Cent. f. Bact., Bd. 33, Orig. S. 481. Baum. Jahres., Bd. 19, S. 496.
Endnote 302:
Rabinowitch, L., ’03. Ueber eine Hauterkrankung der Ratten. Cent. f.
Bact., Bd. 33, Orig. S. 577. Baum. Jahres., Bd. 19, S. 496.
Endnote 303:
Dean, G., ’03. A Disease of Rats caused by an acid-fast Bacillus.
Cent. f. Bact., Orig. Bd. 34, S. 222. Baum. Jahres., Bd. 19, S. 494.
Endnote 304:
Dean, G., ’05. Further Observations on a Leprosy-like Disease of the
Rat. Jour. Hyg., vol. 5, p. 99.
Endnote 305:
Tidswell, F., ’06. Note of Leprosy-like Disease of Rats. Lepra, vol.
6, p. 197.
Endnote 306:
English Plague Commission. Jour. Hyg., vol. 7, p. 337. Cited by
Wherry.
Endnote 307:
Wherry, W. B., ’08. The Leprosy-like Disease among Rats on the Pacific
Coast. Jour. Am. Med. Asso., vol. 50, No. 23. Cent. f. Bact., Ref. Bd.
42, S. 664.
Endnote 308:
Wherry, W. B., ’08. Notes on Rat Leprosy and on the Fate of Human and
Rat Lepra Bacilli in Flies. Public Health Reports, U. S. P. H. and M.
H. S., vol. 23, p. 1841. Jour. Infec. Dis., vol. 5, p. 507.
Endnote 309:
Mezincescu, D., ’08. Maladie Lépreuse des Rats et ses Relations avec
la Lèpre Humaine. Compt. Rend. Soc. Biol., T. 64, p. 514. Cent. f.
Bact., Ref. Bd. 42, p. 664.
Endnote 310:
McCoy, G. W., ’08. Rat Leprosy. Public Health Reports, U. S. P. H. and
M. H. S., vol. 23, p. 981. Jour. Am. Med. Asso., vol. 51, p. 690.
The writer wishes to express his gratitude to Dr. George Dean for
histological material from the natural and experimental disease, and to
Doctors Wherry and McCoy for rats inoculated with the disease and normal
animals for its propagation.
BACTERIAL DISEASES OF THE RAT, OTHER THAN PLAGUE AND RAT LEPROSY.
By DONALD H. CURRIE,
_Passed Assistant Surgeon, United States Public Health and
Marine-Hospital Service_.
So far as is known, the several species of rats that are found about the
habitations of man—_Mus norvegicus_, _Mus rattus_, _Mus alexandrinus_,
and _Mus musculus_—are naturally subject to but few bacterial diseases
as compared to some other animals. Interest in this matter has only
recently been aroused, owing to the rôle played by the rat in the spread
of bubonic plague. When we consider the immense number of rats that have
been examined in connection with antiplague work by trained
investigators in recent years, and that to many investigators the
thought must have come that the discovery of some rat destroying
bacterium would be of the greatest utility, it appears more than
probable that few such natural diseases exist.
Plague is the one natural bacterial disease that has demonstrated its
power to destroy these rodents in numbers sufficiently large to attract
general attention; scientific investigation has only been able to add a
few other bacterial diseases, and these are probably for the most part
rare ones, causing the death of a very small percentage of the total rat
population.
Of the “natural” diseases (i. e., spontaneous, in distinction to
diseases that can only be produced artificially, under laboratory
conditions) the following are the more important ones:
Rat plague and rat leprosy, which are made the subject of special
chapters in this publication, must be mentioned as the most important
diseases observed among rat populations.
DANYSZ’S BACILLUS OR BACILLUS TYPHI MURIUM OF LOEFFLER.
These are probably identical organisms, differing only in their degree
of virulence, at least their pathogenicity alone distinguishes them in
the laboratory. They are both members of the paracolon group. They
produce a diffuse cloudiness in broth, ferment glucose but not lactose
or saccharose, do not liquefy gelatin nor coagulate milk.
_B. typhi murium_ (Loeffler) is fatal to mice (_Mus musculus_), but not
to rats. M. Danysz isolated a bacillus during an epidemic of field mice
which was indistinguishable from the above, except that its virulence
was capable of being raised to a point where it would destroy a
relatively large percentage of rats inoculated with it by feeding. We
see from this that, strictly speaking, it is not a natural disease among
rats, still there are cases where its virulence has for a time remained
high enough to infect a considerable per cent of rats exposed to those
that have sickened of it. Not only is this true in cage experiments, but
probably it sometimes occurs in nature after the virus is once
thoroughly introduced (an article by M. Danysz; also experience of this
service in plague in San Francisco, 1903 to 1905), and may therefore be
grouped under the list of “natural” infections. This bacillus is
unfortunately of a very unstable nature, in so far as its virulence is
concerned; some cultures appearing to be avirulent, while others cause
an all but absolute mortality among the rodents eating it.
The duration of the disease is variable and appears to depend somewhat
on the size of the dose received, as well as virulence of the culture.
We have seen death in thirty-six hours or less following ingestion. On
the other hand, it may occur in two weeks. Usually it occurs in from six
to twelve days. In a typical case when the animal has lived ten or
twelve days it is much emaciated, its tissues are dry, and intestinal
hemorrhages are sometimes met with. When the disease is much prolonged a
pustular eruption may be present over the skin. The organism can often
be isolated from the heart blood by plating, such isolation alone
affording means of diagnosis. The only present interest this organism
has is as a means of destroying the rat. It was believed to be harmless
to man, but more recently cases of human illness have been reported that
were believed to have been caused by infection with this bacillus.
PNEUMONIA.
We have recently seen a case of lobar pneumonia in a rat in which a
diplococcus was present in pure culture. Possibly connected with this is
a condition of abscess of lung, which is not very uncommon. The cavity
is filled with a creamy or cheesy matter composed of broken-down cells.
Often these cavities break into the pleura. Several morphological types
of organisms are found, but from their variation this laboratory has
regarded them as secondary or accidental, especially as we have failed
to demonstrate that this material was infectious.
STAPHLOCOCCUS ABSCESSES.
These are rather common and may occur subcutaneously or in the
superficial muscles of any part of the body.
BACILLUS PSEUDO-TUBERCULOSIS RODENTIUM (PFEIFFER).
This organism that infects rats is of interest from its close
resemblance to the plague bacillus. It is difficult to distinguish the
two organisms by ordinary cultural or animal tests. The earlier writers
claimed that _B. pseudo-tuberculosis rodentium_ could be differentiated
by its power of coagulating milk, but more recently this difference has
been found to be an inconstant one.
TOYAMA’S BACILLUS.
Toyama has described an organism which he states is pathogenic for _Mus
rattus_, field and house mice (_Mus musculus_), but not pathogenic for
_Mus norvegicus_.
It causes congestion of lungs, enlargement of lymph nodes, especially in
the neck, and enlargement of the spleen. It was isolated from a natural
epizootic among _Mus rattus_. It is a nonspore-bearing bacillus, without
capsule, stains without showing bipolarity, and grows upon ordinary
media.
Among other bacteria that have been described as causing diseases in
rats may be mentioned:
_Von Schilling’s bacillus_, allied to Danysz’s organism.
_Bacillus “Eris,”_ a member of the colon group.
_Bacillus muris_, a member of the _B. diphtheria_ group.
Of the bacteria that show virulence for rats under laboratory
conditions, but, so far as is known, cause no spontaneous outbreaks, the
following are the best-known examples:
_Bacillus bovisepticus_ produces a fatal disease bacillus of swine
erysipelas (especially for albino rats), and the bacillus of tetanus.
Of the higher fungi (not strictly bacterial) we have:
_Streptothrix maduræ_ produces local swellings when inoculated
artificially.
It has been stated that rats occasionally suffer from a disease similar
or identical to the affliction in man known as favus (_Achorion
Schönleinii_).
INFECTIONS OF MICE (MUS MUSCULUS).
This species of _Mus_ is very susceptible to a large number of bacterial
diseases when inoculated under laboratory conditions. The following are
some of the best-known examples:
_B. murisepticus_, _Staphlococcus pyogenes_, _Streptococci_,
_Diplococcus pneumoniæ_, _B. pneumoniæ_ (Friedlander), Diplococcus of
pleuro-pneumonia of horses, _B. Typhi murium_, _B. anthracis_, B. of
malignant edema, _B. tetani_, _B. mallei_, _B. diphtheriæ vitulorum_,
_B. bovisepticus_, _B. suisepticus_, the bacillus of Mereshkowsky, and
many others. The last-named organism has been utilized to a limited
extent for the destruction of mice about dwellings.
ORGANIC DISEASES OF THE RAT, INCLUDING TUMORS.
By GEORGE W. MCCOY,
_Passed Assistant Surgeon, United States Public Health and
Marine-Hospital Service_.
The lesions described here are those that have been found in the routine
examination of rats for plague infection in the federal laboratory at
San Francisco during the past year, in which time approximately 120,000
rats have been examined.
As the subject had no special bearing upon the plague investigations,
but little time was spent in examining and recording the nature of
organic lesions that were observed. Notes, however, were made of many of
the conditions which were encountered, and these notes have been used as
the basis of this paper.
It is well known that various lower animals are subject to some of the
so-called organic diseases from which man suffers, and not a little
experimental work has been done in endeavoring to establish in animals
certain of the lesions commonly found in human pathology.
_Usefulness of wild rats for laboratory purposes._
We would call special attention to the fact that wild rats suffer
spontaneously from cirrhosis of the liver, fatty degeneration of the
liver, nephritis, and calculi of the urinary tract, and would,
therefore, probably furnish excellent subjects for the experimental
investigation of these diseases.
The objection may be made that the very fact that these animals do
suffer from these diseases spontaneously makes them unsuitable for
experimental purposes, as one could not be certain that any lesions
found were not spontaneously developed rather than that they were due to
the conditions imposed in an experiment. In reply to this objection we
would say that the most of these organic lesions occur so rarely in rats
in nature that one could almost ignore them.
The ease with which wild rats are obtained and the readiness with which
they adapt themselves to the conditions of life in captivity are factors
which should make them more extensively used for laboratory purposes
than is the case at present. We have described (New York Medical
Journal, Feb. 6, 1909) the methods that have been found useful in
keeping and handling these rodents. Without going into details here we
may say that if rats of approximately the same size are kept together in
a cage there will be practically no mortality from fighting. Of course,
there should be no overcrowding. Rats should be fed meat or cheese and
plenty of green food such as carrots or cabbage. In our experience in
San Francisco it has been found practicable to keep for a year one
series of ten inoculated wild rats without any loss. Judging from my
experience I have no hesitancy in saying that the natural mortality in
the laboratory is higher among both guinea pigs and white rats than it
is among wild rats.
It is almost certain that some of the lesions described below are due to
animal parasites, or to bacteria, but no such causative agent has been
identified.
CIRCULATORY APPARATUS.
We have seen no lesion of the circulatory system with the exception of a
few cases of pericardial effusion. The most extreme example was one in
which the pericardial sac was dilated to such an extent that it filled
almost the entire cavity of the thorax. The fluid in the sac was blood
stained and there were a number of recent adhesions between the visceral
and the parietal surfaces of the pericardium.
PULMONARY APPARATUS.
Pleural effusion, as is stated in another place, is an important sign of
plague infection. A clear, watery effusion has been found in a few cases
in rats that were not plague infected.
One example has come under observation of a large _Mus norvegicus_ that
had both pleural cavities almost entirely filled with a milky fluid. The
lungs were compressed and congested. Microscopical examination for
animal parasites and for bacteria was negative.
A condition of consolidation of the lungs which closely resembles the
stage of gray hepatization in lobar pneumonia in man is seen
occasionally. The area may involve half of a lung. Upon microscopical
examination one finds the air spaces and the small bronchi filled with
leucocytes. There was no cavity formation in any of the cases that have
come under observation.
Two relatively common purulent conditions of the lungs are encountered.
In the first of these, large and more or less distinctly loculated sacs
are found, which are filled with yellow semifluid caseous matter; in the
second, the lesion is of much the same nature, but the material in the
sac has the consistency of tough, ropy mucus. Aside from the main focus
of this sort, numerous smaller areas of the same nature are seen
scattered through the otherwise normal parts of the lungs. The extent of
some of these purulent processes is remarkable. We have seen cases in
which the chest cavity was almost filled by the lesions described.
DIGESTIVE TRACT.
CIRRHOSIS OF THE LIVER.
It was a matter of surprise to find well-marked cases of hepatic
cirrhosis in rats, as this disease in man has been pretty generally
regarded as very largely due to intemperance in the use of alcoholic
beverages. Such an etiology hardly accounts for the condition in the
rat. The lesion is by no means rare; well-marked cases are encountered
probably as often as once in a thousand rats. We have never seen it in a
young rat, probably because the condition develops slowly and the rat
reaches adult life before the process is complete. The organ is usually
somewhat yellowish, very firm, often, but not always, somewhat shrunken
in size. The surface of the whole organ is covered with small, rounded
elevations; a typical “hobnail-liver” in miniature.
Microscopically we find various degrees of increase of connective
tissue. In a well-marked case the capsule is much thickened, and heavy
bands of connective tissue run through the organ in every direction.
This increase of connective tissue is most marked in the vicinity of the
portal vein and its companion vessels. The microscope will show that in
some fields over half of the structure is made up of fibrous tissue. The
liver cells that remain appear to be normal. The presence of animal
parasites in the liver is frequently associated with a considerable
hypertrophy of the connective tissue of the organ. In a majority of
cases of hepatic cirrhosis, however, no parasites are to be found. One
case has come under observation in which the surface of the liver was
covered with a number of flattened, wart-like elevations. Upon section
nothing was to be found to account for this except an enormous
overgrowth of connective tissue.
FATTY DEGENERATION OF THE LIVER.
A considerable number of cases of well-marked fatty degeneration of the
liver have been seen. At times the fatty change is so extensive that the
organ floats when placed in water. Microscopically the liver cells are
found to be extensively infiltrated with fat granules.
HERNIÆ.
A few ventral herniæ have been observed. In the majority of the cases
the sac contained intestine only and this was easily reduced. On two
occasions other viscera have been found in the sac; the spleen on one
occasion and in another case along with several loops of intestine which
were easily reduced there was found the upper extremity of the right
division of the uterus which carried a cyst about 1 centimeter in
diameter. The cyst was partly adherent to the sac of the hernia. The
other division of the uterus was dilated and full of pus. The hernial
sac is rarely situated in the median line. One inguinal hernia has been
seen.
GENITO-URINARY TRACT.
NEPHRITIS.
Nephritis is a rather common condition in rats. Among the large (old)
ones it will be found probably once in every fifteen or twenty examined.
It has been found to be especially frequent in rats that are suffering
from the leprosy-like disease, as probably two-thirds of those having
that interesting infection will show marked evidence of nephritis. The
kidney is usually brownish or grayish, mottled, friable and often shows
cysts upon the surface and in the substance of the organ. Some of these
cysts may be as large as a pea, or indeed even much larger. The capsule
strips very readily.
Microscopically the lesions are found to be due partly to epithelial and
partly to interstitial change. There is a marked increase of connective
tissue rather irregularly distributed throughout the organ. The
epithelial cells show various degrees of degeneration; the nuclei are
stained very lightly, or not at all; granular change of the protoplasm
is well marked. Some tubules are encountered in which the epithelial
cells are entirely wanting.
Cyst formation is a conspicuous feature in many of the cases. These
cysts vary considerably in size, are often filled with granular débris,
and are more or less completely lined with epithelial cells which are
sometimes flattened. At times the epithelial lining is entirely wanting.
The glomeruli, on the whole, appear to be better preserved than are the
tubules. Occasionally areas are found in which there is a very marked
round cell infiltration between the epithelial structure. One of the
most marked cases of nephritis we have observed was in a large female
_Mus alexandrinus_, in which both kidneys were almost entirely replaced
by cystic formation, the largest cyst being perhaps 3 centimeters in
diameter by 4 centimeters in length, and full of a clear, watery fluid.
So extensive was the cystic formation that only a few remnants of kidney
tissue remained. Microscopical examination showed a marked increase in
the capsular and interstitial connective tissue, a shrinking of the
glomeruli, which were surrounded by well-marked fibrous capsules, and
extensive cyst formations. The lining of some of these cysts was made up
of epithelial cells. Others were quite bare. This rat had, in addition,
a large, rough calculus in the urinary bladder.
ABSCESS OF THE KIDNEY.
A female _Mus norvegicus_ had on one side of the neck a large cavity
full of caseous matter. In each kidney there were five or six
circumscribed collections of pus, the largest of which was about the
size of a pea. Microscopical sections through these abscesses showed
that they were walled off from the kidney structure proper by beginning
connective tissue formation. The abscess cavity was filled with
polynuclear leucocytes, some of them very markedly disintegrated. The
epithelial structure of the kidney proper showed some parenchymatous
degeneration.
ATROPHY OF A KIDNEY.
On one occasion we have seen a kidney represented by a very small
flattened mass of tissue, the nature of which was not quite clear until
microscopical examination showed a few fairly well-defined glomeruli and
a few cell groupings suggestive of tubules. Whether the condition was
congenital or acquired is not known. The other kidney appeared to be
normal in every respect. There was no evidence of compensatory
hypertrophy.
VESICAL CALCULI.
The bladder of rats very frequently contains very irregularly shaped,
rough, somewhat branching concretions. These concretions are rather soft
and tough and are dirty white in color.
In addition to these concretions we have seen several cases of
well-marked vesical calculi. In one case 21 smooth round stones which
completely filled the bladder were found. The total weight of the stones
was 3.8 grams. In another case 6 calculi were found, the total weight of
which was 7.8; the largest one weighing 5 grams. In a third case 8
smooth, round stones weighing 1.7 grams were found, the largest of which
weighed 0.6 gram. The last two cases were female rats; the sex of the
first was not recorded.
In each of these cases the bladder showed to the naked eye very marked
evidence of inflammation. The mucous membrane was reddened, villous, and
covered with tenacious mucus. In one case in which microscopical
examination was made the mucous membrane was found to be covered with
pus cells, the surface layers of which were undergoing degeneration.
Diseases of the genital tract in the human race analogous to those
mentioned below are so generally regarded as due for the most part to
infections from impure sexual relations that it was a distinct surprise
to find such lesions in rodents.
In the male abscesses are occasionally met with in connection with the
seminal vesicles. We have seen them varying in size from a pea to a sac
whose contents would have measured 3 or 4 cubic centimeters. In the
female purulent collections in the horns of the bifid uterus are
encountered, but they are rare. We have seen cases that were
anatomically exactly like the purulent lesions so commonly found in the
fallopian tubes of women. In one case one horn of the uterus was closed
at both ends and distended by a thin, watery pus into a large
sausage-shaped mass about the size of an index finger. The opposite horn
of the uterus contained six fœtuses. A very curious case was one in
which four fœtuses, each one a little less than an inch in length, were
found lying in the midst of a large, yellowish, puttylike mass that
distended one horn of the uterus into a balloon-shaped mass about 3
centimeters in diameter. The fœtuses were partly dried, and had
evidently been dead for a long time.
TUMORS.
Tumors among rats and mice are not infrequent when these animals are
kept in captivity, and the tumors of mice especially have been made the
subject of very extensive experiments for the purpose of determining the
mode of transmission, the question of immunity, and other subjects that
might throw light upon malignant growths in the human family. White or
tame rats have been much less used than mice. However, it is interesting
to note that the earliest observations on the successful transplantation
of a malignant growth from one animal to another was that of Hanau[101],
who reported a carcinoma of the external genitals of a white rat and he
succeeded in transplanting this tumor into other white rats.
I shall not make any attempt to review the enormous literature on tumors
in tame rats and mice, but shall merely mention some of the more
important points that have been learned in an experimental way in regard
to this subject. The histological nature of the tumors found in white
rats was of particular interest, as we wished to compare them with the
tumors that have come under observation among the wild rats in San
Francisco.
In addition to Hanau’s case of carcinoma cited above the following
tumors of white rats are mentioned. Herzog[102] observed a cystic
sarcoma of the neck of a white rat. Loeb[103] mentions three tumors of
white rats; an adenoma in the mammary gland, an adenocarcinoma of the
pancreas, and a carcinoma of the thyroid. Flexner and Jobling[104]
report a mixed cell sarcoma of the seminal vesicles of a white rat. This
tumor upon transplantation showed a marked tendency to produce
metastases. Gaylord and Clowes[105] report cases of fibrocarcinoma of
white rats arising apparently from infected cages, and they present
evidence that in certain breeding establishments carcinoma is endemic
among the white mice. Spontaneous tumors are much more frequently met
with in mice than in rats, and a number of epidemics of malignant
growths have been observed among mice in captivity.