or other substances placed in the mouth, or is contained in the inspired air, or enters the mouth and nose through any other medium. The first lesions do not consist in the formation of specific tubercles, but in the so-called lymphatic tuberculosis. This stage lasts a variable time and may end in recovery or may lead to specific tuberculosis either through reinfection, or it may light up itself without a new infection. The specific tubercles may occur either at the portal of entry or in the lungs and bronchial glands or in other organs.

Behring (1903) brought forward the theory that alimentary infection occurs in the early months of life. The tender mucous membrane of babies permits the bacillus to pass readily. The bacilli remain latent in the tissues and acquire increased activity later in life. According to this view tuberculosis of adults is the "end of a song, the beginning of which for the unfortunate patient was sung in the cradle." If this view were correct, the majority of cases of tuberculosis in adults would be associated with the bovine bacillus, unless the bovine bacillus has the power of changing to the human type during its long stay in the body. This is not likely.

It is clear from the evidence at hand that pulmonary tuberculosis may arise either by inhalation or by ingestion. The problem for us now to solve is a quantitative one; that is, what percentage of cases are air-borne and what percentage come through the mucosa of the digestive tract? Opinions differ widely, but opinions are of little value. We must have the facts before we can give the final answer to this very important and practical question.1

Flies. Under certain circumstances flies may readily transfer tubercle bacilli from exposed sputum to fingers, lips, or food. This may account for an occasional case.

Water. Large quantities of tuberculous sputum that escape disinfection and an additional large number of tubercle bacilli in the excreta finally reach the drinking water. The tubercle bacillus is particularly resistant to putrefactive processes, and may live a long time in water. The use of contaminated water can, therefore, not be disregarded. A study of the vital statistics of Hamburg, Lowell, and Lawrence seems to show a diminution in tuberculosis following a purification of the water supply by filtration (Mills-Reinke Phenomenon, page 804).

Contact Infection. The majority of cases of tuberculosis contract the disease through "contact." Contact infection is a general and convenient term; it implies the rather quick transference of fresh inféction in which the bacilli pass from one individual to the other in a brief space of time and through a short distance. Contact infection.

1An exhaustive and able summary of this question will be found in Bulloch's article in Allbutt's "System of Medicine," from which some of the facts in this article have been used.

may be either direct or indirect; through, dust, through bacilli in the air, or through contaminated food, through soiled fingers or objects; through flies, as well as in numerous other ways. The infections transferred through kissing, pencils, pipes, toys, cups, and other objects all come under the convenient category of "contacts." Even the infection through droplets is included in the present-day conception of contact infection. The term is a practical one, and implies close association, though not necessarily actual contact, between the sick and the well. Viewed in this sense, tuberculosis is a house disease or a family disease. With this conception it makes little practical difference whether the infection enters the body through the respiratory tract or the digestive tube. Either or both would be possible in regarding the disease as contagious in the sense of contact infection.

Although there is some doubt concerning the exact mode of transmission and the portal of entry that the tubercle bacillus usually takes, we have sufficient knowledge to guide our preventive measures with every assurance of success. One thing is certain: tuberculosis is an infection spread mainly from man to man, usually through direct association between the sick and the well; and secondarily from cows, through milk.

IMMUNITY

Man possesses a considerable resistance to tuberculosis. This is shown by the fact that many cases recover spontaneously and that perhaps all individuals who reach the age of 30 years and who spend most of this time in association with their fellowmen under the usual urban conditions have at one or more times been infected. The resistance to tuberculosis increases after middle life, due perhaps to the immunity which is induced by these prior infections. There is probably no true racial immunity to tuberculosis. Some races show a smaller incidence to the disease, owing probably to modes of life, habits of nutrition, and conditions of exposure.

The human organism is capable of taking care of a certain amount of infection. The dose, that is, the number, of tubercle bacilli and their virulence, is, therefore, a very important factor in determining infection. This may readily be demonstrated upon susceptible animals and is doubtless true of man. Frequent reinfections occurring at short intervals with small numbers of tubercle bacilli doubtless break down the immunity. In man the balance between immunity and susceptibility to tuberculosis is delicately adjusted: there is a very small factor of safety. The resistance to the infection may be increased by attention to personal hygiene, fresh air, and good food; immunity may readily be broken down by any weakening influence; herein lies the keynote of personal prophylaxis.

The immunity to tuberculosis is not sufficiently strong to overcome a large amount of infection. As in all other infectious processes, the strongest and most robust individuals in the prime of life succumb to the disease in a short time if they receive into their system a large number of virulent tubercle bacilli. Hence the avoidance of the infection is one of the most important of our preventive measures.

The mechanism of the immunity to tuberculosis is probably exceedingly complex. There is no antitoxic immunity. The tuberculins are not true toxins. Phagocytosis and cellular reactions play a very important rôle. The recent studies upon anaphylaxis throw a certain amount of light upon the mechanism of immunity in tuberculosis. The phenomenon of hypersusceptibility is beautifully illustrated in the action of tuberculin, which is a comparatively harmless substance to a normal individual, but produces a marked reaction in a. sensitized individual. This reaction must be useful in protecting the organism against the invasion of the tubercle bacillus, and also in guarding it against the spread of the disease after it has become localized. Thus, if tuberculin is placed upon a normal conjunctiva no reaction follows. This first application, however, sensitizes the tissues of the conjunctiva so that, if the application is repeated after the lapse of a few weeks, there is a violent reaction. The same phenomenon doubtless occurs when a tubercle bacillus lodges in a lymph gland or in the lung or some other part of the body. The first time it meets with little resistance; the next time the tissues react immediately and vigorously. All of nature's protecting agencies, such as the germicidal substances in the blood, the phagocytic cells, and antibodies, are concentrated upon the point where they are most needed. In the same way the body protects itself against the extension of a tuberculous focus. The parts surrounding a tubercle become sensitized and react so as to encapsulate the focus with a cellular and fibrous coat of mail. This reaction is probably stimulated by small amounts of tuberculin produced within the tuberculous focus. When the tuberculin is not produced autogenously in sufficient amounts, as in chronic lesions of the bones, or inactive processes of the glands or skin, the specific reaction may be stimulated to advantage by the injection of small quantities of tuberculin. If, however, the tuberculin is given in too large amounts or too frequently, the power of reaction is readily broken down. When this occurs the mechanism of immunity has been/ destroyed, there is little resistance left to the extension of the infection, and death soon occurs. Clinical experience has demonstrated the danger of large doses of tuberculin or small amounts too often repeated in tuberculosis. The same may readily be demonstrated experimentally in the lower animals. These facts are of fundamental importance in the use of tuberculin.

1

Rosenau and Anderson, J. A. M. A., Vol. I, March 28, 1908, p. 961.

It is quite proper to deny dogmatically the hereditary transmission of tuberculosis in educational pamphlets for popular use. The infectionis not transmitted hereditarily, although it occasionally passes from mother to fetus congenitally. Tubercle bacilli do not occur in the spermatozoon, and do not appear in the seminal fluid. They are not found in the ovum; in fact, a tubercle bacillus in the ovum would doubtless result in the death of the egg. The bacilli, however, may pass from mothe" to fetus through the placenta. Warthin shows that placental tuberculosis is more common than is supposed. The lesions in the placenta are not those of typical tubercle formation.

While the tubercle bacillus itself is rarely transmitted from parent to offspring, an hereditary tendency or disposition to the disease may be transmitted. We have no definite knowledge as to what this decreased resistance consists in; it may be a diminished power of reaction. For this view there is analogy in the experiments upon anaphylaxis in guinea-pigs, in which it has been shown that hypersusceptibility to a foreign protein such as tuberculin may be transmitted from mother to young.

A mild infection with bovine tuberculosis in early life seems to leave a certain degree of immunity against the human strain. At least children who have glandular tuberculosis of the bovine type in childhood are said to be less apt to have tuberculosis of the lungs in later life. Likewise, the human strain injected into cattle produces a definite immunity against the bovine type. Cattle are now immunized by the intravenous injection of 2 c. c. of a suspension of a pure culture of the human tubercle bacillus. This produces an immunity which probably lasts for 1 to 2 years. It should be remembered that the human bacillus under these circumstances remains alive for a very long time, and may appear in the milk provided there is a lesion in the udder. This presents a danger which cannot be disregarded.

Trudeau long ago showed that the only definite immunity that could be induced in experimental animals was through the use of live tubercle Webb and Williams have produced a certain amount of immunity in guinea-pigs and monkeys by the injection of live tubercle bacilli. The first injection consists of the introduction of a few bacilli (from 1-200), which is repeated subcutaneously at varying intervals. Two children have also been successfully "vaccinated" with upward of 600 virulent human tubercle bacilli without infection being produced.

RESISTANCE OF THE VIRUS

We have no easy method of determining just when the tubercle bacillus dies. The criterion of death depends upon animal experimentation. "Immunity in Tuberculosis," J. A. M. A., Oct. 28, 1911, Vol. LVII, No. 18, p. 1431.

The tubercle bacillus has no spore and may be classed with other nonspore-bearing organisms so far as its viability is concerned. Its virulence fades before it dies. It is doubtful whether the waxy substances protect the bacillus against external harmful influences to any unusual extent. The thermal death point is 60° C. for 20 minutes. This is much less than was once considered. Failure to recognize the lesions produced by the dead tubercle bacillus is responsible for some of the false conclusions reached by experimenters upon this subject.

From a practical standpoint the resistance of the tubercle bacillus in sputum is of prime importance. Protected from the sunlight it is now known that they may live in dried sputum for months. All the bacilli do not survive under these conditions, but we lack methods to determine the quantitative reduction.

The tubercle bacillus withstands cold very well. It has a marked resistance against putrefactive processes. It will live a year in water, which is a fact not to be neglected, as many tubercle bacilli finally find their way into drinking water, and infection through this source is possible.

For the destruction of the bacilli in sputum only very strong germicides or exposure to steam or boiling water should be depended upon. Five per cent. carbolic acid is sufficient, provided equal parts of sputum and solution are mixed and the exposure continued for 24 hours. Ten per cent. lysol acts in 12 hours. Bichlorid of mercury is not applicable for sputum disinfection, as it cannot penetrate the albuminous mass. Formalin, 10 per cent., may be used.

Sunlight is one of the best germicides and often destroys tubercle bacilli quickly. In direct sunlight the bacilli die in a few hours, in diffuse sunlight in a few days, provided the sputum masses are not too thick.

Anti

Antiformin is a differential germicide, killing most non-spore-bearing bacteria, but acting more slowly upon the tubercle bacillus. formin is a strongly alkaline solution of sodium hypochlorite. (Page 1020.)

PREVENTION

Preventive measures are based upon two important facts: that tuberculosis is an infection mainly spread from man to man through direct association, and secondarily from cattle through infected milk. Preventive measures fall into two categories: (1) avoiding the infection, and (2) increasing resistance through personal hygiene. Both are necessary. The infection may be avoided through segregation; the use of milk from tuberculin-tested cattle, else pasteurized; education;

The thermal death point of pathogenic microorganisms in milk. M. J. Rosenau, Hyg. Lab. Bull. U. S. Pub. Health and Mar. Hosp. Serv., No. 42.