Chapter VIII: Bacteria and Disease (2)

Thus we have the _S. pyogenes aureus_ (golden yellow), _albus_ (white), _citreus_ (lemon), and others. They occur commonly in nature, in air, soil, water, on the surface of the skin, and in all suppurative conditions. The _aureus_ is the only one credited with much virulence. It occurs in the blood in blood-poisoning (septicæmia, pyæmia), and is present in all ulcerative conditions, including ulcerative disease of the valves of the heart.

The _Staphylococcus cereus albus_ and _S. cereus flavus_ are slightly modified forms of the _S. pyogenes aureus_, and are differentiated from it by being non-liquefying. They produce a wax-like growth on gelatine.

_Staphylococcus pyogenes aureus_, the type of the family, is grown in all ordinary media at room temperature, though more rapidly at 37° C. Liquefaction sets in at a comparatively early date, and subsequently we have in the gelatine test-tube cultures a flocculent deposit of a bright yellow amorphous mass, and in gelatine plates small depressions of liquefaction with a yellow deposit. It renders all media acid, and coagulates milk. Its thermal death-point in gelatine is 58° C. for ten minutes, but when dry considerably higher. It is a non-motile and a facultative anaërobe; but the presence of oxygen is necessary for a bright colour. Its virulence readily declines.

2. _Streptococcus pyogenes._ In this species of micrococcus the elements are arranged in chains. Most of the streptococci in pus, from different sources, are one species, having approximately the same morphological and biological characters. Their different effects are due to different degrees of toxic virulence; they are always more virulent when associated with other bacteria, for example, the Proteus family.

The chains vary in length, consisting of more elements when cultured in fluid media. They multiply by direct division of the individual elements, and in old cultures it has been observed that the cocci vary in form and size. This latter fact gave support to the theory that streptococcus reproduced itself by _arthrospores_, or "mother-cells."

In culture upon the ordinary media streptococcus is comparatively slow-growing, producing minute white colonies on or about the sixth day. It does not liquefy gelatine, and remains strictly localised to the track of the inoculating needle. Like the staphylococcus, it readily loses virulence. The thermal death-point is, however, lower: 54° C. for ten minutes. Marmorek has devised a method by which the virulence may be greatly increased, and he holds that it depends upon the degree of virulence possessed by any particular streptococcus as to what effects it will produce. By the adoption of Marmorek's methods attempts have been made to prepare an antitoxin.

_Streptococcus pyogenes_ has been isolated from the membrane of diphtheria, and from small-pox, scarlet fever, vaccinia, and other diseases. In such cases it is not the causal agent, but merely associated with the complications of these diseases. Suppuration and erysipelas are the only pathological conditions in which the causal agency of streptococcus has been sufficiently established.

3. The _Bacillus pyocyaneus_ occurs in green pus, and is the cause of that colouration. Gessard was the first to prove its significance, and he describes two varieties.

It is a minute, actively motile, non-sporulating bacillus, which occasionally complicates suppuration and produces green pus. Oxygen is necessary for pigmentation, which is due to two substances: _pyocyanin_, a greenish-blue product extracted with chloroform, and _pyoxanthose_, a brown substance derived from the oxidation of the former pigment. Both these colours are produced in cultivation outside the body. On gelatine the colour is green, passing on to olive. There is liquefaction. On potato we generally obtain a brown growth (compare _Bacillus coli_, _B. mallei_, and others). The organism grows rapidly on all the ordinary media, which it has a tendency to colour throughout.

It will be remembered that when speaking of the antagonism of organisms, we referred to the inimical action of _Bacillus pyocyaneus_ upon anthrax.

4. _Micrococcus Tetragonus._ This species occurs in phthisical cavities and in certain suppurations in the region of the face. It is a micrococcus usually in the form of small tetrads. A capsule is always present and sometimes discernible.

5. _Bacillus coli communis_ and many putrefactive germs commonly occur in suppurative conditions, but they are not restricted to such disorders (see p. 64).

6. _Micrococcus gonorrhœæ_ (Neisser, 1879). This organism is more frequently spoken of as a diplococcus. It occurs at the acute stage of the disease, but is not readily differentiated from other similar diplococci except by technical laboratory methods. Each element presents a straight or concave surface to its fellow. A very marked concavity indicates commencing fission. The position which these diplococci take up in pus is _intracellular_, and arranged more or less definitely around the nucleus. Difficulty has often been found in cultivating this organism in artificial media outside the body. Wertheim and others have suggested special formulæ for the preparation of suitable media, but it is a very simple matter to secure cultures on agar plates smeared with human blood from a pricked finger. The plate is incubated at 37° C. At the end of twenty-four hours small raised grey colonies appear, which at the end of about four days show adult growth. The margin is uneven, and the centre more opaque than the rest of the colony. This diplococcus is readily killed, and sub-cultures must be frequently made to retain vitality and virulence. Light, desiccation, and a temperature of 55° C. all act germicidally. The organism stains readily in Löffler's blue, but is decolourised by Gram's method. It is more or less strictly parasitic to man. Its shape, size, character of growth, and staining properties assist in differentiating it from various similar diplococci.[98]

+Anthrax.+ This disease was one of the first in which the causal agency of bacteria was proved. In 1849 Pollender found an innumerable number of small rods in the blood of animals suffering from anthrax. In 1863 Davaine described these, and attributed the disease to them. But it was not till 1876 that Koch finally settled the matter by isolating the bacilli in pure culture and describing their biological characters.

It is owing in part to its interesting bacterial history, which opened up so much new ground in this comparatively new science, that anthrax has assumed such an important place in pathology. But for other reasons, too, it claims attention. It appears to have been known in the time of Moses, and was perhaps the disease described by Homer in the First Book of the _Iliad_. Rome was visited by it in 740 B.C.

Anthrax is an acute disease, affecting sheep, cattle, horses, goats, deer, and man. Cats, white rats, and Algerian sheep are immune. Swine become infected by feeding on the offal of diseased cattle (Crookshank).

The _post-mortem_ signs are mainly three: The _spleen_ is greatly enlarged and congested, is friable to the touch, and contains enormous numbers of bacilli; the _skin_ may show exudations forming dark gelatinous tumours; and the _blood_ remains fluid for some time after death, is black, tar-like, contains bubbles of air, and shows other degenerative changes in the red corpuscles, whilst the _small blood-vessels_ contain such vast quantities of bacilli that they may be ruptured by them. Particularly is this true in the peripheral arteries. Many of the organs of the body show marked congestion.

Clinically there is rise of temperature and rapid loss of muscular power. The _bacilli_ of anthrax are square-ended rods 1 µ broad and 4-5 µ long. In the tissues of the body they follow the lines of the capillaries, and are irregularly situated. In places they are so densely packed as to form obstructions to the onward flow of blood. In cultures they are in chains end to end, having as a rule equal inter-bacillary spaces. In cultures long filaments and threads occur. The exact shape of the bacillus depends, however, upon two things: the staining and spore formation. Both these factors may very materially modify the normal shape. The spores of anthrax are oval endospores, produced only in the presence of free oxygen, and at any temperature between 18 and 41° C. On account of requiring free oxygen, they are formed only outside the body. The homogeneous protoplasm of the bacillus becomes granular; the granules coalesce, and we have spores. Each spore possesses a thick capsule, which enables it to resist many physical conditions which kill the bacillus. When the spore is ripe or has exhausted the parent bacillus, it may take on a resting stage, or under favourable circumstances commence germination, very much after the manner of a seed. The spores may infect a farm for many months; indeed, cases are on record which appear to prove that the disease on a farm in the autumn may by means of the spores be carried on by the hay of the following summer into a second winter. Thus, by means of the spores, the infection of anthrax may cling to the land for very long periods, even for years. Spores of anthrax can withstand 5 per cent. carbolic acid or 1-1000 corrosive sublimate for more than an hour; even boiling does not kill them at once, whilst the bacilli without their spores are killed at 54° C. in ten minutes. When the spores are dry they are much more resistant than when moist. Hence the persistence of the anthrax bacillus is due to its spores.

The bacillus is aërobic, non-motile, and liquefying. Broth cultures become turbid in thirty-six hours, with nebulous masses of threads matted together. The pellicle which forms on the surface affords an ideal place for spore formation.

Cultures in the depth of gelatine show a most characteristic growth. From the line of inoculation delicate threads and fibrillæ extend outwards horizontally into the medium. Liquefaction commences at the top, and eventually extends throughout the tube. On gelatine plates small colonies appear in thirty-six hours, and on the second or third day they look, under a low power of the microscope, like matted hair. The colonies after a time sink in the gelatine, owing to liquefaction. On potato, agar, and blood serum anthrax grows well.

_Channels of Infection._ 1. _The Alimentary Canal._ This is the usual mode of infection in animals grazing on infected pasture land. A soil suitable for the propagation of anthrax is one containing abundance of air and proteid material. Feeding on bacilli alone would probably not produce the disease, owing to the germicidal effect of the gastric juice. But spores can readily pass uninjured through the stomach and produce anthrax in the blood. Infected water as well as fodder may convey the disease. Water becomes infected by bodies of animals dead of anthrax, or, as was the case once at least in the south-west of England, by a stream passing through the washing-yard of an infected tannery. Manure on fields, litter in stalls, and infected earth may all contribute to the transmission of the disease. Darwin pointed out the services which are performed in superficial soils by earthworms bringing up casts; Pasteur was of opinion that in this way earthworms were responsible for continually bringing up the spores of anthrax from buried corpses to the surface, where they would reinfect cattle. Koch disputed this, but more recently Bollinger has demonstrated the correctness of Pasteur's views by isolating anthrax contagium from five per cent. of the worms sent him from an anthrax pasture. Bollinger also maintains that flies and other insects may convey the disease from discharges or carcasses round which they congregate.

Alimentary infection in man is a rare form, and it reveals itself in a primary diseased state known as _mycosis intestinalis_, an inflamed condition of the intestine and mesenteric lymph glands.

2. _Through the Skin._ Cutaneous anthrax goes by the name of _malignant pustule_, and is caused by infective anthrax matter gaining entrance through abrasions or ulcers in the skin. This local form is obviously most contracted by those whose occupation leads them to handle hides or other anthrax material (butchers and cleaners of hides). Two or three days after inoculation a red pimple appears, which rapidly passes through a vesicular stage until it is a pustule. Concomitantly we have glandular enlargement, general malaise, and a high temperature. Thus from a local sore a general infection may result. Unless this does occur, the issue will not be fatal, and the bacilli will never gain entrance into the blood or be anything but local.

3. _Respiratory Tract._ In man this is the commonest form of all, and is well known under the term "wool-sorters' disease," or pulmonary anthrax. This mode of infection occurs when dried spores are inhaled in processes of skin-cleaning. It frequently commences as a local lesion affecting the mucous membrane of the trachea or bronchi, but it rapidly spreads, affecting the neighbouring glands, which become greatly enlarged, and extending to the pleura and lung itself. Such cases, as a rule, rapidly end fatally.

From what has been said, it will be clear that anthrax carcasses are better not opened and exposed to free oxygen. An extended _post-mortem_ examination is not necessary. Burning the entire carcass in a crematorium would be the ideal treatment. As such is not generally feasible the next best thing is to bury the carcass deeply with lime below and above it, and rail in the area to prevent other animals grazing off it.

A very small prick will extract enough blood to examine for the anthrax bacilli which are driven by the force of the blood-current to the small surface capillaries. This occurs, of course, only when the disease has become quite general, for in the early stage the healthy blood limits the bacilli to the internal organs. In such cases examination of the blood of the spleen is necessary.

Anthrax covers a wide geographical area all over the world, and no country seems altogether exempt. In Germany as many as 3700 animals have been lost in a single year. About 900 animals were attacked in 1897 in Great Britain.

+Plague.+ This disease, like anthrax and leprosy, has a long historical record behind it. As the Black Death it decimated the population of England in the fourteenth century, and visited the country again in epidemic form in the middle of the seventeenth century, when it was called the Great Plague. Now, it is highly probable that these two scourges and the recent epidemic in the East are all forms of one and the same disease. As a matter of fact, it is difficult to be sure what was the exact pathology of a number of the grievous ailments which troubled our country in the Middle Ages, but from all accounts bubonic plague and true leprosy were amongst them. The former came and went spasmodically, as is its habit; the latter dragged through the length of several centuries.

The distribution of plague at the present time is fortunately a somewhat limited one, namely, a definite area in Asia known as the "Plague Belt." From Mesopotamia, as a sort of focus, the disease spreads northwards to the Caspian Sea, westwards to the Red Sea, southwards as far as Central India, and eastwards as far as the China Sea. This constitutes the "belt," but the disease may take an epidemic form, and is readily, though very slowly, conveyed by infection or contagion. It appears to be infectious by means of infective dust, and contagious by prolonged and intimate contact with the plague-stricken. Rats have been accused of conveying the disease from port to port, and even infecting man. It is clear that rats are not the only agency acting in this way. Nevertheless it is true that rats contract the disease more readily than any other animals, and that when suffering from it they may spread the infection. How it is thus spread it is not known. Drs. Cantlie and Yersin have pointed out that previously to an epidemic of plague rats die in enormous numbers.

The bacteriology of plague is almost the latest addition to the science. Kitasato, of Tokio, demonstrated the cause of plague to be a bacillus during the Hong Kong epidemic in 1894. This was immediately confirmed by Yersin, and further proved by the isolation in artificial media of a pure culture of a bacillus able to cause the specific disease of bubonic plague.

The bacillus was first detected in the blood of patients suffering from the disease. It takes the form of a small, round-ended, oval cell, with marked polar staining, and hence having an appearance not unlike a diplococcus. In the middle there is a clear interspace, and the whole is surrounded with a thick capsule, stained only with difficulty. The organisms are often linked together in pairs or even chains, and exhibit involution forms. In culture the bacillus is even more coccal in form than in the body.

The plague bacillus grows readily on the ordinary media at blood-heat, producing circular cream-coloured colonies with a wavy outline, which eventually coalesce to form a greyish film. The following negative characters help to distinguish it: No growth occurs on potato, milk is not coagulated, and gelatine is not liquefied; Gram's method does not stain the bacillus, and there are no spores; the bacillus is readily killed by heat and by desiccation over sulphuric acid at 30° C. Both in cultures and outside the body the bacillus loses virulence. To this may be attributed possibly the variety of forms of the plague bacillus which differ in virulence. On gaining entrance to the human body the bacillus affects in particular two organs, the spleen and the lymph glands. The latter become inflamed in groups, commencing frequently with those in the armpit (axillary) or groin (inguinal). The spleen suffers from inflammatory swelling, which may affect other organs also. In both places the bacilli occur in enormous numbers. Kitasato considers that the bacillus may enter the body by the three channels adopted by anthrax, namely, the skin, alimentary canal, and respiratory tract.

Haffkine has prepared a vaccine to be used as a prophylactic. He grows a pure culture of Kitasato's bacillus in broth upon the surface of which some globules of fat ("ghee") have been placed. The bacillus grows upon this fat in copious stalactite form. From time to time this growth is shaken down, until after five or six weeks the shaken broth appears milky. The contained bacilli are killed by heating the fluid to 70° C. for one hour. The resultant is the vaccine, of which the dose is 3 cc. Haffkine believes that inoculated persons in India have suffered twenty times less than non-inoculated living under the same conditions.

Plague is essentially a "filth disease," and it is frequently preceded by famine. Temperature and overcrowding exert an influence upon it. The areas affected by the disease in the Middle Ages, in the seventeenth century, and in 1894-96 are alike in being characterised by filth and overcrowding. There is little fear, speaking generally, of the plague ever flourishing under Western civilisation, where the conditions are such that even when it appears there is little to encourage or favour its development.

+Leprosy.+ This ancient disease is said to have existed in Egypt 3500 B.C., and was comparatively common in India, China, and even in parts of Europe 500 B.C. We know it has existed in many parts of the world in the past, in which regions it is now extinct. Some of the earliest notices we have of it in this country come from Ireland, and date back to the fifth and sixth centuries. Even at that period of time also various classical descriptions of the disease had been written and various decrees made by the Church councils to protect lepers and prevent the spread of the disease, which was often looked upon as a divine visitation. In the tenth century leprosy was prevalent in England; it reached its zenith in the thirteenth century, or possibly a little earlier, and declined from that date to its extinction in the sixteenth. But even two hundred years later leprosy was endemic in the Shetlands, and it is recorded that in 1742 there was held a public thanksgiving in Shetland on account of the disappearance of leprosy.

At one time or another there were as many as two hundred institutions in the British Isles for the more or less exclusive use of lepers. Many of these establishments were of an ecclesiastical or municipal character, and probably the exact diagnosis of diseases was a somewhat lax matter. Bury St. Edmunds, Bristol, Canterbury, London, Lynn, Norwich, Thetford, and York were centres for lepers. Burton Lazars and Sherburn, in Durham, were two of the more famous leper institutions.

At the present time the distribution of the disease is mostly Asiatic. Norway contains about 1200 lepers, Spain approximately the same number. Scattered through Europe are perhaps another 600 or 700, in India 100,000, and a large number in Japan. The Cape possesses a famous leper hospital on Robben Island, with a number of patients. The disease is also endemic in the Sandwich Islands.

Descriptions of the pathological varieties of leprosy have been very diverse. The classification now generally adopted includes three forms: the _tuberculated_, the _anæsthetic_ (or maculo-anæsthetic), and the _mixed_. _Lepra tuberculosa_ is that form of the disease affecting chiefly the skin, and resulting in nodular tuberculated growth or a diffuse infiltration. It causes great disfigurement. The anæsthetic form causes a destruction of the nerve fibres, and so produces anæsthesia, paralysis, and what are called "trophic" changes. Not infrequently patches occur on the skin, which appear like parchment, owing to this trophic change. Bullæ may arise. When the tissue change is radical or far advanced, considerable distortion may result. The mixed variety of leprosy, as its name implies, is a mixture of the two other forms.

The _Bacillus lepræ_ was discovered by Hansen in 1874. He found it in the lepra cells in the skin, lymph glands, liver, spleen, and thickened parts of the nerves. It is common in the discharges from the wounds of lepers. It is conveyed in the body by the lymph stream, and has rarely been isolated from the blood (Köbner).

(From liver of rat)

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_By permission of the Scientific Press, Limited_]

(From the tissues of a leper)

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The bacillus is present in enormous numbers in the skin and tissues, and has a form very similar indeed to _Bacillus tuberculosis_. It is a straight rod, and showing with some staining methods marked beading, but with others no beading at all. It measures 4 µ long and 1 µ broad. Young leprosy bacilli are said to be motile, but old ones are not. Neisser has maintained that the bacillus possesses a capsule and spores. The latter have not been seen, but Neisser holds that this is the form in which the bacillus gains entrance to the body. There is a characteristic which fortunately aids us in the diagnosis of this disease in the tissues, and that is the arrangement of the bacilli, which are rarely scattered or isolated, but gathered together in clumps and colonies. Bordoni-Uffreduzzi and Campania claim to have isolated the bacillus and grown it on artificial media, the former aërobically on peptone-glycerine-blood-serum, at 37° C., the latter anaërobically. But no other worker has been able to do this. Hence we are not able to study the bacteriology of leprosy at all completely, nor have inoculation experiments proved successful. Nevertheless there is little doubt that leprosy is a bacterial disease produced by the bacillus of Hansen. Bordoni-Uffreduzzi maintains that the parasitic existence of the _Bacillus lepræ_ may alternate with a saprophytic stage. This may be of importance in the spread of the disease. There is evidence in support of the non-communicability of the disease by heredity or contagion. Segregation does not appear always to result in a decline of the disease, as we should expect if it were purely contagious. Ehlers, of Copenhagen, has, however, as recently as 1897, reaffirmed his belief in the contagiousness of leprosy; Virchow, on the other hand, has declared that it is not highly contagious. There is evidence to show that persons far advanced in the disease may live in a healthy community and yet not infect their immediate neighbours. Indeed, the transmission of the disease is still an unsolved problem. Mr. Hutchinson suggests diet, particularly uncooked or putrid fish, as a likely channel; on the other hand, leprosy appears in districts where no fish is eaten. Deficiency of salt, telluric and climatic conditions, racial tendencies, social status, poverty, insanitation, drinking water, even vaccination, have all secured support from various seekers after the true channel by which the bacillus gains entrance to the human body. The real mode of transmission is, however, still unknown. The decline and final extinction of leprosy in the British Islands was probably due in part to the natural tendency of the disease, under favourable hygienic circumstances, to die out, and in part to a general and extensive social improvement in the life of the people, to a complete change in the poor and insufficient diet, and to agricultural advancement, improved sanitation, and land drainage.

At the Leprosy Congress held in Berlin in 1897, Hansen again emphasised his belief that segregation was the cause of the decline of leprosy wherever it had occurred. But there appears to be some evidence to show that leprosy has declined where there has been no segregation whatever, and therefore, however favourable to decline such isolation may be, it would seem not to be actually necessary to the decline. At the same Congress Besnier declared in favour of the infective virus being widely propagated by means of the nasal secretion. Sticker states that the nasal secretion contains millions of lepra bacilli, especially in the acute stage of the disease, and Besnier and Sticker have pointed out how frequently and severely the septum nasi and skin over the nose are affected in leprosy. Several leprologists in India have recorded similar observations. These facts appear to support Besnier's contention that the disease is spread by nasal secretion.

We may fitly add here the conclusions arrived at by the English Leprosy Commission[99] in India:

"1. Leprosy is a disease _sui generis_; it is not a form
of syphilis or tuberculosis, but has striking etiological
analogies with the latter.

"2. Leprosy is not diffused by hereditary transmission, and,
for this reason and the established amount of sterility among
lepers, the disease has a natural tendency to die out.

"3. Though in a scientific classification of diseases leprosy
must be regarded as contagious, and also inoculable, yet the
extent to which it is propagated by these means is exceedingly
small.

"4. Leprosy is not directly originated by the use of any
particular article of food, nor by any climatic or telluric
conditions, nor by insanitary surroundings, neither does it
peculiarly affect any race or caste.

"5. Leprosy is indirectly influenced by insanitary
surroundings, such as poverty, bad food, or deficient drainage
or ventilation, for these by causing a predisposition increase
the susceptibility of the individual to the disease.

"6. Leprosy, in the great majority of cases, originates _de
novo_, that is, from a sequence or concurrence of causes and
conditions dealt with in the Report, and which are related to
each other in ways at present imperfectly known."

The practical suggestions of the Commission for preventive treatment included voluntary isolation, prohibition of the sale of articles of food by lepers, leper farms, orphanages, and "improved sanitation and good dietetic conditions" generally. Serum-therapy has been attempted on behalf of the French Academy of Medicine, but without success. Many forms of treatment ameliorate the miserable condition of the leper, but up to the present no curative agent has been found.

+Pneumonia.+ Some of the difficulty which has surrounded the bacteriology of inflammation of the lungs is due to the confusion arising from supposing that attacks of the disease differed only in degree. Pneumonia, however, has various forms, arising now from one cause, now from another. The specific or croupous pneumonia is associated with two organisms: Fraenkel's diplococcus and Friedländer's pneumo-bacillus. Several other bacteria have from time to time been held responsible for pneumonia, a streptococcus receiving, at one time, some support. But whilst opinion is divided on the rôle of various extraneous and concomitant bacteria in lung disease, importance is attached to Fraenkel's and Friedländer's organisms.

The _diplococcus_ of Fraenkel is a small, oval diplococcus found in the "rusty" sputum of croupous pneumonia. It is non-motile, non-liquefying, and aërobic. When examined from cultures the diplococci are frequently seen in chains, not unlike a streptococcus, and there is some reason to suppose that this form gave rise to the belief that it was another species; when examined from the tissues it possesses a capsule, but in culture this is lost. It is difficult to cultivate, but grows on glycerine agar and blood serum at blood-heat. On ordinary gelatine at room temperature it does not grow, or, if so, very slightly. The ideal fluid is a slightly alkaline liquid medium, and in twenty-four hours a powdery growth will occur in such broth. On potato there is apparently no growth. It rapidly loses its virulence on solid media, and is said to be non-virulent after three or four sub-culturings. A temperature of 54-58° C. for a few minutes kills the bacteria, but not the toxin. This, however, is removed by filtration, and is therefore probably intracellular. It is attenuated by heating to 70° C.

Fraenkel's diplococcus occurs, then, in the acute stage of pneumonia, in company with streptococci and staphylococci. It also occurs in the blood in certain suppurative conditions, in pleurisy and inflammation of the pericardium, and sometimes in diphtheria, and therefore it is not peculiar to pneumonia.

There is one other point to which attention should be drawn. Fraenkel's organism is said to be frequently present in the saliva of healthy persons. Pneumonia depresses the resistant vitality of the tissues, and thus affords to the diplococcus present in the saliva an excellent nidus for its growth.

_Friedländer's Pneumo-bacillus_ is a capsulated oval coccus, assuming the form of a small bacillus. It is inconstant in pneumonia, unequally distributed, and scarce; it is aërobic, and facultatively anaërobic; it occasionally occurs in long forms and filaments; it is non-motile, non-liquefying, and has no spores; it does not stain by Gram's method, which stain is therefore used for differential diagnosis; it will grow fairly well in ordinary gelatine at 20° C.; and it is a denitrifying organism, and also an actively fermentative one, even fermenting glycerine. It is not unlike _Bacillus coli communis_, and to distinguish it from that organism we may remember that the _B. coli_ is motile, never has a capsule, produces indol, and does not ferment glycerine.

+Influenza.+ In 1892, during the pandemic of influenza, Pfeiffer discovered a bacillus in the bronchial mucus of patients suffering from the disease. It is one of the smallest bacilli known, and frequently occurs in chains not unlike a streptococcus. Carron obtained the same organism from the blood. In the bronchial expectoration it can retain its virulence for as long as a fortnight, but it is quickly destroyed by drying. The bacillus is aërobic, non-motile, and up to the present spores have not been found. It grows somewhat feebly in artificial media, and readily dies out. Blood serum, glycerine agar, broth, and gelatine have all been used at blood-heat. It does not grow at room temperature. Pfeiffer's bacillus appears most abundantly at the height of the disease, and disappears with convalescence. It is said not to appear in any other disease.

+Yellow Fever.+ Sternberg and Havelburg have both isolated bacilli from cases of yellow fever; but the organism discovered by Sanarelli, the _Bacillus icteroides_, is now accepted as the causal agent of the disease. It is a small, short rod, with round ends, and generally united in pairs; it has various pleomorphic forms; it grows well on all the ordinary media; it is killed in sea-water at 60° C., and also by direct sunlight in a few hours.

+Diarrhœa of Infants.+ From time to time different organisms have been isolated in this diseased condition. _Bacillus coli_ and _B. enteriditis sporogenes_ (Klein) have been held responsible for it. W. D. Booker, of Johns Hopkins University, sums up an extended research into the question as follows:

"No single micro-organism is found to be the specific exciter
of the summer diarrhœa of infants, but the affection is
generally to be attributed to the result of the activity of
a number of varieties of bacteria, some of which belong to
well-known species, and are of ordinary occurrence and wide
distribution, the most important being the streptococcus and
_Proteus vulgaris_.

"The first step in the pathological process is probably
an injury to the epithelium from abnormal or excessive
fermentation, from toxic products of bacteria, or from other
factors.

"Bacteria exert a direct injury upon the tissues in some
instances, whereas in others the damage is brought about
indirectly through the production of soluble poisons."

+Actinomycosis.+ This disease affects both animals and man. As Professor Crookshank points out, it has long been known in this country,[100] but its various manifestations have been mistaken for other diseases or have received popular names.

Here we can only mention the most outstanding facts concerning the disease. It is caused by the "ray fungus," or _Streptothrix actinomyces_, which, growing on certain cereals, often gains entrance to the tissues of man and beast by lacerations of the mucous membrane of the mouth, by wounds, or by decayed teeth. Barley has been the cereal in question in some cases. The result of the introduction of the parasite is what is termed an "infective granuloma." This is, generally speaking, of the nature of an inflammatory tumour composed of round cells, epithelioid cells, giant cells, and fibrous tissue, forming nodules of varying sizes. In some cases they develop to large tumours, in others they soon break down. Actinomycosis in some ways closely resembles tuberculosis in its tissue characters.

In the discharge or pus from human cases of the disease small sulphur-yellow bodies may be detected, and these are tufts of "_clubs_" which are the broken-down rays of the parasite; for in the tissues which are affected the parasite arranges itself in a radiate manner, growing and extending at its outer margin and degenerating behind. In cattle the centre of the old ray becomes caseated, like cheese, or even calcified, like a stone. In the human disease abundant "_threads_" are formed as a tangled mass in the middle of the colony. As clubs characterise the bovine actinomycosis, so threads are a feature of the human form of the disease. But in both there is a third element, namely, _small round cells_, called by some spores, by others simply cocci. Authorities are not yet agreed as to the precise significance and rôle of these round cells. The life-history of the micro-organism may be summed up thus:

"The spores sprout into excessively fine, straight or sinuous,
and sometimes distinctly spirilliform threads, which branch
irregularly and sometimes dichotomously. The extremities of
the branches develop the club-shaped bodies. The clubs are
closely packed together, so that a more or less globular body
is formed, with a central core composed of a dense mass of
threads" (Crookshank).

Possibly these clubs represent organs of fructification, and produce the spores. These latter are, it is believed, set free in the vicinity of the ray, and create fresh centres of disease.

In _man_ the disease manifests itself in various parts according to the locality of entrance. When occurring in the mouth it attacks the lower jaw most frequently. In one recorded case the disease was localised to the bronchi, and did not even extend into the lungs. It was probably contracted by inhalation of the parasite. The disease may spread to distant parts by means of the blood stream, and frequently the abscesses are apt to burrow in various directions.

In the _ox_ the disease remains much more localised, and frequently occurs in the lower jaw, palate, or tongue. In the last site it is known as "wooden tongue," owing to the hardness resulting. The skin and subcutaneous tissues are also a favourite seat of the disease, producing the so-called wens or clyers so commonly seen in the fen country (Crookshank). Actinomycosis in cattle is specially prevalent in river valleys, marshes, and on land reclaimed from the sea. The disease occurs at all seasons, but perhaps more commonly in autumn and winter. It is more frequently met with in young animals. The disease is probably not hereditary nor readily communicated from animal to animal.

Actinomyces may be cultivated, like other parasitic diseases, outside the body. Gelatine, blood serum, agar, glycerine agar, and potato have been used for this purpose. After a few days on glycerine agar at the temperature of the blood little white shining colonies appear, which increase and coalesce. In about ten days' time the culture often turns a bright yellow, though it may remain white or even take on a brown or olive tint. The entire mass of growth is raised dry and crinkled, and composed almost exclusively of threads. In its early stage small bacillary forms occur, and in its later stage coccal forms. True clubs never occur in pure cultures, although the threads may occasionally show bulbous endings.

+Glanders+ in the horse and ass, and sometimes by communication in man also, is caused by a short, non-motile, aërobic bacillus, named, after the old Roman nomenclature (_malleus_), _Bacillus mallei_. It was discovered in 1882 by Löffler and Schütz. It is found in the nasal discharge of glandered animals. In appearance the bacillus is not unlike _B. tuberculosis_, except that it is shorter and thicker. The beading of the bacillus of glanders, like that in tubercle, does not denote spores. _B. mallei_ can be cultivated on the usual media, especially on glycerine agar and potato. On the latter medium it forms a very characteristic honey-like growth, which later becomes reddish-brown.

In the horse glanders particularly affects the nasal mucous membrane, forming nodules which degenerate and emit an offensive discharge. From the nose, or nasal septum, as a centre, the disease spreads to surrounding parts. It may also occur as nodules in and under the skin, when it is known as "farcy." Persons attending a glandered animal may contract the disease, often by direct inoculation.

_Mallein_ is a substance analogous to tuberculin, and is made by growing a pure culture of _Bacillus mallei_ in glycerine-veal broth in flat flasks, with free access of calcined air. After a month's growth the culture is sterilised, filtered, concentrated, and mixed with an equal volume of a .5 per cent. solution of carbolic. The dose is 1 cc., and it is used, like tuberculin, for diagnostic purposes. If the suspected animal reacts to the injection, it is suffering from glanders. Reaction is judged by three signs, namely, a rise of temperature 2-3° C., a large "soup-plate" swelling at the site of inoculation, and an enlargement of the lymphatic glands.

_Swine fever_, _foot-and-mouth disease_, _chicken cholera_, _dysentery_, _rinderpest_, and other diseases of animals have microorganisms intimately related to them.

There is a group of diseases due to the presence in the blood or tissues of _hæmatozoa_, that is, protozoa which can live and perform their function in the blood. Amongst these are malaria, sleeping sickness, and other tropical diseases in man, and surra and various hæmatozoa in horses, fish, frogs, or rats.

_Malaria._ Although a _Bacillus malariæ_ has been described as the cause of this disease, it is now almost universally supposed that the true cause is a protozoan parasite. In 1880 Laveran first described this organism, and the discovery was confirmed by Marchiafava, Celli, and others. Laveran claimed that it occurred in four different forms during the progress of its life-history:

(_a_) _Spherical or Irregular Bodies_ attached to the blood corpuscle, or free in the blood plasma. They are a little smaller than the blood-cells, and may or may not contain pigment. They eventually invade the corpuscles, possess more pigment, and lose their amœboid movement. Within the red blood corpuscles they increase in size until they reach the adult stage.

(_b_) _Segmentation Forms_, often assuming a rosette shape, follow next. They are pigmented, are possibly a sporing stage, and are finally set free in the blood.

(_c_) _The Crescents_, or _Semilunar Bodies_, are free in the blood, but motionless. They are colourless, have a distinct membrane, and generally show a little pigment about the middle; they taper towards the poles. They appear in the blood after the fever has existed for some time, occurring chiefly, sometimes only, in the quotidian and malignant types of malaria.

(_d_) _The Flagellated Bodies_ apparently occur only in the blood outside the body. They are extracorpuscular bodies, and possess several long flagella, and are therefore actively motile. They are derived from the crescents or irregular intracorpuscular bodies.

What is the precise significance of these various forms and modifications of them is not at present known. Possibly the semilune is a resting stage inside the body, and the flagellated body another similar stage outside. Attempts to cultivate the parasite outside the body have failed. There is a good deal of evidence to show that the mosquito is the host outside the human body. There may be different forms and varieties of parasite, if not actually different species, causing the diverse forms of clinical malaria.

The above account of diseases caused by bacteria does not profess to be in any sense exhaustive. It is merely illustrative. It reveals some of the disease-producing powers of micro-organisms. There are a large number of other diseases in which bacteria have been found. They are not the causes, but only accidentally present or associated with "secondary infection." Variola (small-pox), scarlet fever, and measles are excellent examples. It is possible that the danger at the present time is rather in the direction of supposing that every disease will readily yield its secret to the bacteriologist. Such, of course, is not the case. Nevertheless, as in the past, so in the future, constant research and patient investigation is the only hope we have for the elucidation of truth in respect to the causes of disease.