The White Death: Humanity's Oldest Enemy and Current Challenge

Tuberculosis, caused by Mycobacterium tuberculosis, is a stealthy, slow killer with antibiotic resistance and global impact.

### The White Death: Tuberculosis, the Perfect Human Predator
* 🦠 Tuberculosis, caused by Mycobacterium tuberculosis, is an ancient disease that has killed a billion people in the last 200 years, making it the **infectious disease with the highest kill count**.
* 🎯 The bacterium is a "**perfect human predator**," entering the body through the airways, evading immune defenses, and **replicating extremely slowly**.
* 🛡 When immune cells can't kill the bacteria, they form granulomas to contain them, creating a "**stalemate version of Tuberculosis**".
* 🚨 Active Tuberculosis is an emergency, characterized by **granulomas bursting in the lungs**, causing **severe damage** and spreading **millions of bacteria**.
* 🌍 Tuberculosis spreads through tiny droplets from coughs or sneezes, making **close contacts like family, friends, and coworkers most vulnerable**.
* 💊 While most cases of active Tuberculosis can be cured with antibiotics, the disease remains the **deadliest infectious disease on earth** due to **lack of global distribution of the cure** and **antibiotic resistance**.
* Efforts to fight Tuberculosis have seen progress with the development of **new drug classes**, **better vaccines on the horizon**, and the opportunity to **push the disease back until it is eradicated**.

Hello, Steve here. Today I am moving over as the voice of kurzgesagt for something really special. Our dearest friend John Green would like to tell you a story that's very close to his heart. So, let's hear it from him directly. Hey, John! Hey, Steve. Thanks so much! Lets dive right in: The white death has haunted humanity like no other disease following us for thousands, maybe millions of years. It was there when we tamed fire, invented culture, and ventured out of Africa to conquer the world. In 1815 it caused one in four deaths in Britain. In the last 200 years it killed a billion people, way more than all wars and natural disasters combined. Even today it’s the infectious disease with the highest kill count. But… Do you even know what we are talking about? We’re talking about Mycobacterium tuberculosis, which causes tuberculosis or TB – our original arch enemy.

Right now, one in four humans alive are infected with the bacterium – you may be one of them. So how is it possible that we never hear about TB? Well, the White Death is the perfect human predator: very infectious but very quiet most of the time, careful not to murder recklessly. Perfectly adapted to your immune system and just physically incredibly hard to kill. What exactly makes it so powerful? The Perfect Human Predator. Usually, the bacterium enters your body through the airways and sets up home in the lungs, a giant living cave system, defended by billions of macrophages, powerful guard cells that hunt and kill intruders. The TB bug is quickly attacked and devoured alive. Unfortunately, this is its plan. The white death is the worst kind of parasite – an immune system parasite. Macrophages grab their victims, trap them inside a phagosome, and flood it.

with acid that rips them to pieces.
But TB evolved a thick, waxy coat that makes it completely immune to those acids.
Worse, it captures and modifies the macrophage to be a perfect host. Like a tiny vampire, the
parasite slowly consumes the cell. TB then replicates extremely slowly. Other microbes that
make you sick multiply up to 60 times faster, exploding their numbers before the immune system
can eradicate them. But the white death is so well adapted to you, it has already
won by being here. No need to rush things. When its host cell is sucked dry and dies, the bacteria infect new macrophages.
Although these bacteria are stealthy, the decaying corpses they leave behind do
activate a proper immune response – your body knows something is up and mobilizes its
forces. But once again, this is part of the plan. Macrophages and many other immune cells
try to kill the bacteria, but that thick cell wall

makes them a formidable fortress and resistant 
to many attacks. And it infects its attackers in   the process. So when your cells can’t kill them, 
they do the next best thing: keep the parasites   from escaping. A granuloma is formed, a sort of 
white blob. In the center is a core of infected   and dead macrophages – a pleasant home and food 
for the bacterium. Other immune cells surround   this sphere of death to contain it – creating 
a safespace where TB can sit for years. Worse,   it is perfectly protected from medication and 
releases chemicals that make it hard for your   heavy immune weapons to be activated. This 
is the stalemate version of Tuberculosis.   The infection is sleeping and the bacteria is 
doing its thing. This is going on right now in   up to two billion people! But in one in ten 
of them, the disease will become active. Active Tuberculosis is an emergency. But again, a 
slow one. If your immune system can’t contain the

infection anymore. Granulomas burst suddenly. Your lungs are filled with macrophage corpses and fresh bacteria. Your immune system panics and overreacts. Hordes of soldiers leave your blood and rush to the infected areas. They order inflammation and fluids flood into your lungs. But unfortunately, your lungs are not made to be a battlefield. In their panic, your immune cells don’t care – they’re running around with flamethrowers, trying to purge the infection but causing terrible damage. As fluids and dead tissue amass, it becomes difficult to breathe and you begin coughing hard, sometimes even coughing up blood. And again, this is part of the plan because now you spread millions of bacteria catching rides in tiny droplets. You burn a high fever and lose weight as your body is severely stressed. You turn into a ghost version of yourself. Even if you are treated, this phase

can last weeks to months and is very serious. 
Insufficiently treated, TB will over months, years, or even decades slowly overtake your body. 
Especially for children or those already weakened, this can be too much and the disease wins the 
war. The bacterium spreads to other organs, lung function breaks down, and the patient dies. 
1.3 million people died this way in 2023 alone. The Worst Kind of Problem Tuberculosis is the worst kind of 
problem: A slow one. Instead of killing millions quickly like Covid, scaring a 
panicked humanity into frantic action, TB is a smoldering fire. Killing too 
slowly for our short attention span. The symptoms are often mild for many months, so 
you don’t feel in danger. Tuberculosis doesn’t want to kill you, of course, it wants to 
stay alive and spread. And to do this, it exploits human behavior: The people you are 
most likely to infect are your family and friends.

coworkers or neighbors, the people you spend a lot 
of time with. When Covid brought the world to a   halt, the average patient infected 2-3 people. An 
active TB patient infects 5-15 people in a year. Most people catch it via breathing 
in tiny droplets from a cough or   sneeze. This is especially common in crowded,   poorly ventilated housing or workplaces. 
Which is why TB exploded during the   Industrial Revolution. And indeed wherever we 
see new unplanned and overcrowded urbanization,   from Lagos to St. Petersburg, we tend to 
see a rise of the White Death alongside it. Today most cases of active Tuberculosis 
– the version that spreads the disease   further – can be cured with a four-month 
regimen of four different antibiotics. But   if that’s the case… How is this still the 
deadliest infectious disease on earth? Between 1940 and 1965, humans developed 
several drugs to fight TB, finally making it

curable. It was a true achievement of human 
ingenuity. But we didn’t do a great job of distributing the cure. While Tuberculosis 
is almost extinct in much of Europe, the US and the Middle East, it is still a 
very real threat in most of the world. TB kills people primarily in Africa, South 
America and Asia. In 2022, two-thirds of all TB cases were in just six countries: 
India, China, Indonesia, the Philippines, Pakistan and Nigeria. Almost half of all 
Tuberculosis deaths happened in South East Asia. But as it is a slow problem like climate change, 
it was ignored instead of fought aggressively, which enabled more and more strains of 
TB to develop antibiotic resistance. Which is a problem because we 
kinda stopped making new drugs. In the first twenty-five years of the 
antibiotic era, we developed eight different classes of drugs to treat TB. And 
then, in the 47 years between 1965 and 2012,

we developed none. Developing new drugs 
is extremely expensive, and there was no concentrated effort to eradicate TB, 
and there simply wasn’t enough profit incentive. There is a vaccine, but it’s over 
100 years old and not particularly effective. But beginning in 2012, we did finally develop 
two new classes of drugs that treat TB, and we may finally be at an inflection 
point again, as better vaccines are on the horizon. Companies that made Covid tests 
also developed a quick test for TB. So, we now have a real opportunity to push 
this disease back until it dies forever. But only if we get enough people to know about 
TB – like you do now – and to care about it. A century ago in the United States, there were 
almost as many hospital beds for TB patients as for treating all other illnesses and injuries 
combined. The White Death was a leading cause of death in the US, and then one day it just 
wasn’t anymore. And we can do this again.

4,000 people died of tuberculosis yesterday, 
and we simply don’t have to accept a world where so many of us still die of a disease 
we know how to cure. The White Death has been with us for millions of years. It is 
time to continue our journey without it. If you want to learn more about 
tuberculosis and the folks working to fight it through clinical trials and care 
delivery and also learn how you can help, check out the organization Partners in Health 
at pih.org/programs/tuberculosis. We’ve put a link in the description for you. Also, 
if this wasn’t enough TB for you, there’s a Crash Course Lecture on the history and presence 
of TB. We’ll include a link to that as well. Steve, I'll see you on Fri....no! This isn't 
Vlogbrothers...soon. I'll see you soon, Steve.

This Disease is Deadlier Than The Plague

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Kurzgesagt – In a Nutshell

Mycobacterium tuberculosis, also known as TB, has been a deadly force throughout history, causing a billion deaths in the last 200 years.

Despite being highly infectious, it is often undetectable and difficult to eradicate, making it a perfect human predator.

The bacterium's ability to invade the lungs and manipulate the body's immune system makes it a formidable and challenging foe to conquer.

The Stealthy Tactics of Tuberculosis Bacteria

Tuberculosis has evolved to be immune to acids and to slowly consume host cells, making it highly adaptable.

The bacteria's thick cell wall makes it resistant to immune attacks, allowing it to form a protective granuloma and remain dormant for years.

In some cases, the disease can become active, posing an emergency as the immune system struggles to contain it.

Tuberculosis infection triggers an aggressive and damaging response from the immune system, leading to difficulty in breathing and coughing up blood.

If left untreated, the disease can slowly overtake the body, leading to organ failure and death, with 1.

Tuberculosis is a slow yet deadly problem, exploiting human behavior to spread and often presenting mild symptoms, making it challenging to address.

Tuberculosis is highly contagious, with a history of spreading in crowded and poorly ventilated areas.

Despite being curable with a four-month antibiotic regimen, it remains the deadliest infectious disease globally, with the majority of cases and deaths occurring in Africa, South America, and Asia.

The lack of aggressive action against TB has led to the development of antibiotic-resistant strains, while the development of new drugs to treat the disease has significantly declined since 1965.

Developing new drugs to treat TB has been historically neglected due to the lack of profit incentive, but new drug classes and better vaccines are now in development.

Tuberculosis was a leading cause of death in the US, but with the recent progress, there is hope to push the disease back.

Despite the long history of TB, there is now a real opportunity to eliminate it, with ongoing efforts from organizations like Partners in Health.