History of tuberculosis
From Wikipedia, the free encyclopedia
Consumption, phthisis, scrofula, Pott's disease, and the White Plague are all terms used to refer to tuberculosis throughout history. It is generally accepted that the microorganism originated from other, more primitive organisms of the same genus Mycobacterium. Contrary to previous findings stating that tuberculosis passed from animals to humans, scientific research has revealed that tuberculosis passed from humans to animals instead. Scientific work investigating the evolutionary origins of the Mycobacterium tuberculosis complex has concluded that the most recent common ancestor of the complex was a human-specific pathogen, which encountered an evolutionary bottleneck leading to diversification. Analysis of mycobacterial interspersed repetitive units has allowed dating of this Mycobacterium tuberculosis complex evolutionary bottleneck to approximately 40,000 years ago, which corresponds to the period subsequent to the expansion of Homo sapiens sapiens out of Africa. This analysis of mycobacterial interspersed repetitive units also dated the Mycobacterium bovis lineage as dispersing approximately 6,000 years ago, which may be linked to animal domestication and early farming. Human bones from the Neolithic show a presence of the bacteria although the exact magnitude (incidence and prevalence) is not known before the 19th century. Still, it is estimated that it reached its peak (with regard to the percentage of the population affected) between the end of the 18th century and the end of the 19th century. Over time, the various cultures of the world gave the illness different names: yaksma (India), phthisis (Greek), consumptione (Latin) and chaky oncay (Incan), each of which make reference to the "drying" or "consuming" affect of the illness, cachexia. Its high mortality rate among middle-aged adults and the surge of Romanticism, which stressed feeling over reason, caused many to refer to the disease as the "romantic disease."
The term phthisis first appeared in Greek literature around 460 BCE. Hippocrates identified the illness as the most common cause of illness in his time. He stated that it typically affected individuals between 18 and 35 and was nearly always fatal, leading him to forbid physicians from visiting victims of the disease to protect their reputations. Although Aristotle believed that the disease might be contagious, many of his contemporaries believed it to be hereditary. Galen, the most eminent Greek physician after Hippocrates, defined phthisis as the "ulceration of the lungs, thorax or throat, accompanied by a cough, fever, and consumption of the body by pus."
The tuberculosis epidemic in Europe, which probably started in the 17th century and which lasted two hundred years, was known as the Great White Plague. Death by tuberculosis was considered inevitable, being the principal cause of death in 1650. The high population density as well as the poor sanitary conditions that characterized most European and North American cities created a perfect environment for the propagation of the disease.
Tuberculosis in early civilization
In 2008, evidence for tuberculosis infection has been discovered in human remains from the Neolithic era dating from 9,000 years ago, in a settlement in the eastern Mediterranean. This finding was confirmed by morphological and molecular methods; to date it is the oldest evidence of tuberculosis infection in humans.
Evidence of the infection in humans was also found in a cemetery near Heidelberg, in the Neolithic bone remains that show evidence of the type of angulation often seen with spinal tuberculosis. Some authors call tuberculosis the first disease known to mankind.
Signs of the disease have also been found in Egyptian mummies dated between 3000 and 2400 BCE.
The most convincing case was found in the mummy of priest Nesperehen, discovered by Grebart in 1881, which featured evidence of spinal tuberculosis with the characteristic psoas abscesses. Similar features were discovered on other mummies like that of the priest Philoc and throughout the cemeteries of Thebes.
The Ebers papyrus, an important Egyptian medical treatise from around 1550 BCE, describes a pulmonary consumption associated with the cervical lymph nodes. It recommended that it be treated with the surgical lancing of the cyst and the application of a ground mixture of acacia seyal, peas, fruits, animal blood, insect blood, honey and salt.
The first references to tuberculosis in Asian civilization is found in the Vedas. The oldest of them (Rigveda, 1500 BCE) calls the disease yaksma. The Atharvaveda calls it another name: balasa. It is in the Atharvaveda that the first description of scrofula is given. The Sushruta Samhita, written around 600 BCE, recommends that the disease be treated with breast milk, various meats, alcohol and rest. The Yajurveda advises sufferers to move to higher altitudes.
The first mention of tuberculosis in Chinese literature appears in a medical text written by Emperor Shennong of China (2700 BCE). A relative of his, the Yellow Emperor, wrote Huangdi Neijing, another classical Chinese medical text, in which he describes xulao bing (weak consumptive disease), which is believed to be tuberculosis. He describes the persistent cough, abnormal appearance, fever, a weak and fast pulse, chest obstructions, and shortness of breath.
Hippocrates, in Book 1 of his Of the Epidemics, describes the characteristics of the disease: fever, colorless urine, cough resulting in a thick sputa, and loss of thirst and appetite. He notes that most of the sufferers became delirious before they succumbed to the disease. Hippocrates and many other at the time believed phthisis to be hereditary in nature. Curiously, one prominent figure that disagreed with the hereditary nature of phthisis was Aristotle, who believed that it was in fact contagious.
Pliny the Younger wrote a letter to Priscus in which he details the symptoms of phthisis as he saw them in Fannia:
The attacks of fever stick to her, her cough grows upon her, she is in the highest degree emaciated and enfeebled.—Pliny the Younger, Letters VII, 19
Galen proposed a series of therapeutic treatments for the disease, including: opium as a sleeping agent and painkiller; blood letting; a diet of barley water, fish, and fruit. He also described the phyma (tumor) of the lungs, which is thought to correspond to the tubercles that form on the lung as a result of the disease.
Vitruvius noted that "cold in the windpipe, cough, plurisy, phthisis, [and] spitting blood," were common diseases in regions where the wind blew from north to northwest, and advised that walls be so built as to shelter individuals from the winds.
Voice hoarse; neck slightly bent, tender, not flexible, somewhat extended; fingers slender, but joints thick; of the bones alone the figure remains, for the fleshy parts are wasted; the nails of the fingers crooked, their pulps are shrivelled and flat...Nose sharp, slender; cheeks prominent and red; eyes hollow, brilliant and glittering; swollen, pale or livid in countenance; the slender parts of the jaws rest on the teeth as, as if smiling; otherwise of cadaverous aspect...—De causis et signis diuturnorum morborum, Aretaeus, translated by Francis Adams
In his other book De curatione diuturnorum morborum, he recommends that sufferers travel to high altitudes, travel by sea, eat a good diet and drink plenty of milk.
In South America, the first evidence of the disease is found in the Arawak culture around 1050 BCE, although the most significant finding belongs to the mummy of an 8 to 10-year-old Nascan child from Hacienda Agua Sala, dated to 700 CE. Scientists were able to isolate evidence of the bacillus.
Europe: Middle Ages and Renaissance
During the Middle Ages, no significant advances were made regarding tuberculosis. Avicenna and Rhazes continued to consider to believe the disease was both contagious and difficult to treat. Arnaldus de Villa Nova described etiopathogenic theory directly related to that of Hippocrates, in which a cold humor dripped from the head into the lungs.
In the Medieval Hungary many notes of the inquisition were taken while pagans were judged in trials, and one of them from the 12th century contained a very extense explanation of the illnesse's cause. The judged pagans affirmed that the turbeculosis was produced when a dog shaped demon occupied the person's body and started to eat his lungs. When the possessed person coughed, then the demon was barking, and getting close to his objective, kill the victim.
With the spread of Christianity, monarchs were seen as religious figures with magical or curative powers. It was believed that Royal Touch, the touch of the sovereign of England or France, could cure diseases due to the divine right of sovereigns. King Henry IV of France usually performed the rite once a week, after taking communion. So common was this practice of royal healing in France, that scrofula became known as the "mal du roi" or the "King's Evil".
Initially, the touching ceremony was an informal process. Sickly individuals could petition the court for a royal touch and the touch would be performed at the King's earliest convenience. At times, the King of France would touch afflicted subjects during his royal walkabout. The rapid spread of tuberculosis across France and England, however, necessitated a more formal and efficient touching process. By the time of Louis XIV of France, placards indicating the days and times the King would be available for royal touches were posted regularly; sums of money were doled out as charitable support. In England, the process was extremely formal and efficient. As late as 1633, the Book of Common Prayer of the Anglican Church contained a Royal Touch ceremony. The monarch (king or queen), sitting upon a canopied throne, touched the afflicted individual, and then presented that individual with a coin – usually an Angel, a gold coin the value of which varied from about 6 shillings to about 10 shillings – by pressing it against the afflicted's neck. Shakespeare's Macbeth describes the procedure quite accurately:
Strangely visited people,
All swoln and ulcerous, pitiful to the eye
The mere despair of surgery, he cures,
Hanging a golden stamp about their necks,
Put on with holy prayers: and 'tis spoken,
To the succeeding royalty he leavesThe healing benediction—Macbeth, Act 4, Scene 3, 171-7
Although the ceremony was of no medical value, members of the royal courts often propagandized that those receiving the Royal Touch were miraculously healed. André du Laurens, the senior physician of Henry IV, publicized findings that at least half of those that received the Royal Touch were cured within a few days. The Royal Touch remained popular into the 18th century. Parish registers from Oxfordshire, England include not only records of baptisms, marriages, and deaths, but also records of those eligible for the Royal Touch.
Girolamo Fracastoro became the first person to propose, in his work De contagione, that phthisis was transmitted by an invisible virus. Among his assertions were that the virus could survive between two or three years on the clothes of those suffering from the disease and that it was usually transmitted through direct contact or the discharged fluids of the infected, what he called fomes. He noted that phthisis could be contracted without either direct contact or fomes, but was unsure the process by which the disease propagated across distances.
Paracelsus's tartaric process
Paracelsus advanced the belief that tuberculosis was caused by a failure of an internal organ to accomplish its alchemical duties. When this occurred in the lungs, stony precipitates would develop causing tuberculosis in what he called the tartaric process.
Seventeenth and eighteenth centuries
Franciscus Sylvius began differentiating between the various forms of tuberculosis (pulmonary, ganglion). He was the first person to recognize that the skin ulcers caused by scrofula resembled tubercles seen in phthisis, noting that "phthisis is the scrofula of the lung" in his book Opera Medica published posthumously in 1679. Around the same time, Thomas Willis concluded that all diseases of the chest must ultimately lead to consumption. Willis did not know the exact cause of the disease but he blamed it on sugar or an acidity of the blood. Richard Morton published Phthisiologia, seu exercitationes de Phthisi tribus libris comprehensae in 1689, in which he emphasized the tubercle as the true cause of the disease. So common was the disease at the time that Morton is quoted as saying "I cannot sufficiently admire that anyone, at least after he comes to the flower of his youth, can [sic] dye without a touch of consumption."
In 1720, Benjamin Marten proposed in A New Theory of Consumptions more Especially of Phthisis or Consumption of the Lungs that the cause of tuberculosis was some type of animacula—microscopic living beings that are able to survive in a new body (similar to the ones described by Anton van Leeuwenhoek in 1695). The theory was roundly rejected and it took another 162 years before Robert Koch demonstrated it to be true.
In 1768, Robert Whytt gave the first clinical description of tuberculosis meningitis and in 1779, Percivall Pott, an English surgeon, described the vertebral lesions that carry his name. In 1761, Leopold Auenbrugger, an Austrian physician, developed the percussion method of diagnosing tuberculosis, a method rediscovered some years later in 1797 by Jean-Nicolas Corvisart of France. After finding it useful, Corvisart made it readily available to the academic community by translating it into French.
William Stark proposed that ordinary lung tubercles could eventually evolve into ulcers and cavities, believing that the different forms of tuberculosis were simply different manifestations of the same disease. Unfortunately, Stark died at the age of thirty (while studying scurvy) and his observations were discounted. In his Systematik de speziellen Pathologie und Therapie, J. L. Schönlein, Professor of Medicine in Zurich, proposed that the word "tuberculosis" be used to describe the affliction of tubercles.
The incidence of tuberculosis grew progressively during the Middle Ages and Renaissance, displacing leprosy, peaking between the 18th and 19th century as field workers moved to the cities looking for work. When he released his study in 1808, William Woolcombe was astonished at the prevalence of tuberculosis in 18th century England. Of the 1,571 deaths in the English city of Bristol between 1790 and 1796, 683 were due to tuberculosis. Remote towns, initially isolated from the disease, slowly succumbed. The consumption deaths in the village of Holycross in Shropshire between 1750 and 1759 were one in six (1:6); ten years later, 1:3. In the metropolis of London, 1:7 died from consumption at the dawn of the 18th century, by 1750 that proportion grew to 1:5.25 and surged to 1:4.2 by around the start of the 19th century. The Industrial Revolution coupled with poverty and squalor created the optimal environment for the propagation of the disease.
A romantic disease
"Chopin coughs with infinite grace."
|—George Sand in a letter to Madame d'Agoult|
It was during this century that tuberculosis was dubbed the White Plague, mal de vivir, and mal du siècle. It was seen as a "romantic disease." Suffering from tuberculosis was thought to bestow upon the sufferer heightened sensitivity. The slow progress of the disease allowed for a "good death" as sufferers could arrange their affairs. The disease began to represent spiritual purity and temporal wealth, leading many young, upper-class women to purposefully pale their skin to achieve the consumptive appearance. British poet Lord Byron wrote, "I should like to die from consumption," helping to popularize the disease as the disease of artists. George Sand doted on her pthitic lover, Frédéric Chopin, calling him her "poor melancholy angel."
In France, a least five novels were published expressing the ideals of tuberculosis: Dumas's La Dame aux camélias, Murger's Scènes de la vie de Bohème, Hugo's Les Misérables, the Goncourt brothers' Madame Gervaisais and Germinie Lacerteux, and Rostand's L'Aiglon. Even after medical knowledge of the disease had accumulated, the redemptive-spiritual perspective of the disease continued in literature. (More recently the 2001 film Moulin Rouge is based in part on La traviata, which itself is based on La Dame aux camélias.) 
The scientific advances
Though removed from the cultural movement, the scientific understanding advanced considerably. By the end of the 19th century, several major breakthroughs gave hope that a cause and cure might be found.
One of the most important physicians dedicated to the study of pthisiology was René Laennec, who died from the disease at the age of 45, after contracting tuberculosis while studying contagious patients and infected bodies. Laennec invented the stethoscope which he used to corroborate his auscultatory findings and prove the correspondence between the pulmonary lesions found on the lungs of autopsied tuberculosis patients and the respiratory symptoms seen in living patients. His most important work was Traité de l’Auscultación Mediate which detailed his discoveries on the utility of pulmonary auscultation in diagnosing tuberculosis. This book was promptly translated into English by John Forbes in 1821; it represents the beginning of the modern scientific understanding of tuberculosis. Laennec was named professional chair of Hôpital Necker in September 1816 and today he is considered the greatest French clinician.
Laennec's work put him in contact with the vanguard of the French medical establishment, including Pierre Charles Alexandre Louis. Louis would go on to use statistical methods to evaluate the different aspects of the disease's progression, the efficacy of various therapies and individuals' susceptibility, publishing an article in the Annales d'hygiène publique entitled "Note on the Relative Frequency of Phthisis in the Two Sexes." Another good friend and co-worker of Laennec, Gaspard Laurent Bayle, published an article in 1810 entitled Recherches sur la Pthisie Pulmonaire, in which he divided pthisis into six types: tubercular phthisis, glandular phthisis, ulcerous phthisis, phthisis with melanosis, calculous phthisis, and cancerous phthisis. He based his findings on more than 900 autopsies.
In 1869, Jean Antoine Villemin demonstrated that the disease was indeed contagious, conducting an experiment in which tuberculous matter from human cadavers was injected into laboratory rabbits, who then became infected.
On 24 March 1882, Robert Koch revealed the disease was caused by an infectious agent. In 1895, Wilhelm Roentgen discovered the X-ray, which allowed physicians to diagnose and track the progression of the disease, and although an effective medical treatment would not come for another fifty years, the incidence and mortality of tuberculosis began to decline.
|19th-century tuberculosis mortality rate for New York and New Orleans|
|1821||New York City||5.3||9.6|
|1830||New York City||4.4||12.0|
|1844||New York City||3.6||8.2|
|1855||New York City||3.1||12.0|
|1860||New York City||2.4||6.7|
|1865||New York City||2.8||6.7|
Villemin's experiments had confirmed the contagious nature of the disease and had forced the medical community to accept that tuberculosis was indeed an infectious disease, transmitted by some etiological agent of unknown origin. In 1882, Prussian physician Robert Koch utilized a new staining method and applied it to the sputum of tuberculosis patients, revealing for the first time the causal agent of the disease: Mycobacterium tuberculosis, or Koch's bacillus.
When he began his investigation, Koch knew of the work of Villemin and others who had continued his experiments like Julius Conheim and Carl Salmosen. He also had access to the "pthisis ward" at the Berlin Charité Hospital. Before he confronted the problem of tuberculosis, he worked with the disease caused by anthrax and had discovered the causal agent to be Bacillus anthracis. During this investigation he became friends with Ferdinand Cohn, the director of the Institute of Vegetable Physiology. Together they worked to develop methods of culturing tissue samples. 18 August 1881, while staining tuberculous material with methylene blue, he noticed oblong structures, though he was not able to ascertain whether it was just a result of the coloring. To improve the contrast, he decide to add Bismarck Brown[disambiguation needed], after which the oblong structures were rendered bright and transparent. He improved the technique by varying the concentration of alkali in the staining solution until the ideal viewing conditions for the bacilli was achieved.
After numerous attempts he was able to incubate the bacteria in coagulated blood serum at 37 degrees Celsius. He then inoculated laboratory rabbits with the bacteria and observed that they died while exhibiting symptoms of tuberculosis, proving that the bacillus, which he named tuberculosis bacillus, was in fact the cause of tuberculosis.
He made his result public at the Physiological Society of Berlin on 24 March 1882, in a famous lecture entitled Über Tuberculose, which was published three weeks later. Since 1882, 24 March has been known as World Tuberculosis Day.
On 20 April 1882, Koch presented an article entitled Die Ätiologie der Tuberculose in which he demonstrated that Mycobacterium was the single cause of tuberculosis in all of its forms.
In 1890 Koch developed tuberculin, a purified protein derivative of the bacteria. It proved to be an ineffective means of immunization but in 1908, Charles Mantoux found it was an effective intradermic test for diagnosing tuberculosis.
If the importance of a disease for mankind is measured from the number of fatalities which are due to it, then tuberculosis must be considered much more important than those most feared infectious diseases, plague, cholera, and the like. Statistics have shown that 1/7 of all humans die of tuberculosis.—Die Ätiologie der Tuberculose, Robert Koch (1882)
The advancement of scientific understanding of tuberculosis, and its contagious nature created the need for institutions to house sufferers.
The first proposal for a tuberculosis facility was made in paper by George Bodington entitled An essay on the treatment and cure of pulmonary consumption, on principles natural, rational and successful in 1840. In this paper, he proposed a dietary, rest, and medical care program for a hospital he planned to found in Maney. Attacks from numerous medical experts, especially articles in The Lancet, disheartened Bodington and he turned to plans for housing the insane.
Around the same time in the United States, in late October and early November 1842, Dr. John Croghan, the owner of Mammoth Cave, brought 15 tuberculosis sufferers into the cave in the hope of curing the disease with the constant temperature and purity of the cave air. Patients were lodged in stone huts, and each was supplied with a black servant to bring meals. One patient, A. H. P. Anderson, wrote glowing reviews of the cave experience:
[S]ome of the invalids eat at their pavillions while others in better health attend regularly the table d'hote which is very good indeed, having a considerable variety and being almost daily (I've noted but 2-3 omissions) graced with a saddle of venison or other game.—A. H. P. Anderson
By late January, early February 1843, two patients were dead and the rest had left. Departing patients died anywhere from three days to three weeks after resurfacing; John Croghan died of tuberculosis at his Louisville residence in 1849.
Hermann Brehmer, a German physician, was convinced that tuberculosis arose from the difficulty of the heart to correctly irrigate the lungs. He therefore proposed that regions well above sea level, where the atmospheric pressure was less, would help the heart function more effectively. With the encouragement of explorer Alexander von Humboldt and his teacher J. L. Schönlein, the first anti-tuberculosis sanatorium was established in 1854, 650 meters above sea level, at Görbersdorf. Three years later he published his findings in a paper Die chronische Lungenschwindsucht und Tuberkulose der Lunge: Ihre Ursache und ihre Heilung.
Brehmer and one of his patients, Peter Dettweiler, became proponents for the sanatorium movement, and by 1877, sanatoriums began to spread beyond Germany and throughout Europe. In 1885, Edward L. Trudeau founded Adirondack Cottage Sanitarium, the first tuberculosis sanatorium in the United States, at Saranac Lake, New York. Peter Dettweiler went on to found his own sanatorium at Falkenstein[disambiguation needed] in 1877 and in 1886 published findings claiming that 132 of his 1022 patients had been completely cured after staying at his institution. Eventually, sanatoriums began to appear near large cities and at low altitudes, like the Sharon Sanatorium in 1890 near Boston.
Sanatoriums were not the only treatment facilities. Specialized tuberculosis clinics began to develop in major metropolitan areas. Sir Robert Philip established the Royal Victoria Dispensary for Consumption in Edinburgh in 1887. Dispensaries acted as special sanatoriums for early tuberculosis cases and were opened to lower income individuals. The use of dispensaries to treat middle and lower-class individuals in major metropolitan areas and the coordination between various levels of health services programs like hospitals, sanatoriums, and tuberculosis colonies became known as the "Edinburgh Anti-tuberculosis Scheme."
At the beginning of the 20th century, tuberculosis was one of the UK’s most urgent health problems. A royal commission, entitled The Royal Commission Appointed to Inquire into the Relations of Human and Animal Tuberculosis, was set up in 1901. Its remit was to find out whether tuberculosis in animals and humans was the same disease, and whether animals and humans could infect each other. By 1919, the Commission had evolved into the UK's Medical Research Council.
In 1902, the International Conference on Tuberculosis convened in Berlin. Among various other acts, the conference proposed the Cross of Lorraine be the international symbol of the fight against tuberculosis. National campaigns spread across Europe and the United States to tamp down on the continued prevalence of tuberculosis.
After the establishment in the 1880s that the disease was contagious, TB was made a notifiable disease in Britain; there were campaigns to stop spitting in public places, and the infected poor were pressured to enter sanatoria that resembled prisons; the sanatoria for the middle and upper classes offered excellent care and constant medical attention. Whatever the purported benefits of the fresh air and labor in the sanatoria, even under the best conditions, 50% of those who entered were dead within five years (1916).
The promotion of Christmas Seals began in Denmark during 1904 as a way to raise money for tuberculosis programs. It expanded to the United States and Canada in 1907–1908 to help the National Tuberculosis Association (later called the American Lung Association).
In the United States, concern about the spread of tuberculosis played a role in the movement to prohibit public spitting except into spittoons.
The first genuine success in immunizing against tuberculosis was developed from attenuated bovine-strain tuberculosis by Albert Calmette and Camille Guérin in 1906. It was called "BCG" (Bacille Calmette-Guérin). The BCG vaccine was first used on humans in 1921 in France, but it was not until after World War II that BCG received widespread acceptance in the United States, Great Britain, and Germany.
As the century progressed, some surgical interventions, including the pneumothorax or plombage technique—collapsing an infected lung to "rest" it and allow the lesions to heal—were used to treat tuberculosis. Pneumothorax was not a new technique by any means. In 1696, Giorgio Baglivi reported a general improvement in tuberculosis sufferers after they received sword wounds to the chest. F.H. Ramage induced the first successful therapeutic pneumothorax in 1834, and reported subsequently the patient was cured. It was in the 20th century, however, that scientists sought to rigorously investigate the effectiveness of such procedures. In 1939, the British Journal of Tuberculosis published a study by Oli Hjaltested and Kjeld Törning on 191 patients undergoing the procedure between 1925 and 1931; in 1951, Roger Mitchell[disambiguation needed] published several articles on the therapeutic outcomes of 557 patients treated between 1930 and 1939 at Trudeau Sanatorium in Saranac Lake. The search for a medicinal cure, however, continued in earnest.
In 1944 Albert Schatz, Elizabeth Bugie, and Selman Waksman isolated Streptomyces griseus or streptomycin, the first antibiotic and first bacterial agent effective against M. tuberculosis. This discovery is generally considered the beginning of the modern era of tuberculosis, although the true revolution began some years later, in 1952, with the development of Isoniazid, the first oral mycobactericidal drug. The advent of Rifampin in the 1970s hastened recovery times, and significantly reduced the number of tuberculosis cases until the 1980s.
Hopes that the disease could be completely eliminated were dashed in the 1980s with the rise of drug-resistant strains. Tuberculosis cases in Britain, numbering around 117,000 in 1913, had fallen to around 5,000 in 1987, but cases rose again, reaching 6,300 in 2000 and 7,600 cases in 2005. Due to the elimination of public health facilities in New York and the emergence of HIV, there was a resurgence of TB in the late 1980s. The number of patients failing to complete their course of drugs is high. New York had to cope with more than 20,000 TB patients with multidrug-resistant strains (resistant to, at least, both Rifampin and Isoniazid).
In response to the resurgence of tuberculosis, the World Health Organization issued a declaration of a global health emergency in 1993. Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide.
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