The Deadliest Infectious Disease of All Time | Crash Course Lecture

This is the story of the

deadliest

infectious

disease

of all

time

. It has been with us for 3 million years, since before humans were homo sapiens. We have evidence of this in ancient Egyptian mummies and it is mentioned in the Hebrew Bible. We have made extraordinary medical advances. Vaccines, antibiotics and clean water have saved millions of lives. And yet, despite that, in 2022, this

disease

killed more people than malaria, typhoid, cholera, homicides and war... combined. It has had many names. In ancient China, it was known as huaifu, meaning "destroyed palace." In ancient Hebrew, “schachepheth”, which means to waste away.

The 19th century term: "consumption", for the way it seemed to consume the body. Today we call it tuberculosis. But tuberculosis is more than just a disease: it reveals fundamental truths about who we are as human beings and how we have changed or not changed throughout history. We are powerful enough to light the world at night, artificially refrigerate food, and reshape the balance of gases in the atmosphere. And we have even identified the cure for tuberculosis. So why do so many people continue to die from this cause? It has always seemed strange to me that when studying history we tend to focus so little on diseases.

About 90% of people die from disease, a phenomenon so ingrained in human life that we describe many of those deaths as “natural causes,” and yet if you go to a university survey of human history, you will learn more about wars and empires and trade routes than about microbes. As Virginia Woolf wrote in On Being Sick, it is “strange indeed that illness has not taken its place alongside love, battle, and jealousy among the chief themes of literature.” Or put another way: Hamlet never has a headache, but the rest of us do. I suspect we want to imagine that we choose our destiny, that human history is largely the history of human choice.

Perhaps that is why rumors circulated that Alexander the Great died of poisoning, although he almost certainly died of typhoid or malaria. We simply don't want a world where even the most successful emperor in the world can be taken down by a simple infection. And yet, that is the world we live in: a world where diseases shape history in profound ways. But also a world where history shapes the disease. Anyone can get tuberculosis, but not everyone has the same chance of getting it. And certainly not everyone has the same chance of dying from it. And to understand why, I had to go back a long

time

to discover how our early knowledge of tuberculosis evolved, along with culture, into the problem we face now.

First, let me give you a very basic overview of our current understanding of the disease, which can be summarized as: Tuberculosis is rare. It is an

infectious

disease, meaning it is caused by germs. Like COVID-19, it is transmitted through the air we breathe. And you may be surprised to know that about a quarter of all humans are currently infected with Mycobacterium tuberculosis. But only 5 to 10% of them will progress to what is called “active disease,” which is when the infection makes you chronically ill. If an infection develops into an active disease, it usually occurs within two years of the initial infection, but tuberculosis can also lie dormant for decades before suddenly exploding.

What causes this progression to active disease? Well, again, it's complicated. We don't know entirely, but risk factors include malnutrition, lack of access to medical care, crowded housing conditions, and a severely compromised immune system, especially from undertreated HIV infection. But even once the disease becomes active, its

course

is extremely unpredictable: it can kill its victims within a few weeks or many years. It usually attacks the lungs, but can also invade other organs, such as the brain, pancreas, or spine. For reasons we do not fully understand, some patients will recover without treatment, but most, if left untreated, will eventually die of tuberculosis.

Much of this strangeness is related to the bacteria itself. Mycobacterium tuberculosis has an unusually fatty and thick cell wall, making it difficult for infection-fighting cells to destroy bacteria. So the bacteria is surrounded, first by one white blood cell and then by many, which creates this ball of calcifying tissue called a tubercle. As long as these loosely spherical tubercles contain the bacteria within them, active disease never develops, but if the bacteria escape and the immune system is not strong enough to surround all the new bacteria with tubercles, the body can slowly become overwhelmed. for the infection. eventually leading to death.

Now, because it takes so long to build the complicated fortress of its cell wall, Mycobacterium tuberculosis has an incredibly slow growth rate compared to other bacteria. As in laboratory environments, E. coli divides and replicates approximately once every 20 minutes; Mycobacterium tuberculosis divides approximately once a day. And that's why infections simply take longer to make a person sick. In short, tuberculosis is not like a plague that sweeps through a community, where one member of a household becomes ill and everyone else in the household becomes ill three days later. It's not like cancer or heart disease that affects one person in a household but rarely spreads to others.

And it's not like an E. coli infection where you suddenly become violently ill. And being so fundamentally different from other infections is precisely why classical interpretations of tuberculosis varied so much, and why, even today, the stories we tell ourselves about the disease reveal at least as much about humans as they do about the disease. tuberculosis. Therefore, it would not be accurate to say that we thought about tuberculosis in one way or another in ancient times; We thought about it in many different ways. Some communities believed that the disease was genetic; others thought it was contagious. Some thought it was caused by bad air; others due to a lack of harmony of the fluids within the body.

Some even came close to a germ theory of the disease. Hundreds of years before humans invented the microscope, the great Persian scholar and poet ibn Sina wrote that diseases like tuberculosis were caused by “contaminated foreign organisms that are not visible to the naked eye.” Which, very impressive, but there's no way to confirm it before microscopy. I want to pause here to point out a defining characteristic of humans, which is that we like to know why things happen, especially why really bad things happen. And if a reason isn't immediately evident, we'll find it. I am reminded of a short poem by Kurt Vonnegut: “The tiger must hunt, the bird must fly;

The man came to sit and wonder 'why, why, why? The tiger fell asleep, the bird landed; The man has to tell himself that he understands.” And this brings us to an important facet of understanding human responses to illness: stigma. As part of our desire to answer the question “why, why,” by telling ourselves that we understand, humans commonly construct moral and ethical narratives around illness. My father had cancer twice when I was a child and I saw some of this firsthand. People stayed away from us. Some said he got cancer because his parents smoked, or because he didn't exercise enough, or because he didn't eat broccoli, or whatever.

And it is true that secondhand smoke and poor diet are risk factors for cancer, but it is also true that the vast majority of people whose parents smoked do not get cancer when they are 32 years old and the parents of two young children. We don't want to have a world that is simply unfair, where some people get sick not because they have done something wrong, but because the world is unfair, and to the extent that it is fair, it is random. And then we tell ourselves that we understand, which too often means creating explanations that blame the sufferer.

Stigma is a way of saying, "You deserved this to happen," but within stigma it is also implicit: "And I don't deserve it, so I don't need to worry about it happening to me." Stigma can become a kind of double burden for sufferers: in addition to living with the physical and psychological challenges of the disease, there is the additional challenge of having their humanity dismissed. Consider the word, universally used in English, to describe tuberculosis patients in the 18th and 19th centuries: they were called invalids. They were literally invalids. People living with tuberculosis today have told me that fighting the disease was difficult, but fighting the stigma in their communities was even more difficult.

Now, stigma is very complex, of

course

, but researchers have identified certain characteristics of highly stigmatized diseases. Chronic diseases are more likely to be stigmatized than acute ones, for example, as are diseases with high levels of perceived danger. And, fundamental to understanding tuberculosis, stigma can be exacerbated if a disease is understood to be infectious. Finally, the origin – or perceived origin – of a disease also matters. If an illness is seen as the result of a choice, it is much more likely to be stigmatized. So, for example, people with major depression are often told to simply choose to be happier, just as people with substance abuse disorders are told to simply choose to stop drinking.

And some cancers and heart diseases are also stigmatized for being the result of a supposed choice. Of course, biology doesn't work like that: disease has no moral compass. It does not punish evil and reward good. He knows neither evil nor good. But we want life to be a story that makes sense, which is why, for example, until the mid-20th century it was commonly believed that cancer was caused by things like social isolation. In fact, parents were told that their children contracted leukemia because they had not been loved properly as babies. If there is no clear cause and effect, we will invent one, even if it is cruel, because tigers must sleep, birds must land, and man must tell himself that he understands.

Tuberculosis occupies an interesting place in this conversation: it is a chronic disease with high levels of perceived danger, but it was not always understood to be infectious and, in much of the world, it was not considered an option. And yet tuberculosis was a highly stigmatized disease: it was often associated with demonic possession, excessive alcohol consumption, or moral fragility. But in northern Europe, beginning in the mid-18th century, it became untenable to understand the disease then known as consumption through a solely stigmatic lens. The disease had skyrocketed, especially in British cities and the North American colonies. Stigmatizing a disease becomes more difficult when everyone seems to suffer from it, not just the poor or vulnerable, but even the rich.

I mean, the richest individual of the 19th century died of tuberculosis at the age of 56. He killed presidents, kings, poets and actresses. And so, suddenly, consumption became an idealized disease: a disease of beauty, refinement, and intellectual sophistication. “Death and decay are often beautiful,” wrote Henry David Thoreau, “like the pearly tear of shellfish or the frenetic glow of consumption.” Therefore, it may be tempting to think that romanticizing an illness would be better than stigmatizing it. But, as someone who suffers from mental illness, I understand firsthand that the two are not entirely separable. Both strategies ultimately differentiate the victim, imagining them somehow removed from the social order.

Mental illness is often romanticized as a malaise that generates creative genius or other superpowers. But of course, mental illness is also highly stigmatized in our culture. And so, romanticization and stigmatization are essentially complementary strategies for expelling people from society and finding a story that makes sense of why “those people” ended up sick. In the case of consumption, this idealization is deep... and broad. For example, once you start to notice the impacts of this story on contemporary culture, you start to wonder if there is anything in our lives today that is not related to tuberculosis. Classically, consumption was considered a disease of the air.

It was a disease of breathing, of the place where the body interacts with the atmosphere. Let us consider many of our words for the human soul: the ruachHebrew, Chinese chi, English spirit, and Inuit sila are derived from words meaning breath or respiration. Breath is life: being inspired is literally breathing; to be expired is literally to exhale completely. And so it was easy to turn this disease of the breath into a disease of the spirit, of chi, of sila and of ruach. So much so that consumptives were sometimes seen as models of brilliance and beauty. In men, consumption was believed to take creative powers to new levels.

Scholars pointed to the fact that everyone from Stephen Crane to Frederic Chopin to the sculptor of the Statue of Liberty died of consumption. (Less attention was paid to the fact that, in a world where approximately 30% of all northern Europeans died of disease, it should not be especially surprising that many northern European artists and writers died of it.) The magazine at the time linked tuberculosis to authors in particular, writing that an author's “deviance, bad temper, irascibility, misanthropy, murky passions... are attributable to his peculiarities and constitutional conditions.” And that is precisely what I mean when I say that romanticization is not a kind or generous way to treat the sick.

I am an author and, for my part, I am deeply offended by the idea that my rebelliousness, bad temper, irascibility, misanthropy, and murky passions are caused by a disorder of bodily health, even though I am impressed by the capacity of a magazine of the 19th century to absolutely define my personality. It is difficult to overstate how deep the link between consumption and male creative genius was believed to be. It is said that Victor Hugo's friends, for example, joked with him that he could have been a great novelist if he had contracted consumption. Lord Byron wrote: "I think I should like to die of consumption... because then all the women would say, 'Look at that poor Byron, how interesting he looks when he dies!' And if northern European men were considered to reach greater artistic and creative heights through consumption, then women were believed to become more beautiful, ethereal and wonderfully pure.

As Charlotte Brontë said two years after the publication of her novel Jane Eyre: “I am aware that consumption is a flattering disease.” That flattering illness, by the way, would also kill Charlotte and her three sisters. Patients with active tuberculosis often become pale and thin, with rosy cheeks and deep-set eyes due to the low oxygenation of the blood and fever that accompany the disease. Like the English actress Eliza Poe, whose beauty was widely admired, she had a stereotypically tuberculous appearance: her rosy cheeks, alabaster skin, wide eyes, and tiny body were the result of consumption, which killed her in 1811. , when I was 23 or 24 years old.

Her son, Edgar, was two years old. Edgar Allen Poe would go on to describe many of the women in his stories and poems as equally thin, pale, and large-eyed. By the time of Eliza's death, so-called “consumptive chic” had taken over European beauty standards. American and European magazines encouraged women to apply poisonous belladonna to their eyelids to dilate their pupils so they could have that wide-eyed, consumptive look... and offered instructions on how to apply red paint to their lips and cheeks to capture the frenetic glow of the skin. consumptive fevers. It probably doesn't need to be pointed out that, from runway shows to fashion magazines, these beauty standards are still shaping what is considered female beauty.

But tuberculosis not only shaped the makeup and beauty standards of the time, but also fashion, which, for women, sought to emphasize the visible symptoms of the disease. The most striking clothing was the pointed corset, which emphasized the narrowness of women's waists (by the way, the similarity between “waste” and “waist” is an etymological coincidence in English, but revealing). These corsets were so restrictive that women were limited in the types of physical activities they could perform and struggled to breathe deeply, mirroring the experience of actual consumption. And so consumption had become fully glamorized and idealized. "There is a terrible disease," wrote Charles Dickens in Nicholas Nickleby, "...in which the struggle between soul and body is so gradual, silent, and solemn...that the spirit becomes light and sanguine with its burden flash of lightning".

Dickens did not name the disease, nor did his readers need him to. Everyone knew the disease that shrank the body and enlarged the soul. But of course this contradicted the true violence of consumption. Perhaps the most famous tuberculosis victim of the 19th century was the English poet John Keats. When an autopsy was performed on Keats' body a couple of days after his death at the age of 25, the doctor wrote: "The lungs had completely disappeared." This was – and is – the truth of death from tuberculosis. Those affected often suffocate as blood and pus fill their lungs. They die without oxygen, in agony.

This is where the idealization of tuberculosis becomes, believe it or not, even more insidious. For behind all these changes was a feeling that consumption was, as some 18th-century observers put it, a disease of civilization. People at the time knew that city dwellers were much more likely to develop drug use than those in rural communities, and this concept of drug use as a civilized disease also meant that it could not be a disease of uncivilized people, which led to a racialization of the population. the illness. In Europe and the United States, most white doctors believed that tuberculosis could only infect white people, and was sometimes known as “The White Man's Plague.” One American doctor, for example, called it “a disease of the master race, not of the slave race.” As Frank Snowden writes: “In the United States, the prevailing view was that African Americans contracted a different disease.

This phenomenon also spread to other colonial empires. Many European colonialists believed that tuberculosis was rare or nonexistent among people of color. In reality, there were many illnesses and deaths from consumption in colonial South Asia and Africa, and many local health care providers attempted to draw attention to the crisis. But the colonial authorities did not detect it or count it because the entire premise of colonialism was based on white supremacy, and the genetic understanding of consumption was based on the idea that only supreme people could contract it. Recognizing that consumption was common among enslaved, colonized, and marginalized peoples would have undermined not only the theory of consumption, but the project of colonialism itself.

Towards the end of the 19th century, the idealization of consumption began to decline as it became increasingly obvious that the disease was not exclusively or primarily a disease of the rich and brilliant. Scholars had begun to look away “from the languid, fainting young women and their romantic lovers,” write René and Jean Dubos. “Instead, they realized the miserable humanity that lived in the gloomy dwellings born of the Industrial Revolution. In the “tentacular cities” they saw crowds of men, women and children, also pale, often cold and hungry, working long hours in dark, crowded shops, breathing smoke and coal dust.

Tuberculosis was there, generating suffering and misery without romance.” Still, discussions continued over the cause of the disease until 1882, when a “pesky little organism” called m. tuberculosis, was first identified by doctor Robert Koch. In the years that followed, the replication and acceptance of Koch's research meant that the era of consumption—as an inherited condition that grew the soul by shrinking the body—slowly faded. Consumption could no longer be understood as a hereditary condition shaped by sad passions and wonderfully translucent skin. Now it was a disease of germs, a disease of filth, overcrowding and poverty. The era of tuberculosis had begun.

From your local tuberculosis association... Today, we understand that the explosion of tuberculosis in the 19th century was primarily a result of the Industrial Revolution, which led to crowded living conditions in cities where workers could easily spread the disease. tuberculosis among themselves, and where widespread malnutrition – a major risk factor for developing active diseases – made people especially vulnerable. And so, just as Britain was ground zero for the Industrial Revolution, it was also ground zero for the rise of tuberculosis. And we have also seen tuberculosis grow with industrialization in other communities, from India to Nigeria. “The parallel journey of tuberculosis with capital,” as Vidya Krishnan says, has been seen in outbreak after outbreak.

But at that time industrialization was not considered to be the culprit. Instead, as understanding of tuberculosis came to focus on poverty rather than romance, racialized stigma took a 180-degree turn. While previously black and brown people were considered incapable of contracting such a beautiful disease; Now they were blamed for it. "The black race suffers from tuberculosis, which contaminates the country," wrote one American official. Racialized medicine no longer held that high rates of consumption among whites were a sign of white superiority; Instead, racialized medicine now held that high rates of consumption among blacks were a sign of white superiority.

But of course, none of that was true. Blacks were not more susceptible to tuberculosis due to factors inherent to race; They were more susceptible to tuberculosis due to racism. Tuberculosis especially attacks those who are marginalized, not because of their choices or habits, but because they are marginalized. It is important to note that all of this racialized medicine was questioned (it was obvious nonsense from the beginning and there was strong pushback), especially from black healthcare workers. After a white doctor claimed that “the Negro is to blame for his own susceptibility to tuberculosis,” a black doctor wrote a response arguing that this type of racialized medicine “smelled more like a cheap politician seeking notoriety and positions by playing with passion and prejudice than a doctor who discusses, philosophically, a scientific topic for the dissemination of knowledge.” Which is the medical version of an extraordinarily sick burn.

And, in fact, this prejudice against marginalized people and the health workers who care for them has proven to be one of the great enablers of tuberculosis over the last century. Even after establishing that tuberculosis was an infectious disease caused by bacteria, no one was quite sure how this disease spread. But the man had to tell himself that he understood, so the focus was on the types of places and environments that seemed to foster tuberculosis outbreaks: crowded housing and dirty factories. Some public health efforts had a significant impact: covering coughs or sneezes with a tissue, which actually decreased the risk of spreading tuberculosis, as well as discouraging spitting in public places such as trams and sidewalks, which was common in the USA at that time. .

People were also told not to kiss babies. Or…kiss at all. Another obsession was dirt and dust. Which again changed fashion, grooming and social habits. “There is no way to estimate the number of harmful bacteria and germs that can hide in the Amazon jungles from a face with a big mustache, but their number must be legion,” argued Dr. Edwin Bowers in 1916. Fear that the germs of tuberculosis get caught Bearded people sparked what Harper's Weekly called “the anti-mustache revolt,” ushering in an era of clean shaves. For women, hemlines shortened as anxiety grew that floor-length dresses might pick up tuberculosis germs from dirty floors.

Vidya Krishnan notes that “as women's hemlines rose a few inches in the early 20th century, shoes became an important feature of women's fashion.” By the early 20th century, entire industries had sprung up in the United States to try to treat tuberculosis. I felt sad, I felt sad because of the tuberculosis. I became sad about tuberculosis... It was believed that dry air, sunshine and rest were the best treatments available, so sanatoriums sprang up around the world where tuberculosis sufferers could rest and breathe fresh air. world. ...when the doctor can say "Go on your way"... Southern California became known as "the land of new lungs." In a mass migration that rivaled the gold rush, consumptive patients traveled west and, if they survived, started families, reshaping the landscape of the United States.

In 1920, about 10% of all people living in New Mexico were tuberculosis patients whoThey lived in sanatoriums, where dry air and open spaces were said to heal the lungs. Blue and low, very, very, very low, very low Aiming at that doctor in the confrontation. Preparing for that special day when the doctor can say "Go on your way"... Life in these sanatoriums can be terribly boring for those who suffer from it. The job of the so-called “invalids” was to improve their health by being very still. For example, one sanatorium patient, Elizabeth Mooney, wrote: "I don't do anything all day except stand here looking at the mountains.

I wish they would rearrange them a little." Relatives were discouraged from visiting the sick, not only because visits carried the risk of spreading infection but also because they were considered harmful to health. People could get excited and you couldn't be excited because you had to rest. You were often discouraged from even reading books and there was no such thing as YouTube. Many patients recovered in sanatoriums (rest and proper nutrition are much better for the body than malnutrition and stress), but recovery rates do not appear to have been much higher for those who took the so-called “travel cure” than for those who took the so-called “travel cure.” who lived at home as invalids.

However, separating millions of sick people from their homes slowed the spread of the disease within families, and combined with better overall nutrition, safer housing, and lower poverty rates, tuberculosis declined worldwide. Between 1882 and 1930, overall mortality from this disease in the United States fell by about 80%. But those improvements were not evenly distributed across the American population: the declines for African Americans and Chinese Americans were much smaller, and for indigenous peoples, there was very little decline. Even as we developed better tools to diagnose and treat tuberculosis (including the stethoscope, the X-ray machine, and chest drains), the disease remained fundamentally incurable.

But then, between 1940 and 1965, eight different kinds of drugs killed me. tuberculosis were discovered and synthesized. But of course there was a problem. Because the tuberculosis bacteria with its waxy coating is extraordinarily difficult to kill, each of these drugs had to be given long-term to be effective. And that meant the bacteria had more time to develop resistance to the drugs. Furthermore, no single drug was capable of treating tuberculosis. So, it was not until the mid-1950s that a combination treatment involving three different drugs was tested and approved and, for the first time in human history, tuberculosis became curable.

As treatment, case finding and contact tracing improved, new cases of tuberculosis could be identified and treated. But in impoverished communities, which the rich world had long believed were immune to tuberculosis, the disease continued to kill millions each year. Attempts to bring combination therapy to colonized regions were haphazard and inconsistent, forcing many people in poor communities to seek out all the antibiotics they could, regardless of their effectiveness against tuberculosis. In 2000, Ugandan physician Dr. Peter Mugyenyi gave a speech about the global failure to bring HIV medications to impoverished communities. "Where are the drugs?" he asked. “Drugs are where the disease is not.

And where is the disease? The disease is where the drugs are not.” The same thing happened with tuberculosis. By the mid-1960s, curative therapy for tuberculosis was available everywhere except where it was most needed. I mentioned earlier that in the 25 years between 1940 and 1965, eight different classes of drugs were developed to treat tuberculosis. And then, in the 47 years between 1965 and 2012, no new drugs were synthesized to treat tuberculosis. The reason for this is simple: as tuberculosis declined in rich countries, the profit incentive for research into new drugs disappeared, and funding dried up as a result. When tuberculosis stopped being a problem for the rich, it not only stopped being idealized;

It also ceased to exist in the minds of many. But a pharmaceutical research system driven exclusively by the incentive of profit is, of course, not the only way to develop drugs. As Dr. Carole Mitnick told me, the failure to develop drugs for diseases that are not considered profitable is “a human-made problem that needs a human solution. … If drugs were a public good, the disease burden would drive industry priorities and tuberculosis treatment would be varied and abundant.” In short, there is nothing inevitable about living in a world where the development of drugs that lengthen eyelashes is more rewarded than the development of drugs to treat tuberculosis.

So all of this combined to keep tuberculosis death rates stable in much of the developing world, even as they declined precipitously in rich nations. And then, in the early 1980s, doctors and activists in the Global South began sounding the alarm about an explosion of unusually rapid and severe tuberculosis deaths that appeared to be associated with a new pandemic, that of HIV/AIDS. Because untreated HIV reduces resistance to infection, TB infections are much more likely to progress to active disease as the immune system weakens. And although many pointed out this connection in the mid-1980s, little was done to expand access to tuberculosis or HIV medications.

This inaction contributed to tens of millions of deaths from the intertwined HIV and tuberculosis pandemics. In fact, between 1982, when the term AIDS was first used, and 2005, when HIV deaths in poor countries finally began to decline thanks to greater access to treatment, roughly as many people died from tuberculosis as in the First World War. World War and in World War II. II combined. At a tuberculosis conference not long ago, I met a young South African woman named Phumeza Tisile, who was diagnosed with tuberculosis when she was a teenager. She had just received a full scholarship to college, but from the beginning of her freshman year, something felt off.

She had lost weight and had difficulty breathing, and eventually had trouble walking up stairs. “So I went to the clinic and coughed into a cup,” she explained to me. Although we now have extremely accurate molecular tests for tuberculosis, they are still unnecessarily expensive, so tuberculosis is still most commonly diagnosed when a person looks at a sputum sample through a microscope and tries to identify the tuberculosis bacteria in it. that sample, which is exactly how Robert Koch diagnosed tuberculosis in 1882. Unfortunately, microscopy misses about 50% of positive cases, and Phumeza was told, catastrophically, that his tuberculosis result was negative.

But she kept getting sicker and sicker. She had to leave school. Her weight dropped to 70 pounds. “I had a hard time breathing,” she recalled, and they finally took a chest X-ray, after which it was obvious that tuberculosis was in all of her lungs. She immediately began standard treatment for tuberculosis. Now I have to digress a little here to explain a protocol that has been around since the late 70's, called Directly Observed Therapy (short course). The thing to understand about DOT is that it really only exists due to a lack of trust that certain patients will take their medications consistently.

You may remember that tuberculosis is particularly susceptible to developing antibiotic resistance, which worsens with random treatment. So the idea behind DOTs is for a healthcare professional to directly observe patients taking their medications every day. And at first, this protocol helped because any regular access to adequate supplies of appropriate antibiotics was good news. But requiring patients to find their way to a clinic or doctor every day for months, or to live in inpatient facilities to receive their daily medications, creates extreme challenges for many with tuberculosis. As Dr. Jennifer Furin told me, tuberculosis “is the only disease I know whose therapy is based on fundamental mistrust.” It has now long been argued that antibiotic resistance is driven by so-called "patient non-adherence", that is, patients not taking their medications.

And it is true that many tuberculosis patients do not complete their entire regimen. But the concept of “compliance” gets really complicated when you look at the level of the individual patient experience. When she was finally diagnosed, Phumeza couldn't walk to the clinic alone. She was just too sick. And public transportation was expensive, not to mention the potential for spreading the disease. Did his inability to access her daily treatment make her noncompliant? Fortunately, Ella Phumeza was able to avoid DOTs because South Africa had recently started allowing seriously ill people to take home two weeks of treatment. But after two weeks, she had to return to the hospital for more medication and it was clear that she was not getting better.

Eventually, Phumeza was hospitalized, and after months of treatment, it was discovered that the medications were failing because she had multidrug-resistant tuberculosis, also called MDR-TB. When she found out about her diagnosis, she told me, “I was looking for things online and it was really scary to see because on Google a lot of the people in the pictures were already dead. Their ribs were exposed and I thought I would be like that too. “I thought I was probably going to die.” At the time, the only treatment regimen available for Phumeza included painful injections and dozens of pills taken each day, and the injections carried a very high risk of permanent hearing loss.

One day, as Phumeza said, “I woke up and everything was quiet.” As it turned out, Phumeza did not have MDR tuberculosis; her particular strain of tuberculosis was resistant to even more drugs, making it pre-XDR tuberculosis or pre-extensively drug-resistant tuberculosis. The painful injection she received that caused total and permanent hearing loss for four years until she received a cochlear implant? That drug didn't help her at all. If Phumeza had been able to access molecular testing, or if her tuberculosis had been correctly identified from the beginning, her hearing and so much suffering could have been saved. Instead, she was undergoing tuberculosis treatment for three years and eight months, during which time she took between 20 and 30,000 pills before she was finally cured.

For many patients, this will still be the reality in 2024, even though we now have treatment protocols that can cure patients with drug-resistant tuberculosis in just six to nine months, with five to seven pills per day. These medications and protocols are just beginning to reach those who need them most. But every year more people access these best treatments, even if late, and this is due, in large part, to Phumeza herself. Today she is a university graduate, sociologist and a leading voice in the fight against tuberculosis, whose efforts have helped increase access to life-saving medications. But I ask you to act now.

I ask you for change. Thank you. Bedaquiline, first launched in rich countries in 2013, is a key drug for treating drug-resistant tuberculosis, but for years the price had been artificially high due to a lack of competition. With the support of the organization Doctors Without Borders, Phumeza and her friend Nandita Venkatesan filed a lawsuit in India to prevent the pharmaceutical company Johnson & Johnson from extending the drug's patent beyond its initial expiration date of 2023. Phumeza and Nandita were successful convincing Indian courts that J&J should not have a permanent patent on this critical drug, eventually allowing competition from generics and the much less expensive bedaquiline.

Experts estimate that more than 50,000 people with MDR tuberculosis will receive treatment each year who would otherwise have had little or no chance of being cured. Many people with tuberculosis have survived thanks to Phumeza's work to expand access to diagnosis and treatment. And at the same time, she herself only survived thanks to the activism and innovation that preceded her. Until very recently, the World Health Organization's recommendations for people like Phumeza with drug-resistant tuberculosis were "supportive care," which Dr. Carole Mitnick summarized to me as "putting people in a hut on the side." off the road and wait for them to die. .” But in the late 1990s, Partners in Health, known as Socios en Salud in Peru, demonstrated through a study that in theIn poor communities, MDR-TB cure rates similar to those achieved in the best hospitals in the world could be achieved.

Still, many of the drugs that effectively treat highly resistant tuberculosis remain very expensive, not because they are made of gold or platinum, or because we have to fly to the moon to find them. They are expensive because 1) drug companies keep prices artificially high, and 2) We fear that making these drugs less rare will lead to greater antibiotic resistance. And listen, I understand the fear of antibiotic resistance. It's not just about tuberculosis: the idea of ​​a world where we can't treat bacterial infections is truly terrifying. But that should never mean that we reserve the most powerful and effective medications for the rich.

I would not accept my son being denied the best treatment available for tuberculosis. How can I ask Phumeza's family to accept such a world? I recently asked TB doctor KJ Seung: Of the 1.5 million people who will die from TB this year, how many would survive if they had access to the kind of healthcare provided to the wealthy in the UK? Japan or the United States? US.? After all, while tuberculosis is often curable today, it remains a very difficult disease to treat, especially in cases of extensive drug resistance. "How many would die if everyone could access good health care?" He asked me, as if confused by my question. "Yes," I said. "None.

Zero. No person should die from tuberculosis." We could choose to live in a world where no one dies from tuberculosis. That choice would require sacrifices, like most options: it would involve large-scale, long-term investments by countries rich to strengthen the health systems of impoverished countries. And it would require the training and employment of many more health workers and probably investments in new treatments. But we could choose that world. And instead, we choose this world. So I would say that tuberculosis in the 21st century is not really caused by a bacteria that we know how to kill. As Dr.

A. Wilberforce Williams correctly pointed out more than a century ago, the real causes of tuberculosis are "poverty, bad housing, bad sanitary conditions, bad working conditions, long hours, high rents and bad food." To put it another way, in the 21st century, the true cause of contemporary tuberculosis is, in the absence of In a better term, we. And that's bad news. But it is also good news. In 1800, there was nothing anyone could do to prevent people from dying of tuberculosis. But we no longer live in that world thanks to the accumulation and dissemination of knowledge about the disease and how to treat it.

If we are the cause of tuberculosis, we can also be the solution to tuberculosis. And that is the challenge I want to leave you with: in 2000, around 2.3 million people died of tuberculosis. In 2021, 1.5 million did so. By 2032, that figure could be cut in half or even more. Millions of lives can be saved over the next decade if we pressure our governments and other institutions to invest more in research and the global effort to provide curative therapy. We've done it successfully before: thanks to the hard work of activists, researchers and health workers, access to HIV treatment has expanded dramatically over the past two decades.

Malaria deaths have decreased precipitously. And I know that treating tuberculosis is complex – it has always been a strange disease – but it is curable. We can live in a world where no one dies from tuberculosis. We are the cause. But we can also be the cure. Thanks for watching our first

crash

course

lecture

series! Do you want to see Crash Course make more videos like this? What other topics would you like us to cover? Let us know in the comments below. If you are interested in the current fight to end tuberculosis, I invite you to check out the community of tuberculosis fighters at tbfighters.org, where many people have worked together to achieve amazing success in reducing the cost of treatment and diagnosis.

Also, your attention is important. We tend to address the problems we pay attention to, so we need more people like you who make it to the end of very long videos about tuberculosis. This video was filmed here at the Indiana Museum of Medical History and was made with the help of all these kind people. If you want to help keep Crash Course free for everyone, forever, you can join our community on Patreon.