_BACTERIA AND DISEASE_
Probably the most universally known fact respecting bacteria is that
they are related in some way to the production of disease. Yet we have
seen that it was not as disease-producing agents that they were first
studied. Indeed, it is only within comparatively the latest period
of the two centuries during which they have been more or less under
observation that our knowledge of them as causes of disease has assumed
any exactitude or general recognition. Nor is this surprising, for
although an intimate relationship between fermentation and disease had
been hinted at in the middle of the seventeenth century, it was not
till the time of Pasteur that the bacterial cause of fermentation was
experimentally and finally established.
In the middle of the seventeenth century men learned, through the eyes
of Leeuwenhoek, that drops of water contained "moving animalcules." A
hundred years later Spallanzani demonstrated the fact that putrefaction
and fermentation were set up in boiled vegetable infusions when
outside air was admitted, but when it was withheld from these boiled
infusions no such change occurred. Almost a hundred years more passed
before the epoch-making work of Tyndall and Pasteur, who separated
these putrefactive germs from the air. Quickly following in their
footsteps came Davaine and Pollender, who found in the blood of animals
suffering from anthrax the now well-known specific and causal bacillus
of that disease. Improvements in the microscope and in methods of
cultivation (Koch's plate method in particular) soon brought an army
of zealous investigators into the field, and during the last twenty
years first this disease and then that have been traced to a bacterial
origin. We may summarise the vast mass of historical, physiological,
and pathological research extending from 1650 to 1898 in three great
periods: the period of detection of living, moving cells (Leeuwenhoek
and others in the seventeenth century); the period of the discovery of
their close relationship to fermentation and putrefaction (Spallanzani,
Schulze, Schwann, in the eighteenth century); and, thirdly, the period
of appreciation of the rôle of bacteria in the economy of nature and
in the production of disease (Tyndall, Pasteur, Lister, Koch, in the
nineteenth).
But we must look less cursorily at the growth of the idea of bacteria
causing disease. More than two hundred years ago Robert Boyle
(1627-91), the philosopher, who did so much towards the foundation
of the present Royal Society, wrote a learned treatise on _The
Pathological Part of Physic_. He was one of the earliest scientists to
declare that a relationship existed between fermentation and disease.
When more accurate knowledge was attained respecting fermentation,
great advance was consequently made in the etiology of disease. The
preliminary discoveries of Fuchs and others between 1840 and 1850
had relation to the existence in diseased tissues of a large number
of bacteria. But this was no proof that such germs _caused_ such
diseases. It was not till Davaine had inoculated healthy animals with
bacilli from the blood of an anthrax carcass, and had thus produced
the disease, that reliance could be placed upon that bacillus as the
_vera causa_ of anthrax. Too much emphasis cannot be laid upon this
idea, that unless a certain organism _produces_ in healthy tissues
the disease in question, it cannot be considered as proven that the
particular organism is related to the disease as cause to effect. In
order to secure a standard by which all investigators should test their
results, Koch introduced four postulates. Until each of the four has
been fulfilled, the final conclusion respecting the causal agent must
be considered _sub judice_. The postulates are as follows:
(_a_) The organism must be demonstrated in the circulation or tissues
of the diseased animal.
(_b_) The organism thus demonstrated must be cultivated in artificial
media outside the body, and successive generations of a _pure culture_
of that organism must be obtained.
(_c_) Such pure cultures must, when introduced into a healthy and
susceptible animal, produce the specific disease.
(_d_) The organism must be found and isolated from the circulation or
tissues of the inoculated animal.
It is evident that there are some diseases--for example, cholera,
leprosy, and typhoid--which are not communicable to lower animals, and
therefore their virus cannot be made to fulfil postulate (_c_). In
such cases there is no choice. They cannot be classified along with
tubercle and anthrax. Bacteriologists have little doubt that Hansen's
bacillus of leprosy is the cause of that disease, yet it has not
fulfilled postulates (_b_) and (_c_). Nor has the generally accepted
bacillus of typhoid fulfilled postulate (_c_), yet by the majority it
is _provisionally_ accepted as the agent in producing typhoid. Hence
it will be seen that, though there is an academical classification
of causal pathogenic bacteria according as they respond to Koch's
postulates, yet nevertheless, there are a number of pathogenic bacteria
which are looked upon as causes of disease provisionally. Anthrax and
tubercle, with perhaps the organisms of suppuration, tetanus, plague,
and actinomycosis, stand in the first order of pathogenic germs. Then
comes a group awaiting further confirmation. It includes the organisms
related to typhoid, cholera, malaria, leprosy, diarrhœa, and
pneumonia. Then comes in a third category, a long list of diseases,
such as scarlet fever, small-pox, rabies, and others too numerous to
mention, in which the nature of the causal agent is still unknown.
Hence it must not be supposed that every disease has its germ, and
without a germ there is no disease. Such universal assertions, though
not uncommonly heard, are devoid of accuracy.
In the production of bacterial disease there are two factors. First,
there is the body tissue of the individual; secondly, there is the
specific organism.
Whatever may be said hereinafter with regard to the power of
micro-organisms to cause disease, we must understand one cardinal
point, namely, that bacteria are never more than causes, _for the
nature of disease depends upon the behaviour of the organs or tissues
with which the bacteria or their products meet_ (Virchow). Fortunately
for a clear conception of what "organs and tissues" mean, these have
been reduced to a common denominator, the cell. Every living organism,
of whatever size or kind, and every organ and tissue in that living
organism, contains and consists of cells. Further, these cells are
composed of organic chemical substances which are not themselves alive,
but the mechanical arrangement of which determines the direction and
power of their organic activity and of their resistance to the specific
agents of disease. With these facts clearly before us, we may hope to
gain some insight into the reasons for departure from health.
The normal living tissues have an inimical effect upon bacteria.
Saprophytic bacteria of various kinds are normally present on exposed
surfaces of skin or mucous membrane. Tissues also which are dead or
depressed in vitality from injury or previous disease, but which are
still in contact with the tissues, afford an excellent nidus for the
growth of bacteria. Still these have not the power, unless specific, to
thrive in the normal living tissue. It has been definitely shown that
the blood fluids of the body have in their fresh state the germicidal
power (_alexines_) which prevents bacteria from flourishing in them.
Such action does undoubtedly depend in measure upon the number of germs
as well as their quality, for the killing power of blood and lymph must
be limited. Buchner has pointed out that the antagonistic action of
these fluids depends in part possibly upon phagocytosis, but largely
upon a chemical condition of the serum. The blood, then, is no friend
to intruding bacteria. Its efforts are to a certain extent seconded
by the lymphoid tissue throughout the body. Rings of lymphoid tissue
surround the oral openings of the trachea (windpipe) and œsophagus
(gullet); the tonsils are masses of lymphoid tissue. Composed as it is
of cells having a germicidal influence when in health, the lymphoid
tissue may afford formidable obstruction to intruding germs.
All the foregoing points in one direction, namely, that if the tissues
are maintained in sound health, they form a very resistant barrier
against bacteria. But we know from experience that a full measure of
health is not often the happy condition of human tissues; we have, in
short, a variety of circumstances which, as we say, _predispose_ the
individual to disease. One of the commonest forms of predisposition
is that due to _heredity_. Probably it is true that what are known as
hereditary diseases are due far more to a hereditary predisposition
than to any transmission of the virus itself in any form. _Antecedent
disease_ predisposes the tissues to form a nidus for bacteria;
_conditions of environment or personal habits_ frequently act in the
same way. Damp soils must be held responsible for many disasters to
health, not directly, but indirectly, by predisposition; dusty trades
and injurious occupations have a similar effect. Any one of these three
different influences may in a variety of ways affect the tissues and
increase their susceptibility to disease. Not infrequently we may get
them combined. For example, the following is not an unlikely series of
events terminating in consumption (tuberculosis of the lungs):--(_a_)
The individual is predisposed by inheritance to tuberculosis; (_b_)
an ordinary chronic catarrh, which lowers the resisting power of the
lungs, may be contracted; (_c_) the epithelial collections in the air
vesicles of the lung--_i. e._, dead matter attached to the body--afford
an excellent nidus for bacteria; (_d_) owing to occupation, or
personal habits, or surroundings, the patient comes within a range of
tubercular infection, and the specific bacilli of tubercle gain access
to the lungs. The result, it is needless to state, will be a case of
consumption more or less acute according to environment and treatment.
The _channels of infection_ by which organisms gain the vantage-ground
afforded by the depressed tissues are various, and next to the
maintenance of resistant tissues they call for most attention from the
physician and surgeon. It is in this field of preventive medicine--that
is to say, preventing infective matter from ever entering the tissues
at all--that science has triumphed in recent years. It is, in short,
applied bacteriology, and therefore claims consideration in this place.
1. _Pure Heredity._ By this term may be understood the actual
transmission from the mother to the unborn child of the specific virus
of the disease. That such a conveyance may occur is generally admitted
by pathologists, but it is impossible to enter fully into the matter
in such a book as the present. Summarily we may say that, though
this sort of transmission is possible, it is not frequent, nor is
disease appreciably spread through such a channel. Sixty per cent. of
consumptives, it has been estimated, have tuberculous progenitors, and
this is the highest figure. Many would be justified from experience in
placing it at half that number.
2. _Inoculation_, or inserting virus through a broken surface of
skin, is itself a sufficiently obvious mode of infection to call for
little comment. Yet it is under this heading that a word must be
said of that remarkable application of preventive medicine known as
the antiseptic treatment of wounds. When Lord Lister was Professor of
Surgery in Glasgow, he was impressed with the greatness of the evil
of putrefaction in wounds, which was caused, not by the oxygen of the
air, as Liebig had declared, but by the entrance into the wound of
fermentative organisms from the air. This was demonstrated by Pasteur,
who pointed out that they could not arise _de novo_ in the wound. Hence
it appeared to Lister that these fermentative bacteria which produce
putrefaction in wounds must either be kept out of the wound altogether,
or killed, or their action prevented, in the wound. To keep air away
from wounds is an almost impossible task, and thus it came about that
wounds were dressed with a solution of carbolic acid.
From time to time examples occur of bacterial disease being directly
inoculated in wounds made with polluted instruments, or in cuts made by
contaminated broken glass, or in gunshot wounds. Tetanus is, of course,
one of the most marked examples.
3. _Contagion_ is a term which has suffered from the many ways in which
it has been used. Defined shortly and most simply, we should say a
disease is _contagious_ when it can be "caught" by contact, through the
unbroken surfaces, between diseased and healthy persons. Ringworm is an
example, and there are many others.
4. _The Alimentary Canal: Food._ The recent Royal Commission on
Tuberculosis has collected a large mass of evidence in support of the
view that tubercle may be spread by articles of food. Milk and meat
from tuberculous animals naturally come in for the largest amount of
condemnation. To these matters we refer elsewhere.
5. _The Respiratory Tract: Air._ The air may become infected with germs
of disease from dusty trades, dried sputum, etc. If such infected air
be inhaled, pathogenic results will follow, especially if the bacteria
are present in sufficient numbers, or meet with devitalised, and
therefore non-resisting, tissues.
These, then, are the five possible ways in which germs gain access to
the body tissues. The question now arises, How do bacteria, having
obtained entrance, set up the process of disease? For a long time
pathologists looked upon the action of these microscopic parasites in
the body as similar to, if not identical with, the larger parasites
sometimes infesting the human body. Their work was viewed as a
devouring of the tissues of the body. Now, it is well known that,
however much or little of this may be done, the specific action
of pathogenic bacteria is of a different nature. It is twofold.
We have the action of the bacteria themselves, and also of their
products or toxins. In particular diseases, now one and now the other
property comes to the front. In bacterial diseases affecting or being
transmitted mostly by the blood, it is the toxins which act chiefly.
The convenient term _infection_ is applied to those conditions in
which there has been a multiplication of living organisms after they
have entered the body, the word _intoxication_ indicating a condition
of poisoning brought about by their products. It will be apparent
at once that we may have both these conditions present, the former
before the latter, and the latter following as a direct effect of the
former. Until intoxication occurs there may be few or no symptoms, but
directly enough bacteria are present to produce in the body certain
poisons in sufficient amount to result in more or less marked tissue
change, then the symptoms of that tissue change appear. This period of
latency between infection and the appearance of the disease is known
as the _incubation period_. Take typhoid, for example. A man drinks a
typhoid-polluted water. For about fourteen days the bacilli are making
headway in his body without his being aware of it. But at the end of
that incubation period the signs of the disease assert themselves.
Professor Watson Cheyne and others have maintained that there is some
exact proportion between the number of bacteria gaining entrance and
the length of the incubation period.
Speaking generally, we may note that pathogenic bacteria divide
themselves into two groups: those which, on entering the body, pass
at once, by the lymph or blood stream, to all parts of the body,
and become more and more diffused throughout the blood and tissues,
although in some cases they settle down in some spot remote from the
point of entrance, and produce their chief lesions there. Tubercle
and anthrax would be types of this group. On the other hand, there is
a second group, which remain almost absolutely local, producing only
little reaction around them, never passing through the body generally,
and yet influencing the whole body eventually by means of their
ferments or toxins. Of such the best representatives are tetanus and
diphtheria. The local site of the bacteria is, in this case, the local
manufactory of the disease.
Whilst the mere bodily presence of bacteria may have mechanical
influence injurious to the tissues (as in the small peripheral
capillaries in anthrax), or may in some way act as a foreign body and
be a focus of inflammation (as in tubercle), the real disease-producing
action of pathogenic bacteria depends upon the _chemical poisons_
(toxins) formed directly or indirectly by them. Though within
recent years a great deal of knowledge has been acquired about the
formation of these bodies, their exact nature is not known. They
are allied to albuminous bodies and proteoses, and are frequently
described as tox-albumens. It may be found, after all, that they are
not of a proteid nature. Sidney Martin has pointed out that there
is much that is analogous between the production of toxins and the
production of the bodies of digestion. Just as ferments are necessary
in the intestine to bring about a change in the food by which the
non-soluble albumens shall be made into soluble peptones and thus
become absorbed through the intestinal wall, so also a ferment may be
necessary to the production of toxins. Such ferments have not as yet
been isolated, but their existence in diphtheria and tetanus is, as we
have seen, extremely likely. However that may be, it is now more or
less established that there are two kinds of toxic bodies, differing
from each other in their resistance to heat. It may be that the one
most easily destroyed by heat is a ferment and possibly an originator
of the other. A second division which has been suggested for toxic
bodies, and to which reference has been made, is _intracellular_ and
_extracellular_, according to whether or not the poison exists within
or without the body of the bacillus.
Lastly, we may turn to consider the action of the toxins on the
individual in whose body-fluids they are formed. It is hardly necessary
to say that any action which bacteria or toxins may have will depend
upon their virulence, in some measure upon their number, and not
a little upon the channel of infection by which they have gained
entrance. It could not be otherwise. If the virulence is attenuated,
or if the invasion is very limited in numbers, it stands to reason
that the pathogenic effects will be correspondingly small or absent.
The influence of the toxins is twofold. In the first place (i.) they
_act locally upon the tissues_ at the site of their formation, or
at distant points by absorption. There is inflammation with marked
cell-proliferation, and this is, more or less rapidly, followed by
a specific cell-poisoning. The former change may be accompanied
by exudation, and simulate the early stages of abscess formation;
the latter is the specific effect, and results, as in leprosy and
tubercle, in infective nodules. The site in some diseases, like typhoid
(intestinal ulceration, splenic and mesenteric change) or diphtheria
(membrane in the throat), may be definite and always the same. But, on
the other hand, the site may depend upon the point of entrance, as in
tetanus. The distant effects of the toxin are due to absorption, but
what controls its action it is impossible to say. We only know that we
do find pathological conditions in certain organs at a distance and
without the presence of bacteria. We have a parallel in the action of
drugs; for example, a drug may be given by the mouth and yet produce
a rash in some distant part of the body. In the second place (ii.)
toxins produce _toxic symptoms_. Fever and many of the _nervous
conditions resulting_ from bacterial action must thus be classified.
We have, it is true, the chemical symptoms of the pathological tissue
change, for example, the large spleen of anthrax or the obstruction
from diphtheritic membrane. But, in addition to these, we have general
symptoms, as fever, in which after death no tissue change can be formed.
We may now consider briefly some of the more important types of disease
produced by bacteria:
+1. Tuberculosis.+[90] As far back as 1794 Baillie drew attention to
the grey miliary nodules occurring in tuberculous tissue which gave
rise to the term "tubercles." This preliminary matter was confirmed by
Bayle in 1810.
In 1834 Laennec described all caseous deposits as "tubercles,"
insisting upon four varieties:
(1) Miliary, which were about the size of millet seeds, and in groups;
(2) Crude, miliary tubercles in yellow masses;
(3) Granular, similar to the last, but scattered;
(4) Encysted, a hard mass of crude tubercle with a fibrous or
semi-cartilaginous capsule.
The tubercle possesses in many cases a special structure, and certain
cell-forms frequently occur in it and give it a characteristic
appearance. The central part of the tubercle usually contains _giant
cells_ with numerous nuclei. The uninuclear cells are partly lymphoid,
partly large epithelial or endothelial cells; these are called
_epithelioid_ cells.
It was not till 1865 that the specific nature of tuberculosis was
asserted by Villemin. Burdon Sanderson (1868-69) in England confirmed
his work, and it was extended by Connheim, who a few years later laid
down the principle that all is tubercular which by transference to
properly constituted animals is capable of inducing tuberculosis, and
nothing is tubercular unless it has this capability.
Klebs (1877) and Max Schiller (1880) described masses of living
cells or micrococci in many tuberculous nodules in the diseased
synovial membrane and in lupus skin. In 1881 Toussaint declared
he had cultivated from the blood of tubercular animals and from
tubercles an organism which was evidently a micrococcus, and in the
same year Aufrecht stated that the centre of a tubercle contained
small micrococci, diplococci, and some rods. But it was not till the
following year, 1882, that Koch discovered and demonstrated beyond
question the specific _Bacillus tuberculosis_.
It is now held to be absolutely proved that the introduction of the
bacillus, or its spores or products, is the one and only essential
agent in the production of tuberculosis. Its recognised manifestations
are as follows:
Tuberculosis in the lungs = _acute or chronic phthisis_;
" in the skin = _lupus_[1];
" in the mesenteric glands = _Tabes mesenterica_;
" in the brain = _hydrocephalus_;
" in lymphatic glands = _Scrofula_.[91]
The disease may occur generally throughout the body or locally in the
suprarenal capsules, prostate, intestine, larynx, membranes of the
heart, bones, ovaries, pleura, kidneys, spleen, testicles, Fallopian
tubes, uterus, etc.
We may summarise the history of the pathology of tubercle thus:
1794. Baillie drew attention to grey miliary nodules occurring
in tuberculosis, and called them "tubercles."
1834. Laennec described four varieties: _miliary_; _crude_;
_granular_; _encysted_.
1843. Klencke produced tuberculosis by intravenous injection
of tubercular giant cells.
1865. Villemin demonstrated infectivity of tubercular matter
by inoculation of discharges; Connheim, Armanni, Burdon
Sanderson, Wilson Fox, and others showed that nothing but
tubercular matter could produce tuberculosis.
1877. Living cells were found in tubercles, "micrococci"
(Klebs, Toussaint, Schiller).
1882. Koch isolated and described the specific bacillus, and
obtained pure cultivations (1884).
_The Bacillus of Koch_, 1882. Delicate cylindrical rods, measuring
1.5-4 micromillimetres in length and about .2 µ in breadth; non-motile.
Many are straight with rounded ends; others are slightly curved. They
are usually solitary, but may occur in pairs, lying side by side or in
small masses. They are chiefly found in fresh tubercles, more sparingly
in older ones. Some lie within the giant cells; others lie outside;
shorter in tissue sections of bovine tuberculosis, but longer in the
milk (Crookshank).
When stained they appear to be composed of irregular cubical or
spherical granules within a faintly stained sheath. In recent lesions
the protoplasm appears more homogeneous, and takes on the segmented or
beaded character only in old lesions, pus, or sputum.
Morphological differences are found under different circumstances, and
within limits variation occurs according to the environment.
_Cultivation on Various Media._ Koch inoculated _solid blood serum_
with tubercular matter from an infected lymphatic gland of a
guinea-pig, and noticed the first signs of growth in ten or twelve days
in the form of whitish, scaly patches. These enlarged and coalesced
with neighbouring patches, forming white, roughened, irregular masses.
Nocard and Roux showed that by adding 5/8 per cent. of glycerine to the
media commonly used in the laboratory, such as nutrient agar or broth,
the best growth is obtained.
On _glycerine broth_ or _glycerine agar_ abundant growth appears at the
end of seven or eight days. By continuous sub-culture on glycerine agar
the virulence of the bacillus is diminished. But in fifteen days after
inoculation of the medium the culture equals in extent a culture of
several weeks' age on blood serum.
Sub-cultures from glycerined media will grow in ordinary broth without
glycerine (Nocard, Roux, Crookshank).
In _alkaline broth_ to which a piece of boiled white of egg was added
Klein obtained copious growths, and found that continued sub-culturing
upon this medium also lessens the virulence.
_Description of Cultivations:_--On glycerine agar minute white colonies
appear in about six days, raised and isolated, and coalescing as time
advances, forming a white lichenous growth, fully developed in about
two months.
On glycerine broth a copious film appears on the surface of the liquid,
which if disturbed falls to the bottom of the flask as a deposit.
_Spore Formation._ In very old cultivations spore-like bodies can be
observed both in stained and unstained preparations, but neither the
irregular granules within the capsule nor the unstained spaces between
the granules are spores (Babes and Crookshank). That the bacilli
possess spores is believed on account of the following facts:
1. That tubercular sputum, when thoroughly dried, maintains its
virulent character (Koch, Schill, Fischer, etc.). No sporeless bacillus
is known which can survive through drying.
2. That tubercular matter and cultures survive temperature up to 100°
C. Non-spore-bearing bacilli and micrococci are killed by being exposed
for five minutes to a temperature of 65-70° C., whereas spores of other
bacilli withstand much higher temperatures.
3. Tubercular sputum distributed in salt solution does not lose its
virulence by being kept at 100° C. for one or two minutes; sporeless
bacilli certainly would (Klein).
4. A solution of per-chloride of mercury does not kill the tubercle
bacilli, as it does sporeless bacilli (Lingard and Klein).
Koch and many bacteriologists have declared the bacillus to be a "true
parasite." Koch based this view upon the belief which he entertained
that the bacillus can grow only between 30° C. and 41° C., and
therefore in temperate zones is limited to the animal body and can
originate only in an animal organism. "They are," he said, "true
parasites, which cannot live without their hosts. They pass through the
whole cycle of their existence in the body." But at length Koch and
others overcame the difficulties and grew the bacillus as a saprophyte.
Schottelius[92] has observed that tubercle bacilli taken from the lung
of phthisical persons buried for years still retains its virulence and
capability of producing tuberculosis upon inoculation. He further shows
that tubercular lung kept in soil (enclosed in a box) shows a marked
rise in temperature. Klein quotes these experiments as indications that
"_tubercle bacilli are not true parasites, but belong to the ectogenic
microbes which can live and thrive independent of a living host_."
It has now been abundantly proved that the bacillus of tuberculosis is
capable of accommodating itself to circumstances much less favourable
than had been supposed, especially as regards temperature.
_Temperature of Growth of Bacillus._ 30-41° C. have been laid down by
Koch as the limits of temperature at which the bacillus will grow in
culture medium outside the body. The generally accepted temperatures as
most favourable to the growth of the bacillus are between 36° C. and
38° C.
Sir Hugh Beevor, however, was able to grow the bacillus upon glycerine
agar at 28° C. (82° F.), obtaining an ample culture which developed
somewhat more slowly than on blood serum, and to a less extent than
at 37° C. In both Beevor succeeded in growing the bacillus at a lower
temperature even than on agar, viz., at a temperature rarely above 60°
F. Sheridan Delepine and others have also been successful in obtaining
growths at room temperature both in summer and winter.
Although, speaking generally, there is an actual cessation of growth at
low temperature, the bacillus may be exposed to very low temperatures
for a considerable time without losing its power of again becoming
active when returned to a favourable environment (Woodhead).
_The Relation of the Bacillus to the Disease._ All four of Koch's
postulates have been fulfilled in the case of _Bacillus tuberculosis_.
Hence we are dealing with the specific cause of the disease. Yet,
whilst this is so, we may usefully ask ourselves: _How_ does the
bacillus set up the changes in normal tissues which result in
tubercular nodules? In arriving at a solution of this problem we are
materially aided if we bear in mind the fact that such an organism
in healthy tissues has a double effect. First, there is an ordinary
inflammatory irritation, and secondly, there is a specific change
set up by the toxins of the bacillus. Directly the invading bacilli
find themselves in a favourable nidus they commence multiplication.
In three or four days this acts as an irritant upon the surrounding
connective-tissue cells, which proliferate, and become changed into
large cells known as _epithelioid cells_. At the periphery of this
collection of epithelioid cells we have a congested area. This change
has been accomplished by the presence of the bacilli themselves. The
production of their specific poisons changes the epithelioid cells
in the centre of the nodule, some of which become fused together,
whilst others expand and undergo division of nucleus. By this means we
obtain a series of large multi-nucleated cells named _giant cells_.
If the disease is very active, these soon caseate and break down
in the centre. In a limb we get a discharge; in a lung we get an
expectoration. Both discharge and expectoration arise from a breaking
down of the new cell formation. Previously to breaking down we have in
a fully developed nodule healthy tissue, inflammatory zone, epithelioid
cells, giant cells, containing nuclei and bacilli. The sputum or the
discharge will, during the acute stage of the disease at all events,
contain countless numbers of the bacilli, which may thus be readily
detected, and their presence used as evidence of the disease. It is
obvious that if the centre of the nodule degenerates and comes away as
discharge a cavity will be left behind. By degrees this small cavity
may become a very large one, as is frequently the case in the lung,
which particularly lends itself to such a condition. Hence, though at
the outset a tubercular lung is solid, at the end it is hollow.
[Illustration: BACILLUS TUBERCULOSIS
(In sputum from a case of phthisis, "consumption" of the lungs)
× 1000
_By permission of the Scientific Press, Limited_]
[Illustration: BACILLUS TUBERCULOSIS
(The bacilli are arranged within the giant cell)
× 1000]
[Illustration: STREPTOCOCCUS PYOGENES
(From broth culture)
× 1000
_By permission of the Scientific Press, Limited_]
[Illustration: BACILLUS ANTHRACIS
(From splenic blood of cow)
× 1000
_By permission of the Scientific Press, Limited_]
The exact period of giant-cell formation depends on the rapidity
of the formative processes. Thus different conditions occur. Inside
the giant cells the bacilli are arranged in relation to the nuclei
in one of three ways: (_a_) polar, (_b_) zonal, or (_c_) mixed. The
breaking down of the nodule is partly due to the cell-poisons, and
partly because the nodule is non-vascular, owing to the fact that new
capillaries cannot grow into the dense nodule, and the old ones are all
occluded by the growth of the nodule.
From the local foci of disease the tubercle process spreads chiefly by
three channels:
(_a_) _By the lymphatics_, affecting particularly the glands. Thus
we get tuberculosis set up in the bronchial, tracheal, mediastinal,
and mesenteric glands, and it is so frequently present as to be
a characteristic of the disease. This is the common method of
dissemination in the body.
(_b_) _By the blood-vessels_, by means of which bacilli may be carried
to distant organs.
(_c_) _By continuity of tissues_, infective giant-cell systems
encroaching upon neighbouring tissues, or discharge from lungs or
bronchial glands obtaining entrance to the gullet and thus setting up
intestinal disease also.
It has been abundantly proved that the respiratory and digestive
systems are principally affected by Koch's bacillus. Wherever the
bacilli are arrested, they excite formation of granulations or miliary
tubercular nodules, which increase and eventually coalesce. The
lymphatic glands which collect the lymph from the affected region are
the earliest affected, always the nearest first, and then the disease
appears to be appreciably stopped on its invading march. Each lymphatic
gland acts as a temporary barrier to progress until the disease has
broken its structure down. It remains local, in spite of increase in
number and importance of the foci of disease, as long as the bacilli
have not gained access to the blood stream.
_Toxins and Tuberculin._ Koch, Crookshank, and Herroun, Hunter, and
others have isolated products from pure cultures of the tubercle
bacillus. These have comprised chiefly _albumoses_, _alkaloids_, and
various _extractives_. Koch's observations led him to suppose that
in pure cultures of tubercle a substance appeared having healing
action on tuberculosis, and an extract of this in glycerine he termed
"tuberculin." It was made as follows: A veal broth containing peptone
and glycerine was inoculated with a pure culture of the bacillus and
incubated at 38° C. for six or eight weeks. An abundant growth with
copious film formation appeared. The culture was then concentrated by
evaporation over a water-bath until reduced to about one-tenth of its
volume.
[Illustration: FLASK USED IN THE PREPARATION OF TUBERCULIN]
The announcements in 1890 and 1891 to the effect that a "cure" had
been discovered for consumption will be remembered. The hopes thus
raised were unfortunately not to be realised. Koch advocated injections
of this tuberculin in cases of skin tubercle (lupus) and consumptive
cases. In many of these benefit was apparently derived, but its general
application was not founded upon any substantial basis. Dead tissue,
full of bacilli, could not thus be got rid of; nor could the career of
the isolated bacilli distributed through the body be thus checked.
Tuberculin has, however, found a remarkable sphere of usefulness in
causing reaction in animals suffering from tuberculosis. Indeed,
tuberculin is the most valuable means of diagnosis that we possess
(MacFadyen). When injected (dose, 30-40 centigrammes) it causes a
rise of one and a half to three degrees. The fever begins between the
twelfth and fifteenth hour after injection, and lasts several hours.
The duration and intensity of the reaction have no relation to the
number and gravity of the lesions, but the same dose injected into
healthy cattle causes no appreciable febrile reaction. The tuberculous
calf reacts just as well as the adult, but the dose is generally 10-20
centigrammes. Injections of tuberculin have no troublesome effect on
the quantity or quality of the milk of cows or on the progress of
gestation.
_Tuberculosis of Animals._ Cattle come first amongst animals liable
to tubercle. Horses may be infected, but it is comparatively rare,
and among small ruminants the disease is rarer still. Dogs, cats, and
kittens may be easily infected. Amongst birds, fowls, pigeons, turkeys,
and pheasants, the disease assumes almost an epidemic character.
Especially do animals in confinement die of tubercle, as is illustrated
in zoölogical gardens. Respecting the lesions of bovine tuberculosis,
it will be sufficient to say that nothing is more variable than the
localisation or form of its attacks. The lungs and lymphatic glands
come first in order of frequency, next the serous membranes, then the
liver and intestines, and lastly the spleen, joints, and udder (Nocard).
The anatomical changes in bovine tubercle are mostly found in the
lungs and their membranes, the pleuræ. It also affects the internal
membrane lining, the abdomen and its chief organs, the peritoneum,
and the lymphatic glands. In both these localities a characteristic
condition is set up by small grey nodules appearing, which increase
in size, giving an appearance of "grapes." Hence the condition is
called grape disease, or _Perlsucht_. The organs, as we have said, are
equally affected, and when we add the lymphatic glands we have a fairly
complete summary of the form of the disease as it occurs in cattle. As
has been clearly pointed out by Martin, Woodhead, and others in their
evidence before the Royal Commission, the organs, glands, and membranes
are the sites for tubercle, not the muscles (or "meat"). This latter
is most liable to convey infection when the butcher smears it with the
knife which he has used to remove tubercular organs.
As regards the udder in its relation to milk infection, it may be
desirable to state that the initial lesion, according to Nocard and
Bang, takes the form of a progressive sclerosis. The interlobular
connective tissue, normally scanty, becomes thickened, fibrous, and
infiltrated by minute miliary granulations. The granular tissue is
thus "smothered by the hypertrophy and fibrous transformation of the
interstitial connective tissue" (Nocard). The walls of the ducts are
thickened and infiltrated, the lumen frequently dilated by masses of
yellow caseous material. On the whole it may be said that tubercle
of the udder is rare. Usually only one quarter is attacked, and by
preference the posterior. For some time the milk remains normal,
but gradually it becomes serous and yellow, and contains coagula
holding numbers of bacilli. Lastly, it becomes purulent and dries up
altogether. While the milk is undergoing these changes the lesion of
the udder is becoming more marked, the tissue becomes less supple, and
the toughness increases almost to a wooden hardness.
The general anatomical characteristics of the disease are similar to
those occurring in man.
The percentage of cattle suffering from tubercle varies. In Germany it
appears to vary from 2 to 8 per cent. of all cattle, in Saxony 17 to
30 per cent., in England 22 per cent. approximately (in London 40 per
cent.), in France 25 per cent. Lowland breeds are much more infected
than mountain breeds, which possess stronger constitutions.
Tuberculosis of the _pig_ is less common than that of cattle, but not
so rare as that of the calf (Nocard). In nine out of ten cases the pig
is infected by ingestion, particularly when fed on the refuse from
dairies and cheese factories. The disease follows the same course as
in cattle. The finding of the bacillus is difficult, and the only safe
test is inoculation (Woodhead).
_Sheep_ are very rarely tuberculous by nature, though there is evidence
to believe that very long cohabitation with tuberculous cattle would
succeed in transmitting tuberculosis to some sheep.
Tuberculosis in the _horse_ is relatively very rare. It attacks the
organs of the abdominal cavity, especially the glands; it affects the
lung secondarily as a rule. The cases are generally isolated ones, even
though the animal belongs to a stud. Nocard holds that the bacillus
obtained from the pulmonary variety is like the human type, whilst the
abdominal variety is more like the avian bacillus.
Nocard says[93]:
"If the dog can become tuberculous from contact with man, the
converse is equally true. Infection is at any rate possible
when a house-dog scatters on the floor, carpet, or bed, during
its fit of coughing, virulent material, which is rendered
extremely dangerous by drying, especially for children,
its habitual playmates. The most elementary prudence would
recommend the banishment from a room of every dog which coughs
frequently, even though it only seems to be suffering from
some common affection of the bronchi or lung."
Tuberculosis is a common disease among the _birds_ of the poultry-yard:
poultry, pigeons, turkeys, pea-fowl, guinea-fowl, etc. They are
infected almost exclusively through the digestive tract, generally by
devouring infected secretions of previous tubercular fowls. Whatever
the position or form of avian tuberculosis, the bacilli are present in
enormous numbers, and are often much shorter and sometimes much longer
than those met with in tuberculous mammalia, and grow outside the
body at a higher temperature (43° C.). They are also said to be more
resistant and of quicker growth. The species is probably identical with
Koch's bacillus, though there are differences. In the nodule, which is
larger than in human tuberculosis, there are few or no giant cells, and
it does not so readily break down.
Nocard and others have demonstrated the fact that the _Bacillus
tuberculosis_ of Koch is the common denominator in all tubercular
disease, whatever and wherever its manifestations, in all animals. The
bacillus, they hold, may, however, experience profound modifications
by means of successive passages through the bodies of divers species
of animals. But if the modifications which it undergoes as a result of
transmissions through birds, for example, are profound enough to make
the bacillus of avian tubercle a peculiar variety of Koch's bacillus,
they are not enough, it is generally believed, to make these bacilli
two distinct species.
We may, therefore, take it for granted that tuberculosis is one and the
same disease, with various manifestations, common to man and animals,
intercommunicable, and having but one _vera causa_: the _Bacillus
tuberculosis_ of Koch.
_The Prevention of Tuberculosis._ At the present time much attention is
being directed to the administrative personal control of tuberculosis.
How greatly this is needed in so preventable a disease is evident from
a perusal of the following quotation from the Registrar-General's
reports. (See opposite page.)
These figures show a marked decline in the three worst forms of the
disease. But this decline is apparently less marked in tabes than
in phthisis or tubercular meningitis, _i. e._, less in the kind of
tubercle due to the ingestion of infected milk. Fortunately the State
is beginning to realise its duty in regard to preventive measures. The
abolition of private slaughter-houses, the protection of meat and milk
supplies, the seizure of tuberculous milch cows, and such like measures
fall obviously within the jurisdiction of the State rather than the
individual, and claim the earnest and urgent attention of the public
health departments of states.[94]
ENGLISH DEATH-RATES FROM ALL TUBERCULAR DISEASES
THE FOLLOWING IS A TABLE OF DEATH-RATES TO A MILLION LIVING
(ENGLAND), 1877-1897 (_Reg.-Gen. Annual Reports_):--
------------------+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----
|1877 |1878 |1879 |1880 |1881 |1882 |1883 |1884 |1885 |1886 |1887
------------------+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----
Tabes Mesenterica | 316 | 348 | 300 | 370 | 284 | 313 | 289 | 310 | 251 | 300 | 253
Tubercular | | | | | | | | | | |
Meningitis | 319 | 338 | 322 | 330 | 276 | 264 | 262 | 264 | 253 | 257 | 236
Phthisis |2079 |2111 |2021 |1869 |1825 |1850 |1880 |1827 |1770 |1739 |1615
Other Forms | 126 | 124 | 116 | 129 | 145 | 153 | 160 | 170 | 157 | 177 | 179
------------------+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----
Total |2840 |2921 |2759 |2698 |2530 |2580 |2591 |2571 |2431 |2473 |2283
------------------+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----
------------------+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----
|1888 |1889 |1890 |1891 |1892 |1893 |1894 |1895 |1896 |1897
------------------+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----
Tabes Mesenterica | 240 | 269 | 265 | 251 | 242 | 265 | 192 | 243 | 196 | 201
Tubercular | | | | | | | | | |
Meningitis | 239 | 234 | 240 | 247 | 227 | 226 | 211 | 222 | 210 | 213
Phthisis |1568 |1573 |1682 |1599 |1468 |1468 |1385 |1398 |1307 |1341
Other Forms | 174 | 183 | 189 | 203 | 199 | 186 | 185 | 200 | 179 | 175
------------------+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----
Total |2221 |2259 |2376 |2300 |2136 |2145 |1973 |2063 |1892 |1930
------------------+-----+-----+-----+-----+-----+-----+-----+-----+-----+-----
_Tabes mesenterica_ is tuberculosis of the alimentary canal and
mesenteric lymph glands.
_Tubercular meningitis_ is the name of the same disease as it affects
the membranes of the brain (acute hydrocephalus).
_Phthisis_ is the term applied to "consumption," or tubercle in the
lungs.
But personal hygiene and the prevention of the transmission of the
disease depend very largely indeed upon the mass of the population.
Hence we hail with satisfaction the recent endeavours to educate public
opinion. In order to make this matter very simple indeed, we have
placed in a footnote a series of statements embodying some of the chief
facts which every individual in our crowded communities should know.[95]
[Illustration: BACILLUS OF DIPHTHERIA]
+Diphtheria+ (Klebs-Löffler Bacillus, 1882-1884). Diphtheria is an
infective disease characterised by a variety of clinical symptoms, but
commonly by a severe inflammation followed by a fibrous infiltration
(constituting a _membrane_) of certain parts. The membrane ultimately
breaks down. The parts affected are the mucous membrane of the fauces,
larynx, pharynx, trachea, and sometimes wounds and the inner wall of
the stomach. The common sign of the disease is the membrane in the
throat; but muscle weakness, syncope, albuminuria, post-diphtheritic
paralysis, convulsions, and many other symptoms guide the physician in
diagnosis and the course of the disease.
The _Bacillus diphtheriæ_ was isolated from the many bacteria found
in the membrane by Löffler. Klebs had previously identified the
bacillus as the cause of the disease. It is a slender rod, straight
or slightly curved, and remarkable for its beaded appearance; there
are also irregular and club-shaped forms. It differs in size according
to its culture medium, but is generally 3 or 4 µ in length. In the
membrane which is its strictly local habitat in the body--indeed, the
bacillus is found nowhere else in the body--it almost invariably shows
parallel grouping, lying between the fibrin of the membrane, and most
largely in its deeper parts. Here it is mixed with other bacilli,
micrococci, staphylococci, and streptococci, all of which are present
and performing their part in complicating the disease. The bacillus
possesses five negative characters; namely, it has no spores, threads,
or power of mobility, and does not produce liquefaction or gas. It
stains with Löffler's methylene blue, and shows metachromatic granules
and polar staining. Its favourable temperature is blood-heat, though
it will grow at room temperature. It is aërobic, and, indeed, prefers
a current of air. Löffler contrived a medium for cultivation which has
proved most successful. It is made by mixing three parts of ox-blood
serum with one part of broth containing 1 per cent. of glucose, 1
per cent. of peptone, and 1/2 per cent. of common salt; the whole is
coagulated. Upon this medium the Klebs-Löffler bacillus grows rapidly
in eighteen or twenty hours, producing scattered "nucleated" round
white colonies, becoming yellowish. It grows well in broth, but without
producing either a pellicle or turbidity; it can grow on the ordinary
media, though its growth on potato is not visible; on the white of egg
it flourishes extremely well.
It retains its vitality in cultures and sometimes in the throat for
months. Three or four weeks is the average length of time for its
existence in the membrane, but, owing to the difficulty of killing it
_in situ_, it may live on for as long as a year. All the conditions in
the throat--mucous membrane, blood-heat, moisture, air--are extremely
favourable to the bacillus; but it is very materially modified in
virulence. It is secured for diagnostic purposes by one of two methods:
(_a_) Either a piece of the membrane is detached, and after washing
carefully examined by culture as well as the microscope; or (_b_)
a "swab" is made from the infected throat and cultured on serum,
and incubated at 37° C. for eighteen hours and then microscopically
examined. Both methods--and there is no further choice--present some
difficulties owing to the large number of bacteria found in the throat.
Hence a negative result must be accepted with reserve.
We have already referred at some length to the question of _toxins_ in
diphtheria, and need not dwell further upon that matter. Still a word
or two may be said here summarising the general action of the bacillus.
Locally it produces inflammatory change with fibrinous exudation and
some cellular necrosis. In the membrane a ferment is probably produced
which, unlike the localised bacilli, passes throughout the body and
by digestion of the proteids produces albumoses and an organic acid
which have the toxic influence. The toxins act on the blood-vessels,
and nerves, and muscle fibres of the heart, and many of the more highly
specialised cells of the body. Thus we get degenerative changes in
the kidney, in cells of the central nervous system, in the peripheral
nerves (post-diphtheritic paralysis), and elsewhere, these pathological
conditions setting up, in addition to the membrane, the signs of
the disease. The bacillus is pathogenic for the horse, ox, rabbit,
guinea-pig, cat, and some birds. Cases are on record of supposed
infection of children by cats suffering from the disease. The horse, it
will be remembered, yields the antitoxin which has saved so many lives
(_Metropolitan Asylums Board Report_, 1896).
The influence of drainage, milk, and schools must not be forgotten
by sanitary authorities any more than the essential importance of
adequate isolation hospital accommodation. Mr. Shattock's experiments
on the effect of sewer air upon attenuated Klebs-Löffler bacilli have
been mentioned (see p. 105). Nevertheless there can be no doubt that
emanations from defective drains have a materially predisposing effect,
not, it is true, upon the bacilli, but upon the tissues. Sore throats
thus acquired are _par excellence_ the site for the development of
diphtheria.
The influence of school attendance has claimed the recent attention of
the Medical Officer of the London School Board and the Medical Officer
of the administrative County of London. In London since 1881 there has
been a marked increase of diphtheria, which has occurred, though in a
much less degree, throughout England and Wales.
The Registrar-General has only classified diphtheria as a separate
disease since 1855, when the death-rate per 1,000,000 in England and
Wales was stated as 20. The following are the figures for four decades
up to 1895:
AVERAGE DEATH-RATE PER MILLION OF THE POPULATION FROM
DIPHTHERIA IN ENGLAND AND WALES AND IN LONDON (IN DECADES
1856-95)
England and
Wales. London.
1856-65 246.9 225.4
1865-75 124.8 123.5
1875-85 129.0 176.7
1885-95 210.6 421.4
From these figures the extraordinary increase during the last few years
is clearly demonstrated.
Sir Richard Thorne Thorne, in 1891, drew attention to the influence
of damp soils and schools upon diphtheria. In 1894 Mr. Shirley
Murphy, Medical Officer to the London County Council, reported that
there had been an increase in diphtheria mortality in London at
school ages (three to ten) as compared with other ages since the
Elementary Education Act became operative in 1871; that the increased
mortality from diphtheria in populous districts, as compared with
rural districts, since 1871, might be due to the greater effect of
the Education Act in the former; and that there was a diminution of
diphtheria in London during the summer holidays at the schools in 1893,
but that 1892 did not show any marked changes for August.
In 1896 Professor W. R. Smith, the Medical Officer to the London School
Board, furnished a report[96] on this same subject of school influence,
in which he produces evidence to show that the recrudescence of the
disease in 1881-90 was greatest in England and Wales at the age of
two to three years, and in London at the age of one to two years, in
both cases _before school age_; that age as an absolute factor in the
incidence of the disease is enormously more active than any school
influence, and that personal contact is another important source of
infection.
Although it is said that "statistics can be made to prove anything,"
there can be little doubt that both of these reports contain a great
deal of truth; nor are these truths incompatible with each other. They
both emphasise _age_ as a great factor in the incidence of the disease,
and whatever affects the health of the child population, like schools,
must play, directly or indirectly, a not unimportant part in the
transmission of the disease.
_The Pseudo-diphtheria Bacillus._[97] Löffler and Hoffman described a
bacillus having the same morphological characters as the true _Bacillus
diphtheriæ_, except that it had no virulence. Roux believes this is
merely an attenuated diphtheria bacillus. It is frequently found
in healthy throats. The chief differences between the real and the
pseudo-bacillus are:
1. The pseudo-bacillus is thicker in the middle than at the poles, and
not so variable as the _Bacillus diphtheriæ_. Polar staining is absent.
2. Its growth on potato reveals cream-coloured colonies visible in a
couple of days; the real bacillus is invisible.
3. The pseudo-bacillus will not grow at all anaërobically in hydrogen,
but the _Bacillus diphtheriæ_ is able to do so.
4. There is the great difference in virulence.
+Suppuration.+ This term is used to designate that general breaking
down of cells which follows acute inflammation. An "abscess" or
"gathering" is a collection, greater or smaller, of the products of
suppuration. The word _pus_ is generally used to describe this matter.
We may have such an advanced inflammatory condition in any locality
of the body, and it will assume different characters according to its
site. Hence there are connected with suppuration, as causal agents, a
variety of bacteria. Pus is not matter containing a pure culture of
any specific species, but, on the contrary, is generally filled with a
large number of different species. The most important are as follows:
1. _Staphylococcus pyogenes aureus._ These are micrococci arranged in
groups, which have been likened to bunches of grapes. They are the
common organisms found in pus, and were with other auxiliary bacteria
first distinguished as such by Professor Ogston, of Aberdeen. There are
several forms of the same species, differing from each other in colour.
Thus we have the _S. pyogenes aureus_ (golden yellow), _albus_ (white),
_citreus_ (lemon), and others. They occur commonly in nature, in
air, soil, water, on the surface of the skin, and in all suppurative
conditions. The _aureus_ is the only one credited with much virulence.
It occurs in the blood in blood-poisoning (septicæmia, pyæmia), and is
present in all ulcerative conditions, including ulcerative disease of
the valves of the heart.
The _Staphylococcus cereus albus_ and _S. cereus flavus_ are slightly
modified forms of the _S. pyogenes aureus_, and are differentiated from
it by being non-liquefying. They produce a wax-like growth on gelatine.
_Staphylococcus pyogenes aureus_, the type of the family, is grown in
all ordinary media at room temperature, though more rapidly at 37° C.
Liquefaction sets in at a comparatively early date, and subsequently
we have in the gelatine test-tube cultures a flocculent deposit of a
bright yellow amorphous mass, and in gelatine plates small depressions
of liquefaction with a yellow deposit. It renders all media acid, and
coagulates milk. Its thermal death-point in gelatine is 58° C. for ten
minutes, but when dry considerably higher. It is a non-motile and a
facultative anaërobe; but the presence of oxygen is necessary for a
bright colour. Its virulence readily declines.
2. _Streptococcus pyogenes._ In this species of micrococcus the
elements are arranged in chains. Most of the streptococci in pus,
from different sources, are one species, having approximately the
same morphological and biological characters. Their different effects
are due to different degrees of toxic virulence; they are always more
virulent when associated with other bacteria, for example, the Proteus
family.
The chains vary in length, consisting of more elements when cultured
in fluid media. They multiply by direct division of the individual
elements, and in old cultures it has been observed that the cocci vary
in form and size. This latter fact gave support to the theory that
streptococcus reproduced itself by _arthrospores_, or "mother-cells."
[Illustration: TYPES OF STREPTOCOCCUS]
In culture upon the ordinary media streptococcus is comparatively
slow-growing, producing minute white colonies on or about the sixth
day. It does not liquefy gelatine, and remains strictly localised
to the track of the inoculating needle. Like the staphylococcus, it
readily loses virulence. The thermal death-point is, however, lower:
54° C. for ten minutes. Marmorek has devised a method by which the
virulence may be greatly increased, and he holds that it depends upon
the degree of virulence possessed by any particular streptococcus as to
what effects it will produce. By the adoption of Marmorek's methods
attempts have been made to prepare an antitoxin.
_Streptococcus pyogenes_ has been isolated from the membrane of
diphtheria, and from small-pox, scarlet fever, vaccinia, and other
diseases. In such cases it is not the causal agent, but merely
associated with the complications of these diseases. Suppuration and
erysipelas are the only pathological conditions in which the causal
agency of streptococcus has been sufficiently established.
3. The _Bacillus pyocyaneus_ occurs in green pus, and is the cause of
that colouration. Gessard was the first to prove its significance, and
he describes two varieties.
[Illustration: MICROCOCCUS TETRAGONUS]
It is a minute, actively motile, non-sporulating bacillus, which
occasionally complicates suppuration and produces green pus. Oxygen
is necessary for pigmentation, which is due to two substances:
_pyocyanin_, a greenish-blue product extracted with chloroform, and
_pyoxanthose_, a brown substance derived from the oxidation of the
former pigment. Both these colours are produced in cultivation outside
the body. On gelatine the colour is green, passing on to olive. There
is liquefaction. On potato we generally obtain a brown growth (compare
_Bacillus coli_, _B. mallei_, and others). The organism grows rapidly
on all the ordinary media, which it has a tendency to colour throughout.
It will be remembered that when speaking of the antagonism of
organisms, we referred to the inimical action of _Bacillus pyocyaneus_
upon anthrax.
4. _Micrococcus Tetragonus._ This species occurs in phthisical
cavities and in certain suppurations in the region of the face. It is a
micrococcus usually in the form of small tetrads. A capsule is always
present and sometimes discernible.
5. _Bacillus coli communis_ and many putrefactive germs commonly
occur in suppurative conditions, but they are not restricted to such
disorders (see p. 64).
[Illustration: DIPLOCOCCUS OF NEISSER]
6. _Micrococcus gonorrhϾ_ (Neisser, 1879). This organism is more
frequently spoken of as a diplococcus. It occurs at the acute stage
of the disease, but is not readily differentiated from other similar
diplococci except by technical laboratory methods. Each element
presents a straight or concave surface to its fellow. A very marked
concavity indicates commencing fission. The position which these
diplococci take up in pus is _intracellular_, and arranged more or
less definitely around the nucleus. Difficulty has often been found
in cultivating this organism in artificial media outside the body.
Wertheim and others have suggested special formulæ for the preparation
of suitable media, but it is a very simple matter to secure cultures
on agar plates smeared with human blood from a pricked finger. The
plate is incubated at 37° C. At the end of twenty-four hours small
raised grey colonies appear, which at the end of about four days
show adult growth. The margin is uneven, and the centre more opaque
than the rest of the colony. This diplococcus is readily killed, and
sub-cultures must be frequently made to retain vitality and virulence.
Light, desiccation, and a temperature of 55° C. all act germicidally.
The organism stains readily in Löffler's blue, but is decolourised
by Gram's method. It is more or less strictly parasitic to man. Its
shape, size, character of growth, and staining properties assist in
differentiating it from various similar diplococci.[98]
+Anthrax.+ This disease was one of the first in which the causal agency
of bacteria was proved. In 1849 Pollender found an innumerable number
of small rods in the blood of animals suffering from anthrax. In 1863
Davaine described these, and attributed the disease to them. But it was
not till 1876 that Koch finally settled the matter by isolating the
bacilli in pure culture and describing their biological characters.
It is owing in part to its interesting bacterial history, which opened
up so much new ground in this comparatively new science, that anthrax
has assumed such an important place in pathology. But for other
reasons, too, it claims attention. It appears to have been known in the
time of Moses, and was perhaps the disease described by Homer in the
First Book of the _Iliad_. Rome was visited by it in 740 B.C.
Anthrax is an acute disease, affecting sheep, cattle, horses, goats,
deer, and man. Cats, white rats, and Algerian sheep are immune. Swine
become infected by feeding on the offal of diseased cattle (Crookshank).
The _post-mortem_ signs are mainly three: The _spleen_ is greatly
enlarged and congested, is friable to the touch, and contains enormous
numbers of bacilli; the _skin_ may show exudations forming dark
gelatinous tumours; and the _blood_ remains fluid for some time
after death, is black, tar-like, contains bubbles of air, and shows
other degenerative changes in the red corpuscles, whilst the _small
blood-vessels_ contain such vast quantities of bacilli that they may be
ruptured by them. Particularly is this true in the peripheral arteries.
Many of the organs of the body show marked congestion.
[Illustration: BACILLUS OF ANTHRAX AND BLOOD CORPUSCLES]
[Illustration: THREADS OF BACILLUS ANTHRACIS, SHOWING SPORES]
Clinically there is rise of temperature and rapid loss of muscular
power. The _bacilli_ of anthrax are square-ended rods 1 µ broad and
4-5 µ long. In the tissues of the body they follow the lines of the
capillaries, and are irregularly situated. In places they are so
densely packed as to form obstructions to the onward flow of blood.
In cultures they are in chains end to end, having as a rule equal
inter-bacillary spaces. In cultures long filaments and threads occur.
The exact shape of the bacillus depends, however, upon two things: the
staining and spore formation. Both these factors may very materially
modify the normal shape. The spores of anthrax are oval endospores,
produced only in the presence of free oxygen, and at any temperature
between 18 and 41° C. On account of requiring free oxygen, they are
formed only outside the body. The homogeneous protoplasm of the
bacillus becomes granular; the granules coalesce, and we have spores.
Each spore possesses a thick capsule, which enables it to resist many
physical conditions which kill the bacillus. When the spore is ripe or
has exhausted the parent bacillus, it may take on a resting stage, or
under favourable circumstances commence germination, very much after
the manner of a seed. The spores may infect a farm for many months;
indeed, cases are on record which appear to prove that the disease on
a farm in the autumn may by means of the spores be carried on by the
hay of the following summer into a second winter. Thus, by means of the
spores, the infection of anthrax may cling to the land for very long
periods, even for years. Spores of anthrax can withstand 5 per cent.
carbolic acid or 1-1000 corrosive sublimate for more than an hour; even
boiling does not kill them at once, whilst the bacilli without their
spores are killed at 54° C. in ten minutes. When the spores are dry
they are much more resistant than when moist. Hence the persistence of
the anthrax bacillus is due to its spores.
The bacillus is aërobic, non-motile, and liquefying. Broth cultures
become turbid in thirty-six hours, with nebulous masses of threads
matted together. The pellicle which forms on the surface affords an
ideal place for spore formation.
Cultures in the depth of gelatine show a most characteristic growth.
From the line of inoculation delicate threads and fibrillæ extend
outwards horizontally into the medium. Liquefaction commences at the
top, and eventually extends throughout the tube. On gelatine plates
small colonies appear in thirty-six hours, and on the second or third
day they look, under a low power of the microscope, like matted hair.
The colonies after a time sink in the gelatine, owing to liquefaction.
On potato, agar, and blood serum anthrax grows well.
_Channels of Infection._ 1. _The Alimentary Canal._ This is the usual
mode of infection in animals grazing on infected pasture land. A soil
suitable for the propagation of anthrax is one containing abundance
of air and proteid material. Feeding on bacilli alone would probably
not produce the disease, owing to the germicidal effect of the gastric
juice. But spores can readily pass uninjured through the stomach and
produce anthrax in the blood. Infected water as well as fodder may
convey the disease. Water becomes infected by bodies of animals dead
of anthrax, or, as was the case once at least in the south-west of
England, by a stream passing through the washing-yard of an infected
tannery. Manure on fields, litter in stalls, and infected earth may
all contribute to the transmission of the disease. Darwin pointed out
the services which are performed in superficial soils by earthworms
bringing up casts; Pasteur was of opinion that in this way earthworms
were responsible for continually bringing up the spores of anthrax
from buried corpses to the surface, where they would reinfect cattle.
Koch disputed this, but more recently Bollinger has demonstrated the
correctness of Pasteur's views by isolating anthrax contagium from five
per cent. of the worms sent him from an anthrax pasture. Bollinger also
maintains that flies and other insects may convey the disease from
discharges or carcasses round which they congregate.
Alimentary infection in man is a rare form, and it reveals itself in
a primary diseased state known as _mycosis intestinalis_, an inflamed
condition of the intestine and mesenteric lymph glands.
2. _Through the Skin._ Cutaneous anthrax goes by the name of _malignant
pustule_, and is caused by infective anthrax matter gaining entrance
through abrasions or ulcers in the skin. This local form is obviously
most contracted by those whose occupation leads them to handle hides
or other anthrax material (butchers and cleaners of hides). Two or
three days after inoculation a red pimple appears, which rapidly passes
through a vesicular stage until it is a pustule. Concomitantly we have
glandular enlargement, general malaise, and a high temperature. Thus
from a local sore a general infection may result. Unless this does
occur, the issue will not be fatal, and the bacilli will never gain
entrance into the blood or be anything but local.
3. _Respiratory Tract._ In man this is the commonest form of all, and
is well known under the term "wool-sorters' disease," or pulmonary
anthrax. This mode of infection occurs when dried spores are inhaled in
processes of skin-cleaning. It frequently commences as a local lesion
affecting the mucous membrane of the trachea or bronchi, but it rapidly
spreads, affecting the neighbouring glands, which become greatly
enlarged, and extending to the pleura and lung itself. Such cases, as a
rule, rapidly end fatally.
From what has been said, it will be clear that anthrax carcasses are
better not opened and exposed to free oxygen. An extended _post-mortem_
examination is not necessary. Burning the entire carcass in a
crematorium would be the ideal treatment. As such is not generally
feasible the next best thing is to bury the carcass deeply with lime
below and above it, and rail in the area to prevent other animals
grazing off it.
A very small prick will extract enough blood to examine for the anthrax
bacilli which are driven by the force of the blood-current to the small
surface capillaries. This occurs, of course, only when the disease has
become quite general, for in the early stage the healthy blood limits
the bacilli to the internal organs. In such cases examination of the
blood of the spleen is necessary.
Anthrax covers a wide geographical area all over the world, and no
country seems altogether exempt. In Germany as many as 3700 animals
have been lost in a single year. About 900 animals were attacked in
1897 in Great Britain.
+Plague.+ This disease, like anthrax and leprosy, has a long historical
record behind it. As the Black Death it decimated the population of
England in the fourteenth century, and visited the country again in
epidemic form in the middle of the seventeenth century, when it was
called the Great Plague. Now, it is highly probable that these two
scourges and the recent epidemic in the East are all forms of one and
the same disease. As a matter of fact, it is difficult to be sure what
was the exact pathology of a number of the grievous ailments which
troubled our country in the Middle Ages, but from all accounts bubonic
plague and true leprosy were amongst them. The former came and went
spasmodically, as is its habit; the latter dragged through the length
of several centuries.
[Illustration: BACILLUS OF PLAGUE]
The distribution of plague at the present time is fortunately a
somewhat limited one, namely, a definite area in Asia known as the
"Plague Belt." From Mesopotamia, as a sort of focus, the disease
spreads northwards to the Caspian Sea, westwards to the Red Sea,
southwards as far as Central India, and eastwards as far as the China
Sea. This constitutes the "belt," but the disease may take an epidemic
form, and is readily, though very slowly, conveyed by infection or
contagion. It appears to be infectious by means of infective dust, and
contagious by prolonged and intimate contact with the plague-stricken.
Rats have been accused of conveying the disease from port to port,
and even infecting man. It is clear that rats are not the only agency
acting in this way. Nevertheless it is true that rats contract the
disease more readily than any other animals, and that when suffering
from it they may spread the infection. How it is thus spread it is not
known. Drs. Cantlie and Yersin have pointed out that previously to an
epidemic of plague rats die in enormous numbers.
The bacteriology of plague is almost the latest addition to the
science. Kitasato, of Tokio, demonstrated the cause of plague to be a
bacillus during the Hong Kong epidemic in 1894. This was immediately
confirmed by Yersin, and further proved by the isolation in artificial
media of a pure culture of a bacillus able to cause the specific
disease of bubonic plague.
The bacillus was first detected in the blood of patients suffering from
the disease. It takes the form of a small, round-ended, oval cell, with
marked polar staining, and hence having an appearance not unlike a
diplococcus. In the middle there is a clear interspace, and the whole
is surrounded with a thick capsule, stained only with difficulty.
The organisms are often linked together in pairs or even chains, and
exhibit involution forms. In culture the bacillus is even more coccal
in form than in the body.
The plague bacillus grows readily on the ordinary media at blood-heat,
producing circular cream-coloured colonies with a wavy outline, which
eventually coalesce to form a greyish film. The following negative
characters help to distinguish it: No growth occurs on potato, milk is
not coagulated, and gelatine is not liquefied; Gram's method does not
stain the bacillus, and there are no spores; the bacillus is readily
killed by heat and by desiccation over sulphuric acid at 30° C. Both
in cultures and outside the body the bacillus loses virulence. To this
may be attributed possibly the variety of forms of the plague bacillus
which differ in virulence. On gaining entrance to the human body the
bacillus affects in particular two organs, the spleen and the lymph
glands. The latter become inflamed in groups, commencing frequently
with those in the armpit (axillary) or groin (inguinal). The spleen
suffers from inflammatory swelling, which may affect other organs
also. In both places the bacilli occur in enormous numbers. Kitasato
considers that the bacillus may enter the body by the three channels
adopted by anthrax, namely, the skin, alimentary canal, and respiratory
tract.
Haffkine has prepared a vaccine to be used as a prophylactic. He grows
a pure culture of Kitasato's bacillus in broth upon the surface of
which some globules of fat ("ghee") have been placed. The bacillus
grows upon this fat in copious stalactite form. From time to time this
growth is shaken down, until after five or six weeks the shaken broth
appears milky. The contained bacilli are killed by heating the fluid to
70° C. for one hour. The resultant is the vaccine, of which the dose is
3 cc. Haffkine believes that inoculated persons in India have suffered
twenty times less than non-inoculated living under the same conditions.
Plague is essentially a "filth disease," and it is frequently preceded
by famine. Temperature and overcrowding exert an influence upon it. The
areas affected by the disease in the Middle Ages, in the seventeenth
century, and in 1894-96 are alike in being characterised by filth and
overcrowding. There is little fear, speaking generally, of the plague
ever flourishing under Western civilisation, where the conditions are
such that even when it appears there is little to encourage or favour
its development.
+Leprosy.+ This ancient disease is said to have existed in Egypt 3500
B.C., and was comparatively common in India, China, and even in parts
of Europe 500 B.C. We know it has existed in many parts of the world
in the past, in which regions it is now extinct. Some of the earliest
notices we have of it in this country come from Ireland, and date
back to the fifth and sixth centuries. Even at that period of time
also various classical descriptions of the disease had been written
and various decrees made by the Church councils to protect lepers and
prevent the spread of the disease, which was often looked upon as
a divine visitation. In the tenth century leprosy was prevalent in
England; it reached its zenith in the thirteenth century, or possibly
a little earlier, and declined from that date to its extinction in the
sixteenth. But even two hundred years later leprosy was endemic in the
Shetlands, and it is recorded that in 1742 there was held a public
thanksgiving in Shetland on account of the disappearance of leprosy.
At one time or another there were as many as two hundred institutions
in the British Isles for the more or less exclusive use of lepers.
Many of these establishments were of an ecclesiastical or municipal
character, and probably the exact diagnosis of diseases was a somewhat
lax matter. Bury St. Edmunds, Bristol, Canterbury, London, Lynn,
Norwich, Thetford, and York were centres for lepers. Burton Lazars and
Sherburn, in Durham, were two of the more famous leper institutions.
At the present time the distribution of the disease is mostly Asiatic.
Norway contains about 1200 lepers, Spain approximately the same number.
Scattered through Europe are perhaps another 600 or 700, in India
100,000, and a large number in Japan. The Cape possesses a famous leper
hospital on Robben Island, with a number of patients. The disease is
also endemic in the Sandwich Islands.
Descriptions of the pathological varieties of leprosy have been very
diverse. The classification now generally adopted includes three forms:
the _tuberculated_, the _anæsthetic_ (or maculo-anæsthetic), and the
_mixed_. _Lepra tuberculosa_ is that form of the disease affecting
chiefly the skin, and resulting in nodular tuberculated growth or a
diffuse infiltration. It causes great disfigurement. The anæsthetic
form causes a destruction of the nerve fibres, and so produces
anæsthesia, paralysis, and what are called "trophic" changes. Not
infrequently patches occur on the skin, which appear like parchment,
owing to this trophic change. Bullæ may arise. When the tissue change
is radical or far advanced, considerable distortion may result. The
mixed variety of leprosy, as its name implies, is a mixture of the two
other forms.
The _Bacillus lepræ_ was discovered by Hansen in 1874. He found it in
the lepra cells in the skin, lymph glands, liver, spleen, and thickened
parts of the nerves. It is common in the discharges from the wounds of
lepers. It is conveyed in the body by the lymph stream, and has rarely
been isolated from the blood (Köbner).
[Illustration: BACILLUS OF PLAGUE (B. PESTIS BUBONICÆ)
(From liver of rat)
× 1000
_By permission of the Scientific Press, Limited_]
[Illustration: BACILLUS OF LEPROSY (HANSEN)
(From the tissues of a leper)
× 1000]
[Illustration: STREPTOTHRIX ACTINOMYCES (RAY FUNGUS)
× 700]
[Illustration: BACILLUS MALLEI (GLANDERS)
× 1000]
The bacillus is present in enormous numbers in the skin and tissues,
and has a form very similar indeed to _Bacillus tuberculosis_. It
is a straight rod, and showing with some staining methods marked
beading, but with others no beading at all. It measures 4 µ long and
1 µ broad. Young leprosy bacilli are said to be motile, but old ones
are not. Neisser has maintained that the bacillus possesses a capsule
and spores. The latter have not been seen, but Neisser holds that
this is the form in which the bacillus gains entrance to the body.
There is a characteristic which fortunately aids us in the diagnosis
of this disease in the tissues, and that is the arrangement of the
bacilli, which are rarely scattered or isolated, but gathered together
in clumps and colonies. Bordoni-Uffreduzzi and Campania claim to have
isolated the bacillus and grown it on artificial media, the former
aërobically on peptone-glycerine-blood-serum, at 37° C., the latter
anaërobically. But no other worker has been able to do this. Hence we
are not able to study the bacteriology of leprosy at all completely,
nor have inoculation experiments proved successful. Nevertheless there
is little doubt that leprosy is a bacterial disease produced by the
bacillus of Hansen. Bordoni-Uffreduzzi maintains that the parasitic
existence of the _Bacillus lepræ_ may alternate with a saprophytic
stage. This may be of importance in the spread of the disease. There
is evidence in support of the non-communicability of the disease by
heredity or contagion. Segregation does not appear always to result
in a decline of the disease, as we should expect if it were purely
contagious. Ehlers, of Copenhagen, has, however, as recently as 1897,
reaffirmed his belief in the contagiousness of leprosy; Virchow, on
the other hand, has declared that it is not highly contagious. There
is evidence to show that persons far advanced in the disease may live
in a healthy community and yet not infect their immediate neighbours.
Indeed, the transmission of the disease is still an unsolved problem.
Mr. Hutchinson suggests diet, particularly uncooked or putrid fish, as
a likely channel; on the other hand, leprosy appears in districts where
no fish is eaten. Deficiency of salt, telluric and climatic conditions,
racial tendencies, social status, poverty, insanitation, drinking
water, even vaccination, have all secured support from various seekers
after the true channel by which the bacillus gains entrance to the
human body. The real mode of transmission is, however, still unknown.
The decline and final extinction of leprosy in the British Islands was
probably due in part to the natural tendency of the disease, under
favourable hygienic circumstances, to die out, and in part to a general
and extensive social improvement in the life of the people, to a
complete change in the poor and insufficient diet, and to agricultural
advancement, improved sanitation, and land drainage.
At the Leprosy Congress held in Berlin in 1897, Hansen again emphasised
his belief that segregation was the cause of the decline of leprosy
wherever it had occurred. But there appears to be some evidence to
show that leprosy has declined where there has been no segregation
whatever, and therefore, however favourable to decline such isolation
may be, it would seem not to be actually necessary to the decline. At
the same Congress Besnier declared in favour of the infective virus
being widely propagated by means of the nasal secretion. Sticker states
that the nasal secretion contains millions of lepra bacilli, especially
in the acute stage of the disease, and Besnier and Sticker have
pointed out how frequently and severely the septum nasi and skin over
the nose are affected in leprosy. Several leprologists in India have
recorded similar observations. These facts appear to support Besnier's
contention that the disease is spread by nasal secretion.
We may fitly add here the conclusions arrived at by the English Leprosy
Commission[99] in India:
"1. Leprosy is a disease _sui generis_; it is not a form
of syphilis or tuberculosis, but has striking etiological
analogies with the latter.
"2. Leprosy is not diffused by hereditary transmission, and,
for this reason and the established amount of sterility among
lepers, the disease has a natural tendency to die out.
"3. Though in a scientific classification of diseases leprosy
must be regarded as contagious, and also inoculable, yet the
extent to which it is propagated by these means is exceedingly
small.
"4. Leprosy is not directly originated by the use of any
particular article of food, nor by any climatic or telluric
conditions, nor by insanitary surroundings, neither does it
peculiarly affect any race or caste.
"5. Leprosy is indirectly influenced by insanitary
surroundings, such as poverty, bad food, or deficient drainage
or ventilation, for these by causing a predisposition increase
the susceptibility of the individual to the disease.
"6. Leprosy, in the great majority of cases, originates _de
novo_, that is, from a sequence or concurrence of causes and
conditions dealt with in the Report, and which are related to
each other in ways at present imperfectly known."
The practical suggestions of the Commission for preventive treatment
included voluntary isolation, prohibition of the sale of articles of
food by lepers, leper farms, orphanages, and "improved sanitation and
good dietetic conditions" generally. Serum-therapy has been attempted
on behalf of the French Academy of Medicine, but without success. Many
forms of treatment ameliorate the miserable condition of the leper, but
up to the present no curative agent has been found.
[Illustration: DIPLOCOCCUS OF PNEUMONIA]
+Pneumonia.+ Some of the difficulty which has surrounded the
bacteriology of inflammation of the lungs is due to the confusion
arising from supposing that attacks of the disease differed only
in degree. Pneumonia, however, has various forms, arising now from
one cause, now from another. The specific or croupous pneumonia is
associated with two organisms: Fraenkel's diplococcus and Friedländer's
pneumo-bacillus. Several other bacteria have from time to time been
held responsible for pneumonia, a streptococcus receiving, at one
time, some support. But whilst opinion is divided on the rôle of
various extraneous and concomitant bacteria in lung disease, importance
is attached to Fraenkel's and Friedländer's organisms.
The _diplococcus_ of Fraenkel is a small, oval diplococcus found in the
"rusty" sputum of croupous pneumonia. It is non-motile, non-liquefying,
and aërobic. When examined from cultures the diplococci are frequently
seen in chains, not unlike a streptococcus, and there is some reason
to suppose that this form gave rise to the belief that it was another
species; when examined from the tissues it possesses a capsule, but
in culture this is lost. It is difficult to cultivate, but grows on
glycerine agar and blood serum at blood-heat. On ordinary gelatine at
room temperature it does not grow, or, if so, very slightly. The ideal
fluid is a slightly alkaline liquid medium, and in twenty-four hours a
powdery growth will occur in such broth. On potato there is apparently
no growth. It rapidly loses its virulence on solid media, and is said
to be non-virulent after three or four sub-culturings. A temperature
of 54-58° C. for a few minutes kills the bacteria, but not the toxin.
This, however, is removed by filtration, and is therefore probably
intracellular. It is attenuated by heating to 70° C.
Fraenkel's diplococcus occurs, then, in the acute stage of pneumonia,
in company with streptococci and staphylococci. It also occurs in the
blood in certain suppurative conditions, in pleurisy and inflammation
of the pericardium, and sometimes in diphtheria, and therefore it is
not peculiar to pneumonia.
There is one other point to which attention should be drawn. Fraenkel's
organism is said to be frequently present in the saliva of healthy
persons. Pneumonia depresses the resistant vitality of the tissues,
and thus affords to the diplococcus present in the saliva an excellent
nidus for its growth.
_Friedländer's Pneumo-bacillus_ is a capsulated oval coccus, assuming
the form of a small bacillus. It is inconstant in pneumonia, unequally
distributed, and scarce; it is aërobic, and facultatively anaërobic;
it occasionally occurs in long forms and filaments; it is non-motile,
non-liquefying, and has no spores; it does not stain by Gram's
method, which stain is therefore used for differential diagnosis; it
will grow fairly well in ordinary gelatine at 20° C.; and it is a
denitrifying organism, and also an actively fermentative one, even
fermenting glycerine. It is not unlike _Bacillus coli communis_, and to
distinguish it from that organism we may remember that the _B. coli_
is motile, never has a capsule, produces indol, and does not ferment
glycerine.
[Illustration: BACILLUS OF INFLUENZA]
+Influenza.+ In 1892, during the pandemic of influenza, Pfeiffer
discovered a bacillus in the bronchial mucus of patients suffering from
the disease. It is one of the smallest bacilli known, and frequently
occurs in chains not unlike a streptococcus. Carron obtained the same
organism from the blood. In the bronchial expectoration it can retain
its virulence for as long as a fortnight, but it is quickly destroyed
by drying. The bacillus is aërobic, non-motile, and up to the present
spores have not been found. It grows somewhat feebly in artificial
media, and readily dies out. Blood serum, glycerine agar, broth, and
gelatine have all been used at blood-heat. It does not grow at room
temperature. Pfeiffer's bacillus appears most abundantly at the height
of the disease, and disappears with convalescence. It is said not to
appear in any other disease.
+Yellow Fever.+ Sternberg and Havelburg have both isolated bacilli
from cases of yellow fever; but the organism discovered by Sanarelli,
the _Bacillus icteroides_, is now accepted as the causal agent of the
disease. It is a small, short rod, with round ends, and generally
united in pairs; it has various pleomorphic forms; it grows well on all
the ordinary media; it is killed in sea-water at 60° C., and also by
direct sunlight in a few hours.
+Diarrhœa of Infants.+ From time to time different organisms have
been isolated in this diseased condition. _Bacillus coli_ and _B.
enteriditis sporogenes_ (Klein) have been held responsible for it. W.
D. Booker, of Johns Hopkins University, sums up an extended research
into the question as follows:
"No single micro-organism is found to be the specific exciter
of the summer diarrhœa of infants, but the affection is
generally to be attributed to the result of the activity of
a number of varieties of bacteria, some of which belong to
well-known species, and are of ordinary occurrence and wide
distribution, the most important being the streptococcus and
_Proteus vulgaris_.
"The first step in the pathological process is probably
an injury to the epithelium from abnormal or excessive
fermentation, from toxic products of bacteria, or from other
factors.
"Bacteria exert a direct injury upon the tissues in some
instances, whereas in others the damage is brought about
indirectly through the production of soluble poisons."
+Actinomycosis.+ This disease affects both animals and man. As
Professor Crookshank points out, it has long been known in this
country,[100] but its various manifestations have been mistaken for
other diseases or have received popular names.
Here we can only mention the most outstanding facts concerning
the disease. It is caused by the "ray fungus," or _Streptothrix
actinomyces_, which, growing on certain cereals, often gains entrance
to the tissues of man and beast by lacerations of the mucous membrane
of the mouth, by wounds, or by decayed teeth. Barley has been the
cereal in question in some cases. The result of the introduction of the
parasite is what is termed an "infective granuloma." This is, generally
speaking, of the nature of an inflammatory tumour composed of round
cells, epithelioid cells, giant cells, and fibrous tissue, forming
nodules of varying sizes. In some cases they develop to large tumours,
in others they soon break down. Actinomycosis in some ways closely
resembles tuberculosis in its tissue characters.
In the discharge or pus from human cases of the disease small
sulphur-yellow bodies may be detected, and these are tufts of "_clubs_"
which are the broken-down rays of the parasite; for in the tissues
which are affected the parasite arranges itself in a radiate manner,
growing and extending at its outer margin and degenerating behind. In
cattle the centre of the old ray becomes caseated, like cheese, or even
calcified, like a stone. In the human disease abundant "_threads_"
are formed as a tangled mass in the middle of the colony. As clubs
characterise the bovine actinomycosis, so threads are a feature of
the human form of the disease. But in both there is a third element,
namely, _small round cells_, called by some spores, by others simply
cocci. Authorities are not yet agreed as to the precise significance
and rôle of these round cells. The life-history of the micro-organism
may be summed up thus:
"The spores sprout into excessively fine, straight or sinuous,
and sometimes distinctly spirilliform threads, which branch
irregularly and sometimes dichotomously. The extremities of
the branches develop the club-shaped bodies. The clubs are
closely packed together, so that a more or less globular body
is formed, with a central core composed of a dense mass of
threads" (Crookshank).
Possibly these clubs represent organs of fructification, and produce
the spores. These latter are, it is believed, set free in the vicinity
of the ray, and create fresh centres of disease.
In _man_ the disease manifests itself in various parts according to the
locality of entrance. When occurring in the mouth it attacks the lower
jaw most frequently. In one recorded case the disease was localised to
the bronchi, and did not even extend into the lungs. It was probably
contracted by inhalation of the parasite. The disease may spread
to distant parts by means of the blood stream, and frequently the
abscesses are apt to burrow in various directions.
In the _ox_ the disease remains much more localised, and frequently
occurs in the lower jaw, palate, or tongue. In the last site it is
known as "wooden tongue," owing to the hardness resulting. The skin
and subcutaneous tissues are also a favourite seat of the disease,
producing the so-called wens or clyers so commonly seen in the fen
country (Crookshank). Actinomycosis in cattle is specially prevalent
in river valleys, marshes, and on land reclaimed from the sea. The
disease occurs at all seasons, but perhaps more commonly in autumn and
winter. It is more frequently met with in young animals. The disease is
probably not hereditary nor readily communicated from animal to animal.
Actinomyces may be cultivated, like other parasitic diseases, outside
the body. Gelatine, blood serum, agar, glycerine agar, and potato have
been used for this purpose. After a few days on glycerine agar at the
temperature of the blood little white shining colonies appear, which
increase and coalesce. In about ten days' time the culture often turns
a bright yellow, though it may remain white or even take on a brown
or olive tint. The entire mass of growth is raised dry and crinkled,
and composed almost exclusively of threads. In its early stage small
bacillary forms occur, and in its later stage coccal forms. True clubs
never occur in pure cultures, although the threads may occasionally
show bulbous endings.
+Glanders+ in the horse and ass, and sometimes by communication in
man also, is caused by a short, non-motile, aërobic bacillus, named,
after the old Roman nomenclature (_malleus_), _Bacillus mallei_. It
was discovered in 1882 by Löffler and Schütz. It is found in the
nasal discharge of glandered animals. In appearance the bacillus is
not unlike _B. tuberculosis_, except that it is shorter and thicker.
The beading of the bacillus of glanders, like that in tubercle, does
not denote spores. _B. mallei_ can be cultivated on the usual media,
especially on glycerine agar and potato. On the latter medium it
forms a very characteristic honey-like growth, which later becomes
reddish-brown.
In the horse glanders particularly affects the nasal mucous membrane,
forming nodules which degenerate and emit an offensive discharge.
From the nose, or nasal septum, as a centre, the disease spreads to
surrounding parts. It may also occur as nodules in and under the skin,
when it is known as "farcy." Persons attending a glandered animal may
contract the disease, often by direct inoculation.
_Mallein_ is a substance analogous to tuberculin, and is made by
growing a pure culture of _Bacillus mallei_ in glycerine-veal broth
in flat flasks, with free access of calcined air. After a month's
growth the culture is sterilised, filtered, concentrated, and mixed
with an equal volume of a .5 per cent. solution of carbolic. The dose
is 1 cc., and it is used, like tuberculin, for diagnostic purposes.
If the suspected animal reacts to the injection, it is suffering
from glanders. Reaction is judged by three signs, namely, a rise of
temperature 2-3° C., a large "soup-plate" swelling at the site of
inoculation, and an enlargement of the lymphatic glands.
_Swine fever_, _foot-and-mouth disease_, _chicken cholera_,
_dysentery_, _rinderpest_, and other diseases of animals have
microorganisms intimately related to them.
There is a group of diseases due to the presence in the blood or
tissues of _hæmatozoa_, that is, protozoa which can live and perform
their function in the blood. Amongst these are malaria, sleeping
sickness, and other tropical diseases in man, and surra and various
hæmatozoa in horses, fish, frogs, or rats.
_Malaria._ Although a _Bacillus malariæ_ has been described as the
cause of this disease, it is now almost universally supposed that the
true cause is a protozoan parasite. In 1880 Laveran first described
this organism, and the discovery was confirmed by Marchiafava, Celli,
and others. Laveran claimed that it occurred in four different forms
during the progress of its life-history:
(_a_) _Spherical or Irregular Bodies_ attached to the blood corpuscle,
or free in the blood plasma. They are a little smaller than the
blood-cells, and may or may not contain pigment. They eventually
invade the corpuscles, possess more pigment, and lose their amœboid
movement. Within the red blood corpuscles they increase in size until
they reach the adult stage.
(_b_) _Segmentation Forms_, often assuming a rosette shape, follow
next. They are pigmented, are possibly a sporing stage, and are finally
set free in the blood.
(_c_) _The Crescents_, or _Semilunar Bodies_, are free in the blood,
but motionless. They are colourless, have a distinct membrane, and
generally show a little pigment about the middle; they taper towards
the poles. They appear in the blood after the fever has existed for
some time, occurring chiefly, sometimes only, in the quotidian and
malignant types of malaria.
(_d_) _The Flagellated Bodies_ apparently occur only in the blood
outside the body. They are extracorpuscular bodies, and possess several
long flagella, and are therefore actively motile. They are derived from
the crescents or irregular intracorpuscular bodies.
What is the precise significance of these various forms and
modifications of them is not at present known. Possibly the semilune
is a resting stage inside the body, and the flagellated body another
similar stage outside. Attempts to cultivate the parasite outside the
body have failed. There is a good deal of evidence to show that the
mosquito is the host outside the human body. There may be different
forms and varieties of parasite, if not actually different species,
causing the diverse forms of clinical malaria.
The above account of diseases caused by bacteria does not profess to
be in any sense exhaustive. It is merely illustrative. It reveals
some of the disease-producing powers of micro-organisms. There are a
large number of other diseases in which bacteria have been found. They
are not the causes, but only accidentally present or associated with
"secondary infection." Variola (small-pox), scarlet fever, and measles
are excellent examples. It is possible that the danger at the present
time is rather in the direction of supposing that every disease will
readily yield its secret to the bacteriologist. Such, of course, is
not the case. Nevertheless, as in the past, so in the future, constant
research and patient investigation is the only hope we have for the
elucidation of truth in respect to the causes of disease.