Pulmonary tuberculosis

Preface To The Second Edition

It is the purpose of this book to supply the general practitioner with information concerning the etiology, diagnosis, prognosis and treatment of pulmonary tuberculosis, its clinical forms and common complications. An experience of over twenty years with the tuberculosis problems in New York City has convinced the author that: (1) The physician can, and should, do more than recognize phthisis in its earliest or pretuberculous stage and at once consign the patient to a sanatorium. (2) That " incipient" does not always mean curable tuberculosis, and conversely, that "advanced" disease does not necessarily indicate a hopeless outlook. (3) That institutional treatment is not the only effective method of handling the phthisical patient. (4) If all tuberculous persons in this country would consent to hospitalization, the available institutions would hardly accommodate ten per cent, of eligible patients. (5) Even those treated in sanatorium s must be cared for by their family physicians before admission and after discharge. (6) Careful home treatment is productive of practically the same immediate and ultimate results as institutional treatment, and is less costly to the patient and to the community.

Recent investigations of tuberculous infection have radically changed our views on the transmissibility of tuberculosis. On the one hand, it was found that patients who indiscriminately expectorate tubercle bacilli are a greater menace than has hitherto been suspected. Infants may be infected by mere contact with phthisical persons. On the other hand, there is hardly a person living in a large city who has escaped infection with tubercle bacilli. In other words, despite the vigorous and costly efforts which have been made during the past thirty years, the majority of the population in civilized countries harbor tubercle bacilli in their bodies. But, what is of more importance, not every one infected with tubercle bacilli is destined to become sick. For this reason, a sharp distinction is made in the following chapters between infection and disease, or tuberculosis and phthisis.

vi PREFACE

Recent research has also shown that infection with tubercle bacilli endows an organism with a certain degree of resistance, or even immunity, against further and renewed exogenic infection with the same virus. Experimental investigations have proved that it is impossible to reinfect a tuberculous animal with tubercle bacilli. Many clinical phenomena, which have hitherto baffled those who studied the disease, such as the rarity of conjugal phthisis, or of tuberculous disease in those living and working among phthisical patients, and of soldiers in the armies, are now explained by this immunity of the tuberculous against reinfection with tubercle bacilli. Phthisis is at present considered a manifestation of immunity. Prophylaxis of infection has been shifted to the child, while that of phthisis involves more than prevention of infection.

In the discussion of the clinical aspects of phthisis an attempt has been made to elaborate on the constitutional symptoms, which are still the sheet-anchor of the physician who is charged with deciding whether a patient is ill and in need of treatment. Bacteriology and serology are excellent helps in showing whether the patient has been infected with tubercle bacilli; skiagraphy reveals airless areas of lung tissue; but they do not give conclusive proof that the patient is sick and in need of prolonged and costly treatment. We also know that unity of causation is not always an indication of unity of resulting clinical phenomena in tuberculosis : The clinical picture of tuberculosis in infants is different from that in children; in adults some, irrespective of the treatment applied, show a marked tendency to sclerosis or fibrosis of the lesion; in others caseation and destruction of lung tissue go on progressively; in still others there is a sluggish course, marked by periods, of illness alternating with periods of comparative comfort. For these reasons several types of the disease, or syndromes, have been described, each of which has not only a different clinical course, but also a different outlook as to recovery, and the treatment differs markedly in each form of the disease.

It appears that the tuberculosis problem has been handled in the various armies engaged in the recent World War along the lines mentioned above and some have anticipated that the disease will prove as great a menace as many other war plagues, such as typhoid, influenza, dysentery, etc. However, despite the fact that only clinical tuberculosis has been considered cause for rejection by draft boards, and tuberculin (the test for infection) has not been applied for diagnostic purposes at all, the number of cases of active tuberculosis in the armies has not been

PREFACE vii

excessive, considering that soldiers are of the age period when the disease is most likely to occur. This clearly has been an experiment on a large scale showing that tuberculous infection is not acquired by adults; that infection, which is in the vast majority of cases acquired during childhood, is not invariably followed by disease, and that only constitutional symptoms decide whether a patient is sick with phthisis and in need of treatment. Our rather unconventional views on the diagnosis and prophylaxis of phthisis as a disease, which have been emphasized in the first edition of this book, have thus been fully confirmed. Though infection as a factor in phthisiogenesis has been practically disregarded in the various armies engaged in the recent war, no visible harm has resulted.

The treatment recommended in this book is based on experience with patients in New York City. Some were living in the congested neighborhoods of the Metropolis; others in the better parts of the city; still others have been under the author's care in the hospital. A large proportion had been in sanatoriums, but even they had to be cared for in their homes before admission and after discharge. Emphasis is laid on the fact that in most cases we can give the patient the benefit of modern and approved treatment in his home as well as in institutions. The immense utility of sanatorium treatment is emphasized and its limitations are enumerated. It is also shown that institutional treatment is not the only, nor the best, available method of caring for the majority of patients. Experience has taught that we can properly house and feed a patient in the city at a much less expense than in a sanatorium.

Medicinal treatment has been alloted some space for the reason that it is, in many cases, believed to possess more value than it has been accredited by therapeutic nihilists. The most recent method of treatment, artificial pneumothorax, has been given at some detail because of its efficacy in selected patients in whom everything else has failed to afford relief.

In this new edition nearly every chapter has been revised and several have been rewritten. The influence of influenza on the etiology, course and prognosis of phthisis has been given in the light of recent experience. New chapters on tuberculosis of the pleura and on pneumothorax have been added. The differential diagnosis of tuberculosis has been more extensively treated in a new chapter, giving details about the clinical differentiation of cardiac disease, rhinopharyngeal conditions, bronchiectasis, bronchopulmonary spirochetosis, pulmovin PREFACE

nary streptotrichosis, pleural vomicae, cancer of the lung, influenza, etc. Several additional plates have been inserted illustrating the pathology of pulmonary tuberculosis, all drawn from specimens obtained at necropsies at the Montefiore Hospital of cases under the author's care. Many of the radiographic plates have been replaced, and several new ones have been added, so that these illustrations, nearly all prepared under the supervision of Dr. Thomas Scholz, radiographer to the Montefiore Hospital, represent practically an atlas of radiography of pulmonary tuberculosis.

M. F.

New York, 1919.

Chapter I. The Tubercle Bacilli

That tuberculosis is a transmissible disease had been suspected by many ancient physicians and conclusively proved by Villemin in 1865, but it remained for Robert Koch 1 to isolate the microorganism which is the infective agent. In 1882 he published his first communication describing the morphology, staining reactions, cultivation, and the successful animal inoculation of pure cultures of the bacilli invariably found in tissues affected with tuberculosis.

The tubercle bacillus is a parasite in the full sense of the word, living and thriving only in the bodies of animals and man, and perishing outside of the animal body. It has not been decided to which group of microorganisms it belongs; in fact, we do not as yet have a classification of bacteria which is completely satisfactory to all who are competent to judge. It may be said to belong to the group of acid-fast bacteria, of which there are many varieties to be mentioned farther on, and may be classified with the trichomycetes, while some consider it intermediary between the true bacteria and the lower fungi, the hyphomycetes.

Morphology. — The morphological variations of the tubercle bacilli are dependent on their type and virulence, whether human, bovine, or avian, and on the media in which they have been cultivated. In film preparations made from cultures, or from sputum expectorated by tuberculous patients, the tubercle bacillus appears as a slender rod, usually straight, but very often curved, about one-fourth to one-half the diameter of a red blood corpuscle, or 5-^ mm. in length, on the average. These rods, mostly rounded on the two ends, are seen in the preparations from secretions or tissues, singly, in pairs, or in heaps, occasionally imbedded in the tissue cells. They are non-motile, and have no flagella. Microscopically, an enveloping or capsular substance can often be made out around each bacillus, especially in those which have been artificially cultivated in serum for several generations. Some individual bacilli are strikingly pleomorphic,

1 Berl. klin. Wchnschr., 1882, xxxix. An English translation of the complete report, originally appearing in Mitt, aus dem Gesundheitsamte, 1887, vol. ii, made by Stanley Boyd, has appeared in "Recent Essays on Bacteria in Relation to Disease," New Sydenham Society, 1886, pp. 65-201. 2

Is THE TUBERCLE BACILLI

thread, or club-shaped, with thickenings at either or both ends, or with filaments passing out from the main rod at right angles, and finally in Y-shaped branchings. But these are of no practical significance, because they appear to be simply degenerated types of the microorganism, although some look at them as the reverse, the result of active growth on a good culture medium, and amid favorable biological surroundings. In some individual bacilli, vacuoles are seen, giving the rod the appearance of a chain of cocci. The suggestion that they represent spores appears to be erroneous, because they have no stronger resistance than the body of the bacillus, and succumb to heat and chemicals as fast as the entire rod. The fact that it is speedily killed by sunlight also indicates that the tubercle bacillus has no spores.

Staining. — The tubercle bacilli stain with basic dyes, but with great difficulty, and, once stained, they part with the color with difficulty. Their most important characteristic is their acid-fast property. While other microorganisms lose their stain when treated with acids or alcohol, the tubercle bacilli retain it. They are also alkali-fast, and when stained by an acid dye cannot be decolorized by an alkali. But it must be mentioned that they are not the only known acid-fast bacilli. This is one of the sources of error which, at times, interferes with the proper appreciation of acid-fast microorganisms discovered under the microscope.

Much's Granules. — There have also been found tubercle bacilli which, while remaining virulent, have lost their acid-fast characters. Hans Much, 1 who has studied these microorganisms, and by whose name they are generally known, describes two forms of these granules : (1) A rod-shaped granular organism; (2) isolated granules; both of which cannot be stained by the Ziehl method, but only by the Gram method. They are pathogenic to animals and man, and are usually found in some cases of slowly progressing chronic phthisis, fibroid phthisis, cold abscess, etc. It is thus evident that before concluding that a given case lacks acid-fast bacilli, and is therefore not tuberculous, the Much granules are to be looked for by staining with the Gram- Much method. According to W. H. Park, true tubercle bacilli are probably always present together with the granules in cases in which the latter forms are found.

In this country Charles N. Meader 2 has made a careful study of these granules. In his opinion "the biological relationship of Much's forms of tubercle bacilli is a matter of considerable interest. They may be considered as a natural stage in the evolution of the bacillus, as the result of degenerative changes, or may be classed as spores (i. e., as resisting forms). The accumulated evidence tends to show that they are predominantly found in tissues of a distinctly fibroid character, in old cavities, in pus of cold abscesses, in old cultures, in the notably indolent lupus lesions and in sclerosed lymph glands —

1 In Brauer, Schroder, and Blumenfeld's Handbuch d. Tuberkulose, i, 193.

POWERS OF RESISTANCE 19

facts which, taken together, mark them as forms assumed under unfavorable conditions, whether they be the result of sporulation or of degeneration. The same conclusion is suggested by observations that, under favorable cultural conditions, they are rapidly replaced by Ziehl-staining forms. Against their classification as spores, in the commonly accepted sense, is the fact that the granular forms are rather less resistant to the action of antiformin than are the Ziehl forms; their resistance to other chemical agents has not yet been reported upon. It is of interest to note here that the granular forms appear more frequently in the bovine than in the human type of bacillus."

Cultivation. — The tubercle bacilli are obligatory aerobes; they require free oxygen for maintenance of life, activity and propagation. In artificial media they grow very slowly, much more slowly than most bacteria which are not acid-alcohol-fast; they proliferate very slowly, and other saprophytic microorganisms which happen to live with them soon outnumber them. It is also worthy to remember that it is difficult to cultivate them directly from tuberculous lesions, secretions and excretions of patients known to contain tubercle bacilli. But once they have been cultivated, it is rather easy to transplant them to another culture of the same medium, and growth is even more luxuriant in the subsequent cultures. Theobald Smith's method of cultivation on dog serum and Dorset's egg medium, and especially Petroff's medium, are about the best and most used in this country. Pure cultures are best obtained from tubercles of animals inoculated with the bacilli. But it is often possible to obtain pure cultures from closed tuberculous cavities, from lesions of lupus, and even from sputum.

When cultivated on coagulated dog serum, or bovine serum, or in Dorset's egg medium, especially when to the latter there is added glycerin, growth appears usually at the end of ten days at 37° C, and within four weeks the characteristic growth may be expected. On the glycerin-egg medium the human form of organism produces an abundant, wrinkled layer, usually having a yellowish, buff, or pinkish color. The growths are seen as more or less elevated colonies which may coalesce. On glycerin-agar the growth is more rapid than on serum, and appears as a thick, white layer, becoming yellowish. Tubercle bacilli also flourish in glycerin-potato medium.

Powers of Resistance. — The tubercle bacilli grow best at the temperature of the human body, 37° to 38° C, but growth is not abolished at 29° to 42° C. From a practical standpoint it is important to mention that they are not killed when exposed to moist heat of 50° C. for less than twelve hours, but heating to 55° C. for four to six hours does destroy them. They are also killed when exposed to moist heat of 60° C, for one-half hour, and in fifteen minutes at 70° C; in five minutes at 80° to 90° C, and in one minute at 95° C. With sputum, conditions are different: the mucus protects the bacilli and it requires more time to destroy them with heat. However, five minutes' boiling is sufficient to kill the bacilli under all circumstances.

Another practical point is that in milk, tubercle bacilli resist the action of heat with greater tenacity than in pure liquid cultures, or eveo in sputum. From many careful experiments it appears that heating milk for thirty to forty minutes, at a temperature of 65° to 70° C, or boiling for three minutes, destroys tubercle bacilli. Especially resistant are the bacilli when the milk is heated in an open vessel and a pellicle forms on the top of the fluid. This protects the bacilli against a temperature of 60° C. for an hour. William H. Park explains this by the fact that the upper parts of the fluid are not heated to the same degree as the lower, and some bacilli may survive. At any rate, it is important that pasteurization should be done in closed vessels. In butter the virulence of the bacilli is greatly diminished and even abolished when in contact for a long time. In fact, they die out within a few weeks, as a rule. The reasons for this phenomenon are not clear. On the other hand, Schroeder and Cotton have found living tubercle bacilli retaining their virulence for one hundred and sixty days in salted butter when kept without ice in a house cellar; and Mohler, Washburn, and Doane found that they survived a year in cheese. In thoroughly boiled or roasted meat the bacilli are destroyed; but in the rare portions they may survive. Sausages, etc., made of uncooked meat, may contain living tubercle bacilli.

Dry heat is less potent in destroying tubercle bacilli; circulating steam requires one-half hour for this purpose, while bacilli in dried sputum can withstand a temperature of 100° C. for an hour. On the other hand, cold does not destroy their virulence, and freezing, with subsequent thawing, does not hai*m them very much.

It is also important to remember that the fatty substances and wax contained in the tubercle bacilli protect them to a certain extent from the effects of desiccation, and from the bactericidal action of the normal body cells, although for growth and proliferation they require moisture. When dried and pulverized by being converted into dust, as is often the case with tuberculous sputum eliminated indiscriminately by careless patients, most of the bacilli succumb, but some have been found to resist desiccation at ordinary temperature for months.

In this connection it must be borne in mind that the action of light is an important factor. It has been ascertained that light, especially sunlight, decomposes the fatty substances in the bacilli and thus destroys them altogether. When cultures are exposed to direct sunlight for a couple of hours, the vitality as well as the virulence of the tubercle bacilli is destroyed; in sputum the bacilli are protected by the mucus, and it requires a longer time for their destruction. Some maintain that their virulence is destroyed with only partial loss of vitality.

Under the circumstances sputum eliminated in light places is sooner or later rendered harmless, while when expectorated in dark rooms the bacilli may retain their vitality and virulence for a year, and even drying does not harm them much.

POWERS OF RESISTANCE 21

On the whole, tubercle bacilli may retain their vitality for a considerable time if not in exceptionally unfavorable surroundings. In the latter case their growth is soon hampered, and they cannot successfully be transferred by inoculation to another culture medium; but they may retain their virulence much longer and cause disease when inoculated into animals. After several months, however, even this wanes, and after six months this property is completely lost. In laboratories it has been found by experience that it is safer to reinoculate cultures every four to six weeks. Exceptionally, cultures have been found alive and virulent after two years. This is especially the case with potato and bouillon cultures which have been kept under favorable conditions, as to heat, moisture, etc., while in serum and glycerin cultures the bacilli do not survive so long.

Cornet found that serum cultures remain alive for about six months, while glycerin-agar cultures are often partially, or wholly, dead in six to eight weeks. There seems also to be some difference in this respect between the various types of tubercle bacilli: Maffucci states that avian bacilli may remain alive for two years, and Strauss found that cultures of human tubercle bacilli are only exceptionally capable of reproduction after five to six months; after eight to twelve months they fail regularly. Theobald Smith 1 found that a culture three months old failed, as a rule, to yield successful subcultures, and that tubercle bacilli, of both human and bovine types, when kept in fully developed cultures at 40° to 50° F., may remain infectious to guinea-pigs for from seven to nineteen months, but the number of bacilli surviving in such cultures is relatively small. Delepine's 2 experience has been that tubercle bacilli retain some of their pathogenicity as long as 500 days if left in the dark in milk at a low temperature, below 6° C; but after being kept thus for four and one-half years these bacilli, were no longer pathogenic to guinea-pigs. It is, however, important to bear in mind, when considering prophylaxis, that when tubercle bacilli in sputum are deposited in dark rooms they may retain their vitality and power to cause disease for as long as 309 days, as has been found by Soparkar. 3 The oldest tuberculous sputum which has been investigated was that reported by Newell Bly Burns. 4 He examined sputum twenty-two years old and found that the bacilli retained their staining qualities but lost completely their power to grow and their pathogenicity.

Tubercle bacilli display great powers of resistance to the action of the products of other bacterial growths, in spite of the fact that they have no spores. They may survive for months in souring milk, in sewage and in water, and in putrefying matter generally, especially sputum. Lawrason Brown, 5 S. A. Petroff and F. H. Heise found viru-

1 Jour. Med. Research. 1913, xxviii, 91.

2 Ann. de l'lnst. Pasteur, Paris, 1916, xxx, 600.

3 Indian Jour, of Med. Research, 1916, iv, 62.

4 Araer. Review of Tuberc, 1917, i,.484.

5 Tr. Nat. Assn. Prevent. Tuberc, 1916, xii, 286.

22 Tin: tVbercLe MctLLl

lent tubercle bacilli in the water of the Saranac River, into which the sewerage system of Saranac Lake empties. Every sample of water taken from below the surface, from the outlet of the sewer to a point three and a half miles down the stream, showed the presence of acid- Fast organisms. No acid-fast organisms were found above the outlet or twelve miles below the outlet. The bacilli are believed to be derived from the feces of the numerous tuberculous individuals in Saranac. In fact, where no particles of feces were discovered in the water, no viable tubercle bacilli were found.

Virulence. — Long before the discovery of the tubercle bacillus it was known that certain diseases in animals were of the same character as human tuberculosis, and attributed to the same virus. Klenke, in 1846, emphasized the danger of milk from tuberculous cattle as an infective agent to human beings, and Villemin, in 1865, showed by animal experiment that tuberculous disease in man and animals is identical in character. With the study of the virulence of the tubercle bacillus it was found that it is pathogenic to many species of animals. In some tuberculosis is known to occur spontaneously, while others may be infected artificially. There appear to be significant differences in the results of such experimental infections, depending on the method of inoculation of the virus — injections into the subcutaneous tissues, into the peritoneum, into the anterior chamber of the eye, intravenously, by feeding animals with bacilli, or compelling them to inhale the bacilli with inspired air, and also according to the origin of the bacilli.

Tubercle bacilli obtained from different cases of human tuberculosis often show differences in their virulence according to the strain. But when the bacilli obtained from different animals are compared, the differences in their virulence are even more striking. For this reason there have been described different spe?ies, varieties or strains of tubercle bacilli, although some authors maintain that the differences in cultural and virulence characteristics are acquired while the microorganisms are sojourning in the host by adaptation to the conditions favorable for their growth.

HUMAN, BOVINE, AND AVIAN BACILLI.

In the early history of the scientific investigation of tuberculous infection it was already noted that there are some differences between human and bovine tubercle. Villemin was the first to find these differences. "We must note that none of our rabbits," he said, "inoculated with human tubercle have presented a tuberculization so rapid and generalized as that which we have obtained with material from the cow. At first we were inclined to regard this as fortuitous, but subsequent experiment led us to suppose that the tubercle of the bovine race inoculated into rabbits possesses a much greater activity than that obtained from man. It may be supposed that, like all virulent matter, the tuberculous matter is the more virulent the more the affinitv of

HUMAN, BOVINE, AXD AY I AX BACILLI 23

the animal supplying the virus and the animal receiving it." This apparently was entirely forgotten, until Nocard and Roux. and Rivolta and Maffucci again rediscovered it while doing inoculation experiments with tubercle bacilli derived from humans and from cattle.

It remained, however, for Theobald Smith 1 to make the first careful study of differences in morphological, cultural, and pathogenictypes of tubercle bacilli. In 1S9S he showed that there are differences between the bacilli isolated from human beings, when compared with those isolated from cattle. His designation of the former as "human," and the latter as '"bovine," has since been, generally accepted. In 1901 Robert Koch also announced that his studies led him to the conviction that human and bovine tuberculosis are not identical: that the bovine bacilli are, in fact, not pathogenic to man, and that no special measures need be taken to protect man against the consumption of milk and meat from tuberculous cattle. Considering the commercial interest which is centered around this problem, in addition to the problem of human infection, it is clear why studies along these lines have been in abundance during recent years.

Still other types of bacilli have been found. Rivolta and Maffucci have shown that there are certain morphological and biological differences between the tubercle bacilli found in birds and those in human beings. Theobald Smith continued to investigate the problem and arrived at the conclusion that bacilli from human sources are not clearly identical in every respect with those obtained from bovine sources. Official bodies of the Imperial Department of Health in Germany, a Royal Commission in England, and Dr. William H. Park, for the New York City Department of Health, have thoroughly studied the problem, each from a different angle. The result is that we are at present in a position to state conclusively that there is more than one variety of tubercle bacillus.

The conclusions of the British Royal Commission are to the effect that "for the purpose of description it is advantageous to distinguish three types of tubercle bacilli, recognizable by their individual characters. These are the human, the bovine, and the avian. The human type, although so named, is not the only one found in cases of tuberculosis in man. It is the organism present in the majority of such cases, but in some cases of human disease the bacilli present are of the bovine type, and in others the bacilli have special characters distinguishing them from each of the three principal types. In natural cases of tuberculosis in cattle the only type of bacillus present is the bovine type." William H. Park 2 concludes from his extensive study of the subject that "tubercle bacilli, as isolated from man. fall into two groups. One of these groups is identical in all its characters with those found in cattle. That is. all tubercle bacilli from man and

1 Jour. Exper. Med.. 159b. iii. 451.

cattle fall into two groups, which have been designated the human and bovine types."

Human Bacilli. — The human variety grows on all culture media quickly and luxuriantly; the addition of glycerin enhances their growth. On' glycerin bouillon growth is seen during the first few days, and within three weeks there is seen a pellicle on the surface of the culture which spreads laterally and reaches the glass walls. The pellicle is fragile and its surface wrinkled. Morphologically, the human bacilli when grown on serum cultures appear as long, straight, or curved rods which are unevenly stained.

In general it may be stated that the virulence of human bacilli is rather low in various animals. Guinea-pigs are very susceptible and may be infected in various ways, even by rubbing the bacilli into the shaved skin of the abdomen. Rabbits are, however, less susceptible. Even when a milligram of bacilli is injected into a vein of the ear there is only produced a chronic lesion which may heal; subcutaneous injection produces an infiltration at the point inoculated which soon softens and empties itself through a fistulous opening, or may even be absorbed. The regional lymph glands swell, but do not caseate. At times, but not in every case, there may thus be produced a chronic infection of the lungs in the rabbit. Intraperitoneal inoculation produces tuberculous peritonitis, which may extend along the diaphragm; infection of the anterior chamber of the eye produces a lesion which develops more slowly than when bovine bacilli are used. Cattle are infected when large doses are injected intravenously. But with subcutaneous infection there is produced only an infiltration at the point inoculated, which soon suppurates and heals. The regional lymph glands swell up and at times become calcified. Feeding calves with human bacilli never produces any progressive disease. Pigs, dogs, cats, and sheep are not at all affected by human bacilli, while monkeys are very susceptible. Some species of birds are also susceptible.