The Forgotten Disease in a Crowded World

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. Osis, 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.

Tuberculosis: Infection Process

The TB bug is quickly attacked and devoured alive. Unfortunately, this is its plan. The white death is the worst 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.

Formation of Granulomas

So when your cells can't kill them, they do the next best thing, keep the parasites from escaping. A granuloma is formed, 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 safe space 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 2 billion people, but in one in 10 of them, the disease will become active.

Active Tuberculosis Symptoms

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 corps and fresh bacteria. Your immune system panics and overreacts. Hordes of soldiers leave your blood in a 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 flames throwers 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. Insufficiency 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 problem. Tuberculosis is the worst 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.

TB's Spread and Human Behavior

Tuberculosis doesn't want to kill you, of course. It wants to stay alive and spread. 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 tiny drop-wits 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 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.

New Drug Developments and Future Vaccines

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 Southeast 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 stopped making new drugs. In the first 25 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.