Chapter XIII: Plague

DEFINITION AND SYNONYMS

=Definition.=—Plague is primarily a disease of rats or other rodents and is caused by a bacterium of the haemorrhagic septicaemia group, _Bacillus pestis_. The disease exists in the rodent in both an acute and chronic form. Acute plague of the rat is apt to be septicaemic, so that when certain species of fleas which infest the rat feed on the blood of their host they ingest plague bacilli. These seem to multiply in the region of the proventriculus and cause thereby an obstruction to the stomach. As a result the flea makes vigorous and repeated but ineffectual efforts to feed. Regurgitation of the contents of the oesophagus occurs, thereby inoculating plague bacilli. When the rats die these fleas will attack man and cause human plague. The ordinary type in man is bubonic plague, characterized by extremely tender glandular enlargements. This form of the disease is thought to be exclusively transmitted from man to man by fleas or possibly bedbugs. A second type is pneumonic plague which is a surely fatal pneumonia which is transmitted from man to man by droplets of sputum expelled in coughing. Either the bubonic or pneumonic types may become septicaemic or this form may exist from the start.

Plague shows a marked clouding of the consciousness from the onset and is characterized by toxic action on the heart and endothelial lining of capillaries.

=Synonyms.=—Oriental Plague, Black Death, Pestis. French: La Peste. German: Die Peste.

HISTORY AND GEOGRAPHICAL DISTRIBUTION

=History.=—Ancient writers were accustomed to apply the
designation “plague” to any disease which was epidemic in character
and attended with great mortality. This explains why the plague of
Athens and that of Marcus Aurelius, which epidemics did not possess
the characteristics of oriental plague, were so designated. There
exist however writings which show that fatal epidemic diseases
attended with buboes and prostration were noted prior to the
Christian era.

It is probable that the biblical description of a disease among the
Philistines which was attended with buboes and killed the mice of
the field referred to plague.

In the 6th century, during the reign of Justinian, a disease
which was unmistakably plague started from Egypt and reaching
Constantinople caused the death of 10,000 persons in one day. It
spread throughout the entire Roman empire.

_The “Black Death.”_—The most noted epidemic of plague was that of
the “Black Death” of the 14th century. The disease seems to have
originated in the East, possibly in China, and eventually invaded
Asia Minor, Egypt and Europe. The disease was called “Black Death”
in Germany, on account of the petechial spots or “tokens” and in
Italy, the “Great Mortality.”

In the records of the epidemic we note that it was attended with
great stupefaction, the sick losing their speech from palsy of the
tongue. Others noted buboes of groins and arms while some noted a
putrid inflammation of the lungs with the expectoration of blood.
In the plague at Avignon it was noted that at first, for six or
eight weeks, the sick expectorated blood and that to come near them
was certain death. Afterwards buboes appeared in groin and axilla
and some of the sick recovered.

_Quarantine._—It was during this epidemic that quarantine became
a recognized procedure in Europe. The adoption of a period of
detention of forty days probably originated in the medical idea
that the 40th day was the last day of ardent diseases, this being
one of the critical days. The lazarettos, where strangers were held
in quarantine, appear to have first been established on some island
near Venice, in 1485.

It has been estimated that one-fourth of the population of Europe
succumbed to the “Black Death,” but estimates in certain parts
of Europe would indicate a mortality approaching 70% of the
inhabitants.

In 1665 occurred the Great Plague of London, during which year it
was estimated that approximately 60,000 out of a population of
450,000 died. It was thought that this epidemic was introduced from
the Levant by way of Holland.

There was much plague in Europe in the 18th century but it would
seem to have completely disappeared by 1841 and only to have
returned with the present pandemic.

_The Present Pandemic._—The plague epidemic with which all parts
of the world are now so concerned is supposed to have originated
in China, in the province of Yunnan, and from that center to have
reached Canton, in 1894, causing the death of 60,000 people in a
population of 1,500,000. In the same year it extended to Hong Kong
and from that great seaport has spread over the entire world. India
has suffered more than any other country, there having been years
when the plague deaths exceeded 1,000,000.

In a recent article by Low it is noted that the highest death rate
was reached in 1907 when 1,315,892 persons died. From the time of
the introduction of plague into India to the end of 1917 there were
9,841,396 deaths from this disease.

In its spread it has invaded Europe, Egypt, South Africa,
Australia, Japan, Philippine Islands, California and parts of
Central and South America. It has recently made its appearance in
New Orleans.

=Geographical Distribution.=—At present there are only two
important foci of endemicity, one Mesopotamia and another in the
region of the Himalayas (India, Thibet and Yunnan). There also
seem to be less important centers in Uganda, in Africa, and in the
trans-Baikal region of Siberia. In view of the rather widespread
infection of the California ground squirrels, from which rodents
the disease has from time to time spread to man, it would seem
probable that California might be considered another focus of
plague.

ETIOLOGY AND EPIDEMIOLOGY

=Etiology.=—The bacillus of plague was first isolated by Yersin from a plague bubo, in 1894, at Hong Kong. It is true that Kitasato reported a bacillus which he had isolated from the blood of a plague patient, on July 7, 1894 (Yersin’s report was made July 30, 1894). Kitasato’s bacillus was motile, Gram-positive, coagulated milk and gave a turbidity in bouillon, characteristics which were just the opposite of those of the organism reported by Yersin.

As now recognized the plague bacillus, when in smears from
pathological material, shows the form of an oval bacillus, the ends
of which stain more intensely than the central portion (bipolar
staining). When cultured on ordinary agar, the morphology is more
rod-shaped with a tendency to pleomorphism.

These agar cultures are very sticky and mucilaginous. If 3% of
NaCl is added to the agar, this pleomorphism is exaggerated, there
occurring coccoid, root-shaped and various bizarre involution forms.

For obtaining the involution-form appearance on 3% salt agar one should transfer liberally from the ordinary agar growth to the salt agar rather than planting direct from the pathological material.

A bouillon culture, upon the surface of which there has been
deposited drops of oil or melted butter, shows a string-like
downward growth from the under surface of the oil globules. This
“stalactite” growth is very fragile and is difficult to obtain.

Ordinary bouillon cultures show a rather powdery deposit at the
bottom and a hanging-drop preparation from such a culture shows
chains of plague organisms resembling streptococci. Gelatine is not
liquefied. _Bacillus pestis_ grows readily at room temperature as
well as at 37°C, and one may be struck with the fact that colonies
on agar plates may show variations in degree of development so
that the suspicion of a contaminated culture may arise. Human
plague material for cultures or smears is best obtained from the
bubo prior to suppuration in bubonic plague, from the blood in
septicaemic plague and from the watery sputum in pneumonic plague.

_Plague in the Rat._—With acute plague in the rat one finds marked injection of the subcuticular surface of an exposed abdominal flap; certain glands, especially the neck ones, show marked congestion, haemorrhagic necrosis and periglandular infiltration; the pleural cavity contains much fluid; the liver has a yellow mottled appearance liberally sprinkled with discrete, yellowish-white granules about the size of a pin’s head, while the spleen is enlarged. Smears from the spleen or affected glands, as a rule, show the bacilli in great numbers. The San Francisco findings in plague rat autopsies varied somewhat from those noted above, which held for Indian plague rats.

_Confusing Organisms._—Other organisms which may be obtained
from plague-suspected material are those of the proteus or colon
group, which may show bipolar staining, but culturally are quite
different. Klein has noted that a nonmotile rod, which gives a
striking bipolar staining and named _Bacillus bristolensis_, may be
mistaken for the plague bacillus. Its growth in bouillon is similar
to that of _B. coli_ and it coagulates milk.

An organism, _B. pseudotuberculosis rodentium_, resembles the
plague bacillus in a striking manner but is without virulence for
rats. It is virulent however for guinea pigs and these animals can
be immunized against plague with this closely related organism.
Litmus milk cultures of plague show a very slight acidity while
with _B. pseudotuberculosis rodentium_ there is a high degree of
alkalinity produced.

Wherry has reported two cases of ulcerative conjunctivitis with
lymphadenitis of cervical glands, fever and marked prostration,
due to infection with _B. tularense_, occurring in persons who had
handled rabbits which had died of this plague-like infection. The
organism was first noted by McCoy in squirrels in California. The
symptoms and lesions in these animals are those of plague. Guinea
pigs succumb after the cutaneous inoculation of material and show
lesions markedly resembling plague. The organism, however, will
not grow on ordinary simple media as does the plague bacillus. As
will be noted in the chapter on Tularaemia the disease has a very
limited geographical distribution.

The _crucial test_ for any plague material is the power of the plague bacillus to infect a rat or guinea pig, when the material is rubbed on the shaven skin of the animal. _B. tularense_ will also pass through intact shaven skin and it produces lesions in the guinea pig similar to those of plague. Other organisms, however which might infect through intact skin produce lesions unlike those of plague. As a practical point it may be stated that cases showing a profusion of oval, bipolarly staining bacilli, in smears from glands or sputum, and with clinical manifestations of plague, are not likely to be other than plague; still, to be conservative, one should always inoculate animals cutaneously or subcutaneously.

=Epidemiology.=—Plague is primarily a disease of rodents, usually rats, and man contracts his infection from these animals. With the exception of pneumonic plague which, under certain circumstances, is transmitted directly from man to man, plague infections originate from the bite of fleas which have become infected from feeding on the blood of plague rats. Infected fleas act as intermediaries in plague epizootics among rats. It is true that a rat might become infected from bites received in a fight with an infected rat, or man might be infected through a cut on a finger while handling plague material, but such methods play but a small part in plague epidemiology.

_Fleas and Plague._—In 1897, Ogata infected mice by inoculating
them with an emulsion of crushed fleas taken from plague rats. In
1898 Simond showed that if a rat, dead of plague, were placed in a
large bottle and a healthy rat confined in a small cage introduced
into the bottle and suspended above the dead rat, so that there
could be no contact between the dead and the living animal, the
well rat would contract the disease. If however the fleas were
removed from the dead rat, before the introduction of the caged
rat, no infection took place.

By reason of claims that the rat flea would not bite man these convincing experiments were in a measure disregarded. The complete confirmation of the correctness of this view, as to transmission of bubonic plague, was brought about by the Indian Plague Commission. In a large number of experiments it was shown that when healthy and plague-infected guinea pigs were confined together in spaces where there were no fleas, there were no plague infections of any of these well animals.

_Xenopsylla cheopis_ is the most important plague transmitter of the flea family as it is the common rat flea of India where there is so much plague.

_Sarcopsylla_ or _Dermatophilus penetrans_ is an important factor in a disabling skin disease, especially of the feet, in many parts of the tropics.]

On the other hand in 35 experiments, when fleas had access to
the spaces, plague infections were the rule. Again, guinea pigs
in cages which were suspended only two inches above a plague
flea infected floor, became infected, but other animals, which
were suspended so high that the fleas could not jump up to them,
remained well. Two cages, each containing a monkey, were placed in
a plague flea infected room. One was surrounded with a protecting
zone of 6 inches of “tanglefoot” fly paper, this being the limit
of the distance a flea can jump, while the other cage was not
so protected. The monkey in the cage without the sticky paper
contracted plague while the second monkey remained well. It is
only when there is a great incidence of plague among rats that
we have outbreaks of bubonic plague in man, and it has been noted
that the greater the epizootic, the more heavily infected was the
blood of the sick rats with the plague bacilli. A flea with a
stomach capacity of about ½ c.mm. could take in several thousand
plague bacilli in a feeding on a rat whose blood was teeming with
bacilli. The blood of a rat dying with plague may contain as many
as fifty million bacilli to the cc. Human blood rarely contains
more than a million to the cc. There is a multiplication of the
organisms in the flea, so that when it defecates, thousands of
plague bacilli are deposited near the puncture wound made by the
flea when subsequently feeding on a man. The infected faeces are
rubbed into the wound by the man in scratching the site of the
bite, so that we have here an instance of a contaminative method of
infection as contrasted with the inoculative method by the mosquito
in malaria.

Bacot and Martin have shown that while infection may take place as the result of the faeces being rubbed into the wound made at the time of feeding yet the ordinary way is probably by regurgitation from the oesophagus of the flea at the time of feeding.

Upon taking in plague septicaemia blood the bacilli multiply
about the site of the proventriculus as well as distending the
oesophagus. This makes an obstruction to the entrance of the
stomach resulting in starvation of the flea. This naturally makes
the flea more voracious and in the ineffectual muscular efforts
to take in blood, regurgitation of the contents of the oesophagus
occurs, thereby infecting the person upon whom the flea is trying
to feed. This obstruction apparently may be overcome in some way as
the plague-infected flea does not necessarily die. Still from lack
of sufficient fluid such fleas are liable to be killed off if the
relative humidity is low, as in dry weather. Further investigations
have shown that the proventricular plug may be channeled, but in
such case valve action is lost and the contents of the stomach are
regurgitated, thus making such a flea more dangerous than one with
an obstructed proventriculus. Such fleas may continue infectious
for 67 days.

Very interesting in this connection is the fact that Heiser found
plague-infected fleas in the desk of a European at Manila who died
of plague. A mummified rat was found in one of the drawers of
this desk, from which successful animal inoculations for plague
were made. Heiser notes that data would indicate that these fleas
probably remained alive 2 weeks after the death of the rat which
brought about their infection. Another very striking finding during
the same Manila plague outbreak (1912-1913) was that bedbugs found
on the sleeping mat of a human victim of plague showed bipolarly
staining bacilli.

Bacot has carried on experiments in which fleas infected two months
previously and kept in a cool place could transmit plague. This
would indicate the danger from plague-infected fleas which had been
held in material packed away in boxes.

_Method of Spread._—The spread of plague epizootics among rats seems to be rather by the fierce brown sewer rat, _Mus norvegicus_. The more delicate black house rat, _Mus rattus_, usually receives its infection from the sewer rat. When the rat dies the fleas leave the dead body and seek a new host, preferably one similar to the one just abandoned. The sewer rat reaching the basement of houses and dying of plague is deserted by his fleas. These will attach themselves to the house rats which go from basement to roof of the house and later these dying are abandoned by the fleas which, in the absence of a rodent host, will feed on man and infect him.

The house rat is rarely found in Europe while in many parts of the
tropics it is common and in close association with man. The fact
that the sewer rat avoids the upper portions of houses probably
explains the greater infrequency of plague epidemics in Europe
where this rodent is common. In former ages when the house rat was
prevalent in Europe we had great epidemics there. _Mus (Rattus)
norvegicus_ is of stout build with a blunt nose and small opaque
ears which barely reach the eyes when laid forward. The tail is
shorter than the length of the head and body together (89% of such
length). With _Mus rattus_ we have a delicately built rat with a
slender head and sharp nose. The ears are translucent and large
and reach beyond the middle of the eye when extended. The rather
delicate tail is about 25% longer than the length of the head and
body taken together.

Recently it has been found that a guinea pig set free in a house
suspected of having plague fleas becomes infected if such fleas are
present. The fleas would probably prefer the guinea pig to man and
such a measure would in some degree be protective to man. It is
however for the detection of plague infection that the measure is
employed and the guinea pig is termed the “Plague barometer.” In
Madras there is practically an absence of _Mus norvegicus_ although
_Mus rattus_ is present in numbers and the comparative freedom of
the city from plague is striking.

The principal rat flea of the Orient is _Xenopsylla cheopis_. This
flea is without combs like _Pulex irritans_, the human flea, but
is of a lighter color and has an ocular bristle near the upper
margin of eye and two bristles posterior to the antennae. In Europe
and the United States _Ceratophyllus fasciatus_ is the common rat
flea. Many other species of fleas transmit plague and it is also
possible that the bedbug may play a part in spreading infections
from man to man. Vergbitski has transmitted plague from man to the
rat by infected bedbugs. In Siberia, a marmot, the tarabagan, is
supposed to play the part of the rat in plague transmission. In
California, the ground squirrel, _Citellus beecheyi_, has become
infected and may transmit the disease by its flea, _Ceratophyllus
acutus_. In the Tropics plague tends to prevail only at times when
the temperature is between 10° and 30°C. It is the effect on the
flea of cold weather which causes the disappearance of bubonic
plague at such times. The bacillus of plague can withstand freezing
temperatures. Sunlight and drying are the especially inimical
factors for _B. pestis_. Dry seasons are inimical to the spread of
plague and it is especially in very rainy seasons that epidemics
rage.

_Chronic Plague in Rats._—The Indian investigators have called attention to the existence of a chronic plague in rats. In this we have chronic buboes, areas of necrosis in spleen and abscesses of the spleen. It is chiefly in the spleen that the lesions occur, thus differing from the acute plague in rats above described. Of 27,699 _M. norvegicus_, examined in Bombay, O.57% showed signs of chronic plague.

In the necrotic material plague bacilli can be found in
approximately one-half of these rats although frequently the
bacilli are nonvirulent. It is possible that this chronic plague
in rats may serve as the reservoir of infection which keeps up
plague epizootics from year to year. Plague in India, according to
White is less virulent now than formerly and this is attributed to
a greater immunity of the rats.

_As regards pneumonic plague_ the origin of such epidemics is probably from pneumonia occurring secondarily in cases of bubonic plague. Provided the conditions are favorable, particularly as to moisture in the air of the room, the infection spreads directly from man to man as a result of the droplets of heavily infected sputum being sprayed into the air in the act of coughing on the part of the patient. It is an instance of _Flügge’s droplet method of infection_.

In the recent epidemic of pneumonic plague in North China, it was
at first thought that the hunting of the tarabagan for its valuable
skin, which led some of the Chinese to even capture tarabagans,
possibly sick with plague, was the origin of the epidemic. This
view is no longer held and we now know that the outbreak was
independent of any disease in rats, tarabagans or other animals.
Strong has shown that the bacillus which was isolated from these
cases of pneumonic plague was identical with that isolated from
cases of bubonic plague; its virulence was no greater and animals
infected cutaneously or subcutaneously died of bubonic plague.
Experiments by Teague and Barber, with emulsions of plague bacilli,
showed that with a room temperature of 32°C. plague bacilli were
quickly destroyed when the air was comparatively dry. In such an
atmosphere, saturated with moisture, the viability would be greatly
prolonged. In the plague wards in Manchuria the extreme cold which
prevailed, together with the saturation of the atmosphere of the
unventilated rooms by the moisture of the breath of the patients,
made conditions most favorable for the viability of the plague
bacillus. They note that in the plains of India, although about 3%
of bubonic cases assume a pneumonic type, yet epidemics of plague
pneumonia do not occur; this is probably due to the fact that
the higher temperatures and open rooms make evaporation occur 30
times more rapidly there than was the case in the plague wards in
the bitter cold weather of the Manchurian winter. The possibility
of carriers of plague bacilli in those who might go on to
convalescence need not be considered, as practically all cases of
plague pneumonia die. Other material from the patient than sputum
does not seem to be a source of danger in the spread of plague,
so that there is no need for the disinfection of urine and feces.
There has recently been an outbreak of septicaemic plague in Ceylon
in which there was an absence of plague in the rats. The infection
was possibly transferred directly through bedbugs or human fleas.
As a matter of experience the transference of plague from place to
place generally occurs from infected rats or infected fleas which
have been transported by ships. A case of bubonic plague in a ward
with other patients would not be a source of danger provided there
was freedom from fleas and a lack of development of secondary
pneumonias. It is very doubtful as to infection ever taking place
by way of the alimentary canal, although there is some evidence
that rarely the tonsil may be primarily involved. Monkeys are very
susceptible to plague and the possibility of an epizootic among
them should be thought of during plague epidemics.

PATHOLOGY

It is rare that one finds the primary vesicle marking the site of entrance of the plague material. Thus in 13 cases where plague was contracted by direct cutaneous inoculation of those performing autopsies on plague victims only two showed evidences of local reaction as shown by the formation of a primary vesicle.

The chief points noted in a plague autopsy are: (1) The marked
involvement of the lymphatic system as shown by intense congestion
and haemorrhagic oedema of the lymphatic glands. Not only are
the glands tributary to the site of inoculation involved, thus
forming the primary bubo, but there is secondarily more or less
inflammatory change in all the lymphatic glands of the body.
There is also a marked periglandular oedema, with haemorrhagic
extravasations of the connective tissue surrounding the primary
bubo, this mass being made up of a group of glands matted together
by this periglandular exudate.

(2) The destructive effect of a toxic product of the plague
bacillus, which may be designated an endotheliolysin, upon the
endothelial cell lining of blood vessels as well as lymphatic ones.
This causes the extensive blood extravasations so characteristic of
plague as shown by petechial spots, not only of the skin but of the
serous and mucous membranes as well.

There is a general congestion of all organs of the body.

The meninges of the brain are deeply congested and there may be
haemorrhagic extravasations in the brain substance itself. Crowell
has reported two cases of plague meningitis in which plague bacilli
were found in the ventricular pus. The spleen is generally markedly
congested and enlarged to 2 or 3 times its normal size.

There may be haemorrhagic extravasations throughout the spleen
pulp. The bacilli are chiefly scattered throughout the venous
sinuses.

There is also active congestion of the liver. The kidneys are
intensely congested and we often find fibrin thrombi in the tufts
of the Malpighian bodies.

The plague toxin has a marked effect on the cardiac muscle so that we usually find dilatation of the right side of the heart with fatty degeneration of the muscle fibers.

In a study of the pathology of primary pneumonic plague Strong
noted pericardial and pleural ecchymoses with fibrinous pleurisy
over the affected lung areas.

The process was at first lobular but later involved the entire lobe.

There was marked congestion of the bronchial mucosa with
involvement of the bronchial glands. The larynx and trachea are
also intensely congested. Microscopically there is a distension of
the alveoli and bronchial passages with a haemorrhagic exudate.
There is practically no fibrin in the alveolar exudate. The process
seems to extend by continuity along the bronchi and bronchioles.

Plague bacilli pack the exudate found in the bronchi and
bronchioles.

In a report on the autopsy findings of septicaemic plague in Ceylon
in cases where plague bacilli were demonstrated in smears and
cultures from spleen and blood, Castellani noted that other than
meningeal congestion and some splenic enlargement there was nothing
abnormal.

SYMPTOMATOLOGY

In a clinical study of plague it is customary to consider the disease as manifesting itself in a mild form (Pestis minor) and a severe form (Pestis major).

=Pestis Minor.=—Pestis minor, which is sometimes termed pestis ambulans, is that form of plague in which there is only slight fever and comparatively little physical prostration or mental hebetude. These cases usually show moderate enlargement and tenderness of some group of lymphatic glands. It is in this mild form of plague that we are most apt to find the primary vesicle or phlyctenule at the site of the flea bite.

Ordinarily, man is so susceptible to plague that there is no
reaction at the site of inoculation but in these mild cases there
is an inflammatory reaction resulting in a vesicle or pustule,
which may teem with plague bacilli. In such cases it is extremely
important to search for such primary vesicles and examine for
plague bacilli. It is usually stated that only about 5% of cases of
bubonic plague show these vesicles.

=Pestis Major.=—Pestis major can certainly be divided clinically and epidemiologically into two types, pestis bubonica, or bubonic plague, which is the common type of plague, and pestis pneumonica, or pneumonic plague, the contagiousness of which is extreme and the mortality practically 100%.

Both of these types of plague tend finally to show an invasion
of the blood stream with plague bacilli, the case then becoming
one of septicaemic plague. Many authors, however, recognize an
overwhelming plague septicaemia in which the manifestations of
buboes or pneumonia are absent and such cases are designated
septicaemic plague, or _pestis siderans_.

In all forms of pestis major there stand out the characteristics of rather sudden onset, rigors or chilly sensations, rapidly rising but irregular fever, marked giddiness, great prostration, the mental state and speech of an intoxicated person and extreme weakness of the heart with a rapid weak pulse.

Typhus fever alone shows an equal degree of early mental hebetude,
so that it is stated that Clot Bey, who had seen much plague
in Egypt, when elsewhere shown cases of typhus with parotid
involvement, remarked “In Egypt one would call such cases plague.”

=A Typical Case of Bubonic Plague.=—After a period of incubation of from three to seven days the disease may set in quite abruptly, or after a prodromal stage, in which malaise, giddiness, mental hebetude and pains in the back and limbs may be present. With the onset of the attack the effects of the toxaemia upon the nervous system are the most striking. The patient has a pale, drawn, anxious countenance, with injection of the conjunctivae toward the inner canthus.

The speech is thick and difficult, the gait is staggering, so that,
with the stupid mental state and tendency to wander aimlessly
about, one has the symptom-complex of an alcoholic intoxication. In
some cases a delirious tendency may be marked, especially as the
disease develops. After a few hours, or within a day, the fever
begins to rise rapidly and is often associated with shivering
attacks. The face now becomes hot and flushed, the conjunctivae
markedly injected, the pupils dilated, and the eyes rather staring.
The temperature is as a rule from 102° to 104°F., occasionally
higher, with a tendency to rather marked remissions and, on the
whole, of great irregularity of the fever curve. The pulse is rapid
and shows early indications of the extreme toxic effect exercised
upon the heart. Cardiac weakness is a marked feature of plague.

The urinary secretion is diminished but there is rarely more than a
slight amount of albumin.

_The Pathognomonic Bubo._—About the second or third day the
development of an extremely painful bubo practically gives the
diagnosis.

About 70% of these buboes are of the inguinal region, the femoral glands being more frequently invaded than those above Poupart’s ligament. The axillary glands are involved in about 20% and the submaxillary and cervical ones in from 5 to 10% of cases.

There is a question whether the tonsil ever serves as the site of
infection from which cervical buboes result. It would seem that
the greater frequency of inguinal buboes is because a greater area
of skin drains into these glands. There may be multiple buboes
and it must not be forgotten that the lymphatic glands of any
region may become enlarged. There may also be lymphangitis. Only
one gland of a group may be involved or the whole group may show
enlargement. Very characteristic for plague buboes is the oedema
of the periglandular tissues, which is largely responsible for the
great size of some of these buboes; they may vary from the size of
an almond or walnut to that of a child’s head. The patient tends to
assume an attitude to relieve any tension on the very painful bubo.
Particularly over these buboes, but at times elsewhere, the skin
may show areas of inflammation, often several inches in diameter.
Necrosis of this area occurs and a slough separates. These lesions
are often termed carbuncles but are really not such, but only
gangrenous patches of skin.

When these areas of cutaneous necrosis are a marked feature the designation of _cellulo-cutaneous plague_ is at times given.

Petechiae or large purpuric spots may be conspicuous in some
epidemics and it was from these “tokens,” as they were called, that
plague received the designation “black death.”

As the case progresses, the anxious countenance gives way to one of apathy, the control of speech and cerebration become more and more impaired and the patient may go into a typhoid state.

Cases with buboes in the axillae give the gravest prognosis, as
for example, 80% mortality for axillary, and 70% for inguinal.
The buboes may suppurate towards the end of a week or they may
undergo a slow resolution. Secondary broncho-pneumonia may develop
in the course of bubonic plague. Pulmonary congestion is however
not infrequent and may cause dyspnoea, accelerated respiration and
cough. Owing to the tendency to degeneration of the endothelial
lining of capillaries, various haemorrhagic manifestations, other
than those of the skin, may be observed, such as epistaxis,
haematuria, etc. There is usually a rather marked leucocytosis in
which the increase is chiefly of the polymorphonuclears.

=A Typical Case of Pneumonic Plague.=—Besides those cases where pulmonary involvement sets in during the course of an attack of bubonic plague and which are classified as secondary plague pneumonias we have sporadic cases and epidemics when the clinical course of the disease is predominantly and primarily pulmonary.

Although the characteristics of pulmonary involvement, with
expectoration of blood, were noted by many observers of the
14th century and later as manifestations of plague, yet in the
present pandemic, which started in 1894, such cases were at first
overlooked as being plague. The recognition of a primary pneumonic
plague was made by Childe in 1897. The onset is sudden, with a
rise of temperature to 103°F., or higher, during the first day.
The marked physical exhaustion and clouding of the consciousness,
characteristic of any type of pestis major, are intensified in
pneumonic plague. In fact the occurrence of manifestations of such
profound toxaemia in the presence of only slight physical signs,
should make one suspicious. Crepitation over small areas, without
demonstrable dulness on percussion, may be the only sign. There is
often early dyspnoea and rapid shallow respiration. Cough, with the
expectoration of rather abundant watery sputum, which soon becomes
blood-stained or absolutely sanguineous, may be present by the
second day.

There is never the rusty, tenacious sputum of lobar pneumonia. Herpes never appears, according to Childe. Heart failure is a very prominent feature of plague pneumonia.

It is fortunate that this watery sputum teems with bacilli early
in the disease as smears from such sputum give an early and sure
diagnosis of this terribly contagious and fatal malady. The
knowledge that this infection is transmitted from man to man by
the droplets of sputum expelled in coughing demands the protection
by some form of mask of anyone coming near such a patient. Some
observers noted splenic enlargement and tenderness over the
superficial lymphatic glands. Strong has noted that the course of
the disease rarely extends beyond the fourth day and that death is
the invariable termination.

In 1919 thirteen cases of plague pneumonia occurred in California
starting from an at first unrecognized case of bubonic plague of
squirrel origin. These pneumonias were diagnosed as influenza
pneumonias but later the true diagnosis was determined. McCoy notes
in this connection that there is a strong tendency to pulmonary
localization of plague in the squirrel which is not true of the rat.

=Septicaemic Plague.=—As regards the clinical manifestations of septicaemic plague, if such be considered as a separate type, Choksy states that there is no clinical sign by which such a septicaemia can be recognized without the help of the laboratory, although the presence of a thready or imperceptible pulse, in one showing the characteristic toxaemia of plague, should cause suspicion.

The patient may be so overwhelmed from the start that there may be
only a slight rise of temperature. Occasionally, plague bacilli may
be recognized in blood smears, a finding that practically never
obtains in any other bacterial disease. At the same time blood
cultures are solely to be depended upon in diagnosis and even such
examinations may be negative. Liston has noted that plague patients
always die if more than 40 bacilli per cc. are present in the
blood. In a recent outbreak of septicaemic plague in Ceylon the
only clinical manifestations were intense headache, and fever. The
patients died within forty-eight hours. Until properly diagnosed
bacteriologically the disease was thought to be pernicious malaria.

The Symptoms in Detail

_General Appearance._—The face is at first drawn and pallid, the
eyes injected and the expression one of fear or anxiety. As the
temperature rises the pallor is succeeded by a flushed and dry hot
skin. Later on in the disease the expression is more one of apathy.
The staggering gait and the tendency to wander give the impression
of alcoholic intoxication.

_Temperature Curve._—The fever course of plague is very irregular.
The temperature usually rises rapidly to 103° to 104°F., but tends
to exhibit marked remissions by the third day. After a fall, it may
rise to a very high degree just before death. Cases which recover
often show a fall by lysis.

_Nervous System._—Very characteristic for plague is the intense
and early disturbance of the mental condition. The patient presents
the characteristics of alcoholic intoxication, thick speech, lack
of mental concentration and giddiness which causes a staggering
gait. Later on an apathetic or stuporous stage may ensue or there
may be delirium.

Rarely a case of bubonic plague may show marked involvement of the
meninges, giving the clinical picture of meningitis.

_Circulatory System._—The pulse is at first soft, dicrotic and
rapid, 110 to 120 beats per minute. Later on, as the heart begins
to show the toxic effects of the disease, the pulse becomes thready
and irregular, to be followed by cardiac failure. There is a
marked tendency to congestion of various internal organs and to
haemorrhages from the capillaries.

_Respiratory System._—Pulmonary congestion and even
broncho-pneumonia may supervene in bubonic plague. In pneumonic
plague, however, the lungs seem to be the primary seat of the
bacterial development. Plague pneumonia is characterized by intense
toxaemia and few physical signs. The abundant, watery sanguineous
sputum is loaded with plague bacilli. Dyspnoea and cyanosis appear
early.

_The Lymphatic System._—It is the presence of the plague bubo
which differentiates bubonic plague. There is no relation between
the size of the bubo and the severity of the attack. Axillary
buboes are the most fatal. A characteristic of these buboes is
their extreme tenderness, the pain causing the patient to draw up
the legs or assume any attitude which will relieve tension upon the
bubo. The size is mainly due to the periglandular infiltration or
oedema, which causes the glands of a group to be matted together.

The elevation of a plague bubo is rather diffuse, not pointed as
with venereal buboes. Femoro-inguinal buboes are about 6 times as
frequent as cervico-maxillary ones. There may be lymphangitis as
well as lymphadenitis.

_Cutaneous System._—The skin over the buboes often tends to become
necrotic and slough off. This however may occur elsewhere and
such lesions are termed “carbuncles.” Capillary haemorrhages of
the skin may cause petechiae and when the area is large they have
been designated “tokens.” In about 5% of cases there is a small
vesicle or pustule at the site of the flea bite as an indication of
reaction. The contents teem with plague bacilli. It is often termed
the primary lesion.

_The Liver, Spleen and Alimentary Tract._—The spleen may show
enlargement and tenderness on deep pressure, as may also the liver,
these organs being markedly congested. The tongue at first is
coated, with clean tip and sides. Nausea and vomiting frequently
occur and, as a rule, there is constipation. Haemorrhages from the
bowel may occur.

DIAGNOSIS

=Clinical Diagnosis.=—It is well to remember that we have a sure and simple means of diagnosis by bacteriological means so that in the first cases during an epidemic we should rest the determination of the case as one of plague solely upon such methods.

One should be suspicious of any case of fever of rapid onset
in which there is marked dulling of intellect and impairment
of speech, as of one intoxicated, together with evidences of
rapidly developing heart weakness. In septicaemic plague we
practically have no other symptoms to guide us—there is not the
exquisitely tender bubo of bubonic plague nor the abundant, watery,
sanguinolent sputum of pneumonic plague.

Typhus fever probably more nearly resembles plague at its onset than any other disease. There is marked clouding of the consciousness and intense prostration as with plague and the eruption does not appear before about the fourth day.

An influenza pneumonia may show the general prostration and cardiac
weakness of plague. In influenza pneumonia we have an onset
with the features of ordinary influenza, which, however, in the
influenza epidemic in 1918 was often short. In plague pneumonia
we have pneumonia from the start. The pulse in plague is early
weak and rapid and the tendency to a stuporous state more marked.
The early appearance of thin watery sputum, which quickly becomes
blood-tinged and always contains plague bacilli is noted in plague
pneumonia. Only a few hours elapse before we have bloody sputum
which in influenza is a later and not constant sign. The dyspnoea
is earlier and much more pronounced in the pneumonic plague. At
autopsy Crowell notes the almost invariable presence of pleural
exudates in plague while an acute vesicular emphysema is a feature
of influenza pneumonia.

Malaria and septicaemic conditions may be confused with septicaemic
plague. The sudden onset and prostration of relapsing fever may
make one think of plague.

Many have thought climatic bubo a form of ambulant plague but the
gradual onset, only slight tenderness of the swollen glands and
slight prostration should differentiate. Venereal bubo cases are
apt to be regarded with suspicion during epidemics.

Markedly toxic cases of typhoid fever with an exceptionally rapid
onset may give rise to confusion.

=Laboratory Diagnosis.=—If the patient has a bubo we should introduce a hypodermic syringe needle into the swollen, oedematous glandular mass in order to obtain some of the gland juice. Smear a drop of this on a slide, stain with Loeffler’s blue or dilute carbol fuchsin and examine for bipolarly stained oval bacilli. When the bubo begins to soften we may not obtain plague bacilli.

Probably the best stain for plague bacilli is that recommended by Archibald. There are two solutions, one made by dissolving 0.5 gram of thionin and 2.5 grams phenol crystals in a 1% aqueous solution of formalin; the other solution is made by dissolving 0.5 gram methylene blue and 2.5 grams phenol crystals in a 1% formalin solution. Let these stock solutions stand 24 hours before using and then mix equal parts of each solution; filter, and stain smear for 10 seconds. Wash and dry.

In a case of suspected pneumonic plague we stain the smear of
watery or thin blood-tinged sputum as above.

The same procedure may be followed with a rather heavy blood smear of a drop of the 5 or 10 cc. taken from a vein for culturing in a case suspected of septicaemic plague.

Plague is practically the only bacterial disease where there
is likelihood of finding the causative organism in smears. In
septicaemic plague the blood culture is the proper procedure and
one should take 5 to 15 cc. of blood in 15 to 25 cc. of normal
saline containing 1% of sodium citrate. This prevents coagulation
and at one’s leisure 1 or 2 cc. can be added to tubes of melted
agar and plates poured or other portions added to bouillon or 3%
salt agar. This same blood emulsion can be used to infect guinea
pigs subcutaneously or to infect them cutaneously by rubbing on the
shaven surface.

In smears from material from buboes, from sputum, or in blood
smears, as well as from blood or spleen smears from experimental
animals, we obtain the typical morphology of a cocco-bacillus (1.5
× 0.5 microns) with very characteristic bipolar staining, there
being an intermediate, unstained area. Very characteristic also
is the appearance in these smears of degenerate types which stain
feebly and show coccoid and inflated oval types. The presence
of these involution forms associated with typical bacilli is
almost diagnostic for one with experience. Inoculating tubes of
plain agar and 3% salt agar with this same material, we obtain
in plain agar cultures organisms which are, typically, small,
fairly slender rods, which do not stain characteristically at
each end and are not oval. The smear obtained from the salt agar
presents most remarkable involution forms—coccoid, root-shaped,
sausage-shaped forms, ranging from three to twelve microns in
length, more resembling cultures of moulds than bacteria. Another
point is that on the inoculated plain agar we are in doubt at the
end of twenty-four hours whether the dew-drop colonies are really
bacterial colonies or only condensation particles. By the second
day, however, these colonies have an opaque grayish appearance,
so that now, instead of questioning the presence of a culture, we
consider the possibility of contamination.

Blood cultures in septicaemic plague may show from 5 to 500,000 bacilli per cc. Smears from the blood in such cases are positive in only about 17%.

The plague bacillus grows well at room temperature—its optimum
temperature being 30° instead of 37°C., as is usual with pathogens.
Next to the salt agar culture, the most characteristic one is
the stalactite growth in bouillon containing oil drops on its
surface. The culture grows downward from the under surface of the
oil drops as a powdery thread. These are very fragile, and as the
slightest jar breaks them, it is difficult to obtain this cultural
characteristic.

Albrecht and Ghon have shown that by smearing material upon the intact, shaven skin of a guinea pig, infection occurs. This is the crucial test. Smear the material on a shaven surface about 1 inch square.

A pocket made by cutting the skin of a guinea pig with scissors
and extended subcutaneously with scissors or forceps, into which
a piece of the suspected plague tissue is thrust with forceps, is
more practical than injecting an emulsion with hypodermic syringe.

Mice inoculated at the root of the tail succumb quickly. Rats, this
being primarily a disease of rats, are of course susceptible.

When a guinea pig is inoculated with plague material the animal
should be placed in a galvanized iron garbage can or other similar
container and the opening covered with cheese cloth to prevent the
fleas or other vermin which it might harbor from escaping. Again a
6-inch band of tanglefoot fly paper should be attached around the
interior of the upper part of the can to further prevent escape of
fleas. It must be remembered that every precaution must be taken
in the laboratory to prevent the escape of plague-infected fleas.
The guinea pig usually dies in from two to five days and shows
glandular enlargements, and marked congestion of viscera with a
swollen spleen, smears from which may show a profusion of plague
bacilli.

The subcutaneous tissues about the site of inoculation show a haemorrhagic oedema.

If guinea pigs are not available one may use white mice which die
within forty-eight hours or white rats which live about as long as
guinea pigs.

One of the most important points in fighting plague is the
detection of plague in the rats and, from noting the locality in
which such plague-infected rats were caught, to direct our rat
destruction efforts to that particular section of the city. These
dead rats should be dropped into a bichloride solution or petroleum
preparation in order to destroy the rat fleas. In the laboratory
they are dissected and plague-infected ones most easily recognized
by the marked subcutaneous injection of the widely reflected
skin flap. Oedematous or haemorrhagic glandular swellings are
characteristic. The liver shows a yellowish appearance, and as
if sprinkled with small whitish dots and the spleen is swollen
and congested. There may be effusion into the pleural cavities.
Material from the swollen glands or spleen should be stained,
cultured and inoculated into animals as for a human case.

If glandular, splenic or other material from human or rat autopsies has to be sent to a distant laboratory the specimen should be placed in a strong salt mouth bottle containing 20% glycerine in water with 2% calcium carbonate.

Agglutination is not very practical owing to the frequent absence
of agglutinins from the serum of plague patients. Then, too, there
is a marked tendency to spontaneous agglutination on the part of
the plague bacilli. Strong states that culturing at 37°C. lessens
this tendency to spontaneous agglutination. Again, even when
present, the titre of plague-agglutinating sera is usually quite
low so that one must work with dilutions of from 1 to 10 or 1 to 20.

PROGNOSIS

Pneumonic and septicaemic plague give an almost absolutely unfavorable prognosis, many stating that every such case dies.

As regards bubonic plague the mortality averages 75%. The Egyptian
epidemic of 1900 gave an average mortality of 50%. The mortality
in natives is much higher than that among Europeans, these latter
often showing death rates under 25% while in the same epidemic
natives show from 75% to 95% mortality. Plague pneumonia, however,
is absolutely fatal for Europeans as well as natives.

PROPHYLAXIS AND TREATMENT

=Prophylaxis.=—In pneumonic plague it is the human patient and not the rat which has to be considered. The infection is spread by means of droplets of plague bacilli-laden sputum which are sprayed from the mouth of the patient in the act of coughing. As a result any person entering a ward containing plague pneumonia cases is extremely liable to contract the pneumonic form of plague.

The attendants are protected by bag-like masks or successive layers
of gauze and cotton wool applied as bandages over face and neck.
Motoring goggles make a good protection for the eyes and small
rolls of cotton should be placed along the sides of the nose to
absolutely prevent the possibility of bacilli being drawn down to
the entrance of nose or mouth. These masks should not have any weak
spot in their armor.

_Spread of plague pneumonia_.—It has been noted that when
secondary pneumonia develops in the course of bubonic plague in
India, the Philippines, or other hot countries, it is not followed
by primary plague pneumonia outbreaks. This is thought to be due to
the fact that the windows are wide open and the relative humidity
low, conditions which are the opposite of those which existed
in Manchuria where the intense cold made the closing of windows
necessary and where the air of rooms or wards was saturated with
the moisture from the occupants. As the main consideration for the
spread of pneumonic plague seems to be high relative humidity it
would seem that hospital wards could be constructed so that the air
supplied by artificial ventilation would be very dry.

The recent outbreak of septicaemic plague in Ceylon at a time when there was no plague noted in rats would indicate that other transmitting agents than infected rat fleas were operative. The most probable transmitting insects to be suspected would be the bedbug and human flea.

_Spread of bubonic plague_.—With bubonic plague, unless it should
in its course become pneumonic or septicaemic, there is almost
solely the question of the rat and its fleas. Many authorities
consider that pure bubonic plague can be treated safely in a
general ward of a hospital provided there is sure freedom from
bedbugs or other verminous insects.

The various species of fleas which the rat may harbor may be
attacked by the use of various petroleum preparations containing
naphthalene. One preparation known as pesterine, which consists of
kerosene 20 parts, soft soap 1 part and water 5 parts, the soap
being dissolved in the water and the oil being gradually stirred
into the hot mixture, is often recommended as a flea insecticide. A
5% solution of compound cresol to which naphthalene has been added
is also of value.

It is always well to combine flea destruction with rat extermination because, as rats are reduced in numbers, there are fewer hosts, so that man is more liable to infection with fleas deprived of a sufficient number of rat hosts.

This may explain why a high death rate among rats, as the result of
a plague epizootic, may act as a factor in the outbreak of human
plague.

_Rat destruction_.—As a matter of fact, however, it is best to attack the problem from the side of rat extermination which, it must be understood, is most difficult owing to the highly developed suspicious nature of the rat. A successful rat catcher or rat exterminator must have the mind of a detective.

The first measure in rat extermination is the regulation of the
disposal of garbage. It is most important that only cans with
securely fitting tops be used so that rats cannot secure any food
from the contents of the can. Again no particle of food should be
left accessible to the rat. Unless the ordinary food supply of the
rat is denied him he will not eat poisoned bait or bait in traps.
Again rats are not only carnivorous but will eat any kind of cereal
or vegetable, in fact they will eat almost anything and in addition
are cannibals. In a plague outbreak especial attention should be
directed to flooring in stables, under surfaces of board walks,
sealed-in attics of houses, wharves and sewers. Where sewers have
catch-basins at street openings the rat has a means of egress from
the sewer. These sedimenting catch-basins also serve as a breeding
place for mosquitoes. It has been estimated that a sewer rat can
jump 2 feet but not 3 feet.

In rat-proofing houses, double walls should be eliminated and
houses raised well from the ground—at least 18 inches. In
plugging up rat holes with concrete we should add broken glass to
the concrete. Sheets of galvanized iron driven down several feet
have been used as a protecting barrier around grain elevators or
warehouses. Concrete is the proper material to use in rat proofing.

Where rats are on board ship fumigations with sulphur dioxide, carbon monoxide or funnel gases are usually employed.

Hydrocyanic acid gas is a most efficient destroyer of rat and flea
life. The great objection to its use is its danger to those using
it in fumigation. Liston allows this gas, developed from ½ ounce
KCN, to act for four hours in a space of 100 cubic feet. The great
danger from the use of this gas in holds of ships is that it tends
to collect in detached spaces or pockets and remains following
ventilation of the hold so that persons entering such spaces
suffer the poisonous effects of the gas. Some cargo ships have a
rat-run built to extend fore and aft and leading to a receptacle
in which the rats are caught. Rats naturally choose a tube or
similar opening so they get into this little passageway which is so
constructed that their return is obstructed. This scheme is used
in setting traps, either covering the traps with hay and leaving
a small opening or placing the trap under an inclined plank or
placing it at the end of an iron or terracotta pipe. There is not
much danger of rats getting aboard a ship lying out from the dock.
It is when a ship goes alongside a dock that we can expect rats to
come aboard.

Phosphorus paste made up with a glucose base and containing about
4% of phosphorus is spread on pieces of stale bread, 1 inch square
and ¾ inch thick. Whatever poison is used, whether strychnine,
arsenic or phosphorus, it should be placed in boxes which have
openings large enough to let the rats in but too small for
domesticated animals. Barium carbonate is a useful rat poison.

Cats will very rarely attack the fierce sewer rat.

_Danysz virus._—Many workers, during plague outbreaks, have tried
to exterminate rats by impregnating bread or other bait with
bacterial cultures. The best known of these viruses, as they are
called, is that of Danysz. The organism is closely related to _B.
enteriditis_ of Gaertner and is supposed to bring about a fatal
infection in the rats. As a matter of fact the cultures quickly
cease to be virulent and their use has been generally abandoned.
Simpson, however, thinks well of this measure and employed it with
success in South Africa. He kept up the virulence of his cultures
by frequent passage through animals.

In rat extermination it is advisable to employ Heiser’s Manila plan. In this, the location in the city of the plague rats brought into the laboratory is noted and radiating lines made from such foci. Plague-infected rats are rarely found more than a few squares from the focus. The periphery of the infected area is then considered as an outer zone for the fight and the house-to-house extermination is carried on toward the center of the area. If, on the other hand, one should start at the center and work peripherally the infected rats might be spread all over the city.

_Prophylaxis by Immunization._—The best-known bacterial prophylactic is that of Haffkine. Stalactite bouillon cultures are grown in flasks for five to six weeks. The organisms are then killed by heat at 65°C. for one hour. Phenol (½%) is then added and from 0.5 to 4 cc. injected according to the age and size of the individual. Ten days later a still larger amount is injected. The reaction following these injections is apt to be quite severe.

Recent reports show that of 118,148 inoculated persons the plague
incidence was approximately 8 per 1000 while among 321,621
noninoculated the incidence was 34 per 1000.

Statistics from Sagaing show 19 cases with 7 deaths among 4284
inoculated persons while there were 134 cases and 128 deaths among
4467 not inoculated.

The plague mortality in cases which had previously been inoculated
was 40% while that among the noninoculated was 78%.

From the above it will be seen that incidence is reduced to about one-fourth and mortality about one-half as the result of the use of Haffkine’s prophylactic.

Besides this killed culture other material has been used. Lustig
and Galleotti used the nucleo-proteid from plague bacilli for
subcutaneous injection. Kolle and Strong have recommended a vaccine
of living but nonvirulent plague bacilli. A higher degree of
immunity seems to be conferred by this living vaccine but there are
certain dangers in the use of living organisms which outweigh the
advantage noted above.

Yersin’s antiplague serum, which is prepared by injecting horses at
first with killed cultures and later with living plague bacilli,
may be used as a prophylactic as well as in treatment. One point
to consider is that such serum, if used immediately after taking
from the horse, might contain living plague bacilli. The phenol
preservative prevents this. It must be remembered that this is a
passive immunization as against the active one with Haffkine’s
prophylactic, hence the protection is very short, only ten days
or two weeks as against the more enduring immunity of a year or
so following Haffkine’s prophylactic. It must be remembered that
anaphylactic manifestations may follow the repeating of the dose
of Yersin’s serum. It is probably advisable for one who is to be
exposed to plague for a short time only to receive an injection of
the serum. As regards pneumonic plague there seemed to be little
protection attaching to either active or passive immunization.

=Treatment.=—It may be stated that the only treatment which has any curative value is that with antiplague serum. This would appear to be of considerable value in bubonic plague provided it is administered in the first day or two of the disease. It must be given in large amounts, from 50 to 100 cc. or even to the extent of 250 cc. Then too such enormous doses apparently require to be repeated. Intravenous administration gives a better chance for success in desperate cases. In septicaemic and pneumonic plague the use of serum has been without result.

Salvarsan, as might be expected, has been tried but did not prove
of any value.

Connor has reported success with the intravenous injection of one
dram of a dilution of 1 part of tincture of iodine in 10 parts of
sterile water. He gave 6 such injections to a severe case with good
result.

In the way of symptomatic treatment one should use ice-bags to head
and cold sponging to the body.

Morphine seems to be the best drug to calm the patient. Cardiac
stimulants, especially strychnine, are indicated for the heart
weakness so much a feature of plague. Some consider incision or
enucleation of the bubo of value in treatment but it has always
seemed to me that the going into the periglandular exudate might
serve to set up a septicaemic condition when otherwise it might not
supervene.