History

Chapter 1: History

Sylvia Cardoso Leão and Françoise Portaels

Nowhere in these ancient communities of the Eurasian land mass, where it is so common and feared, is there a record of its beginning. Throughout history, it had always been there, a familiar evil, yet forever changing, formless, unknowable. Where other epidemics might last weeks or months, where even the bubonic plague would be marked forever afterwards by the year it reigned, the epidemics of tuberculosis would last whole centuries and even multiples of centuries. Tuberculosis rose slowly, silently, seeping into homes of millions, like an ageless miasma. And once arrived, it never went away again. Year after year, century after century, it tightened its relentless hold, worsening whenever war or famine reduced the peoples’ resistance, infecting virtually everybody, inexplicably sparing some while destroying others, bringing the young down onto their sickbeds, where the flesh slowly fell from their bones and they were consumed in the years-long fever, their minds brilliantly alert until, in apocalyptic numbers, they died, like the fallen leaves of a dreadful and premature autumn.

The Forgotten Plague:

How the War against Tuberculosis was Won – and Lost

Frank Ryan, 1992

 

Tuberculosis (TB) has a long history. It was present before the beginning of recorded history and has left its mark on human creativity, music, art, and literature; and has influenced the advance of biomedical sciences and healthcare. Its causative agent, Mycobacterium tuberculosis, may have killed more persons than any other microbial pathogen (Daniel 2006).

1.1. Primeval tuberculosis

It is presumed that the genus Mycobacterium originated more than 150 million years ago (Daniel 2006). An early progenitor of M. tuberculosis was probably contemporaneous and co-evolved with early hominids in East Africa, three million years ago. The modern members of M. tuberculosis complex seem to have originated from a common progenitor about 15,000 – 35,000 years ago (Gutierrez 2005).

TB was documented in Egypt, India, and China as early as 5,000, 3,300, and 2,300 years ago, respectively (Daniel 2006). Typical skeletal abnormalities, including Pott’s deformities, were found in Egyptian and Andean mummies (Figure 1-1) and were also depicted in early Egyptian and pre-colombian art (Figure 1-2).

 

 

Figure 1-1: Left: Mummy 003, Museo Arqueológico de la Casa del Marqués de San Jorge, Bogota, Colombia. Right: Computerized tomography showing lesions in the vertebral bodies of T10/T11 (reproduced from Sotomayor 2004 with permission).

Figure 1-2: Representation of a woman with pronounced gibbus (Pott’s disease?). Momil culture, 200 BC to 100 AD, Sinú River, Colombia (reproduced from Sotomayor 1992, with permission).

 

Identification of genetic material from M. tuberculosis in ancient tissues has provided a powerful tool for the investigation of the incidence and spread of human TB in historic periods. It also offers potential new insights into the molecular evolution and global distribution of these microbes (see Chapter 2). Research on ancient DNA poses extreme technical difficulties because of the minute amounts of DNA remains, their oxidation/hydrolysis, and the extremely high risk of contamination with modern DNA. For this reason, stringent criteria of authenticity for analysis of ancient DNA were recently proposed, among them: work in physically isolated areas, strict protocols to prevent contamination with modern DNA, the use of negative controls, evaluation of reproducibility in different laboratories, cloning and sequencing, and the study of associated remains (Coper 2002).

Mycobacteria are assumed to be better preserved than other bacteria due to the resistant lipid-rich cell wall and the high proportion of guanine and cytosine in their DNA, which increases its stability. M. tuberculosis are found only in the tissues of an infected host, and the characteristic pathology induced by this strictly mammalian pathogen tends to show residual microbial DNA contained in localized lesions. These bacteria are, therefore, ideal microorganisms for studying ancient DNA and were the first to be pursued. These investigations have answered important questions. They proved that TB is an ancient disease with a wide geographical distribution. The disease was widespread in Egypt and Rome (Zink 2003, Donoghue 2004); it existed in America before Columbus (Salo 1994, Konomi 2002, Sotomayor 2004), and in Borneo before any European contact (Donoghue 2004). The earliest DNA-based documentation of the presence of M. tuberculosis complex organisms was accomplished in a subchondral articular surface from an extinct long-horned Pleistocene bison from Wyoming, USA, which was radiocarbon-dated at 17,870 +/- 230 years before the present (Rothschild 2001).

Another important achievement of the studies on ancient DNA was the confirmation of the TB diagnosis in human remains that showed the typical pathology. Mycobacterial DNA was detected in bone lesions in the spine of a male human skeleton from the Iron Age (400-230 BC), found in Dorset, United Kingdom (Taylor 2005); skin samples from the pelvic region of Andean mummies, carbon-dated from 140 to 1,200 AD (Konomi 2002); and calcified pleura from 1,400 year-old remains, found in a Byzantine basilica in the Negev desert (Donoghue 1998). DNA techniques have also shown the presence of mycobacterial DNA, at a lower frequency, in bones with no pathological changes, suggesting either dissemination of the TB bacilli immediately prior to death or chronic milliary TB (Zink 2003).

Molecular methods other than PCR have also been used to demonstrate the presence of the TB bacillus in ancient remains, including mycolic acid analysis by high performance liquid chromatography (HPLC), which is used for authentication of positive PCR findings in calcified pleura remains (Donoghue 1998). Spoligotyping is a PCR-based technique used for identification and typing of M. tuberculosis complex bacteria (see chapter 9). It is a valuable tool for the study of archeological material, especially when the DNA is highly fragmented, because fragments as small as 55-60 bp long are sufficient to provide a positive result (Donoghue 2004). Spoligotyping was the method used to study the Plesitocene remains of a bison (Rothschild 2001) and was also applied to a subculture of the original tubercle bacillus isolated by Robert Koch, confirming its species identification as M. tuberculosis rather than Mycobacterium bovis (Taylor 2003).

Until recently, the search for mycobacterial DNA in human archeological specimens failed to find evidence of the presence of M. bovis, a member of the M. tuberculosis complex with a remarkably wide spectrum of susceptible mammalian hosts, and once considered a putative ancestor of M. tuberculosis (Donoghue 2004). In an up to date publication, the identification of M. bovis DNA in South Siberian human remains was confirmed by amplification of pncA and oxyR genes and analysis of regions of difference (RD) (for a comprehensive review on differentiation of species belonging to the M. tuberculosis complex, see chapters 2 and 8). These findings were obtained from remains that showed skeletal evidence of TB. Carbon-dated from 1,761 to 2,199 years ago, they seem to indicate that this population was

continuously exposed to wild or domesticated animals infected with M. bovis, which could have been reservoirs for human infection (Taylor 2007).

1.2. Phthisis/consumption

The patients suffer from a latent fever that begins towards evening and vanishes again at the break of day. It is accompanied by violent coughing, which expels thin purulent sputum. The patient speaks with a hoarse voice, breathes with difficulty and has hectically flushed cheeks. The skin on the rest of the body is ashen in color. The eyes have a weary expression, the patient is gaunt in appearance but often displays astonishing physical or mental activity. In many cases, wheezes are to be heard in the chest, and when the disease spreads, sweating is seen on the upper parts of the chest. The patients lose their appetite or suffer hunger pangs. They are often also very thirsty. The ends of the fingers swell and the fingernails curve greatly.

Caelius Aurelianus, 5th century AD (Herzog 1998)

The term phthisis (meaning consumption, to waste away) appeared first in Greek literature. Around 460 BC, Hippocrates identified phthisis as the most widespread disease of the times. It most commonly occurred between 18 and 35 years of age, and was almost always fatal. He even warned physicians against visiting consumptives in advanced stages of the disease, to preserve their reputation! Although Aristotle (384-322 BC) considered the disease to be contagious, most Greek authors believed it to be hereditary, and a result, at least in part, of the individual’s mental and moral weaknesses. Clarissimus Galen (131-201 AD), the most eminent Greek physician after Hippocrates, defined phthisis as an ulceration of the lungs, chest or throat, accompanied by coughs, low fever, and wasting away of the body because of pus. He also described it as a disease of malnutrition (Pease 1940).

The initial tentative efforts to cure the disease were based on trial and error, and were uniformly ineffective. Heliotherapy was advocated as early as the 5^th century AD by Caelius Aurelianus. Roman physicians recommended bathing in human urine, eating wolf livers, and drinking elephant blood. In the Middle Ages, it was believed that the touch of the sovereigns of England and France had the power to cure sufferers of the King’s Evil or scrofula (scrophula or struma) – the swellings of the lymph nodes of the neck, frequently related to TB. Depending upon the time and country in which they lived, patients were urged to rest or to exercise, to eat or to abstain from food, to travel to the mountains or to live underground.

1.3. The White Plague

Yet the captain of all these men of death that came against him to take him away was consumption, for it was that that brought him down to the grave.

The life and death of Mr. Badman, presented to the world in
a familiar dialogue between Mr. Wiseman and Mr. Attentive

John Bunyan, 1680

The TB epidemic in Europe, later known as the “Great White Plague”, probably started at the beginning of the 17^th century and continued for the next 200 years. Death from TB was considered inevitable and, by 1650, TB was the leading cause of mortality. The high population density and poor sanitary conditions that characterized the enlarging cities of Europe and North America at the time, provided the necessary environment, not met before in world history, for the spread of this airborne pathogen. The epidemic spread slowly overseas by exploration and colonization.

TB existed in America before Columbus’ arrival but was rare among the natives. The major outbreaks of TB among the native people of North America began in 1880, after they were settled in reservations or forced to live in barracks in prison camps. Death rates increased rapidly, and by 1886, reached 9,000 per 100,000 people (Bates 1993).

TB was also rare among Africans who lived in small remote villages. When exposed to the disease by contact with Europeans, these populations experienced a high mortality rate. Africans taken as slaves were free from TB on arrival to the Americas. Then, cases of sub-acute fatal TB developed among them. After their liberation from slavery and movement into the cities, TB morbidity and mortality rose quickly, reaching 700 per 100,000 in 1912 (Bates 1993).

There is also evidence of the presence of the disease in pre-historic Asia, but it was only toward the end of the 19^th century that peaks in incidence were observed in India and China.

In the 18^th century, TB was sometimes regarded as vampirism. These folk beliefs originated from two observations: firstly, following the death from consumption of a family member, household contacts would lose their health slowly. This was attributed to the deeds of the recently deceased consumptive, who returned from the dead as a vampire to drain the life from the surviving relatives. Secondly, people who had TB exhibited symptoms similar to what people considered to be vampire traits, such as red, swollen eyes, sensitivity to bright light, pale skin, and a blood-producing cough. They “waste away” and “lose flesh” and at the same time remain active, and conserve a fierce will to live. This dichotomy of lust and “wasting away” was reflected in the vampires’ desire for “food”, which forced them to feed off living relatives, who, in turn, suffered a similar wasting away (Sledzik 1994).

Precise pathological and anatomical descriptions of the disease began to appear in the 17^th century. Franciscus Sylvius de la Böe of Amsterdam (1614-1672) was the first to identify the presence of actual tubercles as a consistent and characteristic change in the lungs and other areas of consumptive patients. In his Opera Medica, published in 1679, he also described the progression of the lesions from tubercles to ulcers and cavities. The Latin word tuber means all kinds of degenerative protuberances or tubercles.

The English physician Richard Morton (1637-1698) confirmed that tubercles were always present in TB of the lungs. He believed that the disease had three stages: inflammation (tubercle formation), ulceration, and phthisis. Both Sylvius de la Böe and Morton regarded the disease as hereditary, although Morton did not rule out transmission by intimate contact.

Gaspard Laurent Bayle

(1774-1816) definitely proved that tubercles were not products, or results, but the very cause of the illness. The name ‘tuberculosis’ appeared in the medical language at that time in connection with Bayle’s theory. More precisely, the name ‘tuberculosis’ was coined in 1839 by the German professor of Medicine Johann Lukas Schönlein (1793-1864), to describe diseases with tubercles; but he considered scrofula and phthisis to be separate entities. These ideas were also acknowledged by Giovanne Battista Morgagni in Padua (1682-1771) and Rudolf Virchow in Berlin (1821-1902) (Herzog 1998). In contrast, René Théophile Hyacinthe Laënnec (1781-1826) from Paris, inventor of the stethoscope, and the Viennese Karl von Rokitansky (1804-1878) emphasized the unitary nature of both conditions.

The earliest references to the infectious nature of TB appeared in 17^th century Italian medical literature. An edict issued by the Republic of Lucca in 1699 stated that, “… henceforth, human health should no longer be endangered by objects remaining after the death of a consumptive. The names of the deceased should be reported to the authorities and measures undertaken for disinfection” (Herzog 1998).

1.4. The discovery of the tubercle bacillus

Not bad air, not just a weakness of the infected human body’s immune system, not any of the myriad theories that had filled the puzzled heads of his audience all of their working lives…but a bacterium. Not just a bacterium, but a bacillus the like of which had never been even suspected before, a most singular life form, with a frightening propensity to infect every cat and chicken, pigeon and guinea pig, the white mice and rats, oxen and even two marmosets, into which Koch had injected it.

The Forgotten Plague: How the War against Tuberculosis was Won – and Lost

Frank Ryan, 1992

The book De Morbus Contagiosus, written in 1546 by Girolamo Fracastoro (1478-1553), explained the contagious nature of TB. He pointed out that bed sheets and clothing could contain contagious particles that were able to survive for up to two years. The word “particles” may have alluded to chemicals rather than to any kind of living entity.

In his publication A New Theory of Consumptions, in 1720, the English physician Benjamin Marten (1704-1722) was the first to conjecture that TB could be caused by “minute living creatures”, which, once they had gained entry to the body, could generate the lesions and symptoms of phthisis. He further stated, that consumption may be caught by a sound person by lying in the same bed, eating and drinking or by talking together so close to each other as to “draw in part of the breath a consumptive patient emits from the lungs“.

In 1865, the French military doctor Jean-Antoine Villemin (1827-1892) demonstrated that consumption could be passed from humans to cattle, and from cattle to rabbits. On the basis of this revolutionary evidence, he postulated that a specific microorganism caused the disease. At this time William Budd (1811-1880) also concluded from his epidemiological studies that TB was spread through society by specific germs.

On the evening of March 24, 1882, in Berlin, before a skeptical audience composed of Germany’s most prominent men of science from the Physiological Society, Robert Koch (1843-1910)made his famous presentation Die Aetiologie der Tuberculose. Using solid media made of potato and agar, Koch invented new methods of obtaining pure cultures of bacteria. His colleague Julius Richard Petri (1852-1921) developed special flat dishes (Petri dishes), which are still in common use, to keep the cultures. Koch also developed new methods for staining bacteria, based on methylene blue, a dye developed by Paul Ehrlich (1854-1915), and counterstained with vesuvin. “Under the microscope the structures of the animal tissues, such as the nucleus and its breakdown products are brown, while the tubercle bacteria are a beautiful blue“, he wrote in the paper that followed his dramatic presentation that March evening (Koch 1882).

He had brought his entire laboratory with him: his microscopes, test tubes, small flasks with cultures, and slides of human and animal tissues preserved in alcohol. Showing the presence of the bacillus was not enough. He wanted his audience to note that bacteria were always present in TB infections and could be grown on solidified serum slants, first appearing to the naked eye in the second week. Then, he showed that, by inoculating guinea pigs with tuberculous material obtained from lungs, intestines, scrofula or brains of people and cattle that have died from TB, the disease that developed was the same, and cultures obtained from the experimental animals were identical on the serum slopes. Koch continued his speech, proving that whatever the dose and/or route he used, no matter what animal species he inoculated, the results were always the same. The animals subsequently developed the typical features of TB. He concluded saying that “…the bacilli present in tuberculous lesions do not only accompany tuberculosis, but rather cause it. These bacilli are the true agents of tuberculosis” (Kaufmann 2005).

Koch fulfilled the major prerequisites for defining a contagious disease that had, in fact, been proposed by his former mentor Jacob Henle (1809-1885). The reknowned Koch’s postulates (or Henle-Koch postulates) were then formulated by Robert Koch and Friedrich Loeffler (1852-1915) in 1884, and finally polished and published by Koch in 1890. The postulates consist of four criteria designed to establish a causal relationship between a causative microbe and a disease:

• The organism must be found in all animals suffering from the disease, but not in healthy animals
• The organism must be isolated from a diseased animal and grown in pure culture
• The cultured organism should cause disease when introduced into a healthy animal
• The organism must be re-isolated from the experimentally infected animal.

In 1890, at the 10^th International Congress of Medicine held in Berlin, Koch announced a compound that inhibited the growth of tubercle bacilli in guinea pigs when given both pre- and post-exposure. It was called ‘tuberculin’ and was prepared from glycerol extracts of liquid cultures of tubercle bacilli. Clinical trials using tuberculin as a therapeutic vaccine were soon initiated. The results were published in 1891 and revealed that only few persons were cured, at a rate not different from that of untreated patients. But, although results for treatment were disappointing, tuberculin was proven valuable for the diagnosis of TB (Kaufmann 2005).

One of Koch’s papers (Koch 1891), describing the preparation and partial purification of tuberculin served as the first description of the production

of the partially purified derivative (PPD) of tuberculin, presently used in the Mantoux test, also known as the Tuberculin Skin Test, Pirquet test, or PPD test (see chapter 13).

1.5. Sanatorium and initial therapies

…not for nothing was it famous far and wide. It had great properties. It accelerated oxidization, yet at the same time one put on flesh. It was capable of healing certain diseases which were latent in every human being, though its first effects were strongly favorable to these, and by dint of a general organic compulsion, upwards and outwards, made them come to the surface, brought them, as it were, to a triumphant outburst.

– Beg pardon — triumphant?

– Yes; had he never felt that an outbreak of disease had something jolly about it, an outburst of physical gratification?

The Magic Mountain [Der Zauberberg]

Thomas Mann, 1924

Translated from the German by H. T. Lowe-Porter, 1953

Dialogue between Hans Castorp and consul Tienappel

The introduction of the sanatorium cure provided the first widely practiced approach to anti-tuberculosis treatment. Hermann Brehmer

(1826-1889) a Silesian botany student suffering from TB, was instructed by his doctor to seek out a healthier climate. He traveled to the Himalayas where he studied the mountain’s flora. He returned home cured and began to study medicine. In 1854, he presented his medical dissertation Tuberculosis is a Curable Disease. Brehmer then opened an in-patient hospital in Gorbersdorf, where patients received good nutrition and were continuously exposed to fresh air. This became the model for all subsequent sanatoria, including the one depicted in Thomas Mann’s The Magic Mountain.

A young doctor named Edward Livingston Trudeau (1848-1915) established the most famous sanatorium in the United States at Saranac Lake, in New York’s Adirondak Mountains

(http://www.trudeauinstitute.org/info/history/history.htm). He also suffered from TB and, in 1882, became aware of Koch’s experiments with TB bacteria and of Brehmer’s sanatorium. Trudeau established the Saranac Laboratory for the Study of Tuberculosis. It was the first institution devoted to TB research in the United States (US).

Sanatoria, increasingly found at that time throughout Europe and the US, provided a dual function. Firstly, they protected the general population by isolating the sick persons, who were the source of infection. Secondly, they offered TB patients bed-rest, exercise, fresh-air, and good nutrition, all of which assisted the healing process. Many of them improved and returned to “life in the flatland”; many did not. The TB specialist, the phthisiologist, was responsible for the complete physical and mental care of the patient and the separation of TB care from the practicing clinician became commonplace.

Architectural features were essential to early sanatorium design (Figure 1-3). These included deep verandas, balconies, covered corridors, and garden shelters, furnished with reclining couches for the “Cure”, the obligatory two-hour period of rest in the open air that was frequently observed in silence (Figure 1-4). Furniture for TB patients had to be robust, able to be thoroughly cleaned and disinfected, and shaped with a concern for the patient’s anthropometric needs.

Alvar Aalto

(1898-1976), Jan Duiker (1890-1935) and Charles-Edouard Jeanneret (Le Corbusier) (1887-1965) were modernist architects and designers that adapted and interpreted the ideas of functionality and rationality derived from concepts used in the treatment of TB, and their designs for buildings and furniture became icons of modernism. Aalto won the competition of Architecture, Interior Design and Furniture Design for the constuction of the Paimio Tuberculosis Sanatorium in 1928, and Duiker designed the Zonnestraal Sanatorium. The symbolic association of light and air with healing made a profound influence on modernist ideas for design. Flat roofs, balconies, terraces and reclining chairs were subsequently adopted for the design of fashionable buildings in rapidly expanding cities such as Paris and Berlin (Campbell 2005).

Figure 1-3: Sanatorio Pineta del Carso, Trieste, Italy.

Figure 1-4: Sanatorio Pineta del Carso. Bed-rest, fresh air and good nutrition were the hallmarks of sanatorium cure.

Probably, it will never be known whether sanatorium treatment was a success or a failure, because no study was undertaken comparing the rates of mortality of sanatorium patients with those of TB patients who were similar in age, sex, and economic position, but who remained untreated or were treated by other methods. Nevertheless, physicians with a long and intimate experience with the disease were unanimous in the opinion that open-air treatment was an improvement for the average consumptive (McCarthy 2001).

During the early ’60s, many sanatoria started to close. By the middle of that decade only a few beds remained available for patients suffering from TB. Yet, the real end of the TB sanatorium began even earlier, when the depressing era of helplessness in the face of advanced TB was substituted by active therapy.

The Italian physician Carlo Forlanini (1847-1918) discovered that the collapse of the affected lung tended to have a favorable impact on the outcome of the disease. He proposed to reduce the lung volume by artificial pneumothorax and surgery, methods that were applied worldwide after 1913. These and other initial therapies are now considered dangerous and, at least, controversial:

• • Artificial pneumothorax

– pleural cavities were filled with gas or filtered air, with the result of splinting and collapsing that lung (Sharpe 1931).

• • Bilateral pneumothorax

– only parts of the lungs were collapsed in such a way that the patient could still live a relatively normal live. The patient suffered from shortness of breath caused by the reduction in the gas exchange surface.

• • Thoracoplasty

– ribs from one side of the thorax were removed in order to collapse the infected portion of the lung permanently (Samson 1950).

• • Gold Therapy

– Holger Mollgaard(1885-1973) from Copenhagen introduced the compound sanocrysin in 1925, which is a double thiosulphate of gold and sodium. He tested the compound on animals and considered it safe for human use. However, it was too toxic even in low doses. A controlled trial, completed in the USA in 1934, proved the toxic effects of gold therapy. Within a year, most European countries had ceased to use it (Bedenek 2004).

1.6. 19^th and 20^th centuries

There is a dread disease which so prepares its victim, as it were, for death; which so refines it of its grosser aspect, and throws around familiar looks unearthly indications of the coming change; a dread disease, in which the struggle between soul and body is so gradual, quiet, and solemn, and the result so sure, that day by day, and grain by grain, the mortal part wastes and withers away, so that the spirit grows light and sanguine with its lightening load, and, feeling immortality at hand, deems it but a new term of mortal life; a disease in which death and life are so strangely blended, that death takes the glow and hue of life, and life the gaunt and grisly form of death; a disease which medicine never cured, wealth never warded off, or poverty could boast exemption from; which sometimes moves in giant strides, and sometimes at a tardy sluggish pace, but, slow or quick, is ever sure and certain.

Nicholas Nickleby

Charles Dickens, 1870

When, in 1820, the poet John Keats (1795-1821) coughed a spot of bright red blood, he told a friend, “It is arterial blood. I cannot be deceived. That drop of blood is my death warrant. I must die“. He died within a year, at just 25 years of age. Keats never wrote specifically about phthisis, but his life and his works became a metaphor that helped transform the physical disease “phthisis” into its spiritual offspring, “consumption”.

The central metaphor of consumption in the 19^th century was the idea that the phthisic body is consumed from within by its passions. Spes phthisica (spes – hope + phthisis – consumption) was a condition believed to be peculiar to consumptives in which physical wasting led to a sense of well-being and happiness, an euphoric blossoming of passionate and creative aspects of the soul. While the body expired from phthisis, the prosaic human became poetic and the creative soul could be released from the fevered combustion of the body. The paleness and wasting, the haunted appearance, the burning sunken eyes, the perspiring skin – all hallmarks of the disease – came to represent feminine beauty, romantic passion, and fevered sexuality (Morens 2002).

In the 19^th century, it seemed as if everyone was slowly dying of consumption. The disease became to be viewed in popular terms, first as romantic redemption (Figure 1-5), then as a reflection of societal ills (Figure 1-6) (Morens 2002). In Alexandre Dumas’ tale “The Lady of the Camellias”, the heroine was a courtesan regenerated by love and made unforgettable by progressive consumption. It was adapted to the theatre and the movies and also inspired Giuseppe Verdi‘s opera “La Traviata”. The plot develops around the consequences of the heroine’s scandalous past, which prevents her marriage to an honorable youngster whose father objects to the relationship. Redemption is possible only through death, and, in taking her life, consumption also serves as a vehicle for punishment.

Figure 1-5: Romantic view of TB: “The Lady of the Camellias” represented by Brazilian actress Cacilda Becker under Italian director Luciano Salce, in São Paulo, Brazil (1952).

By 1896, the cause of consumption had been discovered, and TB was definitively linked to poverty and industrial disfigurement, child labor, and sweatshops. A contagious disease and shameful indicator of class, it was no longer easily romanticized in conventional artistic terms. Giacomo Puccini‘s “La bohème” (1896) portrays TB in a new environment, affecting street artists struggling with poverty and disease (Figure 1-6).

At the end of the 19^th century, the association of TB with poor living conditions and hygiene, brought to life the differenti