Pathogenesis.-The pneumococcus is very pathogenic for mice and rabbits, less so for guinea-pigs.

Subcutaneous inoculation with virulent cultures causes the death of mice in from twenty-four to thirty-six hours, and of rabbits in from thirty-six to forty-eight hours, with septicemia.

This infection is the "sputum-septicemia" of Sternberg. At the autopsy there will be found in the blood everywhere the characteristic encapsulated lancet-shaped organisms, usually in pairs (Fig. 33). Great variation in the virulence of the organism is observed. In some cases no effect will be produced by the inoculation; in others a more or less extensive fibrino-purulent exudation will be produced about the point of inoculation, and the animal will survive for a considerable length of time or recover. Inoculation into the ear-vein or peritoneal cavity of a rabbit will sometimes cause a rapidly fatal septicemia, when subcutaneous inoculation with the same culture will only cause a local reaction. The virulence of the pneumococcus is quickly lessened by cultivation.

Occurrence. The pneumococcus may be demonstrated in the pulmonary exudate of practically all cases of genuine lobar or croupous pneumonia. At autopsies on cases of this disease it may be found in large numbers in the consolidated lung, and sometimes in smaller numbers in the blood of other internal organs. Cultures from the lung may sometimes show the presence of other bacteria in addition to the pneumococcus, but these are to be regarded as either secondary infections or contaminations from the smaller bronchi.

The pneumococci in the pneumonic exudate die in large numbers after a time, and in cases near resolution numerous capsules may be found in cover-glass preparations from the lung in which it is impossible to demonstrate the organism by staining methods.

The pneumococcus is also frequently found in bronchopneumonia, acute peri- and endo-carditis, acute pleuritis and empyema, acute purulent meningitis, and in otitis media. In cases of pneumonia and bronchitis it may be present in the

sputum in large numbers. It has been observed in cases of peritonitis, of synovitis, of osteomyelitis, and of abscess-formation in various situations.

At autopsies on individuals dead of these conditions it may be frequently found, by means of cultures and animal inoculations, generally distributed throughout the internal organs in variable numbers. It is also often present in the mouth and in the saliva of healthy individuals.

Diagnosis. If the pneumococcus be present in very small numbers in pathological material, the quickest and most certain method of demonstrating its presence is the inoculation of a mouse with some of the material (see page 119). This is also the best way to prove the identity of the organism.

The pneumococcus can usually be identified in exudates, blood, tissues, or sputum by examination of cover-glass preparations alone, by reason of its peculiar morphology and its possession of a capsule. The capsule can be seen in most instances in cover-glass preparations, stained in the usual manner, if they be examined in water-mount. The capsules appear as a hyaline material usually with definite outlines surrounding the paired organisms. If it be desired to stain the capsules the following methods may be used. Their working is somewhat uncertain.

Streptococcus Capsulatus.—This seems to be the best name to apply to a capsule-bearing bacterium resembling both the pneumococcus and the streptococcus pyogenes in morphology, but differing definitely from them in cultural and other peculiarities. It has been found chiefly in lobar pneumonia, but occurs in other inflammatory processes and probably has been sometimes mistaken for the pneumococcus or the streptococcus pyogenes. The lack of general recognition of this micro-organism as a separate and distinct species vitiates, to some extent, the value of statistical studies of infections with the streptococcus and the pneu

mococcus.

The best description of the streptococcus capsulatus is

that of Oscar Richardson,' based upon observations on 4 cases of lobar pneumonia in the laboratory of the Massachusetts General Hospital. Richardson points out the following chief characteristics by which it may be distinguished from the pneumococcus and the streptococcus pyogenes:

FIG. 36.

FIG. 36.-Streptococcus capsulatus; glucose-agar stab culture (Oscar Richardson; photos by L. S. Brown).

1. The capsules persist in cultures (see Fig. 37).

2. On the surface of coagulated blood-serum its colonies. are flat, colorless, viscid, mucus-like, of irregular outline, and may attain a diameter of 2 or 3 mm. They may become confluent and form large patches of mucus-like material (see Fig. 35).

3. In glucose-agar stab, adjusted to a reaction of 0.5, there is growth all along the line of inoculation, from which, in Pseudopneumococci in Lobar Pneumonia," Journal of Boston Society of Medical Sciences, vol. v., No. 2, p. 499.

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places, fusiform or hemispherical masses of growth extend into the surrounding medium in a vertical plane, apparently occupying clefts in the medium (Fig. 36). It is very important for the development of these characteristic appearances that the glucose-agar be known to have at the time of inoculation a reaction very close to that above indicated.

FIG. 37. Streptococcus capsulatus from culture (Oscar Richardson; photo by L. S. Brown).

Gonococcus.'-Morphology.-Cocci of medium size, composed usually of two hemispheres separated by a narrow unstained interval. Sometimes two of these pairs of hemispheres are joined together in the manner of "tetrads," or groups of four, showing evidence that division occurs in two directions at right angles to each other (Fig. 38). ized by Gram's method.

Decolor

The gonococcus will not grow satisfactorily upon any of the culture-media ordinarily employed, but requires special

media for its cultivation.

The colonies on suitable culture-media appear after eighteen to twenty-four hours as minute, grayish, translucent points. Later they may attain a diameter of 2 mm. Under

1 Neisser: Centralbl. f. d. med. Wissenschaften, No. 28, 1879; Bumm: Der Mikroorganismus der gonorrhoischen Schleimhauterkrankungen-" Gonococcus Neisser," Wiesbaden, 1887; Wertheim: Archiv f. Gynäkologie, Bd. 42, 1892.

low magnifying power a well-developed colony is seen to consist of a generally circular expansion, with thin, translucent, sharply defined margins, becoming brownish, granular, and denser toward the center, which is made up of coarse brownish clumps closely packed together (Fig. 39).

Special Culture-media.-The essential constituent of culture-media upon which the gonococcus will grow seems

FIG. 38-Gonococci from a culture, showing formation of tetrads and variability in the size of the cocci; X 2000 (Wright and Brown).

to be the blood-serum or similar albuminous fluid from the animal body.

Probably the most convenient culture-medium for the cultivation of the gonococcus is hydrocele-fluid agar. This medium consists of sterile hydrocele fluid mixed with fluid agar-agar at a temperature of 40° C., in the proportion of I part of hydrocele fluid to 2 or 3 parts of agar-agar. The hydrocele fluid is to be obtained under the strictest precautions to avoid contamination with bacteria, thoroughly sterilized vessels, etc., being used.

Ordinary tubes of plain agar-agar (2 per cent.) which have been previously sterilized in the usual manner are melted and