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.

[Illustration: FIG. 63.—Pest bacilli from spleen of rat. (Kolle and Wassermann.)]

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.

[Illustration: FIG. 64.—Plague bacillus involution forms produced by growing on 3% salt agar. (Kolle and Wasserman.)]

=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.

[Illustration: FIG. 65.—1 and 2, male and female _Xenopsylla cheopis_. 3, Head of _Ceratophyllus_. 4 and 5, male and egg-distended female of _Sarcopsylla penetrans_.

_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.

[Illustration: FIG. 66.—1, _Ctenocephalus felis_. 2, _Ceratophyllus fasciatus_. 3, _Hoplopsyllus anomalus_. 4, _Ctenopsylla musculi_. 5, _Xenopsylla cheopis_. 6, _Pulex irritans_. 7, Internal anatomy of flea. (After Fox.) (_a_) Maxillary palpus; (_a_-1) epipharynx; (_a_-2) mandible; (_a_-3) labial palpi; (_a_-4) maxillae; (_a_-5) basal elements of rostrum and mandibles; (_b_) salivary pump; (_c_) hypopharynx; (_d_) aspiratory pharynx; (_e_) muscles of the aspiratory pharynx; (_f_) eye; (_g_) oesophageal ganglia (brain); (_h_) thoracic ganglia; (_i_) oesophagus; (_j_) salivary duct; (_k_) gizzard; (_l_) salivary gland; (_m_) stomach; (_n_) aorta; (_o_) ovaries; (_p_) malpighian tubules; (_q_) pygidium; (_r_) rectum showing rectal glands; (_s_) anus; (_t_) intestines; (_u_) bursa copulatrix; (_u_-1) ductus obturatorius (blind duct); (_v_) receptaculi seminis or spermatheca; (_w_) ducts of spermatheca; (_x_) vagina; (_y_) uterus; (_z_) abdominal ganglia.]

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.

[Illustration: FIG. 67.—A, Temperature chart of fatal case of bubonic plague. B, Chart of case of bubonic plague going on to recovery but with suppuration of plague bubo. C, Chart of fatal case of pneumonic plague.]

=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.

[Illustration: FIG. 68.—Axillary Bubo. (Reproduced from Simpson’s Treatise on Plague, 1905.) From Jackson’s Tropical Medicine.]

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.

[Illustration: FIG. 69.—Plague Carbuncle. (Reproduced from Simpson’s Treatise on Plague 1905.) From Jackson’s Tropical Medicine.]

_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.

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