In the 1800s, it was called 'consumption', and it can be seen in a lot of historic movies. People would cough into handkerchiefs, and it would come away bloody. It has been called 'white death', but most often today it is referred to as just 'TB'.

Even though there successful treatments now, it is still the most deadly disease in the world, killing 1.25 million people in 2023. More people are getting TB than have ever been previously recorded. The WHO says, "approximately 8.2 million people were newly diagnosed with TB in 2023 – the highest number recorded since WHO began global TB monitoring in 1995".

In the primary stage, the person gets infected, typically from respiratory droplets of someone with active TB infection who shares the same space as the person newly infected. Prolonged contact in enclosed spaces increases the chances of getting infected.

Many people have no symptoms during this stage. Their body is busy finding the Mycobacterium tuberculosis and capturing it. The body can't always destroy the TB bacterium, but it can usually 'capture' them. A structure called a granuloma can form around it. The cells then are captured or trapped, and it is harder for them to spread and multiply. The image here shows the bacterium surrounded by all the different things that form a granuloma.

There can be some symptoms in this stage. Per the WHO, they include low-grade fever, a cough, and fatigue. These are symptomatic of many different diseases, and without testing, it's not possible to tell what disease has infected the person experiencing these symptoms.

The above diagram shows different ways that TB can show up in an x-ray of the lungs. The types of above damage to the lungs happen over time and can make it more difficult to breathe, cause chest pain, or many of the other symptoms. Scars or calcified spots can develop during active infection.

Each of these drugs do something different. Isoniazoid interferes with the synthesis of mycolic acid, which is a necessary component of cell walls in acid-fast organisms. This is only effective against growing cells, however.

These 'first-line' treatments if taken as prescribed are effective for most people with TB.

In many places, they are part of the DOT program, which was developed by WHO in 1991. People are diagnosed with Sputum Acid-Fast Bacili Smear, and then if positive, the patient starts a six month treatment period of 'directly observed therapy', usually with HRZE, depending on drug availability. This means the person has to be present every single day at the clinic to receive their prescribed doses. This makes treatment difficult or even impossible for those who do not live close, have transportation, or who have other limitations, such as disability or lack of community support.

If the first-line program is not able to be followed as prescribed or if the person has treatment resistant TB, other drugs can be prescribed. Some of these second-line drugs include bedaquiline, linezolid, moxifloxacin, and levofloxacin. These are often difficult to get in countries that need the TB drugs the most. Interruptions in treatment also are huge barriers in the effectiveness of TB treatment and contribute to drug resistance.

There has also been an increasing prevalence of individualized second-line treatments, where people get varied personalized doses based on their reaction to first-line drugs, their treatment history, and other comorbidities. I recently learned about this in John Green's book "Everything is Tuberculosis", where he discusses the individual case of Henry Reider.

All of these factors (first and second-line treatment options, drug resistance, and invidiualized treatments) are important to understand TB treatment and its effectiveness. There are also important sociological and cultural components to TB that affect treatment, which can't be discussed effectively here.

https://pmc.ncbi.nlm.nih.gov/articles/PMC3395138/

https://www.cdc.gov/tb/webcourses/TB101/page16489.html

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147744

https://www.ncbi.nlm.nih.gov/books/NBK310759/

https://www.cdc.gov/mmwr/volumes/72/wr/mm725253a2.htm

https://pmc.ncbi.nlm.nih.gov/articles/PMC8663011/

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.820134/full

https://www.cdc.gov/tb-data/2024-provisional/index.html

It is easier to spread in enclosed spaces over prolonged contact, so households can spread it internally, or it can spread in crowded children's homes. It is spread through respiratory droplets, so when people with active TB are living with people who are not infected, they are likely to spread it to those who are not infected. Poor diet, which is a reality in many places in the world due to lack of access to food or affordable food, and overall poor health make it easier for TB, like many diseases, to infect the body and become active. In the U.S., TB is often culturally associated with the unhoused population. Lack of stable housing and transportation contribute to difficulties getting regular treatment, and so the disease continues to spread.

Since it happens less in the U.S. than in other countries, U.S. drug companies are not focused on creating new drugs and U.S. policies don't demand lower and more affordable drug prices, even though it could save millions of lives.