_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.

CHAPTER XIV

TULARAEMIA

DEFINITION AND SYNONYMS

=Definition.=—This is a plague-like disease of various rodents,

transmissible to man, caused by an organism _Bacterium tularense_,

which is not closely allied to any other species. A number of human

cases have been reported from Utah, where the disease is prevalent

among the jack rabbits, and the transmission to man is through the

bite of a horsefly, _Chrysops discalis_, which has previously sucked

the blood of infected jack rabbits.

The site of the bite in man is usually marked by a punched-out

ulcer, which is associated with swelling and suppuration of the

glands draining the area. The general symptoms are sudden onset,

with rigors, followed by an irregular fever of three or four weeks’

duration and by a prolonged convalescence. Several cases have been

reported in the middle west due to handling infected rabbits. There

have been a number of infections in laboratory workers where the

local signs have been absent. In man death rarely results from the

disease.

=Synonyms.=—Deer-fly fever (in man). Plague-like disease (in

rodents).

HISTORY AND GEOGRAPHICAL DISTRIBUTION

=History.=—In 1911 McCoy and Chapin discovered the _B. tularense_

in a plague-like disease, first described by McCoy in the

California ground squirrel. They described the organism, succeeded

in cultivating it on special media, transmitted the infection to

various rodents by feeding, nasal inoculation and injection of

infected blood, and demonstrated the probable natural mode of

transmission by the squirrel flea.

In recent publications, Francis, Lake and Mayne, and Wayson have

recorded the transmission of the disease experimentally by the

house fly (_Musca domestica_), the horsefly (_Chrysops discalis_),

the stable fly (_Stomoxys calcitrans_), the rabbit louse, the mouse

louse and the bedbug, and have shown that the freshly recovered

organism can be grown on other than the special media previously

recommended.

=Geographical Distribution.=—The first case of infection occurring

in man was reported from Ohio by Wherry and Lamb in 1914. Since

then a number of cases have been reported by Francis among rural

residents of Utah and by Francis and Lake among laboratory workers

handling animals infected with _B. tularense_.

ETIOLOGY AND EPIDEMIOLOGY

=Etiology.=—_Bacterium tularense_ is a small nonmotile Gram-negative

cocco-bacillus, from 0.3 to 0.7µ long and gives the appearance in

stained preparations of being surrounded by capsular material. It is

very difficult to cultivate and until recently it has been grown only

on coagulated egg yolk as used by McCoy and Chapin.

[Illustration: FIG. 70.—_Chrysops discalis._ The transmitting agent

of tularaemia.]

Recently Francis has shown that the organism will grow scantily on

serum or blood agar. However, by adding a piece of fresh sterile

spleen to such media he has obtained a more satisfactory culture

medium, although for routine work the egg yolk medium is preferred.

The organism refuses to grow on ordinary media such as nutrient

broth or agar. Material from a culture, or pus from bubo, or an

emulsion of the spleen of an infected guinea pig, when rubbed into

the abraded skin of an experimental animal brings about infection,

in this respect showing a similarity to plague infection. Upon

autopsy of such an experimentally infected guinea pig we find

haemorrhagic oedema at the site of inoculation with caseation of

lymph glands and small necrotic foci in spleen and liver. Smears

from the spleen show the organism in varying numbers. In infected

rodents the organism is often found abundantly in the blood and in

man a bacteriaemia may occur.

=Epidemiology.=—The infection of ground squirrels with this

organism was noted by McCoy in his plague work in California.

Francis in studying the disease in man in Utah found infection of

the jack rabbits and ground squirrels of the region and showed that

the transmission of the disease could be carried out by a biting

fly (_Chrysops discalis_) and reported this fly as the common

transmitting agent of the human infection. He regarded the sick and

dying jack rabbits as the reservoir of virus. Tularaemia is chiefly a

disease of the rural population attacking those at work in the fields.

As a result of accidental laboratory infections it would seem that

almost 100% of those carrying on extensive animal experimentation

with this organism become infected.

The louse infesting jack rabbits _Haemodipsus ventricosus_, can

transmit the infection from rabbit to rabbit so that the infection

in the jack rabbits is probably kept up by this agency. Recent

experiments have shown that the infection in white mice can be

transferred by the bites of the mouse louse and also by bedbugs.

Again if the mice are fed on infected bedbugs transmission is found

to take place by such feeding experiments. The faeces of such

bedbugs prove infectious. Guinea pigs injected subcutaneously with

the urine of white mice suffering from the disease die acutely with

typical lesions of tularaemia.

Mice fed on the liver of a rabbit dying of the disease succumbed to

the infection within five days.

As noted under etiology the most important method of spread of the

disease to man is by the bite of an infected horsefly (_Chrysops

discalis_). From experimental studies it would seem that any biting

arthropod might prove a transmitting agent. In view of the fact that

the infected deer fly tends to lose its infectivity after about five

days Francis is of the opinion that the fly is only a mechanical

transmitter of the organism.

Wherry reported the infection as manifested by conjunctivitis with

glandular involvement and due to handling infected wild rabbits.

Lake and Francis have reported that of six investigators from

the Hygienic Laboratory working with this infection all have

contracted the disease. There were fortunately no fatalities. Such

an experience demonstrates the great infectivity of this virus and

must lead to the conclusion that the few cases so far reported of

the disease do not represent the importance of tularaemia in man.

With a knowledge of the existence of such an infection and with

satisfactory methods of laboratory diagnosis we shall probably

have other reports of the infection. We now know that the ground

squirrels of California and Utah, the jack rabbits of Utah and the

wild rabbits of the middle west furnish important reservoirs of

virus.

PATHOLOGY

In experimental animals we have lesions which cannot well be

differentiated from those of plague. There is not sufficient data for

a statement as to the pathology in man.

In experimental animals we have a definite bacteriaemia but in man

the organism has only in rare instances been obtained from the

blood.

SYMPTOMATOLOGY

It has been difficult to determine the period of incubation but in

one laboratory infection the disease set in seven days after the

patient began tularaemia work. There do not seem to be any prodromata.

[Illustration: FIG. 71.—Temperature chart of a case of laboratory

infection (tularaemia.)]

In Utah most of the cases showed local lesions at the site of the

fly-bite and subsequent swelling and suppuration of adjoining lymph

glands. The local lesions were generally observed about the head or

on parts of the body not covered by the clothing. There is a rather

sudden onset with chilliness or rigors, generally associated with

dizziness, prostration and malaise. Headache is usually present

and there may be complaints of pains in the back and limbs. The

temperature rises rapidly and when first taken during the rigors may

reach 103° or 104°F. An irregular fever course follows for two or

three weeks. There is practically no apathy, thus differentiating

the mental state of typhoid fever or the marked clouding of the

consciousness of plague. At times we may have rhinitis and epistaxis.

Physical examination is almost invariably negative. The spleen is

not palpable. The pulse is rather rapid and the blood pressure

uninfluenced.

The white and differential counts vary but little from normal.

The main feature of the disease, aside from local lesions when

these are present, is prostration and this continues marked during

the several weeks or months of convalescence.

It is a disabling illness rather than a dangerous one though a fatal

case is recorded.

In the six laboratory infections above referred to, there were no

local lesions except in the case of one man who had had previously

an attack of the disease. In the second attack, two years after the

first one, there was noted a papule on one finger with subsequent

involvement of the epitrochlear and axillary glands. A guinea pig

inoculated with blood taken from the papule became infected and

showed the typical lesions of tularaemia.

There was no fever or malaise in this second attack, thus showing

a degree of immunity. In cases showing conjunctival ulcerations

with glandular involvement Wherry and Lamb obtained cultures of _B.

tularense_ from inoculated animals.

DIAGNOSIS

There is very little in the clinical picture, other than the local

lesions, to indicate a diagnosis.

Material from ulcers or glands should be inoculated into guinea

pigs or white mice. The organism is almost invariably absent

from the blood of human cases so that blood cultures or animal

inoculation from such blood are almost always negative.

Complement fixation and agglutination tests are the methods of

diagnosis to be relied on. In the Hygienic Laboratory an antigen

is prepared by washing off the 72 hour growth from egg yolk

medium with small amounts of saline. The suspension is heated for

30 minutes at 56°C. and then preserved by the addition of O.3%

tricresol. Such an antigen is used for each type of test.

PROGNOSIS

This disease is but rarely followed by death. It is however a most

incapacitating disease by reason of the three or four months of

convalescence during which time the strength and energy of the

patient are markedly affected.

PROPHYLAXIS AND TREATMENT

=Prophylaxis.=—In view of the very great liability to infection

of those carrying on autopsies of animals experimentally infected

with the disease it would seem advisable to wear rubber gloves when

doing such work. It would appear that house flies, stable flies

and horseflies may transmit the disease in nature and we know that

bedbugs and lice can transmit the disease among experimental animals.

When we consider the natural infection of ground squirrels and jack

rabbits in California and Utah and wild rabbits in the middle west,

the problem of prophylaxis looms to great proportion.

=Treatment.=—At present treatment is entirely symptomatic. Those who

go to bed at once and remain in bed during the stage of fever seem to

be less seriously affected.

CHAPTER XV

CHOLERA

DEFINITION AND SYNONYMS

=Definition.=—Cholera is a disease caused by a spirillar type of

bacterium, _Spirillum cholerae asiaticae_. The organism multiplies in

the small intestines and, undergoing lysis, liberates an endotoxin,

which is responsible for the desquamation of the epithelium of the

mucosa and other manifestations of the disease. Cholera appears to

be endemic in the delta of the Ganges and the various world-wide

epidemics can generally be traced to that source. The rice-water

stool of cholera teems with the spirilla, and infections of water or

food supplies can be traced to such a contamination. The importance

of the cholera carrier has been thoroughly demonstrated from the time

of the Hamburg epidemic of 1892. The clinical course of the disease

is divided into a stage of evacuation, in which we have diarrhoeal

discharges of rice-water character along with very painful cramps of

the muscles. Following increasing cyanosis we have almost a cessation

of circulation often associated with anuria, the algid stage. With

the return of activity of circulation and urinary secretion we have

the stage of reaction.

=Synonyms.=—Cholera Asiatica.

HISTORY AND GEOGRAPHICAL DISTRIBUTION

=History.=—Although the word χολέρα, meaning flow of bile, is found

in the writings of Hippocrates, it certainly does not refer to the

disease we now recognize as cholera. The older writers noted the

characteristics of bilious discharges in the disease they termed

cholera, which could not apply to the bile-free rice-water discharges

of what we now term cholera. Koch rather doubted the antiquity of

cholera but Susruta, in India, in the 7th century A. D., described a

disease in which there were diarrhoea and vomiting, stabbing pains,

cyanosed lips and nails, with sinking in of the eyes and weak voice.

Detailed accounts of the presence of cholera in India were

published from the 16th to 18th centuries when the Portuguese,

English and French were carrying on their wars of conquest in

India. These wars naturally spread the disease all over India.

It is thought that true cholera did not exist in China until 1669

when it was carried there from India. It is first described from

Japan in 1821 although an epidemic which devastated Tokyo in 1718

may have been cholera.

A great pandemic of cholera started in India, in 1817, extending

over Asia but not invading Europe. The second great pandemic is of

importance as being the first to invade Europe. It started in India

in 1826 and advancing slowly reached Persia in 1829, going thence

by way of Astrakhan to Russia, Sweden, Northern Europe and England.

By 1832 it had spread over the whole of Europe.

In the same year, 1832, it reached Canada and thence spread to Fort

Dearborn where it infected the soldiers who subsequently carried

the disease down the Mississippi valley. It was also introduced

into New York and spread thence South and West so that by 1836

cholera was present all over the U. S., not disappearing until

1838. It disappeared from Europe in 1839.

The next European outbreak or third pandemic lasted from 1846 to

1862 and was traced to India by way of land and sea, that by land

following the caravan route by way of Persia and Russia and that

by sea from Indian pilgrims going to Mecca and there causing the

infection of Mahommedan pilgrims from Egypt and European Turkey.

This pandemic reached the U. S. in 1848, starting at New Orleans

and going up the Mississippi valley. Central and South America and

the West Indies were also invaded by the third pandemic.

The fourth great pandemic invaded Europe by the usual routes and

continued from 1863 to 1875. During its continuance there were two

outbreaks in the U. S., one in 1867 and another in 1873.

That in 1873, when it was introduced into three widely separated

parts of the country, was the last appearance of cholera in the U. S.

The fifth pandemic began in 1883 and affected particularly the

Mediterranean seaports of France, Spain and Italy. It was during

this epidemic, in 1883, that Koch, working in Egypt, discovered the

cause of cholera, the _Spirillum cholerae asiaticae_.

A very serious outbreak of cholera, which originated in 1891, in

pilgrims from the delta of the Ganges, reached Europe in 1892,

almost a million deaths occurring in Russia. It was during this

epidemic that cholera appeared in Hamburg and gave opportunity for

those careful studies as to transmission of the disease to be later

referred to.

It is usual to recognize a sixth pandemic which began in 1902

and spread over India, China and the Philippines. This pandemic

continuing was a cause of great mortality among the soldiers

of the recent Balkan war. During the World War there was much

cholera among the Austrian forces in Galicia. It also prevailed in

Bulgaria, Greece and Turkey.

=Geographical Distribution.=—Practically every pandemic when

studied can be traced back to India and particularly to the delta

of the Ganges, which may be considered the enduring focus of the

disease.

ETIOLOGY AND EPIDEMIOLOGY

=Etiology.=—The cholera vibrio, _Spirillum cholerae asiaticae_, was

discovered by Koch in 1883 and is a short curved organism which,

from its shape, is often called the comma bacillus. In addition to

single spirilla there may be “S” shapes from attachment of pairs.

In cultures in peptone solutions long filamentous forms may be

seen which however are exceedingly rare in the rice-water stools.

A stained smear from a fleck of mucus gives the fish-in-the-stream

appearance. Besides comma-shaped organisms we may have coccoid or

rod-shaped forms. In old cultures marked pleomorphism is often seen.

[Illustration: FIG. 72.—Cholera vibrios, short forms. (MacNeal from

Kolle and Schurmann after Zettrow.)]

It is Gram-negative and stains best with a dilute (1-10) carbol

fuchsin. There is a single terminal flagellum, which endows

the organism with great motility, which may best be termed

scintillating. It has been estimated that its motility is five

times greater than that of the typhoid bacillus. It grows best on

media with an alkaline reaction (—0.4%) and it is this tolerance

for media of high alkalinity that permits the separation of the

cholera spirillum from the ordinary faecal bacteria by the use of

Dieudonne’s alkaline blood agar or similar media. This is equal

parts of defibrinated ox blood and N/1 NaOH, 3 parts of which

are added to 7 parts of nutrient agar. It thus has 15% of normal

sodium hydrate, instead of the 1% acid reaction of the usual media.

Unfortunately, other spirilla tolerate this high alkalinity.

The cholera organism is strongly aerobic and grows quickly and

luxuriantly in the upper part of a tube of Dunham’s peptone

solution, this property enabling one to separate it from other

organisms of faeces by taking up loopfuls from the surface layer

to plate out on agar of about 0 or -0.3% reaction. When grown in

peptone solution the cholera spirillum produces a nitroso body so

that one obtains an indol reaction (cholera red) by simply adding 5

or 6 drops of concentrated H_{2}SO_{4}.

When this test is employed it is necessary to determine whether the

peptone used is suitable for the reaction. As a matter of fact this

test is now rather discredited. Blood serum is digested. Recently

much discussion has arisen as to the value of the haemolytic power

possessed by noncholera vibrios on blood agar plates.

It is true that the digestive action which true cholera has on

the red cells of the medium may give the appearance of a zone of

haemolysis. Therefore, for the demonstration of this haemolytic

action of noncholera spirilla, fluid blood media should be used.

The El Tor spirillum, isolated from Egyptian pilgrims without

symptoms of cholera, is haemolytic, but gives the immunity

reactions of the true cholera vibrios which are not haemolytic.

Gelatine is liquefied and the stab shows an air bubble liquefaction

at the summit of the stab. On gelatine plates a powdered glass

center with an encircling zone of liquefaction was formerly

considered characteristic of cholera, but at the present time

gelatine cultures have been almost abandoned in practical work.

As a rule animals cannot be infected by feeding them cholera

material unless the acidity of the gastric juice be neutralized

and intestinal peristalsis checked by opium (procedure of Koch).

Injected intraperitoneally, the cholera vibrio produces a fatal

peritonitis. Recently monkeys have been infected after purgation

with sulphate of soda and administration of bicarbonate of soda.

They died in from one to forty-eight hours with symptoms of cholera.

There have been instances where cholera has been caused in laboratory

workers by the accidental ingestion of cholera cultures, thus Orgel

was infected from sucking up peritoneal fluid in doing Pfeiffer tests

for bacteriolysis and died.

Emmerich and Pettenkofer swallowed cholera cultures, the former

experiencing a severe attack of cholera and the latter a diarrhoea

in which cholera spirilla were present. On the other hand similar

experiments have resulted negatively but this is what should be

expected from the epidemiological facts as to carriers.

The virulence of the cholera vibrio can be exalted by passage

through guinea pigs—successive culturing of the peritoneal exudate

of intraperitoneally infected animals alternating with culture

media growth inoculations. Such a fixed virus, the virulence of

which cannot be exalted, is the material used by Haffkine in

his cholera vaccine. The toxicity of cholera is supposed to be

due to an endotoxin which is set free when the vibrios undergo

disintegration when lying between the basement membrane and

epithelial lining of Lieberkühn’s glands. Others think the vibrios

may enter the blood stream, there to be immediately disintegrated

with toxin production. The usual idea, however, is that the cholera

spirilla never invade the blood stream—they are confined to the

alimentary canal. Macfadyen obtained the endotoxin by grinding the

frozen spirilla. This toxin was destroyed by a temperature of 60°C.

The spirillum of cholera has but little resistance to disinfecting

agents or to drying. It is also rapidly overgrown by putrefactive

bacteria and tends to disappear from sewage-contaminated water in a

short time. In stools the vibrio dies in about one or two days in

summer and in about a week in winter.

The inoculation of animals by cholera cultures tends to produce an

immune serum which is remarkable for its high agglutinating power,

the titre at times going as high as 1 to 20,000. For agglutination

tests in proving spirilla isolated from stools to be true cholera

ones we use a serum of at least 1 to 4000 for its specific vibrio.

Such a serum should agglutinate any true cholera spirillum in a

1 to 500 or 1 to 1000 dilution. The occurrence of bacteriolysis,

when a small loopful of the culture emulsified in 1 cc. of 1 to

1000 dilution of the immune serum and then introduced into the

peritoneal cavity of a guinea pig, is the surest proof that a

suspected organism is that of cholera.

This is shown when, upon removing a drop of the peritoneal fluid

fifteen to twenty minutes afterward, there is noted an absence

of motility and disintegration of the spirilla (_Pfeiffer’s

phenomenon_).

Complement fixation tests, using the rice-water stools or peptone

solution cultures as antigen, are of less value than those above

noted. Agglutination is the practical test and is almost as

specific as that for bacteriolysis.

=Epidemiology.=—Until recently our attention as to the methods

of transmission of cholera was directed almost exclusively to the

water and food supply, with a certain degree of consideration of

danger from fomites, especially to that connected with clothing

soiled by cholera discharges, it having been noted that those who

wash such clothing showed a high incidence of infection. Later on

the importance of flies in the spread of the disease was strongly

insisted upon. At the present time we consider the cholera carrier

the most important factor in cholera epidemiology and it is to the

detection and isolation of such persons that we now chiefly direct

our attention in the keeping out of a country of this dread disease.

It will be remembered that Pettenkofer and Emmerich insisted upon

the factors of soil and ground water in the spread of cholera.

Emmerich now admits that the spirilla excreted by carriers can

produce cholera but that such transference never gives origin

to epidemics. For this to take place he thinks that the vibrios

excreted by a carrier must come in contact with a soil which has

been impregnated with a suitable medium drawn to the surface from

the deeper layers of the soil by capillary suction. In such medium

the vibrios flourish and acquire the property of actively producing

nitrites from nitrates.

Emmerich considers that the symptoms of cholera are those of

nitrite poisoning so that only such organisms as possess this

nitrite-forming function in high degree can produce virulent

outbreaks of cholera.

All facts in connection with the spread of cholera by land or water

routes can be best explained by the cholera carrier; the individual

who is excreting vibrios, while in apparent health, being far more

dangerous than the one excreting such organisms in the rice-water

stools of a well-recognized case of the disease.

_Water Transmission._—There are two types of outbreaks of cholera

according as the general water supply is contaminated or when such

contamination is localized to certain wells, cisterns or other

nongeneral supplies. In the former the onset is explosive and cases

occur almost simultaneously and with equal distribution in all parts

of the city, to disappear with almost equal suddenness.

In the latter mode of infection, cases will appear from day to day

and often peculiarly localized to certain definite districts of a

city or to certain definite users of a particular water supply.

[Illustration: FIG. 73.—An instructive contrast between Altona and

Hamburg before the latter filtered its water, having learnt its

lesson from a sharp outbreak of cholera. (After G. E. Armstrong.)]

As an example of the first type of outbreak the Hamburg epidemic of

1892 is most instructive.

During a period of only about two months cholera attacked about

17,000 persons causing 8605 deaths in a city with a population of

600,000. This outbreak was attributed to the washing of clothes in

the water of the Elbe River by Russian immigrants. These immigrants

had come from cholera-infected districts and among them there

undoubtedly were cholera carriers.

The water supply of Hamburg was taken directly from the river.

The adjoining city of Altona, with a population of 140,000, is

further down the river but filtered its water by a slow sand

process. Although the water as taken from the river contained

the sewage of Hamburg yet there were only 328 deaths or 2.1 per

thousand as against 13.4 per thousand for Hamburg. There were many

interesting points in connection with the exemption of certain

places in Hamburg, of which may be noted the instance of the entire

freedom from cholera of a group of houses (Hamburg Hof), with 345

occupants. This was the only section of Hamburg which was supplied

with Altona water. As Hamburg and Altona are only separated by the

width of a street and hence practically form a single city, the

factor of food and contact transmission could easily explain the

cases in Altona.

To illustrate the second type of water transmission we have the

well-known incident of the Broad Street pump.

This was about the first definitely proven connection between water

and cholera. In 1854 it was noted that cholera was about 10 times

as prevalent in Golden Square as in other adjacent parts of London.

Various factors, such as previous droughts, stagnation of lower

strata of the atmosphere, sewerage defects and subsoil drainage

were found to be the same in Golden Square as elsewhere. It was

noted that the number of cases increased in the neighborhood of

the Broad Street well. The employees of a cartridge factory where

this well water was used gave a large number of cases while an

adjoining brewery, which had a well of its own and served out beer

to its employees, did not furnish a single case. Very striking was

the case of a lady living at Hampstead, a section of London which

was then free from cholera, who had acquired a liking for the

water of this well and had brought out to her regularly bottles of

water from the well. This lady drank some of the water on August

31 and was seized with cholera the next day. A niece drank of the

same water and died of cholera as well as the aunt. A servant also

contracted the disease but recovered.

Macnamara has noted the circumstance of a vessel of water, which

became contaminated with cholera stools, but which at the time it

was drunk by 19 persons did not show anything suspicious in odor,

color or taste. One person was stricken one day afterward, two on the

third day and two others came down with cholera on the fourth day. It

will be noted that only 5 of the 19 were attacked. A similar lack of

susceptibility of a certain proportion of people, equally exposed,

has been noted in all cholera outbreaks. It is probable that of those

of the 19 who did not contract cholera there were developed a certain

number of cholera carriers.

_Food Transmission._—Food contaminated by dejecta from cholera

patients or carriers is dangerous in proportion to its condition of

moisture. Drying and the development of inimical organisms are the

two chief factors in destroying the cholera vibrio. Temperature and

sunshine are operative in assisting the drying process.

Lettuce and celery are particularly dangerous because of the

favorable condition of moisture in their folds and imbrications.

Furthermore these vegetables are eaten uncooked and may have been

fertilized with night soil (human excrement) which material, if

containing cholera dejecta, would infect the plants. Milk is a

splendid culture medium for cholera vibrios but, upon becoming

acid, sterilizes itself of these vibrios. In sterilized milk,

however, they live for extended periods, as long as sixty days

and, even when such milk is contaminated by faecal material

containing other organisms besides the cholera vibrio, the vibrios

live much longer than they do in raw milk.

Milk is liable to be contaminated by flies which have been in

contact with cholera stools. Water that has been boiled and food

that has been cooked should subsequently be scrupulously protected

from flies or other contaminating agents. Uncooked shell fish are

peculiarly dangerous in cholera outbreaks.

In India, sun-dried fish, which are frequently covered with flies

during the curing process, are a factor in the spread of cholera.

_Transmission by Carriers._—This is now universally recognized as

the most important factor in the spread of cholera. Dunbar was the

first to draw attention to the presence of virulent cholera spirilla

in the faeces of apparently healthy persons during the Hamburg

epidemic of 1892.

Since that time these observations have been generally confirmed.

In some instances as many as 20% of those who have been in

immediate contact with a cholera patient have become carriers,

some showing symptoms of cholera but a larger proportion excreting

cholera spirilla while continuing in health.

While cholera prevailed in Manila, McLaughlin found from 6 to 7% of

carriers among healthy persons living in the infected districts.

Pottevin has recently reported that of 13,000 pilgrims examined 1.7

per thousand carried cholera vibrios. The carriers were especially

common among the dysenteric patients. During the Naples epidemic

of 1911 it was found that on the average 10% of healthy people in

contact with cholera cases became carriers. It was estimated that

90% of the cases in this epidemic were infected by sick or healthy

carriers.

Sergeant has recently reported the case of a healthy carrier who

continued to excrete cholera vibrios for two months and during this

time was in contact with 8 persons, 7 of whom became infected and 4

died. In Manila it was found that many of the children reported as

dying of meningitis or infantile beriberi were cholera cases.

The vibrios are rarely excreted in the faeces of the cholera patients

longer than seven to ten days. Frequently they disappear in three or

four days.

With healthy cholera carriers the period of the continuance of

vibrio excretion is equally short but cases have been reported

where periods of from three weeks to two months have been noted. It

is usually stated that 97% of carriers become vibrio free within a

month.

Greig has found infection of the bile of the gall bladder or ducts

in 80 cases in 271 cholera autopsies. When living organisms are

injected into the ear vein of a rabbit they pass into the bile.

An examination of the epithelial layers of the gall-bladder of

such a rabbit shows destruction of the cells and the presence of

vibrios in the underlying tissues. While cholera spirilla are soon

crowded out by intestinal bacteria, thus explaining the short

period during which cholera spirilla are excreted by convalescents,

this is not true when the cholera vibrio gets into the bile ducts

or gall bladder. Greig found one cholera convalescent excreting

cholera vibrios forty-four days after the attack. Of 27 persons who

had been in contact with cholera patients 6 were excreting cholera

vibrios although apparently well.

A very important matter is that persons who fail to show

cholera vibrios may begin to excrete such organisms after the

administration of a purgative or following some intestinal

disorder. In fact purgatives may set up an attack of cholera in a

cholera carrier.

The spread of cholera is intimately connected with the great

religious festivals and pilgrimages of Oriental people. Not only

do those of India keep up the dissemination of the disease there

but pilgrims going from the delta of the Ganges to Mecca carry the

infection and transmit it to their fellow pilgrims from Egypt and

Algiers. Greig examined a number of cholera convalescents who were

about to return to their homes in India and found 30 per cent of

these pilgrims excreting cholera vibrios in their stools.

In India cholera accounts for about 1 to 1.5 deaths per 1000 of

population. Malaria and plague are other great causes of death.

The intimate commercial relations between Europe and Egypt and

Algiers make the introduction of the disease into European ports an

easy matter. Of particular importance is the fact that so many sick

people make pilgrimages, these being peculiarly liable to act as

carriers.

Excesses in eating, often of badly prepared or decomposing food,

following periods of religious fasts, predispose the natives of

India to cholera.

Lowered resistance, as from disease or from gastric disorder,

increases the susceptibility to cholera. Errors in diet and in

particular the effects of alcoholic excesses markedly predispose to

infection.

PATHOLOGY

The cholera spirillum does not produce a soluble toxin, the toxic

principle being intracellular. The organism rarely penetrates

more deeply than just under the epithelial layer of the glands of

Lieberkühn. As a result of the outpouring of the fluid into the lumen

of the gut we have an increase in the red cells (7,000,000 per cu.

mm.) and leucocytosis of from 12,000 to 50,000. The specific gravity

of the blood is greatly raised, 1073 to 1078, and the alkalinity

diminished. The blood pressure is markedly lowered, 60 mm. in very

severe cases and 75 mm. in less severe ones.

The lower portion of the small intestines is the favorite location

for the action of the endotoxin of cholera. Early and marked

postmortem rigidity is a striking characteristic of the cholera

cadaver. Muscular contractions, causing odd positions of the

limbs, have at times given a basis for the idea that the victim had

been buried alive.

Besides marked rigor mortis the emaciation, leaden hue of skin and

shrivelled hands are noteworthy.

In opening up the body there is a striking dryness of all the

structures. The dry and dark-red muscles stand out prominently.

The lungs are dry and shrunken. The right heart is full of a dark,

jelly-like, viscid blood. The leading changes are found in the

abdomen. The omentum is dry, sticky and shrivelled looking. The

intestines have a ground glass appearance with a lilac-pink color of

the small intestines which is in contrast with the normal color of

the large intestines.

There is congestion of the affected intestinal mucosa and the lumen

is filled with the alkaline rice-water material. If the case is of

some days standing we have a rather brownish, foul-smelling bowel

content. There is usually a parenchymatous nephritis and on section

the medullary portion is much congested.

Crowell gives the following points as indicating cholera upon

autopsy: (1) Cyanotic finger nails, (2) dry tissues, (3) dry and

sticky peritoneum with pink serosa of ileum, (4) contracted and empty

urinary bladder, (5) shrunken dry spleen and liver, (6) rice-water

intestinal contents and (7) prominence of lymphoid tissues in the

ileum.

In his studies of the pathology of cholera Greig drew attention to

the frequency of the involvement of the gall-bladder. He also noted

the presence of small areas of consolidation in the lungs of those

developing pneumonia during the early days of convalescence. In the

exudates of such areas cholera vibrios could be seen thus showing

their penetration of the lung. Although rare instances of recovery

of the cholera spirillum from the blood have been reported Greig

was unable to accomplish this in any instance. In his opinion the

spirilla travel by way of the lymphatic system. In eight cases out

of fifty-five cases he recovered the spirilla from the urine.

SYMPTOMATOLOGY

=A Typical Case of Cholera.=—The so-called prodromal or premonitory

diarrhoea is not a feature of the onset of _cholera gravis_, the type

of the disease which characterizes the cholera epidemic.

The period of incubation is usually from one to five days. Longer

periods are possibly explained by some exciting intestinal disorder

in a cholera carrier. The course of the disease is conveniently

divided into a stage of evacuation, an algid one and a stage of

reaction.

_The Stage of Evacuation._—A profuse and frequent diarrhoea comes on

without colic or tenesmus. In fact the stools are voided with a sense

of relief as when an enema is gotten rid of.

The striking feature, however, of these movements is the sensation

of prostration which accompanies them.

The faecal character of these diarrhoeal stools is soon lost and the

typical rice-water stool is now passed. This designation is very apt

and the flocculi of intestinal epithelium, in a watery, slightly

opaque fluid, suggests rice-water. The odor is slightly albuminous.

Early in this stage cramps of the muscles set in. The muscles of

the legs, especially the calf muscles and those of the feet, are

particularly liable to these very painful contractions which may

cause the patient to cry out for relief. The muscles of the abdomen

and back may also be involved as may at times the muscles of the

entire body.

Vomiting, at first of the contents of the stomach and later of

rice-water material, is a distressing feature to the patient and by

reason of the manner in which it often gushes from the patient’s

mouth is liable to contaminate the attendants.

Along with the excessive loss of fluid the tissues, especially

of the face, become shrunken, the eyeballs with their congested

conjunctivae sink back in the orbits, and the nose becomes pinched.

The pulse becomes more and more feeble and there is a steady

diminution in the secretion of urine. An increasing duskiness

of the skin, which is cold and clammy to the touch, denotes the

setting in of the algid stage.

_Algid Stage._—In this stage there is almost complete cessation of

circulation, even the incision of a vein is only followed by a drop

of black tarry blood. Anuria is practically complete.

The vomiting, purging and cramps may or may not subside and in the

patient, with his great thirst, intense exhaustion and cadaveric

appearance, with mental faculties fairly well preserved, we have

an example of a living death. The temperature of the sodden,

inelastic, clammy skin is markedly depressed, even below 90°F.,

while the rectal temperature may approximate normal or be elevated.

Some authorities consider a marked difference between the

superficial and rectal temperatures as of bad prognosis.

The voice becomes husky and finally so feeble that the patient can

only whisper and the breath feels cold.

The sodden shrivelled hands, as those of a washerwoman, are very

characteristic. Thirst is intense.

The patient now falls into a listless, motionless state in which,

however, the apathy is more apparent than real. The algidity may

deepen and death ensue or the stage of reaction may set in. The

algid stage may last from a few hours to two or three days.

Collapse and uraemia are the two most frequent causes of death.

_Stage of Reaction._—The pulse returns, urine is again secreted and

the duskiness and coldness of the skin give way to normal conditions

and a favorable convalescence sets in. At other times, however, the

rise of surface temperature and restoration of the circulation are

not attended by urinary secretion.

In such cases a typhoid state ensues with accelerated respiration,

dry, brown tongue and muttering delirium.

It is customary to divide the types of cholera cases into:

1. _Cholera gravis._ The type above described.

2. _Cholerine._ In this there is a more or less marked stage of

evacuation with possibly the appearance of rice-water stools. The

urine, however, does not become suppressed and the algid stage is

not entered upon.

3. _Cholera sicca._ This type of the disease is more apt to be seen

in old or debilitated people. The patient dies of collapse without

showing symptoms of vomiting or diarrhoea. At the autopsy one may

find the bowels distended with rice-water contents.

The so-called _cholera ambulans_ is simply another designation for

the more or less ill cholera carrier.

=Sequelae.=—Following an attack of cholera we may have abscess of

the parotid gland or gangrene of various parts of the body. There may

be ulceration of the cornea. In pregnant women the disease almost

invariably causes abortion. Post-choleraic pneumonias and renal

inflammations are to be considered.

Symptoms in Detail

_General Appearance._—A typical case of cholera, with its

cyanosed, drawn, pinched face, cold, clammy skin and the eyes

deeply sunken in the orbits, makes a picture rarely seen in other

conditions. The washerwoman’s hands appearance should always be

looked for.

_Temperature Record._—The temperature of the skin surface is

lowered from the normal while that of the rectum may be normal or

even elevated. There may be a difference of 10° or more between

rectal and surface temperature. In the stage of reaction the

temperature may continue to rise to high fever points and this

so-called hyperthermic type is very fatal.

_Circulatory System._—The pulse is rapid and feeble in the stage

of evacuation to become imperceptible in the algid stage. The

circulation is practically at a standstill so that only a few drops

of black tarry blood, which does not coagulate readily, flow from

a wound of a vein when giving an intravenous injection. The blood

is concentrated and has a specific gravity of 1072 to 1078. The

systolic pressure falls greatly, even to 60 mm. of mercury in a

severe, or 75 mm. in a less serious case. The red cell count is

increased to 7 or 8 million red cells per c.mm. and the leucocyte

count reaches 15,000 to 50,000.

_Nervous System._—The mind is clear, even when the patient seems

profoundly apathetic. The muscle cramps are characteristic of the

disease.

DIAGNOSIS

=Clinical Diagnosis.=—It is customary to state that cholera

nostras and infections with virulent meat poisoning bacteria of the

paratyphoid group show bile in the intestinal discharges and not the

typical rice-water stools of true cholera. It must be remembered

that these affections can at times show as marked muscular cramps,

emaciation, cyanosis and weak voice as cholera so that only the

bacteriological examination can differentiate.

Algid pernicious malaria generally shows a rather high axillary

temperature and the stools are rarely so profuse as in cholera.

In ptomaine or mushroom poisoning the vomiting usually precedes the

diarrhoea—the opposite of the order in cholera.

Acute intestinal obstructions may simulate but here we have faecal

vomiting and constipation.

With irritant poisons as arsenic or antimony there is the metallic

taste and the pains are chiefly colicky rather than muscular and

the stools rather dysenteric.

I have seen severe cases of bacillary dysentery which could not

be differentiated clinically from cholera, and it is interesting

to note that many cases of cholera occurring in the Balkan war

were diagnosed as bacillary dysentery. In children cerebral

manifestations are very common so that in the Philippines many such

cholera cases were diagnosed as meningitis.

=Laboratory Diagnosis.=—Agglutination is the practical aid in

diagnosis. The serum from cholera convalescents, or those vaccinated

against cholera, show agglutinins. It has been stated that properly

vaccinated cases show a titre of from 1 to 2 thousand in about

70% of cases. Normal human serum does not agglutinate in a higher

dilution than 1 to 20. Greig has found that fatal cholera cases

rarely give higher than 1 to 40. In cases recovering he found

well-marked agglutinating power by the 6th day, titres of 1 to 500

or 1 to 1000 being frequently obtained. Janoue and Watanabe found

the agglutinating power of the sera of convalescents to fall rapidly

after the third week. As a rule the titre varied from 1 to 100 to 1

to 400. The highest titre noted was 1 to 10,000.

It is well to first make a microscopical examination of the stool

by taking one of the whitish epithelial flakes from the rice-water

material and making a straight smear which is then dried and fixed

with heat. This may be stained best by a dilute carbol fuchsin (1

to 10). Methylene blue makes a good stain, or more differential

is that by Gram’s method which shows the Gram-negative spirilla

stained by the bismarck brown counterstain, giving the appearance

of fish parallel to one another in a stream. According to Koch a

diagnosis can be made in this way of one-half the cases during an

epidemic.

The scintillating motility of cholera spirilla may strike one in the

examination of the stool in hanging drop.

Dunbar has a quick diagnostic method in which epithelial flakes

from the stool are emulsified in peptone solution. Then on a

slide, according to the method to be later described, is deposited

a drop of 1 to 50 normal serum dilution and on the same slide a

second drop of 1 to 500 dilution of cholera serum. A loopful of

the suspected stool emulsion is rubbed up in each of these serum

dilutions and we should have cessation of motility and clumping in

the cholera immune serum provided the organisms in the stool are

true cholera spirilla.

In case of an autopsy on a suspected case of cholera one should

tie off, between double ligatures, at least two 5-inch sections

of small intestines, one just above the ileo-caecal valve and one

taken from about the middle of the ileum. These portions of gut

should be dropped into sterile salt mouth bottles, well stoppered

and sent to a bacteriological laboratory as soon as possible. As

the cholera spirilla, when associated with faecal bacteria, tend

to die off within twelve to twenty-four hours it would probably be

advisable to inoculate an agar or blood serum slant with material

from the ileum at the same time the sections of gut are removed.

For diagnosis of a cholera carrier with a normal stool or a cholera

suspect with a diarrhoeal one inoculate 2 or 3 tubes of peptone

solution with 2 or 3 loopfuls of material from the stool. With

suspected carriers who are constipated and to whom one should not

give purgatives we may insert into the rectum a rubber tube or a

throat swab in order to obtain material immediately. The cholera

spirilla grow rapidly and being strong aerobes, they grow on the

surface of the fluid so that by taking a loopful from the surface,

we may in three to eight hours obtain a pure culture. Should there

be a pellicle present, this should be avoided in transfer by

tilting the tube slightly, so that the material near the surface

be obtained without touching the pellicle. Inoculate a second

tube from the surface of this first and, if necessary, a third

(_enrichment method_).

Smear the three-hour surface growth of a peptone culture on a

dry agar surface in a Petri dish. From colonies developing make

agglutination and, if desired, cultural tests. It is by immunity

reactions and not by cultural ones that we identify cholera

spirilla. The surface moisture of plates is best dried by the

filter-paper top.

The cholera colony is easily distinguished from the ordinary faecal

bacterial colonies by its transparent, bluish gray, delicate

character.

A practical quick method is to make smears from suspicious

colonies, stain for one minute with dilute carbol fuchsin and if

vibrios are present to make 2 vaseline rings on a single slide

allowing ample space at one end for handling the preparation

safely. Inside of one ring deposit with a platinum loop a drop of

salt solution and inside the ring nearest the end which is to be

held by fingers or forceps deposit a loopful of 1 to 500 or 1 to

1000 dilution of cholera serum. The emulsion in the salt solution

remains uniformly turbid and under a low power of the microscope

(⅔-inch) shows a scintillating motility. The emulsion made into

the drop of serum quickly shows a curdy agglutination and upon

examination with the ⅔-inch objective shows clumping and absence of

motility. Cover-glasses placed over the two vaseline rings assist

in the study of the preparation.

The best-known selective medium for plating out cholera material is

that of Dieudonne which is referred to under etiology. Apparently

a more satisfactory medium is that proposed by Goldberger, this

medium being transparent.

First prepare a 100% meat infusion by treating 500 grams of finely

chopped lean beef with 500 cc. water and after three hours strain

the infusion, adjust reaction to neutral with 5.3% anhydrous sodium

carbonate, then add to each 100 cc. 2½ cc. of the 5.3% anhydrous

sodium carbonate, sterilize in Arnold for one-half hour and filter.

Next prepare a 3% meat extract agar and mix one volume of the

alkaline meat infusion with 3 volumes of the hot melted 3% meat

extract agar. Pour plates and cover with a piece of filter-paper

and place in incubator for one-half hour until they are quite dry.

The necessity for a surface without moisture applies to Dieudonne’s

and Krumwiede’s alkaline egg media as well as this one. On this

medium cholera grows well while faecal bacteria are restrained.

The cholera colony is clear, round and shows a brownish center but

is without that striking bluish opalescence shown on ordinary agar

plates.

While peptone solution is a more favorable enrichment medium and

answers perfectly when cholera organisms are fairly abundant yet,

when scarce, selective enrichment media may be desirable. Of these

the best known is Ottolenghi’s alkaline bile. Goldberger prefers an

alkaline egg peptone solution made as follows:

Shake up an egg with an equal quantity of water and add to this

egg solution an equal quantity of a 5% solution of anhydrous

sodium carbonate. Steam one hour. Then add 1 part of this alkaline

egg medium to 9 parts of peptone solution, filter and sterilize.

Recent reports on _Aronson’s cholera medium_ would indicate its

great value in stool examination for cholera. The organisms taken

from such plates emulsify easily and there is no interference with

their agglutinability. To prepare it add to 100 cc. of 3% nutrient

agar, 6 cc. of 10% solution of exsiccated sodium carbonate and

steam in Arnold sterilizer for fifteen minutes. Then add 5 cc. of

20% saccharose solution, 5 cc. of 20% dextrin solution, 0.4 cc.

saturated alcoholic basic fuchsin and 2 cc. of 10% sodium sulphite.

A precipitate forms which quickly settles and plates can be poured

from the supernatant fluid. Cholera colonies develop in twelve

hours and show as red colonies in fifteen to twenty hours.

Test for _cholera red_ reaction. Add from three to five drops of

concentrated chemically pure sulphuric acid to the first or second

peptone culture after eighteen to twenty-four hours growth. Some

specimens of peptone do not give the reaction. At times we only get

the cholera red when we have a pure culture of cholera.

PROGNOSIS

There is the greatest variation in the mortality in different

epidemics as is true of most other epidemic diseases. At any rate 50%

may be considered an average mortality.

Young children and old people give a very high mortality rate as is

also true of alcoholics and those with kidney disease.

PROPHYLAXIS AND TREATMENT

=Prophylaxis.=—Of all the quarantinable diseases cholera is the one

in which personal prophylaxis is apparently of greatest influence in

protection from infection.

In the presence of cholera one should not only drink recently

boiled water, which has been protected from the contaminating

influence of flies, but all forms of uncooked food should be

avoided. In the first rank of prohibited foods should be raw shell

fish and uncooked salads. Such articles as lettuce and celery are

particularly dangerous on account of the moisture retained. Fruits

such as bananas and oranges can be made safe by covering them with

boiling water for two or three minutes and subsequently peeling.

Care must be taken that native servants do not put fish, which may

have been contaminated with cholera-infected water, on the ice in

an ice box and through such a source to have the butter, etc.,

infected. The most scrupulous attention should be given the matter

of the care of the ice-box in the tropics.

If conditions are such that boiled water cannot be obtained the

water may be treated with good quality chlorinated soda. As a

stock solution we use 1 teaspoonful of chlorinated soda to 1 pint

of water and of this 1 teaspoonful to 2 gallons of the water

to be disinfected. Pottevin recommends six hours contact with

hypochlorite of soda, 1 mg. per liter.

Besides care of the food and water ingested particular attention

should be paid to the washing of the hands before eating and if in

contact with cholera cases careful disinfection of the hands.

Experience in cholera epidemics has shown the importance of avoiding

anything which might lower resistance. In particular are fatigue,

excesses in alcohol or the taking of any kind of indigestible foods

to be avoided. It must be remembered that the use of purgatives may

set up cholera in a cholera carrier so that this possibility should

be thought of.

Tea has been recommended as a prophylactic, as has also eucalyptus

oil, 10 minims twice daily.

As acids have an inimical effect on the cholera spirilla some have

recommended the use of acid drinks but as a matter of fact the best

prophylactic is the normal gastric juice and there is a possibility

that the use of such acid drinks might upset the digestion and thus

defeat the object desired.

As to municipal measures for the control of a cholera outbreak the

most important one is to diagnose cholera carriers, such cases often

occurring in those associated with a cholera case. Such carriers

should be isolated and their stools disinfected until at least

2 negative examinations show them to have ceased being cholera

carriers. Of course a cholera case should be isolated and kept in a

fly-screened room.

For disinfection of stools one requires an equal amount of a 5%

compound cresol solution which when mixed with the same amount of

stool becomes a 2½% solution. This should be in contact with the

stool at least one hour before emptying the container. Chlorinated

lime, 1 pound to 4 gallons, makes a splendid disinfectant for

stools—equal parts of this 1 to 16 chlorinated lime solution and

stool.

Bed clothing or other material contaminated by vomitus or faeces

should be immersed in a 2½% compound cresol solution. All food

utensils should be disinfected by boiling.

Persons attending cholera cases should wear gowns and remove the

same upon leaving the room. Particular care should be exercised in

hand disinfection after attending a cholera case.

There is no danger from aerial conveyance of infectious material

other than the possibility of one’s coming within the danger zone

of a vomiting patient. Therefore, for disinfection of a room

occupied by a cholera patient we need not use formaldehyde gas but

washing of floors and lower part of walls with 2½% compound cresol

solution is sufficient. The stock solution of chlorinated lime, 1

pound to 4 gallons, is suitable for mopping floors and walls.

_Vaccination prophylaxis_ against cholera has been less used than

has been the case with plague or typhoid fever. The anti-cholera

sera have no practical value prophylactically and the same statement

applies to the use of such sera in treatment of cholera.

Ferran, in 1885, was the first one to use cholera vaccines in

prophylaxis. Haffkine, in 1893, adopted the use of a preliminary

subcutaneous injection of an attenuated cholera organism to be

succeeded later by one, the virulence of which had been exalted by

passage through animals to a fixed virulence. (Pasteur’s anthrax

method.) He now only uses the fixed virulence vaccine. This vaccine

is not killed by heat.

The statistics indicate quite a reduction in susceptibility on

the part of vaccinated persons (probably 8 to 1) but only slight

lessening of mortality rate. Of 5549 nonvaccinated 198 contracted

cholera and 124 died. Of 5778 vaccinated 27 contracted cholera and

14 died.

In the recent Balkan war (1913) Kolle’s vaccine was employed with

considerable success. This vaccine is killed by exposure to 58°C.

for one hour. It was found that this vaccine was not only of value

prophylactically but diminished case mortality as well. With 91,224

persons vaccinated and 8,968 not vaccinated, the case rate among

the inoculated was 0.7% and the death rate 10.2%, while among the

noninoculated the case rate was 9.3% and the death rate 27.5%.

Ottolenghi prefers to sterilize with a temperature of 53°C. He

gives 500 million at the first injection and 2 billion at the

second.

Among 72,653 soldiers, having 2 inoculations of this vaccine, the

incidence of cholera was about 13 times less than among 14,332 who

were not vaccinated.

Of 2897 Greek sanitary corps men inoculated 0.45% were attacked

while of 114,805 combatants, not inoculated, about 2% were attacked

by cholera. One would naturally consider the greater exposure of

the sanitary forces.

Cholera vaccines made from killed cultures are the ones now

generally used.

During the World War a Roumanian regiment numbering 4,500 soldiers,

had 386 cases of cholera develop in the course of six days, with

166 deaths. Vaccination was commenced and during the interval

between the first and second injections, new cases continued to

appear. Two days after the second injection the epidemic ceased. In

another regiment the commandant refused to have his men vaccinated.

A group of Jewish soldiers, 200 in number, insisted on being

vaccinated, which was done. Later the regiment was stricken by

cholera and 450 cases developed. None of the vaccinated Jewish

soldiers contracted the disease.

Some prefer sensitized living cultures for prophylaxis but such

vaccines are less practical.

There is much to indicate that Strong’s cholera autolysate is of

value prophylactically. In this cholera cultures are killed at

60°C. The killed culture is then allowed to digest itself in the

incubator at 37°C. for three or four days (peptonization). The

preparation is then filtered and from 2 to 5 cc. of the filtrate is

injected.

=Treatment.=—Many of the older authorities recommended the use

of various astringent medications for the checking of suspicious

diarrhoeas and most of these prescriptions contained opium in some

form, such as lead and opium pills or aromatic sulphuric acid and

laudanum. In view of the fact that for the infection of animals

Koch had to employ opium for checking peristalsis in addition to

neutralization of gastric juice it would seem very undesirable to

use opium by mouth. Calomel in divided doses and continued over one

or two days, but not exceeding 7 or 8 grains, has been recommended.

At present the treatment which is thought to give the best results is

the permanganate one proposed by Rogers. In this the patient is given

calcium permanganate water ad libitum and 2-grain pills of potassium

permanganate every half hour until the stools become more faecal in

character. These pills are made up with vaseline and coated with a

mixture of a 1 part salol and 5 parts of sandarach varnish.

Reports as to the use of kaolin in treatment and as a prophylactic

have been favorable. The suspension in water is given as a drink

and as an enema.

Rogers has recently been administering 1/100 of a grain of atropine

sulphate morning and evening. His statistics would indicate a

reduction in mortality of about one-half. Cases treated with

atropine also rarely show collapse. Injections of adrenalin

solutions have been recommended.

A great objection to any form of oral medication is the tendency to

vomiting. This can in a measure be controlled by cracked ice or by

a small hypodermic of morphia. The latter drug also relieves the

very painful cramps.

One danger which must always be borne in mind in giving more than

one dose of any drug subcutaneously is that with the slowing or

cessation of circulation, coming on with the algid state, we have

no absorption but, when the stage of reaction sets in and the drug,

whether morphine or toxic stimulant, begins to be taken up, there

may ensue a fatal poisoning.

However the views of authorities may conflict as to special forms

of treatment, there is universal acceptance of the employment of

intravenous injections of fluid to combat collapse. Normal saline

is the fluid usually used, but Rogers recommends his hypertonic

solution which consists of 120 grains of sodium chloride, 6 grains

of potassium chloride and 4 grains of calcium chloride to the pint of

water.

In the Philippines the normal saline seemed to answer as well as

the hypertonic solution.

Sellards had success in combating anuria, which is one of the most

dangerous conditions encountered in cholera, and at the same time

answered equally well with normal saline in relieving collapse, by

giving 2% sodium bicarbonate injections.

There is a marked acidosis in cholera and this form of treatment

seems indicated.

The objection to using sodium carbonate is that the salt has

a lytic action on red cells in vitro and furthermore Sellards

found that it tended to cause convulsions in one of his cholera

cases. Sodium bicarbonate, even in 4 or 5% concentration, does

not have any haemolysing effect on the red cells. Of course it is

true that in sterilization the bicarbonate tends to be converted

into carbonate but Sellards found that by sterilization in an

autoclave connected with live steam, at 7 pounds pressure, this was

minimized, only about 25% of the bicarbonate being converted into

carbonate after 1 hour.

If the temperature by rectum is about normal or slightly below, the

temperature of the fluid should be 102° to 104°F. and one usually

gives about 2 quarts.

Owing to the collapse of the veins it is usually necessary to cut

down on them instead of inserting the needle through the skin as for

salvarsan injections. The same apparatus as for salvarsan injections

is suitable but with a somewhat larger container as we give from 1 to

2 quarts of fluid. At least fifteen minutes should be taken up for

the introduction of 1 quart of fluid.

To determine the necessity for intravenous infusion in cholera

Rogers has recently recommended the employment of small bottles

containing aqueous solution of glycerine with specific gravities

varying from 1048 to 1070, increasing the specific gravity in each

successive bottle by 2°.

Drops of blood from the cholera patient are deposited at the

center of the surface of the fluid in the bottles from a capillary

pipette. If the specific gravity of the blood is 1062 at least a

liter of saline or sodium bicarbonate solution is needed. If 1066,

at least 2 liters. Formerly he estimated the indications by blood

pressure, considering a pressure of 80 in Europeans or of 70 in

natives as indicating intravenous injections.

On the whole the reports from the use of anti-cholera sera are

not very encouraging. Savas, however, was favorably impressed by

such treatment during the Balkan war. It should be administered

intravenously and early in the attack and given in doses of 50 cc. Of

61 severe cases, so treated, the mortality was 55.7%. Of 17 severe

cases, not receiving serum treatment, all died.

Hot water bottles should be used to keep up the body heat. No food

should be given during the first thirty-six hours but after that

time we may give broths or albumin water.

CHAPTER XVI

MALTA FEVER

DEFINITION AND SYNONYMS

=Definition.=—Malta fever is a septicaemic condition due to the

presence of the specific organism, _Micrococcus melitensis_, in the

blood and various organs, especially spleen. It runs a protracted

course, averaging three or four months, but is attended with very

slight mortality (2%). Rare cases may run an acute course and show a

high death rate. The fever course resembles that of a typhoid fever

with two or more relapses, in that a step-like rise of fever for ten

or twelve days is followed by a similar fall during the succeeding

week or ten days, an afebrile interval of a few days then ensuing, to

be followed by a second or third or even tenth febrile wave with the

separating days of apyrexia. The course of the disease may last for

a year or more attended with progressive anaemia and manifestations

of neurasthenia. Very characteristic are sudden swellings of various

joints which subside in a few hours to entirely disappear in a few

days. Neuralgic manifestations, especially sciatica, are prominent

features of the disease. It is chiefly spread by the milk of infected

goats and can best be prevented by boiling such milk.

=Synonyms.=—Febris undulans (from the wave-like monthly accessions

of fever). Mediterranean, Gibraltar or “Rock,” Neapolitan, Cyprus

fever (from the geographical distribution). Febris sudoralis (from

the night sweats). Mediterranean phthisis (from the bronchitis,

anaemia and night sweats resembling phthisis). Melitensis

septicaemia. Febris melitensis.

HISTORY AND GEOGRAPHICAL DISTRIBUTION

=History.=—It is generally considered that a disease described by

Hippocrates, in which there was an irregular febrile course without

crisis but showing relapses and running a very prolonged course, was

probably Malta fever.

In 1861 Marston showed on clinical and pathological grounds that

the disease was different from typhoid fever.

In 1887, Colonel Bruce isolated the causative organism from the

spleen at autopsy and established the demands of Koch’s postulates

by reproducing the disease in monkeys with cultures from the spleen

and then recovering the organism from the monkeys.

Our present accurate knowledge of the epidemiology of Malta fever

and its connection with the use of the milk of goats is due to the

work of a Commission appointed to investigate the disease—1904 to

1907.

[Illustration: FIG. 74.—Geographical distribution of Malta fever.]

=Geographical Distribution.=—It is usual to consider Malta as the

focus of the disease, with the cities of the Mediterranean shores

showing quite a degree of infection. It is probable that the spread

of the disease has been in part connected with the importation

of Maltese goats, these animals being desirable on account of

their superior yield of milk. It is now known that outside of the

Mediterranean basin the disease exists in India, East and South

Africa as well as Northern Africa, China, North and South America

and the West Indies.

Mohler has shown that the disease under the names of “slow fever”

and “mountain fever” has existed in Texas and New Mexico for at

least twenty-five years.

ETIOLOGY AND EPIDEMIOLOGY

=Etiology.=—The causative organism, _Micrococcus melitensis_, is

a small coccus, rather oval than round and about 0.4 micron in

diameter. In morphology it is quite variable and may occur in pairs

or in short chains and is Gram-negative. It emulsifies evenly and

rapidly in a hanging-drop preparation and is nonmotile. Possibly on

account of its showing a rather active Brownian motion there has been

a reporting of slight motility by some authorities. Very striking is

the characteristic of very slow growth so that cultures on agar fail

to show colonies before the fourth day.

These minute transparent colonies become somewhat opaque and about

1/10 inch in diameter by the tenth day. Gelatine is not liquefied

and litmus milk is not altered. The optimum reaction of media

is about +0.75 to phenolphthalein and it grows best at the body

temperature. It has great powers of resistance to drying so that it

survives in dust for long periods.

Horses, cows, asses, as well as goats, are susceptible. It is very

difficult to infect rabbits, mice and guinea pigs. Monkeys have

been chiefly utilized in experimental work.

It would appear as if there were other organisms closely related

to _M. melitensis_ and a great deal is now being written as to

confusing serum reactions from the use of _M. paramelitensis_.

Evans and others have studied the relationship between _Bacillus

abortus_ and _M. melitensis_. Morphologically and culturally these

organisms are quite similar and Evans has demonstrated a marked

degree of cross-agglutination. This is a probable explanation of

the finding by Kennedy of agglutinating power in the sera and milk

of certain cows, but inability to isolate _M. melitensis_ from the

agglutinating milk.

=Epidemiology.=—Many experiments have failed to show any mosquito,

biting fly or louse as a probable factor in the transmission of

the disease. The infection is readily transmitted by subcutaneous

inoculation so that in a case in goat or man, with the cocci in the

peripheral circulation, it is reasonable to suppose that a biting

insect might transfer the infection by going directly from one

animal to another. There have been several laboratory infections,

but when we consider that of the great number of cases treated at

Haslar hospital and elsewhere in England, with frequent elimination

of the organism in the urine, and practically no infections among

the friends or attendants, it would seem as if usual methods of

infection were inoperative. There does not seem to be a carrier

problem in this disease. Urine showing bacterial contamination,

when dried and mixed with dust, has caused infection and

contaminated urine applied to the glans penis of a monkey caused

the disease.

As a large proportion of the prostitutes of Malta showed infection

and as _M. melitensis_ was found in urine and vaginal discharges

of many of these it is possible that sexual intercourse may be a

factor in transmission.

The Commission noted many cases of Malta fever among the goatherds.

By agglutination tests it was found that one-half of the goats

showed agglutinins in their serum. Of 28 monkeys given infected milk

26 became infected. Very conclusive was the case of the “Joshua

Nicholson,” which ship carried 65 Maltese goats from Malta to the

United States. Of ten of the crew who drank goats’ milk on the

voyage, eight became infected. Two who boiled the milk escaped

infection. It is reported, that when the goats reached the United

States and were quarantined, a woman drank of their milk and became

infected.

What may be deemed proof positive is the practical disappearance of

the disease among the naval and military forces of Malta, as the

result of boiling the milk, while still continuing among native

civilians. Bassett-Smith has noted that in 1905 there were 798 cases

among civilians and 245 naval cases. In 1907 there were 457 cases

among civilians and only 12 cases in the naval forces.

There are however occasional cases which Shaw has considered as due

to carriers. As the organisms are excreted in faeces as well as in

urine, and as the course of the disease is so protracted, as well

as the convalescence, it would seem that the carrier factor should

be of more importance than facts would justify.

Mohler has noted that in Texas, where the disease has existed for

twenty-five years, the Mexican goatherds boiled their milk and hence

were rarely infected.

Gentry and Ferenbaugh, in Texas, noted that cases of Malta fever were

most common in the spring and early summer months when the goats were

in full milk and the ranchmen were caring for the kids and teaching

them to suckle. The disease in certain areas was called “goat fever”

and in others “dust fever,” this latter name coming from the idea

that the dust-filled goat pens had to do with the disease.

The souring of milk does not destroy the germs of the disease,

hence transmission may be brought about by butter and cheese.

Malta fever was stamped out of Port Said by destroying all infected

goats.

Infection may occur: (1) By the stomach atrium (usual); (2)

contaminated dust reaching lungs; (3) by subcutaneous injection.

PATHOLOGY AND MORBID ANATOMY

The germs are found early in the blood and spleen; and are also

present in lymphatic glands and kidneys.

The blood is most apt to contain them at the height of the fever

curve and a striking feature is the appearance in waves of the

organisms in blood, urine or milk. While serum immunity reactions are

striking features, there is some question as to the conference of

immunity by an attack.

At postmortem we have an enlarged, congested, soft spleen with

swollen Malpighian bodies. The kidneys may show a nephritis and

the mesenteric glands be swollen. The intestines fail to show the

characteristic lesions of typhoid fever.

There may be evidences of myocarditis.

SYMPTOMATOLOGY

_A Typical Case._—Following a period of incubation, varying from

ten to fifteen days, headache, malaise and anorexia set in with a

step-like rise of fever from day to day.

The tongue is not heavily coated and is red at the tip and sides.

Constipation is the rule and there is an early tenderness and

enlargement of the spleen. There is much to suggest typhoid fever in

the gradual ascent of the remittent fever for about ten or twelve

days and the gradual descent during the succeeding ten or twelve

days, but the lack of apathy and slighter evidences of toxaemia

differentiate. The patient is dejected rather than apathetic.

There is often a slight bronchitis, with cough, which, when

associated with a profuse sweating at night, may suggest phthisis.

[Illustration: FIG. 75.—Temperature chart of Malta fever. (After

Scheube.)]

Following the initial period of fever there is usually a short

afebrile interval of a few days to be succeeded by a second, third

or many of these febrile waves, thereby making one of the names,

undulant fever, appropriate. Anaemia becomes marked and cardiac

weakness, as shown by palpitation and rapid, irregular pulse,

apparent.

The symptoms which aid us most in diagnosis are joint

manifestations and neuralgic pains. These may come on quite early

in the course of the disease or be delayed until succeeding febrile

waves set in. Swelling and pain, but without redness, of a single

joint may come on rather suddenly, to have the acute symptoms

subside in a few hours and to be entirely normal in three or four

days.

Pains in the sacro-iliac region or pains resembling those of

hypertrophic arthritis of the spine may be noted.

It is however the peripheral nerves, even more than the joints,

for which the toxic effects of _M. melitensis_ show a preference.

The sciatic nerve seems to be most often involved and sciatica may

set in suddenly and acutely, to pass off in two or three days,

leaving a soreness over the course of the nerve and a tendency to

recurrence. Orchitis may occasionally set in. There is usually

albuminuria.

Insomnia is usually quite a prominent feature of the disease and

there is a great tendency for nervous prostration to develop.

The usual course of the disease runs for three or four months but may

last almost a year.

=Other Clinical Types.=—(1) _The Malignant Form._—In such cases

instead of the insidious onset we have the characteristics of a

severe acute infection with high temperature from the beginning,

ranging from 103° to 105°F. Such cases may show vomiting and

early diarrhoea. This is followed by a typhoid state with cardiac

manifestations in the way of irregularity of the pulse. An ordinary

type of case may assume this malignant form and such cases may

develop a broncho-pneumonia.

(2) _The Intermittent Form of Hughes._—Here we have a type of case

similar to the typical one but less severe. It is a subacute form

which from time to time shows an intermitting fever. These cases

may fail to show evidence of serious illness and the patient may

continue his work although noting a progressive deterioration of

health. Some very mild cases which only rarely show slight fever of

a few days’ duration have been reported as _ambulatory_ cases.

(3) _The Disease in Infants._—Di Cristina and Maggiore have

described various forms of the disease as observed in infants in

Palermo. They note a hyperpyrexial type and an undulant type. A

type with anaemia and marked cachexia is very severe. Another form

shows cyanosis, irregular pulse and irregular respiration with

marked sweats. Again the symptoms may be those of a cerebro-spinal

meningitis.

=Sequelae and Complications.=—It should be borne in mind that

while not serious from a standpoint of mortality this disease is

to be dreaded by reason of the possibility of invalidism. The

neuralgic pains, insomnia and mental depression render patients

liable to the morphine habit. In pregnant women there is a tendency

to abortion. In rare cases we may have intestinal haemorrhages with

asthenic manifestations. Bassett-Smith has reported a case with

extensive purpura. The same author in paramelitensis cases has

noted the susceptibility to secondary streptococcal infections.

SYMPTOMS IN DETAIL

_Temperature Chart._—Except in the malignant form of the disease,

when the temperature may be rather continuous, the fever course is

a step-like ascent with daily remissions for about ten days and

then a similar descent. Following an evening rise of temperature

night sweats may be noted.

It is the wave-like succession of such courses of fever, separated

by afebrile intervals, that suggests the name undulant fever.

_Circulatory System._—The disease shows rather a toxic effect on

the heart as shown by palpitation and irregularity and rapidity of

pulse rate.

In the beginning of the fever, however, the pulse rate is not very

fast. Anaemia is a rather marked feature.

_Respiratory System._—A slight bronchitis with cough tends to

suggest phthisis in those cases which show rather marked night

sweats.

_Nervous System._—The organism seems to have a selective action

on the nervous system as shown by headache, various neuralgias,

insomnia, apathy and neurasthenia. Sciatica is probably the most

common peripheral nerve involvement.

_Joint Symptoms._—Very characteristic are the sudden and painful

swellings of various joints, especially hip, shoulder, ankle and

knee. Not rarely the costo-sternal articulations may be involved.

The acute symptoms subside in a few hours and the joints become

normal in a few days.

_Alimentary Tract Symptoms._—The tongue may have a slight furring

but the edges and tip are quite clean and red. Although anorexia

exists with the fever the appetite tends to return with apyrexia.

Constipation is usual. There is frequently tenderness of the

epigastric region.

_Genito-urinary System._—Other than for albuminuria and the

presence at intervals of the causative bacteria in the urine, there

is nothing of note, except the occurrence of orchitis in about 3

per cent. of cases.

_The Blood._—The white count is about normal or slightly

reduced—6500 on the average. The cells of lymphocyte type tend to

show an increase in percentage with a corresponding reduction of

polymorphonuclears.

There is a secondary anaemia.

The spleen shows early enlargement and tenderness.

DIAGNOSIS

=Clinical Diagnosis.=—The diseases most apt to be confused with

Malta fever are typhoid fever, malignant tertian malaria, liver

abscess, influenza, phthisis and kala-azar.

Besides the agglutination, complement fixation or blood culture

aids, we rely upon the sudden onset of joint involvement or

neuralgic manifestations as indicating Malta fever.