cultivating them separately in vehicles composed of water holding in
solution inorganic constituents, or sterilized fluids containing
organic matters, or of the semi-solid gelatinous substances
recommended by Koch, have been only partially successful in proving
them to be the sole source of {996} infection. Some earlier
experiments of Tiegel and Klebs[22] were attended with positive
results, and more recently confirmatory evidence has been furnished by
Pasteur and Doléris.[23] Hiller, rarely quoted now, arrived at
different conclusions. He found that bacteria washed in pure water
were innocuous.[24] But pure water had long before been proven by
observers to be inimical to the well-being of the organisms in
question. Schüller says that Hiller's experiments prove apparently
that while a putrid fluid may be in the highest degree poisonous, its
component parts--viz. either the fluid or the bacteria singly--are
neither deadly nor poisonous.[25] The fact is, that isolation
experiments are subject to what has hitherto been in most experiments
an unavoidable source of error. As Davaine noted early in his
observations, the physiological action of bacteria is very dependent
on the constitution of the medium in which they are developed, which
is in entire harmony with what is known of organisms much higher in
the scale. "Many plants," says Burdon-Sanderson,[26] "containing
active principles, become inert when transplanted from an appropriate
soil." Bucholtz, in a series of experiments designed to test the
influence of antiseptics upon the vitality of bacteria, found not only
a difference between those taken directly from the infusion and those
cultivated in artificial fluids, but between bacteria derived from the
same source and cultivated in modifications of the nutrient
medium.[27] Then, too, it is not always safe to transfer to the human
species the results of experiments made upon the lower animals.
Indeed, among animals, not only in different species, but in varieties
of the same species, differences in the susceptibility to septicæmic
poisons are found ranging from gradations as to the intensity of the
effect produced to absolute immunity. In anthrax, a disease analogous
to the one in question, the bacterial origin has been established
beyond dispute by the inoculation of isolated bacilli, which multiply
in the blood and permeate in enormous numbers the lungs, liver,
kidneys, spleen, and glandular structures. If the same unequivocal
testimony has as yet not been obtained from isolation experiments as
regards septicæmia, it is reasonable to suppose that this is due to
the defects in the technique, for which it is presumable the ingenuity
of investigators will in future find the remedy.
[Footnote 22: _Archiv für exp. Pathologie und Pharmakologie_,
"Beiträge zur Kenntniss der Pathogenen Schistomyceten," Band iv. Heft
3, S. 241 und ff.; Tiegel, _loc. cit._]
[Footnote 23: In this connection may be mentioned some very
interesting experiments by Dr. George Gaffky (_Experimentellen
Erzengte Septicæmie, Mittheilungen aus den Kaiserlich, Gesundh.
Amte_), in which micrococci from the blood of septicæmic mice were
successfully cultivated in a gelatine preparation, and produced, when
inoculated in small quantities, the symptoms identical with those
obtained by inoculating the blood itself.]
[Footnote 24: "Exp. Beiträge zur Lehre von der organisirte Natur der
Contagion und von der Faülniss," _Archiv für klinische Chirurgie_, Bd.
xvii. Heft 4, S. 669 u. ff.]
[Footnote 25: "Exp. Beiträge zum Studium der septischen Infection,"
_Deutsche Zeitschrift für Chirurgie_, Bd. vi. S. 162.]
[Footnote 26: "Lectures on the Relations of Bacteria to Disease,"
_British Med. Journal_, March 27, 1875. See also Klebs, "Beiträge zur
Kenntniss der Pathogenen Schistomyceten," _Arch. für Pathol. und
Pharmakol._, Bd. iii. S. 321.]
[Footnote 27: "Antiseptica und Bacterien," _Arch. f. exp. Pathol. und
Pharmakol._, Bd. iv., Heft 1 und 2.]
It is, however, from the constant presence of the bacteria in infected
wounds, and their distribution through the tissues, that the argument
in favor of connecting septic symptoms with the bacteria has been
mainly deduced. Here the ground is sufficiently solid, and, judged by
ordinary laws of scientific evidence, the pathological importance of
the microspores {997} may be regarded as established. To be sure, we
find them in tongue-scrapings of healthy individuals, but
tongue-scrapings are poisonous if injected into the tissues. That they
do not ordinarily prove so in the mouth is no more singular than that
woorari can be swallowed with impunity. Tiegel[28] has endeavored to
show that round bacteria are found normally in the internal organs of
the body; but Koch[29] states that he has on many occasions examined
normal blood and normal tissues by means which prevented the
possibility of overlooking bacteria, or of confounding them with
granular masses of equal size, and that he has never in a single
instance found organisms.
[Footnote 28: _Arch. f. Path. Anat. u. Physiol. u. f. klin. Med._,
vol. lx. p. 453.]
[Footnote 29: On _Traumatic Infective Diseases_, New Sydenham Soc.
publication p. 15.]
It is stated that bacteria are sometimes absent from the blood
withdrawn during life in septic diseases. As, however, their constant
presence has been confirmed in the vessels and glomeruli of the
kidneys, it is fair to assume that those organs, acting as filters,
must have received the colonies observed in them from the general
circulation.
The difficulty of obtaining bacteria from the blood in many cases
during life in septic diseases does not, however, as was once
supposed, invalidate the theory of their pathogenic importance.
Septicæmia is at present employed as a collective term for a number of
processes which may occur singly or in combination with one another.
When a relatively large quantity of a putrid fluid is injected into
the veins of an animal, death follows from the action of a chemical
poison (sepsin). The blood during life rarely displays the presence of
bacteria, the latter disappearing in the circulation. In animals thus
poisoned blood does not possess infectious properties. This form is
termed putrid intoxication. That the poison in these cases is,
however, produced by the bacteria is shown by experiments of
Gutmann,[30] who demonstrated that bacteria from a drop of putrid
blood cultivated in Cohn's solution developed in the fluid a poison
which, when injected into the veins of dogs, occasioned death with all
the symptoms of putrid intoxication. Still more conclusive were the
experiments of Koch. This observer injected four drops of putrid blood
beneath the skin of mice. The latter died in from four to eight hours.
There were no bacteria in the blood, and the blood was not infectious.
When, however, a single drop was injected, the mice often remained
unaffected, but in a third of the cases they became ill after
twenty-four hours, death occurring in from forty to sixty hours. The
blood during life communicated the same disease to other mice, and
bacilli were always present in large numbers. In these cases the
dissolved poison in the fluid injected was too small in amount to
destroy life, and death resulted only after a period of incubation as
a consequence of the multiplication of bacilli in the blood and in the
tissues.
[Footnote 30: Vide Semmer, "Putride Intoxication," etc., _Virchow's
Arch._, vol. lxxxi. p. 109.]
In another class of cases Koch experimented, not with putrid blood,
but with a fluid produced by macerating a piece of mouse-skin in
distilled water. Of this he injected a syringeful into the back of a
rabbit. The result was peritonitis, swelling of the spleen, gray
wedge-shaped patches in the liver, and in the lungs were found
dark-red patches the size of a pea, devoid of air--all appearances in
harmony with what is designated as pyæmia. Oval micrococci were found
in great numbers {998} everywhere throughout the body. But the point
of special interest in the present connection is the fact that
wherever these micrococci come in contact with the red
blood-corpuscles the latter stick together and become arrested in the
minute capillary network. The thrombi thus formed are further enlarged
by the deposition of micrococci, which multiply, block up individual
capillary loops, and invade contiguous tissues. In the blood-current
itself, however, the micrococci do not increase in numbers, and cannot
always be found in the circulation upon a single examination, but
Doléris[31] assures us that in puerperal fever by repeated trials,
especially after a chill, he has never failed to demonstrate their
presence.
[Footnote 31: _La Fievre Puerperale, etc._, p. 120.]
As to the exact manner in which these minute bodies exercise their
pernicious influence, whether they operate mechanically, or whether
they produce a virus in the process of nutritive activity, or whether,
as is probable, both suppositions are correct, must be decided by
future investigations. It is enough for us to note that the connection
between sepsis and bacteria is intimate and vital.
3d. _Pathogenic bacteria are invariably associated with puerperal
fever, and to them the infectious qualities of the disease are due._ I
have been explicit regarding the evidence concerning bacteria in
septic diseases, because it places the question of the infectious
group of puerperal fever cases in the following position: Experiences
occurring clinically, as well as those produced upon animals, teach us
that certain lesions and symptoms, similar to those we are accustomed
to regard as characteristic of puerperal fever, results from septic
poisoning. In a large class of cases, however, the connection between
childbed fever and sepsis has been deduced rather from analogy than
direct proof. For those who chose to regard such as due to a specific
poison peculiar to the puerperal state there was really no objection.
If, however, bacteria are characteristic of septic poisoning, the
question presents itself in a different light, and we have to inquire
whether, in the less obvious cases, bacteria are present in puerperal
fever in the proportions and groupings that we find them in other
diseases due to putrid infection. Now, it is precisely proof of this
nature that has recently been abundantly rendered.
Waldeyer,[32] Orth,[33] Heiberg,[34] and Von Recklinghausen[35] found
the tissues and lymphatics of the parametria filled with pus-like
masses, which consisted, in addition to pus-cells, chiefly of
bacteria. Bacteria swarmed in the fluid of the peritoneal cavity. In
one case examined by Waldeyer six hours after death, while the body
was still warm, the peritoneal exudation was like an emulsion, and
furnished an abundant deposit which consisted almost entirely of
bacteria. Orth injected ten minims of peritoneal fluid from a woman
dead of puerperal fever into the abdomen of a rabbit. As the animal
was dying he broke up the medulla oblongata, and found in the
peritoneal fluid enormous quantities of these {999} organisms. In
puerperal fever round bacteria have been likewise found, though in
less quantities, in the lymphatics of the diaphragm and in the fluids
of the pleura, the pericardium, and the ventricles of the brain. In
post-mortem examinations of fresh subjects the serous fluids,
withdrawn under proper precautions, do not contain round bacteria
except in cases of septic infection.[36] Orth found in the purulent
contents of the vessels of the funis, in children who died of sepsis,
precisely the same formations as existed in the exudations of the
mother.
[Footnote 32: "Ueber das Verkommen von Bacterien bei der
diphtheritischen Form des puerperal Fiebers," _Archiv für
Gynaekologie_, vol. iii. p. 293.]
[Footnote 33: "Untersuchungen über puerperal Fieber," _Virchow's
Archiv_, vol. lviii. p. 437.]
[Footnote 34: _Die puerperalen und pyæmischen Processe_, Leipzig,
1873.]
[Footnote 35: For the views of Von Recklinghausen I am indebted to his
pupil Steurer. Vide the writer's paper on "The Nature, Origin, and
Prevention of Puerperal Fever," _Trans. of the International Med.
Congress_, Phila., 1876.]
[Footnote 36: Klebs, "Beiträge zur Kenntniss der Pathogenen
Schistomyceten," _Archiv für exp. Pathol. und Pharmakol._, vol. iv. p.
441 _et seq._]
Doléris, in a remarkable essay already referred to, published in
1880,[37] furnishes not only conclusive evidence of the presence of
bacteria in the various tissues and serous cavities of women dying of
puerperal fever, but has added the evidence of their pathogenic
character by cultivating them apart in sterilized fluids, and by
reproducing in animals, by means of subcutaneous injections of the
isolated bacteria, the infarctions, the blood-changes, and the
suppurative processes of the original disease.
[Footnote 37: _La Fievre Puerperale et les Organismes Inférieurs._]
So far, the generic term bacteria has been employed to indicate the
disease-germs which are the active agents of infection in puerperal
fever. It is not, however, intended to assume that the germs of septic
processes are all identical, or that they all produce precisely the
same pathological conditions. Koch, indeed, maintains that a distinct
specific bacterial form is found in such closely-allied affections as
pyæmia, septicæmia, gangrene, and erysipelas, the different forms
possessing, however, this link in common--viz. that they are alike
generated in putrefying media. Singularly enough, the bacterium termo
and the bacterium commune--to which the fetidity of matters undergoing
putrefaction is due--are in themselves harmless. They are rapidly
destroyed in the circulation, and are not inoculable. Fetid discharges
from wounds are not therefore necessarily dangerous. The putrid odor
serves a useful purpose, as it gives warning of the existence of
conditions which favor the development of life-destroying organisms;
but the latter may develop without the concurrence of the forms which
give rise to putrefaction--a fact of considerable importance in view
of the common belief that septic infection is excluded by the absence
of fetid odors.
In puerperal fever Doléris found the prevailing pathogenic organisms
consisted of bacilli or rods, and micrococci or round bacteria in the
varieties of micrococci, simple points; diplococci, double points; and
chains or wreaths. The bacilli he regarded as the source of acute,
rapid septicæmia, while pus-production was associated with the
multiplication of the round bacteria, and especially of the
diplococci.
4th. _The presence of germs in puerperal fever serves not only to fix
cases hitherto doubtful in the category of septic diseases, but
affords the most satisfactory explanation of the protean phenomena of
puerperal fever itself._
We have seen, from both Koch's and Gutmann's experiments upon animals,
that death may occur independently of bacteria by the rapid absorption
of a chemical poison developed in a putrefying fluid. Clinical
experiences, such as the speedy death sometimes observed when retained
coagula or portions of placenta undergo decomposition within the
uterine cavity, renders it probable that similar cases of putrid
intoxication are {1000} not unknown in puerperal women, though, so
far, the anatomical demonstration of the fact has not been furnished.
In cases, however, where puerperal fever has a distinct period of
incubation, and progresses step by step to the fatal ending, bacteria
are always found invading the tissues of the genital canal. In rare
cases they pass by the Fallopian tube to the peritoneal cavity and
excite salpingitis and peritonitis. More commonly from local lesions
they enter the canalicular spaces of the connective tissue forming the
framework of the genital canal, which is continuous with the
subperitoneal connective tissue of the pelvis. From the canalicular
space they enter the lymphatics. Cellulitis is excited by their
presence, and the lymphatic glands become inflamed and enlarged. In
pernicious forms they produce a sero-purulent oedema, which spreads
rapidly with a wave-like progress after the manner of erysipelas; or
in milder cases the progress of the disease-germs is arrested by the
lymphatic glands or the resistance offered by the tissues themselves,
and the ordinary circumscribed phlegmon is produced. By the lymphatics
which accompany the vessels of the Fallopian tubes they reach the
ovaries (puerperal ovaritis), and by the broad ligaments they pass to
subperitoneal tissues of the iliac and lumbar regions. Through the
same system they are conveyed to the great serous cavities of the
body. In the peritoneum they give rise, unless death occurs too
speedily, to pyæmic peritonitis, which, unlike the traumatic form, is
attended with but little pain, and for which the claim has been set up
that it is peculiar to puerperal fever. The wide stomata upon the
abdominal surface of the diaphragm allows the facile entrance of the
organisms into its lymphatics. Waldeyer found in diaphragmitis the
lymphatics of the diaphragm filled with bacteria. And thus, following
the lymphatic system, if we only admit that bacteria are the active
agents of sepsis, the frequency, in severe types of puerperal fever,
of inflammation of the serous membranes of the peritoneum, the pleuræ,
the pericardium, the meninges, and the joints finds an easy
explanation. Nor is it altogether accident which determines in
different cases the precise serous membranes which are affected. The
widespread ramifications of the lymphatic system would naturally give
rise to eccentric inflammations in place of those following the
apparent continuity of tissues.
The ductus thoracicus is the principal channel through which the
bacteria enter the blood. It is possible that they may further obtain
access into the circulation through the radicles which furnish the
communications between the capillaries and the lymphatics. We have
seen that bacteria are found with difficulty in the blood during life.
A few hours after death they swarm in that fluid. That they do,
however, enter the general circulation during life is incontestable.
Steurer writes: "As the kidneys are the great filters of the human
system, I never neglected to examine them, and almost invariably found
micrococci filling the arterioles and glomeruli." This is in
correspondence with what occurs in other septic diseases, and accounts
for the albuminuria and interstitial nephritis which often supervene
in the advanced stages.
The action of the bacilli upon the blood differs materially from that
of the round bacteria. So soon as the latter come in contact with the
red corpuscles, the corpuscles stick together and form larger or
smaller clots in the blood. They then are no longer able to pass
through the minute {1001} capillary networks, but are arrested in the
larger or smaller vessels (Koch). The micrococci in the resulting
infarctions multiply, and migrate into the vessels and cellular tissue
of the neighborhood. Thus fresh foci of infection are formed. Or by
their destructive action they may, when situated near the serous
surfaces, penetrate into the serous cavities, and in this way
indirectly occasion peritonitis, pleurisy, meningitis, and purulent
inflammations of the joints. When the micrococci enter directly into
the circulation, they sometimes, in passing through the heart, adhere
to the endocardium and the valves, where they cause exudation and
ulceration, and give rise to the so-called endocarditis ulcerosa
puerperalis.[38] The red globules of the blood undergo changes of
shape, assume a stellate aspect, and rapidly disappear. The white
globules are greatly increased in numbers, and the blood itself
becomes nearly colorless. A certain amount of light is thrown upon
these blood-changes by Doléris, who added micrococci to the fresh
blood of a frog and watched the ensuing changes under the microscope.
The micrococci could be seen in the act of penetrating the red
globules, which thereupon lost their color and became shrunken, and,
following the discharge of the organisms, which meantime had
multiplied in an astonishing manner, little or nothing of the original
globules remained.
[Footnote 38: Heiberg, _Die puerperalen und pyæmischen Processe_,
Leipzig, 1873, pp. 22 and 34, with references to cases reported by
Wiege and Eberth.]
In the bacillar form of septicæmia the blood is dark and has a
semi-gelatinous appearance, compared by French writers to
partially-cooked gooseberry jelly. The red globules, though they
exhibit the various stages of deformation, are not diminished in
number. The disease is further characterized by ecchymoses and minute
apoplectic effusions, and by the absence of pus-formation. In the
artificial septicæmia produced by Koch in mice by means of bacilli the
rod-like organisms were found to enter the white corpuscles and to
compass their destruction. They did not cause the red globules to
adhere together, and there was no clogging of the capillary
circulation. All the principal structures of the animals subjected to
experiment were infiltrated with bacilli. The distribution of the
latter was apparently accomplished by the blood-vessels, and not by
the lymphatics, the bacilli probably effecting their entrance into the
vessels by virtue of their penetrative power, in place of traversing
preformed pathways. Possibly it is this action of the bacilli which
causes the weakening of the vessel-walls, as evidenced by the large
number of red corpuscles which pass out from them.
In puerperal fever it is rare to find either round bacteria or bacilli
acting singly as the agent of infection. As a rule, both forms exist
together in varying proportions, the predominant form, however,
determining in general the character of the symptoms.
Thrombosis of the veins may be a physiological phenomenon, or may be
due to an alteration of the blood, to weakness of the heart, or to
local influences. So long as the clot remains firm its influence is
limited to disturbances of the circulation. The pyæmic symptoms--viz.
suppuration of the coagulum, the separation of emboli, and the
formation of metastatic abscesses--are always dependent upon the
presence of round bacteria. In phlebitis the latter are found in the
endothelium and in the sheaths of the veins. The inflammation of the
veins is followed by {1002} thrombosis. According to Doléris,
micrococci derived from the blood are deposited upon the central
extremities of the clots; beyond these dépôts a fresh inflammation is
set up, followed by fibrinous coagulation. Thus the micrococci become
imprisoned between two plugs. The same process may be repeated until a
series of abscesses are formed. For a time no mischief may ensue.
Finally, however, the resistance of the outworks is overcome, an
embolus becomes detached, and an infectious abscess is opened into the
blood--an event which is announced by an intense chill and the
familiar systemic derangement.
In septic diseases death takes place from apnoea, partly from the
inability of the blood-corpuscles to carry oxygen to the tissues, and
partly from paralysis of the nerve-centres.[39]
[Footnote 39: Schüller, "Exp. Beiträge zur Studium der Septischen
Infection," _Deutsche Zeitschr. f. Chir._, vol. vi. p. 149 _et seq._]
In hospital epidemics of puerperal fever diphtheritic patches situated
upon the lesions of the vulva and in the course of the utero-vaginal
canal are sometimes observed. Steurer found these patches were always
associated with loss of substance, and were composed of disintegrated
fibrin, white and red blood-globules, and colonies of round bacteria
in great abundance. Morphologically, these so-called diphtheritic
patches are identical with those which appear in the throat.
Pallen[40] has reported an instance of the simultaneous occurrence of
puerperal diphtheritis in the mother and throat diphtheritis in the
two-weeks' old child. In lying-in hospitals it is the genital organs,
as the locus resistentiæ minoris, and not the throat, which are the
usual points of attack.
[Footnote 40: _Trans. N.Y. Obst. Soc._, 1876-78, p. 78.]