuberculosis cases on the planet are China, Indonesia, and India. These three countries also have some of the largest populations on the planet.(14) Remember, TB spreads in the air and thrives in close, cramped quarters. These are nations with some of the largest, most crowded cities on the planet. Is it a surprise then that there are so many tuberculosis cases?

Large populations are not the only factor in a nation's TB burden. In the cases of China, India, and Indonesia, having such huge populations can obscure the fact that other, smaller nations have higher rates of tuberculosis. So who are some of the countries with the highest rates of tuberculosis infection and death? They are Angola, the Democratic Republic of the Congo, North Korea, Mozambique, South Africa, Lesotho, and other nations.(14) Some of these nations also have high numbers of HIV and AIDS cases, a weakness TB exploits. Many of these nations are some of the world's poorest, lacking the funds, medicine, and public health infrastructure to control a more and more drug-resistant tuberculosis. North Korea starves its people and funnels money into its nuclear program. Is it much of a surprise to see a high TB rate in their people?

When we talk about infectious disease, it is important that we don't merely write something like TB off as another country's problem. As per their name, infectious diseases spread. They will never remain one country's problem. TB is a global issue, and it remains a major concern for the United States and other nations with low (but rising) levels of tuberculosis cases. Remember, one-in-three are infected. TB will remain a problem for a long time.

You won't be seeing a new post for a bit as I do more research. Then, we will continue covering the Big Three and talk about HIV.

Sources

The Big 3: Tuberculosis Part 2

2017-09-10T06:21:00.000-07:00

Here we are for part two of the posts covering the basics of tuberculosis. Part one is over here if you haven't read that yet.

Last time we talked a little about the history of tuberculosis as well as the biology of bacteria. So today we're going to dive back in and talk about how TB spreads.

Transmission and Spread

One of the biggest benefits of living in the 21st century is that we have a much better understanding of the world around us compared to our ancestors. For example, nowadays we know that tuberculosis is caused by a tiny infectious organism. For the majority of our species' existence (which is also probably how long TB has been infecting us), we thought otherwise. Before germ theory got going, it was a common belief that tuberculosis was a hereditary disease that spread among family members.(6)

But now we know better. The tuberculosis bacteria spread from person to person through airborne droplets. We produce these droplets by coughing, sneezing, and talking. Once it's in the air, Mycobacterium tuberculosis can remain suspended for a bit of time. How long is a question of how ventilated the environment is as well as how much sunlight is present because UV light kills TB bacteria.(10)

So remember how the physicians of antiquity thought tuberculosis was hereditary? That observation makes some sense when you consider that families tend to live together in close, unlit, and poorly ventilated spaces. Any location with those three characteristics is a perfect place for tuberculosis to hang out in the air until someone breathes it in.

Tuberculosis has had a large impact on how we design the modern hospital simply because the goal of a hospital is to heal patients, not infect them with deadly organisms. Look carefully in some of the waiting rooms and wards and you may notice UV lighting. It is also becoming more common for hospital rooms to have negative pressure, meaning the air within a patient's room stays in the patient's room and doesn't go anywhere else. Whenever health care workers deal with a possible TB case, they get to put on their individually fitted masks. Tuberculosis is a strong impetus for theses changes and reforms.

So you might be imagining one-third of the world population hacking tuberculosis up into the air. This thought might make you never want to go into crowded spaces ever again. But don't worry, that's not an accurate image because most of those people are not infectious.

Why's that? Well, let's look at what happens inside your body.

What TB does in your body: Latent vs Active

So M. tuberculosis was hanging out in the air and then someone inhaled it. Where does it go?

Your lungs of course. The bacteria arrive and look for a nice patch of lung tissue to set up in. Then your body notices the squatters. A macrophage shows up on the scene and promptly eats M. tuberculosis.

As we explore the multitude of nasty infections which can show up in humans, we will be talking about various components of your immune system as well. So let's get introduced to our first character: the macrophage. A macrophage is an immune cell. It patrols its beat keeping an eye out for anything that doesn't really belong, and when it catches sight of trouble, that trouble get's engulfed. Once inside, the invader gets to experience the chemical funhouse that is a macrophage and dies.

Having acquainted itself with M. tuberculosis, the macrophage gets down to business with a barrage of powerful chemicals. But it has some trouble here because unlike your typical bacteria, tuberculosis is not affected by the chemicals. Remember that nice thick layer of fat I mentioned that surrounds M. tuberculosis? Well, that fat prevents the macrophage from killing the bacterium.

Eventually, the macrophage realizes that it ate something really bad, feels regret, and calls in backup. Your immune system deploys in force and realizes that it can't destroy whatever is inside their buddy the macrophage. So they build a wall encasing the doomed macrophage and the bacterium. Then your immune cells shake hands and congratulate each other for a good day's work. The medical term for this is a granuloma.

So now tuberculosis has been encased within a wall of cells. It sits there patiently, dividing slowly and waiting. But if you have a fully functioning immune system, your cells probably did a good job. TB is stuck. Technically, you are infected but you show no symptoms and don't feel anything. This is called a latent infection. For that one-third of the world infected with tuberculosis, most of them have this. Depending on where they live, those people may never even know they're infected. They could live a full life without tuberculosis ever giving them a problem.

Yet, tuberculosis is a patient disease. It's not in a hurry. It can wait for the perfect moment when your body's defenses are worn down and distracted by other problems. Now TB strikes, and you have an active infection. The bacteria break out of the granuloma and start giving you problems. When patients have this form of TB, they are infectious. The more out of control the bacteria divide, the more infectious the patient becomes. Of all the people who have a latent infection, 10% of them will transition to the active infection at some point in their life.(2)

Symptoms and Advanced Infection

When you have an active tuberculosis infection, it can manifest with a number of symptoms. Most of the time, the symptoms of an infection are just your body trying to get rid of it. When your body realizes, "Hey, there's bloody gunk in my lungs," it tries to cough the bad stuff up. But remember, that's what tuberculosis wants your body to do so it can spread. It is a parasite using your body's innate functions and reactions to survive and propagate itself.

In addition to coughing, a tuberculosis patient may experience chest pain and bloody phlegm. The other two big symptoms are night sweats and weight loss. After that, you have the more general symptoms of fever and chills.(2) The weight loss and wasting away is a consequence of your immune system kicking into overdrive.(10)

So now we are talking about an active TB infection that the immune system is struggling to keep under control. The bacteria can stay in your lungs, or they can go on a bit of an adventure. Remember, your macrophages and the bacteria are duking it out in your lungs, specifically around your alveoli. Your alveoli are the part of your lungs where oxygen is transferred to red blood cells. Well, if tuberculosis gets loose it can hop straight into your bloodstream. Now it goes on a wild rollercoaster ride through your circulatory system, and where it'll hop off, nobody knows.

Pictured: Your bloodstream.

This form of TB is known as miliary tuberculosis. It's called this because people thought the lumps it left in tissue bore a resemblance to millet seeds.(6) And it is very deadly without treatment. In some ways, this stage of disease progression isn't so different from a cancer metastasis because it can go anywhere in your body. It can lead to meningitis and other nasty conditions. One such ailment is called scrofula, which arises when tuberculosis gets into your lymph nodes. This can lead to visible swelling and ulceration.

However, these conditions only happen when a tuberculosis infection leaves your lungs. TB is perfectly capable of killing you by staying in your wind pipes. These severe forms of infection are more common in those who are more susceptible to TB, so let's talk about who is most at risk for tuberculosis.

Risk factors

At risk groups for tuberculosis infection can be divided into two groups: those who spend time around people with tuberculosis, and those who have impaired immune systems. When we talk about the first group, many people who fall into this category do some form of institutional work. If you work or live in a hospital, correctional facility, nursing home, or homeless shelter, you are at risk. You are also at risk if you live in close contact with people with active TB, are homeless, or a drug user.(2)

Then there are those whose immune systems aren't quite up to snuff. Remember, most people infected with TB aren't actually spreading the disease because their immune systems wall the bacteria away. If your immune system isn't working, you're more susceptible to infection by TB as well as more likely to spread the disease. First obvious group: AIDS patients. I'll talk about that in the next post though. Two other big groups are the very young and the very old. Infants and the elderly are almost always an at risk group when we talk about infectious disease, and TB is no exception. Typically this is because the very young don't have much of an immune system yet, and in geriatric populations the immune system is breaking down.

Substance abusers are another at risk group, whether the substance in question is legal or otherwise. Too much alcohol weakens your immune system. Smoking nicotine or marijuana irritate your lungs, and remember, TB targets your lungs. Other drugs like meth or cocaine dehydrate your body, and a body without enough fluid will not have a top notch immune system. Having a low body weight also puts you at risk.(2)

If you have received an organ transplant, you are taking medication to suppress your immune system. Therefore, you are at risk for tuberculosis. The same goes if you have an autoimmune disease such as arthritis or Crohn's disease and are being treated with immune suppressants. Diabetics and kidney disease patients are at risk. Those with head and neck cancer are at risk, and so are those with a lung disease called silicosis. People who fall in these groups are the ones who tend to see the really nasty parts of TB infection.

So how do we get rid of tuberculosis?

Check out the next post when it comes out in a couple of days.

It's up.

Sources

The Big 3: Tuberculosis Part 1

2017-09-08T08:33:00.002-07:00

Welcome to the first disease post of TB Honest. If you haven't already, I recommend you take a look at the introduction.

This post took me some time to get together because TB is complicated and I'm figuring out how I want to format my disease posts. I'll keep refining this as I go, but I realized that the original post was way too long so I'm cutting into multiple, more digestible posts. The next part should be up in a couple days.

Well, here we are talking about our very first disease. One of the oldest and most feared infectious diseases on the planet, it has been called the White Plague, phthisis, and consumption. It holds epithets such as the robber of youth, the graveyard cough, and Captain of all these men of Death.(6) It's the namesake for this blog. It's tuberculosis.

Along with HIV and malaria, TB is one of the top priorities for public health. Of all infectious diseases in the world, it is the number one killer. In 2015, tuberculosis killed 1.8 million people and infected another 10.4 million.(2) As of today, the world population stands at around 7.5 billion people. One-third of them have tuberculosis.(2)

No, I did not mistype that. One out of three people is infected with tuberculosis. But that's from a global perspective. If you look at the United States, the case incidence rate comes out to about 3 people per 100,000 persons.(2) It joins Canada, Australia, New Zealand, and the nations of Western Europe as one of the countries with the lowest TB burden. Indonesia and India have the most TB cases in the world.(14) [Edit: after reviewing the numbers, I realized Indonesia has a much higher TB rate than China. Corrected.] The point I'm trying to make is that the distribution of tuberculosis worldwide is not equal. We are going to talk about why that is. However, tuberculosis is a global, complex topic and I will not be able to cover everything in this one series of posts. So we will be revisiting this topic from time to time with supplemental posts. We're covering the basics right now.

So let's talk about where TB came from.

A brief history of TB

Tuberculosis is nothing new. It is an ancient disease. We found traces of it in the mummies of Ancient Egypt. (18) References to the disease are in the Bible, the Vedas, Hammurabi's Code, and Homer's Odyssey.(4,6,11) Now, the question of how long tuberculosis has been a part of the human experience is a matter of debate. Some experts say 40,000 years, while others put it around 6,000.(1,16) Regardless, TB has a rich history that spans multiple volumes, so there is no way a humble blog post can cover everything. Remember, we're going shallow here.

As for how tuberculosis first found its way into humans, studies seem to suggest that it may have been a cross-species hop from animals to humans when we started taking up agriculture. Tuberculosis is a disease that does not confine itself to one species. We see that nowadays when it infects animals such as cows and elephants. So it shouldn't be much of a surprise that there is a study that suggests tuberculosis may have crossed the Atlantic Ocean and came to the Americas through seals.(1)

Throughout human history, tuberculosis made its way through societies and civilizations and racked up an impressive death toll. Towards the close of the 19th century, some European officials believed that the infection rate in their cities was close to 100%. There was a strange period in the 1800s when the disease was romanticized by poets and writers (because it killed a lot of them), and the pale, thin figure common in TB patients became a standard of beauty for the time. That trademark, wasting pallor is why the disease was known as consumption and may be where its name the White Plague came from. The literary tradition for describing vampires and their victims, which started in this time period, probably came from the common sight of individuals with tuberculosis.(7) So next time you see a vampire or Tim Burton movie, remember TB.

March 24, 1882 was an important date for tuberculosis because that was when Dr. Robert Koch, a legendary physician and hero for the field of infectious disease, discovered the bacteria that causes it: Mycobacterium tuberculosis. (There are other bacteria that cause tuberculosis, but M. tuberculosis is the main species and we don't need to get into that nuance right now.) This day is now memorialized by the World Health Organization as World TB Day. As technology steadily advanced, we became better equipped at detecting and preventing the spread of tuberculosis. 1895 was the discovery of the X-ray, which helped us detect TB infection of the lungs. In 1900, a pair of French scientists began developing a vaccine against tuberculosis. This became the Bacille Calmette-Guérin (BCG) vaccine which is still in use today.

However, the biggest development was the discovery of streptomycin, the first effective antibiotic against tuberculosis. The guy who discovered the drug, Selman Waksman, was also the person who coined the term "antibiotic." In countries with the infrastructure and resources to implement effective public health policy and treatment options, tuberculosis, our old scourge of antiquity, began to drop off. Countries that did not have access to antibiotics nor the public health infrastructure did not see the significant drop off with tuberculosis. Yet, those countries that started to bring their TB cases under control became confident in their medicine. This was that nice optimistic period I mentioned in my introductory post where we began to dream of a world without infectious disease.

Then the 1980s arrived, and along with it came the AIDS crisis. As it turns out, tuberculosis is a major opportunistic infection for HIV patients, so the number of tuberculosis cases exploded. Then we noticed that the bacteria that causes TB was becoming resistant to our antibiotics. And that brings us to today.

So now that we've covered a small portion of the rich history of tuberculosis, we are going to some basic biology to talk about bacteria.

Image credit to U.S. Centers for Disease Control and Prevention - Med Illustrator. Provided by CDC/ James Archer.

What are bacteria?*

*A Caveat Concerning Biology

Of the three basic sciences, biology is the most complicated. That is because physics is the cornerstone: it attempts to understand the physical laws of reality. Chemistry examines how matter is composed, interacts, and changes. Biology then studies how living organisms survive as they abide by the laws of chemistry and physics.

When I said "law" back there, I'm referring to a scientific law which is a little different from our concept of law in day-to-day society. In science, a law is a statement that describes or predicts natural phenomena. A lot of times those laws can be written out as math equations. Physics has Newton's law of gravity, Kepler's law of planetary motion, and plenty of others. Chemistry has the laws of thermodynamics. These laws were developed by empirical study and experimentation, and they are used to predict the behaviors of the known universe. If a law has an exception, then it is not a law. And the problem with biology is it is full of exceptions because it deals with life. Life is diverse. This makes biologists cautious when they go about naming the rules of their field. You have probably heard about Darwin's Theory of Evolution. It is the most groundbreaking and revolutionary concept in biology because it affects every subset of biology. Yet, we are still figuring out the mechanisms behind evolution, so scientists are not comfortable with making it Darwin's Law of Evolution.

The reason I spent time talking about the laws of science is to warn you, dear reader. The science behind biology is extremely complicated, and I am not going into that level of detail. I will generalize. For every generalization I am about to give you, there's probably at least one exception. Tuberculosis itself breaks a few nice, easy generalizations I will attempt to make about bacteria. So keep that in mind.

Bacteria

Bacteria are some of the smallest and most successful forms of life on this planet. Look under a microscope and you'll see circles, rods, cones, spirals, helixes, and all sorts of squiggling shapes. The largest bacterium on the planet is three-fourths of a millimeter wide and lives in ocean sediment. The smallest bacterium is between 200 and 300 nanometers, lives in the human urogenital tract, and is a cousin of chlamydia. They are a diverse group of life forms. And they are everywhere. They live inside of us and on everything we touch. We use them to make cheese and yogurt. And then, of course, there are some that make us sick.

So why are bacteria so successful?

Let's compare a human cell to a bacterial cell. If we want to throw scientific terms around, we would say that a human cell is eukaryotic and a bacterial cell is prokaryotic and leave the discussion there. However, that doesn't mean anything to most people, so let's dig a bit. The very first difference is in size. A human cell is typically at least ten times bigger than a bacterium. If you compare the two, the human cell is also much more complicated. A human cell has to work together with the other cells in your body to break down your food, tell your muscles to move, be your muscles, or whatever task it's been assigned. It has tiny organs, called organelles, that help facilitate whatever task that cell is made to do. The human cell has a nucleus, the "brain" of the cell if you will. When you look at DNA, the human genome is about 60 times larger than an average bacterial genome. Human cells are so much more complicated than bacteria.

If you look at bacterium, you will see a much starker structure: smaller, no organelles, less DNA, no nucleus. That's why bacteria are so successful: they're simpler so it's easier for them to replicate. It takes nine months to make a human. If you look at us at the cellular level, our fastest dividing cells are in our skin and intestinal lining. It takes 20 hours to make a new cell to line your colon.

Now, what about bacteria?

If you want to look at a "typical" bacteria, we look at E. coli. Yep, that's the same E. coli you hear about in the news when it gets in your lettuce. An E. coli cell replicates every 20 minutes. That is one-sixtieth of the time it takes your fastest cells to divide. E. coli is so good at replicating itself that it will start copying its DNA for another division as it is in the process of dividing. Human cells can't do that (and if they did, they'd be cancer cells).

The strategy of bacteria for surviving a harsh world is to make so many copies of themselves that their species will survive simply because it's so hard to kill them all. Give them 40 minutes and they're grandparents. And since they're producing so many of themselves, you see a much faster rate of natural selection and adaptation to a changing environment. If you want to generalize this even further, bacteria emphasize quantity over quality.

...except for tuberculosis. One of the reasons why tuberculosis, HIV, and malaria are a part of the big three is because they do not adhere to our typical frames for bacteria, viruses, and parasites. Here is where the distinctive personality of tuberculosis begins to shine through. TB is patient. It isn't in a hurry. Whereas most bacteria divide quickly, TB takes its time. The doubling time for a tuberculosis bacterium is 18 to 54 hours.(9)

That slow division time is a feature for the Mycobacterium genus. Whenever you see a scientific name, it is a way to classify how related different organisms are and are written Genus species. So remember, humans are Homo sapiens. What I'm saying is that tuberculosis has some pretty slow cousins. One of those cousins is the bacterium that causes leprosy.

The biggest effect that this slow growth has is on research. One of the reasons why E. coli is the "typical" bacteria in science is because it's easy to grow a ton of it and do tests. If you are researching tuberculosis and trying to grow your own bacteria, it's going to take a while to do anything. There are some implications to this which will come later.

Gram Staining

Bacteria are small, and they are transparent. Consequently, they're hard to see. So one of the very first steps to researching any bacteria is to visualize them on a microscope slide. The way we do that is called a Gram stain. We wash the bacteria with a couple of different chemicals, and when we look at them under a microscope we can see them because they've been stained a certain color. What color bacteria turn is a result of their membrane, the part of a cell that divides the cell from everything else. You can just think of a membrane as like skin.

So if a Gram stain turns a bacterium red, we'd classify it as a Gram positive. If the bacterium is blue, it's Gram negative. The reason this is important is that this is one of the basic ways we sort types of bacteria.

...except for tuberculosis. Gram stains don't work.

The reason why Gram stains don't work is that the tuberculosis bacterium is surrounded by a thick layer of fat which prevents the chemicals from staining. Mycobacterium tuberculosis is what is known as an acid-fast bacteria because before it can be visualized on a microscope slide, you need to dissolve the fat with an acid.

Okay, so I'm cutting this post off right here. The next post we will be going into the transmission and pathophysiology of tuberculosis infection. See you in a few days.

Part two is now up.

Sources

The Persistent Relevance of Infectious Disease: An Introduction

2017-08-09T17:29:00.001-07:00

Closing the Book on Infectious Disease

If you lived in the United States in 1900, life was pretty rough. Back then, the average lifespan was 47 and the leading causes of death were influenza, tuberculosis, and gastrointestinal disorders. What happened? Well, we figured out our public health. Physicians started washing their hands. A scientist got mold on his bread, and then BAM, we had penicillin. Vaccines were developed and the populace was immunized. Death by infection plummeted down the lists to be outpaced by chronic disorders like cancer and heart disease. As medicine became more powerful, so too did human ambition to curb the old threats of the past. Aspirations were high. Polio vaccines saved lives. The World Health Organization began to put together campaigns to exterminate Malaria-carrying mosquitos as well as smallpox. As a testament to the times, the U.S. Surgeon General at the time said:

"It’s time to close the books on infectious diseases, declare the war against pestilence won, and shift national resources to such chronic problems as cancer and heart disease."

-Dr. William H. Stewart, U.S. Surgeon General (1965-1969)

It's a nice quote because it's a succinct snapshot of the attitudes of the time that puts us in the shoes of health authorities. In one sentence, we see the unbridled optimism and arrogance of medicine equipped with antibiotics and modern sanitation methods. It's perfect. As soon as I even considered blogging about infectious disease, I knew I had to include that quote. You may have even heard this quote before because hundreds of writers, teachers, and authors have referenced it. You also may have noticed that I didn't put a citation on the quote. That's because, unfortunately, Dr. Stewart never said it. Whoops.

Did you see that? Here I was, trying to make a blanket statement about the beliefs of the time. I had the perfect quote to unpack, a quote which I was familiar with and believed was true. Yet, it wasn't until I went to write this post and looked it up that I realized someone had debunked it as an urban legend four years ago. Dr. Stewart supposedly said the above text during a speech in 1968. However, the transcript of the speech does not contain the quote. In fact, it appears Dr. Stewart said the opposite. So where did this apocryphal quote originate? Apparently, from someone who didn't attend the speech and heard the quote from someone else. Evidently, someone who wasn't paying good attention.

Before we dive into the rich histories of these diseases and the people who suffer them, we should remember this example of how a fake quote became real. All of the people I linked above believed the quote, as did I until I learned otherwise. When we condemn an entire generation to one viewpoint, we need to be very careful with our sources. History is a product of humans, and humans are nuanced. Believing that everyone in a time period was of one thought and mind is a gross simplification for the messiness of reality.

That complexity is where my interest in infectious disease stems. So let's get back to that.

What makes a disease?

The fundamental task of medicine and public health is drawing the line between wellness and disease. By its very definition, a disease is abnormal. It is bad. It is a state of being we strive to avoid, and the prime directive of public medicine is to prevent and treat it. Before a disease can be treated, it must be defined. And oftentimes, that definition is a matter of culture.

In order to define a disease, we must also come to an understanding of what is normal. Changes in culture invariably lead to a shift in how we define a disease or disorder. In the 1980s, the American Psychiatric Association added ADHD to the list of psychiatric disorders. It also removed homosexuality from that list. These changes in the listing do not mean that the symptoms and behaviors which constitute ADHD suddenly appeared in the 20th century. Nor does it signify that homosexuality is or has always been considered a disorder. These changes reflect shifts in culture and awareness.

Going about our day to day lives, we understand basic elements of sickness. When our fevers go past 100 degrees Fahrenheit (or 37 degrees for my metric friends out there), we feel muggy and sweaty and gross, or when our throats are sore we know something is wrong. But those are symptoms. More often than not, we feel a bit under the weather and it goes away without any need to bring physicians into the picture. Is that disease if there's no diagnosis?

The paradox of good health is that we strive to possess it, but fail to notice it until it's gone. Disease touches every aspect of the human experience, and is there anything more human than fighting off a cold by curling under a blanket and sipping soup?

Disease is a source of morbidity and mortality. It is the lens through which we are forced to focus our lives and find meaning for them. In one way or another, medicine and health touch every aspect of our lives and civilization. But remember, this isn't a blog about just disease. I'm focusing on infectious diseases. So let's talk about why am I interested in that particular subset.

All diseases are complicated because they are the sum of a slew of personal, genetic, and cultural factors. What makes communicable disease interesting is in the name: they are (mostly) living things that spread from person to person. Many diseases can be tied to lifestyle choices, but you don't acquire them when a random person on the bus sneezes on you. Infectious disease is a direct, traceable consequence of our interactions with others and the environment. Cancer and heart disease are worthy topics for a blog, but they do not spread person to person (with three notable exceptions for cancer which I will probably discuss at some point). That is where my fascination with infectious disease stems from.

Why is infectious disease still relevant?

If you've paid any attention to the news for the last four decades, you may have noticed that our world is not an idyllic pasture bereft of pestilence. We found plenty of new nasties like HIV, Ebola, and Legionnaires. The old threats slain by antibiotics gained resistance. Previously rare viruses such as Zika found a niche and leaped to the headlines. As society has evolved, so has infectious disease. Globalization, air travel, and population booms have brought great strides to our civilizations. At the same time, these changes to our way of life have provided opportunities for both old and new parasites to establish themselves.

My plan for the future will be to focus on different pathogens and diseases with each post. My intention is to write so that people without a science background can follow and understand the various challenges and characteristics of modern communicable disease. I will also be touching on the nuances of various pathogens as they interact with our history, culture, and ways of life, so hopefully, those of you with solid foundations in science will also find something to take away from this blog. The first diseases we will discuss are what public health scientists call the Big Three: malaria, tuberculosis, and HIV. Of all infectious diseases, they are the greatest inflictors of morbidity and mortality on the planet as well as what sucks up the most public health funding. In these three diseases we also see a parasite, bacterium, and virus so we can speed through the basics of these three classes of pathogens as we talk about what makes each of the three unique for their class.

Now remember, I am NOT a physician and I am only human. That means nothing I post should be taken as medical advice. It also means I will likely make mistakes like all the people above who misquoted Dr. Stewart. I will be attempting to simplify complex scientific topics for the general public, and sometimes generalization will misconstrue the truth. If there's ever an error or you have trouble following something, tell me and I can fix or try to explain it another way. Blogs are good for that.

So I guess I'll see you guys next time when we talk about our first disease and namesake for the blog: tuberculosis.