Typically, when we talk about tuberculosis (TB), we’re talking about Mycobacterium tuberculosis, which is the bacteria that causes the disease.
In research settings we often refer to the pathogen itself as MTB and the disease as TB.
While TB is most commonly known as an affliction of the lungs, you can also get it in a variety of organs and body parts: the spinal cord, the lymph nodes, the scrotum, even in your bones!
Historically, bone TB was often caused by consuming raw milk, as cows can be infected with bovine TB.
It’s estimated that bovine tuberculosis was responsible for 15% of TB deaths in 1900.
And given that TB was the second leading cause of death at that time, that’s a significant amount of deaths!
There’s also a class of bacteria known as “non-tuberculosis mycobacteria” which can cause lung disease but are not contagious between people.
Tuberculosis has been around since ancient times and caused documented illness for thousands of years before the pathogen itself was identified.
You may have heard it called “consumption” (from the Latin roots “completely” and “to take up from under”) due to the weight loss associated with the disease.
This is an extremely apt name as the bacteria in the lungs consumes the tissue, breaking it down and causing the tell-tale sign of blood-tinged coughs.
Prior to the identification of the M. tuberculosis bacteria, it was thought that TB was an affliction of the creative mind due to its prevalence in authors. It was more likely that writers were poor and lived in cramped housing, a factor that greatly increases the spread of TB.
It was also thought to be related to vampirism because of the way it would work its way through families, slowly draining the life out of each member.
It was called the “romantics disease” because of the thinness (from extreme weight loss) and skin pallor.
By the early 19th century, TB killed one out of every seven people who had ever
While today, the image of someone covering an absent-minded cough, only to pull their kerchief away to reveal a spot of blood is used as a symbol of the beginning of the end, before effective treatments for TB it was a very literal sign of the beginning of the end.
English Poet John Keats, upon seeing blood in his sputum, wrote to a friend “that is arterial blood…That blood is my death warrant. I must die.” And he did, one year later at the age of 24.
One year after that, on March 24th, 1882, Robert Koch (of Koch’s postulates) announced he’d discovered the bacteria responsible for the disease (this is why we celebrate World TB Day on March 24th every year).
Even today, 143 years after the discovery of MTB, tuberculosis is the number one infectious cause of death in the WORLD.
One quarter of the world’s population is currently infected with TB—about 2 billion people. In 2023, around 10 million people were sickened by TB, including 1.3 million children, and 25 million people died of the disease.
These numbers are extra crazy when you consider the fact that TB is, actually, curable.
So why is this curable disease so hard to control?
There are a number of reasons. The first issue is with the bacteria itself: it has a thick lipid layer which makes it hard for our immune systems to latch on and destroy it.
It’s also slow to multiply which means it can take a long time for someone to realize they’re infected.
There are basically two stages of TB: latent and active.
Latent TB is when someone is infected with the bacteria, but their body’s immune defenses have surrounded it in their cells and basically created a little prison for it so it can’t easily multiply and spread.
In this stage, a person is not actively ill or contagious to others. Over time though, the bacteria can break free and start multiplying again, which is what we call “active TB.”
It’s much easier to treat latent TB than it is to treat active TB, but because there are no outward signs that someone has latent TB it’s hard to identify. And it can take years for latent TB to develop into active TB, if it ever does.
Only about 5-10% of latent TB cases will go on to develop active TB.
A lot of the regions of the world that have the highest burden of TB are relying on extremely slow, or not very sensitive, tests to detect it.
Many places still only have access to smear microscopy, which requires a prepared sample and a trained microbiologist to identify the bacteria with a microscope.
It’s actually the same 143-year-old technology that Koch used to first identify TB.
And that’s just for smear positive cases which have a lot of TB bacteria.
Someone could be smear negative but culture positive (meaning they are less infectious but still have active disease), but you have put sputum samples on a plate and put those plates in an incubator for several days to weeks to see if the bacteria grow.
And then you need to figure out the drug susceptibility of the TB. Because it’s a bacteria, it runs the risk of developing resistance to the antibiotics used to treat it. And it has developed resistance.
There are two kinds of antibiotic resistance: primary and secondary.
Primary resistance is when someone becomes infected with bacteria that’s already resistant to one or more of the most commonly used antibiotics.
Secondary, or “acquired,” resistance is when someone who was originally infected with drug-susceptible TB develops resistance, usually as a result of patients not being able to take all of their treatment or not being able to take their medications as often as prescribed.
Despite the fact that the technology exists to rapidly test for drug resistance in TB (within a few hours), many of the places with the highest TB incidence don’t have access to these machines.
Instead, they have to rely on growing the bacteria on plates or in tubes with antibiotic samples, which can take weeks to determine if the bacteria is resistant to drugs.
So, in the meantime you have to start treatment with a broad level of coverage (which means multiple antibiotics) in case the bacteria are resistant to one or more drugs.
This comes with a huge risk of things like people discontinuing due to side effects, not being able to maintain taking the high number of daily pills or injections, or the potential for their access to treatment to be interrupted over the sometimes two years of daily medication it can take to fully treat an infection.
So, getting better diagnostics and susceptibility testing for the areas most affected would be a huge game changer.
One of the single most important issues is still treatment.
Prior to the discovery and synthesis of antibiotics, people tried all sorts of things to cure TB: There are the classics like bloodletting or purging, you could inhale various vapors, or even have your diseased lung collapsed by a surgeon to let it “rest.”
While all these “treatments” were attempts to grasp at straws, one of the most pleasant was certainly the increased popularity of sanatoriums—specialty hospitals for convalescing the chronically ill before we had any treatments.
Born of the idea that a "change of air” could help cure the disease, sanatoriums were often found out west, or by the seaside, or in mountains, or in Italy, and involved long days of rest in the fresh air.
Tuberculosis sanatoriums are responsible for a number of history tidbits you might not be aware of.
For example, the Adirondack chair was designed for TB consumptives to comfortably sit and wait for death or recovery in the brisk mountain air.
The obvious cure for the wet cough of TB was thought to be the dry air of the West.
It wasn’t until New Mexico saw an influx of people seeking respite from TB in the sanatoriums there that the U.S. government finally decided the territory was worthy of statehood.
These western centers are also responsible for giving us cowboy hats, as a young consumptive hatmaker by the name of John Stetson left his home in New Jersey to heal in Missouri and noticed the headwear in the area was not appropriate for the climate.
And the Beatles! Ringo Star had TB as a youth and his time in a sanatorium is where he first began learning to drum to pass the time.
Finally, in 1943, the first antibiotic to treat TB was developed.
Streptomycin changed the game for TB treatment options, as in, there finally were some.
There were few other drugs and combinations that came along until 1968, when rifampicin was developed. Then there were no new treatments for 25 years.
We get Rifapentine in 1998, and then 14 years after that we get bedaquiline. We stopped TB drug development for nearly 40 years because what we had was working and it stopped affecting high income countries.
That’s why it can be the number one infectious disease killer that you personally don’t worry about. But, just like with every infectious disease, when you don’t care about it because it’s not directly affecting you, it eventually comes back to bite you in the buns, and TB has developed massive resistance to the very few drugs we have.
We now have multidrug resistant TB.
Multidrug resistant TB has always been an issue. That’s TB that is resistant to isoniazid and rifampin, two of the most effective first-line TB medications.
But in 2006, Extensively Drug-Resistant TB (XDR TB) was identified as a huge problem.
XDR-TB is resistant to multiple of the first and second line TB drugs, greatly limiting options for treatment.
There are a number of reasons it could have developed, due to incorrect antibiotic prescribing or not having broad enough coverage in immunocompromised people which leads to resistance, but in any case it’s been an uphill battle—but there are some rays of light.
In 2019, we got pretomanid. And the combination of bedaquiline (which you’ll recall was developed in 2012), pretomanid and linezolid (adorably called BPal) took the treatment of XDR from 23 pills a day for 20-24 months including daily injections for the first six months to 5 pills a day for, on average, six months.
But we are already seeing resistance to BPal.
When HIV develops resistance to antiretrovirals used to treat it, people are simply given a different antiretroviral.
This is able to happen because there has been so much funding, advocacy, and political will to respond to HIV that there are over 30 different antiretrovirals available for treatment.
We have known what causes TB for over 140 years, and yet between the 1960s and the late 1990s, drug development just
If we could develop new antibiotics to make new combination therapies, we wouldn’t even have to worry about who had drug susceptible TB or MDR or XDR. We could just treat everyone the same way, because we’d have so many options. Resistance wouldn’t be an issue.
The biggest problem with controlling TB is getting people to care.
Have you ever met someone who has TB? If the answer is “no,” I invite you to think about how that’s possible, given that a quarter of the world's population has it.
TB is predominantly an affliction of the poor, it’s not a disease the makers of drugs or diagnostics can really profit off of, and that makes it hard to encourage the development of new products and discourages tactics that keep the profit margins as wide as possible.
Even with the drugs we do have, most of which have been around so long they have no patent and are very cheap, we lack the political will to get those drugs to the people who need them.
Beyond treatment, a huge amount of TB disease could be prevented even if we just made sure people had enough to eat.
Malnutrition is the number one indicator for someone’s risk of developing active TB.
We have the potential to prevent millions of TB cases just by feeding people.
So, there are a lot of little problems in trying to control TB.
But the thing that all of these really have in common is they can pretty easily be overcome if we had more funding. TB kills twice as many people every year as HIV does and yet has a fraction of the funding.
Now, with the cuts to USAID, TB has even less funding.
Many countries depend on foreign aid to keep their tuberculosis control programs running, USAID provides about a quarter of all donor funding for TB, and the United States provides half of all international funding for TB—or at least it did.
It’s estimated that as a result of the USAID funding freeze, which began January 24 of this year, there have been nearly 4,000 additional TB deaths, and over 6,000 additional infections.
And if I can’t convince you to care about the impact TB has on others, maybe I can convince you to care about the impact it could have on you.
TB cases in the U.S. have been on the rise. There’s a saying that TB anywhere is a threat to people everywhere, and without continued commitment to global tuberculosis control, you might end up finally meeting someone who has TB a lot sooner than you’d like to.
