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Mycobacterium tuberculosis has been around for at least 70,000 years.

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".

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There are three main stages of TB infection: primary, latent, and active TB infection.

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.

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Robert Koch discovered the pathogen. Prior to this, some people thought that TB was passed down genetically. Others thought that TB was a function of a certain type of personality. Koch proved that it was another communicable disease.

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During latent TB, people experience no symptoms. The disease multiplies during this time, and it can take months or even years for more symptoms to show because TB's generation time is close to 24 hours. The next stage with symptoms is called active TB.

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Active TB happens when a person's body is no longer able to control the spread of Mycobacterium tuberculosis. According to the Mayo Clinic, symptoms will appear after months or years of Latent infection. They will worsen over the weeks following their initial appearance, and they can include: fever, chills, night sweats, weight loss, not wanting to eat, fatigue, cough, coughing up blood or mucus, chest pain, and pain with breathing or coughing.

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.

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This diagram shows the standardized dosages for first-line treatments. 

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The standard treatment generally includes four drugs, HRZE. Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), and Ethambutol (E). Sometimes, there is a fifth drug, called streptomycin (S).

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.

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https://www.who.int/news/item/29-10-2024-tuberculosis-resurges-as-top-infectious-disease-killer

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

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The Radiology Assistant : Imaging findings in TB

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About 10,000 people in the U.S. were diagnosed with TB in 2024. However, these numbers are just a drop in the bucket compared to the worldwide prevalence of TB. In 2023 and 2024, TB was again at the number one spot for deadliest disease in the world. It has been at that spot (accept during the Covid years of 2020-22) for several years. India and China account for the largest portion of individual country's with high TB incidents. It is easier to spread in already vulnerable populations, such as those that have HIV, especially untreated HIV, which is more common in poorer countries. It is easier to spread when the full round of first line treatment is stopped, which is more common when there are treatment interruptions from supply chain issues or when drugs are too expensive for a country to afford under their public health programs. It is made worse, and thus the spread is increased, when said treatment is stopped.

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.

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Mycobacterium tuberculosis is an acid-fast, gram-positive bacterium. It has a capsule and is a rod-shaped bacterium. It is very resilient because of its capsule. This makes it difficult, especially for people who are already experience other negative health outcomes, for the body to fight Mycobacterium tuberculosis, the pathogen of the disease Tuberculosis.

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1. Like most respiratory illnesses, some basic protections are possible, including, washing your hands regularly, coughing into your elbow, and limiting exposure to others.

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What individuals who are taking treatment can do

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What individuals who are taking treatment can do

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2. People with TB can help prevent the spread by following through on their prescribed meds for the entire duration of their prescribed treatment. This can be months or even years. This has understandable difficulties in some parts of the world and for some people, but if we can make it easier for people to get access to treatment, we can help prevent the further spread of TB.

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3. Continued and expanded investment in TB treatment options and accessibility would further help prevent the spread of TB. TB is treatable, and thankfully it mutates slowly, but the spread of drug resistant TB is concerning, on top of the preventable deaths that happen every year. If TB continues to mutate and become drug resistant, it could have a truly crazy spread and kill millions and millions a year more than it already does. We need to focus on prevention to make the world healthier. The largest group that funds access to TB medications and treatment is the Global Fund. They, and other well-organized groups, can help fight TB on a global scale.