Disease and Its Causes by William Thomas Councilman

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So far it has been shown that the best defence of the body is, as is
the best defence in war, by offensive measures, as illustrated by
phagocytosis and destruction by the serum. Both of these actions can
be increased by their exercise just as the strength of muscular
contraction can be increased by exercise, and the facility for doing
everything increased by habit. Certain of the infectious diseases are,
as has been said, essentially toxic in their nature, and in cultures
the organisms produce poisonous substances. By the injection into the
tissues of such substances the same disturbances are produced as when
the bacteria are injected. Such a disease is diphtheria. In this there
is only a superficial invasion of the tissues. The diphtheria bacilli
are located on the surface of the tonsils or pharynx or windpipe,
where, as a result of their action, the membrane so characteristic of
the disease is produced. The membrane may be the cause of death when
it is so extensively formed as to occlude the air passages, but the
prominent symptoms of the disease, the fever, the weakness of the
heart and the great prostration are due not to the presence of the
membrane, but to the action of toxic substances which are formed by
the bacteria growing in the superficial lesions and absorbed. Tetanus,
or lockjaw, is another example of these essentially toxic diseases.
The body must find some means of counteracting or destroying these
injurious toxic substances. It does this by forming antagonistic
substances called antitoxines, which act not by destroying the
toxines, but by uniting with them, the compound substance being
harmless. It has been found that the production of antitoxine can be
so stimulated by the injection of toxine that the blood of the animal
used for the purpose contains large amounts of antitoxine. The horse
is used in this way to manufacture antitoxine, and the serum injected
into a patient with diphtheria has a curative action, a greater amount
being thus introduced than the patient can manufacture.

[Illustration: FIG. 18.--DIAGRAM TO ILLUSTRATE EHRLICH'S THEORY OF
ANTITOXINE FORMATION. The surface of the cell (_n_) is covered with
receptors some of which (_b_) fit the toxine molecule, (_a_) allowing
the toxine to act upon the cell. Under the stimulus of this the cell
produces these receptors in excess which enter into the blood and
there combine with the toxine as in _a^1 b^1_, thus anchoring it and
preventing it from acting upon the cells. The receptors _c_ and _d_ do
not fit the toxine molecule.]

A very ingenious theory which well accords with the facts has been
given by Ehrlich in explanation of the production of antitoxine and of
the reaction between toxine and antitoxine (Fig. 18). This is based on
the hypothesis, which is in accord with all facts and generally
accepted, that the molecules which enter into the structure of any
chemical substance have in each particular substance a definite
arrangement, and that in a compound substance each elementary
substance entering into the compound molecule has chemical affinities,
most of which may be satisfied by finding a suitable mate. Ehrlich
assumes that the very complex chemical substances which form the
living cells have many unsatisfied chemical affinities, and that it is
due to this that molecules of substances adapted for food can enter
the cells and unite with them; but there must be some coincidence of
molecular structure to enable the union to take place, the comparison
being made of the fitting of a key into a lock. The toxines--that
produced by the diphtheria bacillus being the best example--are
substances whose molecular structure enables them to combine with the
cells of the body, the combination being effected through certain
chemical affinities belonging to the cells termed _receptors_.
Unless the living cells have receptors which will enable the
combination with the toxine to take place, no effect can be produced
by the toxine and the cells are not injured. This is the case in an
animal naturally immune to the action of the diphtheria bacillus or
its toxines. In the case of the susceptible animal the receptors of
the cells of the different organs combine with the toxine to a greater
or less extent, which explains the fact that different degrees of
injury are produced in the different tissues; the toxine of tetanus,
or lockjaw, for example, combines by preference with the nervous
tissue, that of diphtheria with the lymphatic tissue. It is known that
in accordance with the general law of injury and repair, a loss in any
part of the body stimulates the tissue of the same kind to new growth
and the loss is thus repaired; it is assumed that the cell receptors
which combine with the toxine are lost for the cell which then
produces them in excess. The receptors so produced pass into the
blood, where they combine with the toxine which has been absorbed; the
combination is a stable one, and the toxine is thus prevented from
combining with the tissue cells. The antitoxine which is formed during
the disease, and the production of which in the horse can be
enormously stimulated by the injection of toxine, represents merely
the excess of cell receptors, and when the serum of the horse
containing them is injected in a case of diphtheria the same
combination takes place as in the case of receptors provided by the
patient. In the case of the destruction of bacteria in the blood by
the action of amboceptor and complement, the amboceptor must be able
to combine with both the bacterial cell and the complement which
brings about its destruction, and just as antitoxine is formed so new
amboceptors may be formed.

Few hypotheses have been advanced in science which are more ingenious,
in better accord with the facts, have had greater importance in
enabling the student to grasp the intricacies of an obscure problem,
and which have had an equal influence in stimulating research. The
immunity which results from disease in accordance with this theory, is
due not to conditions preventing the entrance of organisms into the
body, but to greater aptitude on the part of the cells to produce
these protective substances having once learned to do so. An
individual need not practise for many years, having once learned them,
those combinations of muscular action used in swimming; but the habit
at once returns when he falls into the water.

Infectious diseases and recovery are phases of the struggle for
existence between parasite and host, and illustrate the power of
adaptation to environment which is so striking a characteristic of
living matter.

FOOTNOTES:

[1] The comparison here is with the atrium of a Pompeiian house.

CHAPTER VIII

SECONDARY, TERMINAL AND MIXED INFECTIONS.--THE EXTENSION OF INFECTION
IN THE INDIVIDUAL.--TUBERCULOSIS.--THE TUBERCLE BACILLUS.--FREQUENCY
OF THE DISEASE.--THE PRIMARY FOCI.--THE EXTENSION OF BACILLI.--THE
DISCHARGE OF BACILLI FROM THE BODY.--INFLUENCE OF THE SEAT OF DISEASE
ON THE DISCHARGE OF BACILLI.--THE INTESTINAL DISEASES.--MODES OF
INFECTION.--INFECTION BY SPUTUM SPRAY.--INFECTION OF WATER
SUPPLIES.--EXTENSION OF INFECTION BY INSECTS.--TRYPANOSOME
DISEASES.--SLEEPING SICKNESS.--MALARIA.--THE PART PLAYED BY
MOSQUITOES.--PARASITISM IN THE MOSQUITO.--INFECTION AS INFLUENCED BY
HABITS AND CUSTOMS.--HOOKWORM DISEASE.--INTER-RELATION BETWEEN HUMAN
AND ANIMAL DISEASES.--PLAGUE.--PART PLAYED BY RATS IN
TRANSMISSION.--THE PRESENT EPIDEMIC OF PLAGUE.

The infectious diseases are often complicated by secondary infections,
some other organism finding opportunity for invasion in the presence
of the injuries produced in the primary disease. In many diseases,
such as diphtheria, scarlet fever and smallpox, death is frequently
due to the secondary infection. The secondary invaders not only find
local conditions favoring a successful attack, but the activity of the
tissue cells on which the production of protective substances
essentially depends has suffered by the primary infection, or the
cells are occupied in meeting the exigencies of this. The body is in
the position of a state invaded by a second power where all its forces
and resources are engaged in repelling the first attack.

What are known as terminal infections occur shortly before death. No
matter what the disease which causes death, in the last hours of life
the body usually becomes invaded by organisms which find their
opportunity in the then defenceless tissues, and the end is often
hastened by this invasion.

There are also mixed infections in which two different organisms unite
in attack, each in some way assisting in the action of the other. The
best known example of this is in the highly infectious disease of
swine known as hog cholera. It has been shown that in this disease two
organisms are associated,--one an invisible and filterable organism,
and the other a bacillus. It was first supposed that the bacillus was
the specific organism; it was found in the lesions and certain, but
not all, the features of the disease were produced by inoculating hogs
with pure cultures. The disease so produced is not contagious, and the
contagious element seems to be due to the filterable virus.

The modes of transmission of infectious diseases are of great
importance and are the foundation of measures of public health. In the
preceding chapter we have seen that in the infected individual the
disease extends from one part of the body to another. There is a
primary focus of disease from which the extension takes place, and the
study of the modes of extension in the individual throws some light on
the much more difficult subject of the transmission of disease from
one individual to another. There are four ways by which extension in
the individual may take place.

1. By continuity of tissue, an adjoining tissue or organ becoming
infected by the extension of a focus of infection.

2. By means of lymphatics. Organisms easily enter these vessels which
are in continuity with the tissue spaces and receive the exudate from
the focus of infection. The organisms are carried to the lymph nodes,
which, acting as filters, retain them and for a time prevent a further
extension. The following illustrates the importance of the part the
nodes may play in mechanically holding back a flood of infection. A
physician examined after death the body of a person who died from
infection with a very virulent micrococcus and in the course of the
examination slightly scratched a finger. One of the organs of the body
was removed, sent to a laboratory and received by a laboratory worker,
a woman physician, who had slight abrasions and fissures in the skin
of the hands from contact with irritating chemicals. In the course of
a few hours the wound on the finger of the man became inflamed,
intensely painful, and red lines extended up the arm in the course of
the lymphatic vessels, showing that the organisms were in the
lymphatics and causing inflammation in their course. The lymph nodes
in the armpit into which these vessels empty became greatly inflamed,
swollen, and an abscess formed in them which was opened. There was
high fever, great prostration, a serious illness from which the man
did not recover for several months. The woman only handled the organ
which was sent to the laboratory in order to place it in a fluid for
preservation. She also had a focus of infection of a finger with the
same red lines on the arm, showing extension by the lymphatics; but
there was no halt of the infection in the armpit, for all the lymph
nodes there had been removed several years before in the course of an
operation for a tumor of the breast. A general infection of the blood
took place, there was very high fever, and death followed in a few
days. The halt of the infection is important in allowing time for the
body to make ready its means of defence. One cannot avoid comparing
the lymph node with a strong fortress thrown in the path of a
victorious invading army behind which the defenders may gather and
which affords them time to renovate their strength.

3. By means of the blood. The blood vessels are universally
distributed, the smaller vessels have thin walls easily ruptured and
easily penetrated. It is probable that in every infection some
organisms enter the blood which, under usual conditions, is peculiarly
hostile to bacteria. These may, however, be carried by the blood to
other organs and start foci of infection in these.

4. By means of continuous surfaces. The bacteria may either grow along
such surfaces forming a continuous or more or less broken layer, or
may be carried from place to place in the fluids which bathe them.

All these modes of extension are well shown in tuberculosis. This
disease is caused by a small bacillus which does not produce spores,
has no power of saphrophytic growth under natural conditions, and is
easily destroyed. Moisture and darkness are favorable conditions for
its existence, sunlight and dryness the reverse. There are three
varieties or strains of the tubercle bacilli which infect respectively
man, cattle and birds, and each class of animals shows considerable
resistance to the varieties of the bacillus which are most infectious
for the others.

The primary seat of the infection in man is generally in the upper
part of the lung. The organisms settle on the surface here and cause
multiplication of the cells and an inflammatory exudate in a small
area. With the continuous growth of the bacilli in the focus,
adjoining areas of the lung become affected, and there is further
extension in the immediate vicinity by means of the lymphatics. Small
nodules are formed and larger areas by their coalescence. Infection
with tuberculosis is so common that at least three-fourths of all
individuals over forty show evidences of it. The examination of two
hundred and twenty-five children of the average age of five years who
had died of diphtheria showed tuberculous infection in one-fifth of
the cases and the frequency of infection increases with age. The
defence on the part of the body is chiefly by the formation of dense
masses of cicatricial tissue which walls off the affected area and in
which the bacilli do not find favorable conditions for growth. This
mode of defence, which is probably combined with the production of
substances antagonistic to the toxines produced by the bacilli, is so
efficacious that in the great majority of cases no further extension
of the process takes place. In certain cases, however, the growth of
the bacilli in the focus is unchecked, the tissue about them is killed
and becomes converted into a soft semi-fluid material; further
extension then takes place. All parts of the enormous surface of the
lungs are connected by means of the system of air tubes or bronchi,
and the bacilli have favorable opportunity for distribution, which is
facilitated by sudden movements of the air currents in the lung
produced by coughing. The defence of the body can still keep pace with
the attack, and even in an advanced stage the infection can be checked
in some cases permanently; in others the check is but temporary, the
process of softening continues, and large cavities are produced by the
destruction of the tissue. On the inner surface of these cavities
there may be a rapid growth of bacilli.

From the lungs the bacilli are carried by the lymphatics to the lymph
nodes at the root of the lungs, in which a similar process takes
place; this, on the whole, is favorable, because further extension by
this route is for a time blocked. The extension by means of surfaces
continues, the abundant sputum which is formed in the lungs and which
contains large numbers of bacilli, becomes the vehicle of
transportation. The windpipe and larynx may become infected, the back
parts of each are more closely in contact with the sputum and are the
parts most generally infected. A large part of the sputum is swallowed
and infection of the intestine takes place, the lesions taking the
form of large ulcers. From the intestinal ulcers there is further
extension by means of the lymphatics, to the large lymph nodes in the
back of the abdominal cavity (Fig. 8-25); the bacilli may also pass
from the ulcers into the abdominal cavity and be distributed over the
surface of the peritoneum resulting in tuberculous peritonitis. When
the disease has reached an advanced stage, bacilli in small numbers
continually pass into the blood and are distributed by this over the
body, producing small nodules in many places. In rare cases
distribution by the blood is the principal method of extension, and
immense numbers of small foci of disease are produced, the form of
disease being known as acute miliary tuberculosis. Although the
bacilli are distributed everywhere, certain organs, as the brain and
muscles, are usually exempt, because in these the conditions are not
favorable to further growth of the bacilli. Tuberculosis, although
frequently a very acute disease, is usually one of the best types of a
chronic disease and may last for many years. The chronic form is
characterized by periods of slow or rapid advance when conditions
arise in the body favorable for the growth of the bacilli, and periods
when the disease is checked and quiescent, the defensive forces of the
body having gained the upper hand. Often the intervention of some
other disease so weakens the defences of the body that the bacilli
again find their opportunity. Thus typhoid fever, scarlet fever and
other diseases may be followed by a rapidly fatal advance of the
tuberculosis, starting from some old and quiescent focus of the
disease.

Tuberculosis is also one of the best examples of what is known as
latent infection. In this the infectious organisms enter the body and
produce primary lesions in which the organisms persist but do not
extend owing to their being enclosed in a dense and resistant tissue,
or to the production of a local immunity to their action. Dr. Head has
recently examined the children of households in which there was open
tuberculosis in some member of the household. By open tuberculosis is
understood a case from which bacilli are being discharged. He found
with scarcely an exception that all the children in such families
showed evidences of infection. The detection of slight degrees of
tuberculous infection is now made easy by certain skin reactions on
inoculation of the skin with a substance derived from the tubercle
bacilli. Such latent infections may never become active and in the
majority of cases do not. When, however, in consequence of some
intercurrent disease or conditions of malnutrition the general
defences of the body become weakened extension follows. Such latent
infections explain the enormous frequency of tuberculosis in prisons.
Under the general prison conditions infection in the prisons probably
does not take place to any extent, and the disease is as common when
the prisoners are kept in individual cells as in common prisons. It is
probable that in these cases the prisoners have latent tuberculosis
when entering, and the disease becomes active under the moral and
physical depression which prison life entails.

For the extension of infection from one individual to another the
infecting organisms must in some way be transferred. The most
important of the conditions influencing this are the localization of
the disease and the character of the infectious organisms,
particularly with regard to their resistance to the conditions met
with outside of the body. The seat of disease influences the discharge
of organisms; thus, if the disease involve any of the surfaces the
organisms become mingled with the secretions of the surface and are
discharged with these. If the seat of disease be in the lungs, the
throat or the mouth, the sputum forms the medium of extension, which
can take place in many ways. The sputum may become dried, forms part
of the dust and the organisms enter with the inspired air. The
organisms which cause most of the diseases in which the sputum becomes
infectious are quickly destroyed by conditions in the open, such as
the sunlight and drying; street dust does not play so prominent a part
in extension as is generally supposed. Organisms find much more
favorable conditions within houses. It is now generally recognized
that infection with tuberculosis does not take place in the open, but
in houses in which the bacilli on being discharged are not destroyed.
The hands, the clothing and surroundings even with the exercise of the
greatest care may become soiled with the saliva.

It has been shown that in coughing and speaking very fine particles of
spray are formed by the intermingling of air and saliva, which may be
projected a considerable distance and remain floating in the air for
some time. These particles are so fine as to be invisible; they may be
inspired, and their presence in the air forms an area of indeterminate
extent around the infected person within which such infection is
possible. Such spray formation is also an important means of the
extension of infection in the sick individual, for it is continually
formed and inspired. It is in this way that the extreme prevalence of
broncho-pneumonia in infants and young children is to be explained. No
matter what the essential disease, an almost constant finding in young
children after death is small areas of inflammation in the lungs in
and around the terminations of the air tubes. The situation renders it
evident that the organisms which caused the lesions entered the lung
by the air tubes. The mouth of the child is unclean and harbors
numbers of the same sort of organisms as those causing the lung
inflammation; but in the absence of such a mode of infection as is
given by spray formation it is difficult to see how the extension from
the mouth to the lungs could take place. The weakened condition of the
body in these cases favors the secondary infection.

If the disease be located in the intestines, as in typhoid fever and
dysentery, the organisms are contained in the fecal discharges, and by
means of these the infection is extended. In typhoid fever, dysentery
and cholera massive infections of the populace may take place from the
contamination of a water supply and the disease be extended over an
entire city. One of the most striking instances of this mode of
extension was in the epidemic of cholera in Hamburg in 1892. There
were two sources of water supply, one of which was infected, and the
cases were distributed in the city in the track of the infected
supply. Many such instances have been seen in typhoid fever. Certain
articles of food, particularly milk, serve as sources of infection.
This is more apt to happen when the organism causing the infection
grows easily outside of the body. A few such organisms entering into
the milk can multiply enormously in a few hours and increase the
amount of infectious material. In all these cases the sick individual
remains a source of infection, for it is almost impossible to avoid
some contamination of the body and the immediate surroundings with the
organisms contained in the discharges.

Transmission by air plays but little part in the extension of
infection. In such a disease as smallpox, where the localization is on
the surface of the body, the organisms are contained in or on the thin
epithelial scales which are constantly given off. These are light, and
may remain floating in the air and carried by air currents just as is
the pollen of plants. There seem to have been cases of smallpox where
other modes of more direct transmission could be excluded and in which
the organisms were carried in the air over a considerable space. All
sorts of intermediate objects, both living and inanimate, such as
persons, domestic animals, toys, books, money, etc., can serve as
conveyors of infection.

Insects play a most important part in the transmission of disease, and
in certain cases, as when a disease is localized in the blood, this is
the only means of transmission. There are three ways in which the
insect plays the role of conveyor.

1. The insect may play a purely passive part in that its exterior
surface becomes contaminated with the discharges of the sick person,
and in this way the organisms of disease may be conveyed to articles
of food, etc. The ordinary house fly conveys in this way the organisms
of typhoid and dysentery. Flies seek the discharges not only for food,
but for the purpose of depositing their eggs, and the hairy and
irregular surface of their feet facilitates contamination and
conveyance. When flies eat such discharges the organisms may pass
through the alimentary canal unchanged and be deposited with their
feces; they also often vomit or regurgitate food, and in this way also
contaminate objects. Flies very greedily devour the sputum of
tuberculous patients, and the tubercle bacilli contained in this pass
through them unchanged and are deposited in their feces.

[Illustration: FIG. 19.--TRYPANOSOMES FROM BIRDS. All the trypanosomes
are very much alike. They contain a nucleus represented by the dark
area in the centre and a fur-like membrane terminating in a long
whip-like flagellum. They have the power of very active motion within
the blood.]

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