147 Tuberculosis

Tuberculosis is an infectious disease most commonly associated with the lungs, but which can affect al­most any tissue or organ in the body. Its primary cause is an acid-fast bacillus, Mycobacterium tubercu­losis.

Etiology and Epidemiology

Perhaps no other disease better illustrates the princi­ple of multifactorial causation: The tubercle bacillus is a necessary but not the only condition. In addition, the host and the host’s environment contribute nu­merous other causes central to its pathogenesis.

Species Classification

Over 30 species of the genus Mycobacterium have been identified, more than 15 of which can cause disorders similar, but not identical, to tuberculosis. Human disease typically is caused by members of the species Mycobacterium tuberculosis. In addition, mycobacteria can cause disease in a wide variety of animals, including birds, fish, rodents, elephants, and cattle. Of its animal forms, only the bovine can infect people. Some bacteriologists consider the bo­vine form a separate species of the tubercle bacillus, whereas others group it with several variants that they classify together as the M. tuberculosis complex.

The human bacillus has also been divided into three types according to immunologic responses (phage types), which show marked variations in viru­lence. These are type I, found in India; type A, found in Africa, China, and Japan as well as in Europe and North America; and type B, found exclusively in Europe and North America. Type I is the least viru­lent of the three, making Indians more susceptible to disease when infected with type A or B. These differ­ences probably result from the evolution of widely separated organisms over long periods of time. How­ever, all forms of M. tuberculosis show a strong resis­tance to mutation, and thus it is unlikely that an increase in virulence caused the disease to become epidemic, or that a decrease in virulence prompted the decline in tuberculosis mortality rates that oc­curred in England, the United States, and other Western nations before the introduction of strepto­mycin and other specifics.

Transmission

Except for the bovine types, tubercle bacilli reach human hosts almost exclusively through aerial transmissions.

Incubation Period

After entering the body, tubercle bacilli are remark­ably durable and persistent. They can remain viable throughout their host’s lifetime, dormant until resis­tance fails, whereupon they can cause active disease even if they failed to do so when they first entered the body. In contrast to most other infectious dis­eases, tuberculosis has an indefinite and variable incubation period.

Host-Dependent Factors

Whether or not tubercle bacilli cause active disease upon entering the body depends primarily on several host-dependent factors. Age, gender, and immuno- genetic factors along with a number of environmen­tal factors such as crowding, quality of nutrition, and working conditions are all of importance.

A,ge. Once a person becomes infected with the bacil­lus, age has a powerful influence on what follows. Infancy, puberty, and old age are periods of low resis­tance and high susceptibility to tuberculosis. The younger the individual, the more likely that pri­mary infection will become active disease and result in death.

Gender. Gender is also an important determinant. Although the reasons remain as yet undiscovered, more females die from tuberculosis than do males in populations where tuberculosis epidemics are just beginning, and the converse is usually true where the disease is declining. In youth and early adult­hood, females generally experience greater mortal­ity from tuberculosis than males, but after age 30 years the mortality of males surpasses that of fe­males. Biological evidence suggests that the onset of the menses brings on metabolic changes that in­crease the body’s need for protein, and that when it is unavailable, resistance drops. Childbirth can in­duce or aggravate the disease by lowering resistance to infection and this contributes to increased mortal­ity in females up to age 30.

Genetic Factors. Extensive research on heredity in tuberculosis has produced only ambiguous results. Some families experience more tuberculosis than others in similar circumstances, and specialists do agree that heredity influences an individual’s risk of developing the disease, but the mechanisms of hered­ity have not been demonstrated. The role of race in tuberculosis also presents a difficult problem to re­searchers. For decades, American scientists at­tempted to ascertain whether blacks, who long had higher rates of mortality from the disease than whites, were biologically more susceptible to it be­cause of an inherited characteristic. Results have been indeterminate, because in this case constitu­tion and environment remain inseparably inter­twined. Nevertheless, a population’s genetic pool is an important influence on resistance to the tubercle bacillus. A long history of inhabiting urban environ­ments seems to have made Jews more resistant to the disease than are most other ethnic groups.

Some epidemiologists assert that natural selection determines the course of tuberculosis epidemics, based on the idea that genetic background and resis­tance to the disease are of paramount importance. Mortality rates drop, they say, as the more suscepti­ble are weeded out. Others oppose this theory, in part because tuberculosis epidemics in Europe and the United States subsided more quickly than the theory would have predicted. Moreover, although natural selection has doubtless reinforced resistance to the disease, it has not played a leading role in the decline of its epidemics. Rather it would seem that economic and social changes made the most impor­tant contributions to the decline in tuberculosis mor­tality rates until the late 1940s, when medicinal cures became available.

Primary Environmental Factors

Where tuberculosis is present, the specific fac­tors most important in the etiology of the disease are crowding, quality of nutrition, and working conditions.

Crowding. Crowding, as a function of persons per room, increases a person’s chances of infection when diseased individuals are constantly releasing the ba­cilli into the air of small and cramped quarters. Population density, on the other hand, which is a ratio of persons per measure of land area, has little impact on tuberculosis mortality rates. Indeed, in most industrial nations, those rates are higher in rural than in urban areas because in sparsely popu­lated rural areas, substandard living conditions, in­cluding crowded housing, often make the disease a major health problem.

Nutrition. Nutrition also plays a key role in the etiology of tuberculosis. Both epidemiological and laboratory evidence demonstrate the importance of protein in resistance to tuberculosis.

Working Conditions.

This combination of factors means that industrial­ization alternatively exacerbates and improves rates of mortality from tuberculosis. The early stages of an industrial economy are generally those in which crowded and impoverished living conditions prevail for numerous people and lead to increased tuberculo­sis mortality. Eventually, however, industrializa­tion’s material benefits improve housing and nutri­tion, and reduce risks for infection and reinfection, thereby lowering both morbidity and mortality rates.

Other Environmental Factors. Other environmen­tal factors seem to have little influence on tuberculo­sis mortality. Researchers long considered climate an important factor in the pathogenesis and treat­ment of tuberculosis, but recent studies have not found that temperature, humidity, or other climatic factors influence either one’s risk of developing tu­berculosis or its course once the disease is developed.

Epidemiologists have faced numerous difficulties in the study of tuberculosis, and found it particularly difficult to determine the mortality from the disease until the advent of mass screening programs using tuberculin and X-ray photography. Nonetheless they have played a primary role in unraveling some of the mysteries of tuberculosis and determining the factors, such as age and nutritional deficiencies, which put populations at greater or lesser risk of developing the disease.

Clinical Manifestations and Pathology

Tuberculosis most commonly infects the lungs, but it can infect almost any other part of the body, and fre­quently causes disease in the meninges, intestines, bones, lymph glands surrounding the neck, skin, spine, kidneys, and genitals. Most of these forms, with the exception of tubercular meningitis, are chronic, taking months and sometimes years before resulting in either recovery or death. Miliary tuber­culosis concurrently affects almost every vital organ.

Because pulmonary tuberculosis is by far the most common form of this disease, it usually brings to mind its most familiar symptom: an increasingly fre­quent and violent cough that produces a purulent sputum sometimes streaked with blood. Coughing up larger amounts of blood hemorrhaged in the lungs is not uncommon in advanced cases, but this is by no means a universal symptom. Indeed, until the dis­ease reaches its advanced stages, many victims are completely free of symptoms or experience only the mild respiratory symptoms similar to those of influ­enza or a common cold. The systemic symptoms of tuberculosis generally include fatigue, lethargy, an­orexia, weight loss, irregular menses, ill-defined anxi­ety, chills, muscular aches, sweating, and low-grade fevers that continue indefinitely. In the past, how­ever, many people developed mild or even asympto­matic cases of the disease and recovered before realiz­ing it, as autopsies, and later X-rays, revealed.

Because in its early stages tuberculosis has only unalarming symptoms and myriad possible manifes­tations, diagnosis is difficult even today. Preliminary diagnosis can be made with a tuberculin test, which usually indicates whether a person has become in­fected with the tubercle bacillus. On the other hand, although tuberculin testing is highly reliable today, false-positive responses are not unknown.

The tubercle bacillus by itself does not damage the normal human body; it neither contains nor exudes any toxic materials. Rather cellular and tissue dam­age arises from an allergic reaction in the body, or hypersensitivity, which occurs in response to contact with the bacillus. In other words, after the body has become allergic to invading tubercle bacilli, the im­mune system destroys them. This process, however, releases proteins and fatty substances that in turn can cause inflammation and can damage surround­ing tissue and cells. This same process also creates the tubercles that distinguish the disease. Experts sometimes refer to tubercles as caseous areas be­cause they often have a cheesy consistency, although they can become as hard as rocks. Alternatively, caseous areas can liquefy, leaving a cavity. If this occurs close to a major blood vessel, it may result in a hemorrhage.

Immunology

The immune system’s role in the development of tuberculosis is complicated, and part of that role still remains obscure. The complexity of the role has made it difficult to determine the extent to which antibodies protect the body against active disease and to what extent they cause it. Individual resis­tance to tuberculosis undergoes marked fluctua­tions: Quiescent infections often flare up under condi­tions that depress resistance, only to be suppressed when resistance is recovered. Acquired resistance to the tubercle bacillus confers no stable and durable protection as it does in diseases such as measles and smallpox, and can, to the contrary, make the develop­ment of active disease even more likely.

The efficacy of immunization against tuberculosis is still debated. Antituberculosis vaccination usu­ally consists of administering the famous strain BCG (bacillus Calmette-Guerin), an attenuated form of the bovine bacillus first isolated in 1921 by the French bacteriologists A. Calmette and C. Guerin after years of laboratory cultivation. Clinical tests and epidemiological evidence indicate that it offers some degree of immunity when the recipient has not been infected before.

History

Antiquity

Archaeological evidence indicates that tuberculosis afflicted prehistoric men and women in Eurasia and Africa at least from the Neolithic period. Stone Age skeletons with lesions apparently caused by tubercu­losis of the spine have been unearthed in Britain and Germany, and spinal tuberculosis has been found in numerous Egyptian mummies dating from the third millennium before Christ. In China, a woman’s mum­mified body dating from the early Han dynasty (206 B.C. - A.D. 7) clearly displays tuberculosis scars on her lungs. Trade and migration patterns ensured the dissemination of China’s chronic diseases throughout East Asia during the first three centuries of the pres­ent era. Skeletal evidence strongly suggests that na­tive Americans suffered from the disease as early as 800 B.C., and pulmonary lesions that contain acid­fast bacilli dating from A.D. 290 have been discov­ered in Chilean mummies.

This physical evidence suggests two important points concerning the prehistory of tuberculosis. First, the disease quite possibly evolved together with humans from the earliest of times. Some spe­cialists have presented the view that tuberculosis was originally limited to animals and first affected humans only after people started to domesticate cat­tle and other beasts. Others have contested this view, asserting that in the case of such a chronic disease, no animal intermediary is necessary to maintain viable bacilli even in relatively small popu­lations. The second point is that tuberculosis af­flicted most people worldwide from prehistoric times, save for small numbers of peoples, such as the Maori, who lived in isolation for centuries. Because of this, most epidemics of the disease resulted not from the introduction of foreign pathogens into vir­gin populations but from changes in the host popula­tion and its environment.

Textual sources support these conclusions, al­though not always with complete clarity because of marked differences in the ways people in different times and cultures have perceived the symptoms and course of tubercular disease. Until the present concept of tuberculosis - as a single disease caused by the tubercle bacillus - emerged during the last decades of the nineteenth century, its various forms were often known by separate names and thought of as different diseases. For example, the pulmonary forms were commonly called phthisis or pulmonary consumption; infections of the lymph glands sur­rounding the neck were termed scrofula; and those of the skin referred to as lupus vulgaris. This nosological confusion makes identification of the dis­ease from historical texts difficult, and consequently conclusions concerning tuberculosis based on most written sources up to the mid-nineteenth century necessarily engender some skepticism.

Nevertheless, classical Hindu, Babylonian, Assyr­ian, Chinese, Greek, and Roman sources all describe

the signs and symptoms of tuberculosis. Hindu texts dating from 1200 B.C. and perhaps earlier, along with Mesopotamian texts from the seventh century B.C., had established procedures for treating pulmo­nary tuberculosis and scrofula. The first description of the disease in Chinese may date back to 2700 B.C., and texts from around 400 B.C. clearly de­scribe the symptoms of tuberculosis. The first Greek mention of what probably was tuberculosis is that of Homer, about 800 B.C. Hippocratic writings from approximately 400 B.C. discuss phthisis, the Greek term for consumption, which they attributed to the effects of evil airs. Phthisis then became the stan­dard European term that signified a cluster of symp­toms akin to and including those of pulmonary tuber­culosis. Other Greek and Roman writers of both medical and nonmedical texts use the term exten­sively, including Galen, who during the second cen­tury of the Christian era recommended a change of climate as therapy for consumption. Rene and Jean Dubos, in their classic study of tuberculosis, The White Plague (1952), note that the ancient cultures that described the signs and symptoms of the disease were primarily urban, whereas pastoral cultures make scarce mention of the disease. Biblical litera­ture, for example, makes scant reference to it.

Medieval Period

Medieval Europeans suffered considerably from tu­berculosis, although contemporary documents men­tion it more often in its glandular form rather than its pulmonary form - that is, as scrofula or tuberculo­sis. This was because of the custom of the “king’s touch,” in which kings of France and England were believed to have the power to cure scrofula simply by touching its victims. The custom originated in the twelfth century and continued through the eigh­teenth to its demise along with the divine right of kings at the end of that century.

Chinese medical texts that provide the most de­tailed treatments of the disease were written during the Sui (581-617) and Tang (618-907) dynasties. Japanese physicians appropriated the Chinese texts, and with their aid clearly described the symptoms of tubercular diseases in their own country. By the twelfth century, Chinese Taoist priests had attrib­uted phthisis both to infection by evil airs (qi) and to animalculae, which attacked a physically or men­tally exhausted individual. The disease was said to pass through six stages in which these animalculae underwent a series of metamorphoses and in the last stage became highly infectious. In positing this sys­tematic germ theory of tuberculosis, the Chinese anticipated Western medical theorizing by two centu­ries. In the first half of the sixteenth century, Girolamo Fracastoro, better know as Fracastorius, became the first Western physician to propose such a theory. Unlike the Chinese theory, however, Fra- castorius’s was not limited to phthisis, which he believed was only one of many diseases caused by the spread of animalculae.

Sixteenth Through Eighteenth Century

Dtwing the sixteenth century, mortality from tuber­culosis increased noticeably in countries with grow­ing urban populations. In England, for example, it caused about 20 percent of all deaths at midcentury, with the greatest concentrations of the disease found in London. A similar phenomenon occurred in Japan at nearly the same time: Contemporary observers remarked that phthisis had become widespread in the rapidly growing administrative capital of Edo at the beginning of the seventeenth century. It was during the eighteenth century, however, that the world’s great epidemics of tuberculosis began, and they were well underway by the beginning of the following century. The nations that suffered most severely from tuberculosis at this time also were experiencing intense urbanization and industrializa­tion. Thus physicians and other writers reported that phthisis was common in the cities of England, the United States, Italy, and France.

Autopsies showed that close to 100 percent of some urban populations, such as those of London, Paris, and other major industrial cities, had at some point in their lives developed the disease, although they had died of some other cause. Rates of mortality from tuberculosis in most major American cities dur­ing the early nineteenth century ranged from 400 to 500 per 100,000 of population, and in Philadelphia (1811-20) they reached 618. Women workers in tex­tile industries generally led other groups in tubercu­losis mortality in every country where modem tex­tile factories were appearing. When statistics for tuberculosis mortality became available for most in­dustrial countries of western Europe and the United States after 1860, they showed that its epidemics were declining. In the developing countries of the time, however, including most eastern European na­tions and Japan, tuberculosis epidemics were just starting at the end of the nineteenth century.

Increasing attention was given to tuberculosis by European physicians beginning with the seven­teenth century, in part because of major changes in medical theory and in part because of growing mor­tality from phthisis and scrofula. In 1685 Richard Morton became the first Western physician to pub­lish a single text on phthisis, a term which he used to embrace a number of wasting diseases, including pulmonary consumption and scrofula. Morton de­pended on traditional humoral theory to describe the etiology of phthisis. By the eighteenth century, how­ever, physicians were redefining their concepts of diseases, and searching for new explanations for their causes. As a result, the nineteenth century became a period of intense research into and specula­tion about tubercular diseases. In Europe and espe­cially in the United States, physicians and lay­persons alike looked for elements in both life-style and environment that made a person “susceptible” to it. Among those “elements” were dissolute and immoral living, alcohol and tobacco consumption, along with various developmental crises in the host’s physical well-being such as puberty or child­birth. In addition, damp soil and filth in general could make an individual susceptible to consump­tion. Others, however, believed that pulmonary con­sumption was a hereditary affliction - a belief that became a powerful social stigma in much of the world. Indeed, throughout much of the nineteenth century, popular (and some medical) concepts of tu­berculosis resonated with the notion that the disease expressed a person’s inherent nature as opposed to just being something that one had. In fact, those considered susceptible to tuberculosis were said to have a phthisical diathesis.

Nineteenth Through Twentieth Century

Theories of Etiology. A major break with previous theories of tubercular diseases occurred at the begin­ning of the nineteenth century, which initiated a process that had transformed their classification by the 1880s, especially among European medical scien­tists. From the early 1800s, the French clinical school analyzed pathological phenomena by compar­ing the course of disease observed at the bedside with autopsy observations. Rene Theophile Hya­cinthe Laennec, a leading physician of this school, postulated the theory that all tubercular phenom­ena, including phthisis, scrofula, and miliary tuber­cles, in fact constituted a single disease.

German physicians of the “physiological” school, who opposed the “ontological” view of diseases, which posits clearly definable entities for which dis­tinct species can be established, vigorously attacked Laennec’s theory of tuberculosis. A leading theoreti­cian of German “physiological medicine,” Karl Wunderlich, asserted that it was impossible to draw a distinct line between, for example, dysentery and enteric diarrhea. Wunderlich thought of disease names only as conveniences, not as linguistic sym­bols for specific entities. In his views of tuberculosis, Wunderlich echoed the ideas of his contemporary, Rudolph Virchow. Virchow, in many respects one of the greatest medical theoreticians of the nineteenth century, also repudiated the ontological theory of diseases, including Laennec’s idea that all tubercu­lar phenomena manifested a single, specific disease. Rather, he divided tubercular manifestations into the two separate categories of inflammatory and neoplastic phenomena, and thought that some forms fundamentally resembled cancer. Virchow consid­ered the important difference between diseases not to be one of cause but of pathological processes within individual cells.

Despite Virchow’s views, however, the tradition of combining clinical and pathological investigations continued in France, most notably in the work of Jean-Antoine Villemin, who followed Laennec in say­ing that tuberculosis was a specific disease caused by a specific agent, but went one step beyond him by demonstrating in practice what Laennec had postu­lated in theory. In 1865 Villemin caused tuberculosis in rabbits by injecting them with matter from hu­man tubercles. Although this work had a negligible impact on German ideas concerning tuberculosis, the notion that it was a specific disease was provided an unshakable scientific foundation in the work of the Prussian bacteriologist Robert Koch.

Using the clearly defined bacteriologic methods he had developed, Koch proved in 1882 that it was possible to give animals tuberculosis by inoculating them with bacteria - and not simply tubercular matter - that he had isolated from human tubercles. Although a number of problems in the identification of tuberculosis remained (such as the identity of scrofula, which some still maintained was a separate disease), the discovery of the tubercle bacillus fi­nally established tuberculosis as a single disease clearly distinguishable by a single cause. It is true that for several more years, some circles, particu­larly the group led by Virchow, disputed Koch’s methods and conclusions. Nonetheless his discovery of the tubercle bacillus changed the way not only members of the medical profession thought about tuberculosis but also how most people viewed the disease: No longer was it the result of an inherent susceptibility but, rather, something that one “had.”

Early Attempts at Prevention. Koch’s discovery had little effect on attempts to treat tuberculosis, but it had important implications for prophylaxis. Observ­ers attempting to establish the most important routes of infection concluded that dry tubercle bacilli in dried sputum presented the greatest threat. To prevent the disease, they recommended the general removal of dust from all public and private places, restrictions on spitting and the use of spittoons in all places, and the disinfection or destruction of the belongings and surroundings of tuberculosis vic­tims. In some places, such procedures were already “on the books,” because many national and local governments had passed laws specifying some or all of them. It was not until the 1930s that researchers demonstrated that, in most cases, infection was the result of airborne infection and that dried sputum or other forms of contact with the bacillus played little role in the transmission of the disease.

Early Treatment. The primary interest of most practicing physicians at this time, however, was not in ascertaining the etiology of tuberculosis but, rather, in treating the disease. The many hundreds of thousands of tuberculosis victims worldwide were desperate to be cured, and created an unbounded demand for remedies, making equally large oppor­tunities for both physicians and quacks - although by today’s standards it is often difficult to separate the two. Some of the most popular cures for tubercu­losis that physicians advocated during the nine­teenth century included creosote, carbolic acid solu­tions, gold, iodoform, arsenic, and menthol oil; at various times all were administered orally, inhaled, or injected directly into the lungs. More unusual treatments ranged from drinking papaya juice to enemas of sulfur gases. Starting during the late nineteenth century and continuing well into the twentieth, physicians practiced surgical therapies, including pneumothorax, or collapsed-lung treat­ments, and the surgical removal of ribs with the objective of reducing the size of the thoracic cavity.

Advances in Diagnosis. It was the search for a rem­edy, rather than his discovery of the tubercle bacillus, that brought Koch international fame. In 1890, at the strong urging of Kaiser Wilhelm IPs government, he announced that he had discovered a cure for tubercu­losis, which attracted hundreds of scientists and thou­sands of the afflicted to his laboratory in Berlin. Within a year, however, many were questioning the efficacy of “Koch’s lymph” (a glycerol-based extract from the tubercle bacillus). As a cure it was not effec­tive; in fact, it proved harmful in advanced cases. On the other hand, it soon became the extremely impor­tant diagnostic tool better known as tuberculin and the primary means of determining infection by the tubercle bacillus.

Along with the discoveries of the tubercle bacillus and tuberculin, the X-ray, discovered in 1895, helped change the way in which both physicians and lay­persons thought about tuberculosis. It made visible to the eye lesions in the lungs and other parts of the body caused by the disease long before its symptoms became noticeable, allowing physicians to start treat­ment at a much earlier stage in the disease. Al­though they did not become a dependable diagnostic tool until the end of the second decade of the twenti­eth century, X-ray photographs together with tuber­culin became the basic tools of the mass screening programs that governments and antituberculosis as­sociations implemented from the 1920s to the 1950s.

Later Therapies and Prevention. As diagnostic tech­niques improved but medicinal cures remained inef­fective, therapies based on climate and regimen be­came increasingly popular. Hippocrates had first rec­ommended a change of climate as a treatment for phthisis, and from the seventeenth century onward physicians in both the West and the East continued to recommend healthful climates and life-styles as consumption cures. From the mid-nineteenth cen­tury, open-air and rest therapies became increas­ingly popular throughout Europe and the United States, and as an extension of rest therapy, pneumo­thorax, or the collapsing of a heavily diseased lung so that it could “rest,” became popular in the late 1800s and remained common in many countries un­til the 1940s. The systematic integration of these therapies with other forms of treatment culminated in the sanitorium. From the 1880s, luxury sanitoria for the wealthy, like the one in Davos, Switzerland (immortalized in Thomas Mann’s The Magic Moun­tain), drew patients from around the world. And about 1900, state-sponsored sanitoria began to ap­pear throughout western Europe, North America, and Japan.

Where sanitoria were not feasible, such as in in­ner cities, public health bureaucrats and physicians developed alternatives that offered open-air treat­ment for the diseased as well as preventive regimens for those who seemed susceptible.

Many sanitoria and prevention programs were sponsored or managed by private or semiprivate antituberculosis organizations. These had been es­tablished in most of western Europe and North America from the 1890s, and in much of the rest of the world during the first two decades of the twenti­eth century. Such organizations also supported edu­cational programs, which became a mainstay of tu­berculosis control movements. Their purpose was to inform the public of the ways in which the disease was transmitted and developed, and to encourage people to secure frequent checkups and early treat­ment if they were infected. The most commonly af­flicted groups, however - factory laborers, other in­dustrial workers, and the urban poor - rarely had the necessary resources to secure treatment for the disease even if they received an early diagnosis.

Mortality and Incidence. Understandably, medical scientists, public health bureaucrats, and workers in such prevention movements where rates of mortal­ity from tuberculosis declined dramatically from the late nineteenth century onward concluded that the decline was the direct result of their efforts. This was especially the case in Great Britain, Germany, and the United States. Yet the experience of others contradicted such claims. During the first four de­cades of the twentieth century, the Japanese, for example, implemented almost all the tuberculosis control measures that Western countries had devel­oped, including extensive legislation aimed at the control of tuberculosis, state-sponsored sanitoria in the major urban centers, intensive education pro­grams, and government-administered mass screen­ings and BCG immunizations. Throughout the first three decades of this period, however, Japan’s rates of mortality from tuberculosis hovered at around 200 per 100,000, and then actually increased from the early 1930s. It was not until the late 1940s that the rates of tuberculosis mortality began a sustained fall. In the case of Japan, the prevention movement was much less important than later improvements in living standards and working conditions and even later government intervention with nationwide treatment programs using streptomycin, PAS, and, after 1952, isoniazid.

Since the 1950s, the countries with the highest tuberculosis mortality rates have been those with low standards of living, poor working conditions, and inadequate treatment programs. Medicine has learned that the mere availability of specifics against tuberculosis is not enough to stem the dis­ease; their administration must be coordinated with reforms that raise living standards and improve working conditions, or the incidence of the disease will remain inordinately high. During the early 1970s, over 20 nations worldwide - all of them devel­oping countries - had new case rates for tuberculosis of over 150 per 100,000 per year; Macau (in 1973), Swaziland (in 1970), and Bolivia (in 1972) all had incidence rates of over 400.

Thus although the leaders of antituberculosis movements long spoke of eradicating the disease, it remains a major health problem in many countries, and serves as an index of social conditions world­wide. Even in developed, industrial countries, when social conditions deteriorate, the incidence of tuber­culosis rises quickly. Clearly, the disease remains far from eradicated in the developing world. But even in the developed world, tuberculosis retains the poten­tial ofbecoming a significant health problem during times of economic depression, war, and social unrest.

William D. Johnston

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