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HE organisms most commonly met with in acute inflammation of the lungs are the pneumococcus and streptococcus. Other organisms occasionally encountered are the bacillus influenzæ, Friedlander's bacillus, Staphylococcus aureus and Staphylococcus albus. Cases of mixed infection often occur with a combination of any of these, a mixed infection with pneumococcus and streptococcus being quite common.

The etiological agent concerned in the majority of cases of acute lobar pneumonia is the pneumococ

cus.

This organism was first described independently by Pasteur and Steinberg, and later in 1884 the investigation of Frankel and Weichselbaum established the causal relationship of the pneumococcus to pneumonia.

Morphologically the pneumococcus is a small oval shaped coccus usually occurring in pairs-whence the synonym "diplococcus lanceolatus." Variations in size and form often occur, however, especially in culture media. The frequent formation of short chains produces a very striking resemblance to streptococcus, from which it is often distinguished with difficulty. Pneumococcus, however, possesses the property of undergoing solution in bile or its salts. Bile solubility is now recognized as a distinctive biological character of pneumococcus which serves to differentiate it from streptococci and closely allied

organisms. Pneumococcus stains readily with the aniline dyes and by Gram's method retains the stain. In sputum, blood and exudates, the organism is surrounded by an envelope called a capsule which can be demonstrated by appropriate staining methods. In cultures grown outside the body the capsule has a tendency to disappear and cannot be demonstrated except in certain strains and under certain conditions.

Four Types of Pneumococci.

It has been known for some time that all races of pneumococci are not identical, which fact has formerly been the cause of much disappointment in the treatment of pneumonia by serum therapy. Through the researches of Avery, Cole, Chickering and Dochez, at the Rockefeller Institute, it has been shown that the pneumococci fall into four groups, designated a: Types I, II, III and IV, each possessing common immunologic characters. Types I, II and IV are indistinguishable from each other morphologically and are only separated by serological reactions.

Type III consists of pneumococcus mucosus. It is somewhat larger and rounder than the others, possesses a large distinct capsule which usually retains the pink counter stain with Gram's method. Colonies of Type III on blood media are moist, mucoid and confluent, in contrast to the distinct,

From the above table it would appear that. Types I and II are the most common causes of pneumococcus infection in man, giving rise to more than sixty percent of the cases of lobar pneumonia. Type III (pneumococcus mucosus) gives the lowest incidence in disease of the different types of pneumococcus. Similar studies conducted at various hospitals give results which tend to confirm these.

The large number of cases of pneumonia which have developed in army cantonments during the past year has afforded an unusual opportunity for studying the relative frequency of these types. At

All of these cases were classed as lobar pneumonia, although it was admitted that not infrequently at necropsy it was found they had been dealing with broncho pneumonia. At this camp it is seen that Type II gave the highest incidence of the pneumococcus infections.

In a study of thirty-two cases of lobar pneumonia at Fort Sam Houston, seventeen were associated with Type I pneumococcus, three with Type II, four with atypical Type II, one with Type III, six with Type IV and one with streptococcus mucosus: of these cases more than one-half were due to Type I. In contrast to these findings, a summary of 165 determinations of pneumococci made at Camp Zachary Taylor showed Type IV as the etiological agent in 56.3 percent of the cases, while Types I and II were found in 22.4 percent and 21.3 percent respectively; Type III was entirely ab

sent.

From the above data it is evident

that Type III is only occasionally the cause of pneumonia. The frequency of the other types seems to vary in different localities and at different times. In one group of cases, Type I may show the highest incidence, whereas in another group Types II or IV may predominate.

Although very few cases of pneumonia are due to Type III pneumococcus, it gives rise to the highest mortality. Reports of bacteriological findings of the broncho pneumonia occurring as a sequel to the present epidemic of Spanish influenza show that the pneumococcus is the causative organism. At Camp Sherman Type IV has been responsible for the majority of such cases. At Camp Devens Type I occurred in a normal number of cases, or about twenty percent.

Methods of Identifying Types.

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Various methods have devised for isolating and determining these four types. The most successful and rapid method for isolating the pneumococcus has been the inoculation test upon white mice, which are highly susceptible to pneumococcus inoculations and usually succumb within five to twenty-four hours. This method, briefly, consists in injecting an emulsified kernel of the suspected sputum into the peritoneal cavity of a white mouse. The pnemococcus grows rapidly in the peritoneum of the mouse, while the majority of other organism rapidly die off, with a few exceptions, notably B. influenzae and Friedlander's bacillus. Pneumococcus invasion of the blood stream occurs early. As a rule there is sufficient growth in the peritoneum for type determination in six to eight hours. As soon as the mouse appears sick

a drop of peritoneal exudate is removed, by puncture with a capillary pipette, and examined to determine if there is an abundance of growth. If there is an abundant growth, of pneumococci alone, the peritoneal exudate is washed out with four to five cubic centimeters of sterile salt solution into a centrifuge tube. The washings are then centrifuged slowly to throw down the fibrin and cells and the supernatant fluid is then drawn off and centrifuged at high speed to throw down the cocci. The sediment cocci are suspended in saline. This suspension is used directly for microscopic agglutination tests, being mixed with the specific immune serum of types I, II, and III, of the optimum dilution, and incubated for one hour. If agglutination does not take place with any of these serums the pneumococci are assigned to group IV. Presence of other organisms in the peritoneal fluids often interferes with agglutination. To obviate this a precipitin test is made, which depends upon the fact that during the period of active growth of the pneumococci in the peritoneum a soluble substance is produced which gives a specific precipitin reaction with its homologous antipneumococcic serum,. In this method the peritoneal washings are centrifuged at high speed to throw down fibrin, cells and bacteria and the clear supernatant fluid is mixed with the diluted specific antipneumococcic sera in equal amounts. An immediate specific reaction occurs in the tube containing homologous immune sera, the others remaining clear. The entire process of obtaining the organisms and performing the differentiation tests may be accomplished in a little more than six hours.

Owing to the difficulty of procuring white mice for inoculation purposes, a method has been devised by Avery for growing the pneumococci from sputum. This method, which has proved quite successful, consists in inoculating beef infusion broth containing one percent dextrose to which is added one cubic centimeter of sterile defibrinated blood with an emulsified kernel of the patient's sputum. This medium is particularly selective for the pneumococcus, which outgrows the usual throat organisms and gives a luxuriant growth usually in five or six hours. Agglutination reactions are carried out with a suspension of the cocci in the same manner as with with the peritoneal washing of the mouse. In carrying out the precipitin test the pneumococci are dissolved with bile and the resultant solution is mixed with the specific immune sera in the proper proportions.

Not only are the pneumococci found in the sputum but they also may be obtained from blood culture. It has been stated by Fränkle that in most, if not all, cases of lobar pneumonia, at some time during the disease the pneumococci can be found. The larger percentage of blood cultures, however, has given negative findings. Where it is impossible to obtain a suitable specimen of sputum, lung puncture is occasionally resorted to and cultures made of the material obtained. In case of empyema the organisms are found in the fluid in large numbers.

Distribution of Pneumococci.

The pneumococcus is a widely distributed organism and is a common inhabitant of the healthy mucous membrane of man. Туре

IV is the organism usually present in healthy persons. Types I and II are practically never found except in the environment of persons ill with the disease or carriers. Pneumatic sputum dried in the air and exposed to diffuse daylight retains its virulence for several weeks. In spray from coughing the organisms probably never survive over a few hours. In pneumonia the influence of predisposing factors is of almost supreme significance. When the resistance of the body is lowered by exposure to cold, dampness or by disease, especially measles and influenza, the pneumococci normally present in the respiratory passages may gain a foothold and cause infection. Infection is more apt to occur, however, when pneumococci from patients ill with the disease or convalescent are transferred to persons with a lowered resistance. În accordance with the biological law that the virulence of an organism is enhanced by continued passage through animals, pneumococci from a pneumonia patient are far more virulent than those that have been leading a more saprophytic existence.

Anti-Pneumococci Serum.

It has been known for some time that the serum of animals which have been immunized against pneumococci is able to protect other animals against a fatal infection. Early attempts, however, to apply the same principles to man by employing immune horse serum met with disappointing and inconclusive results. Further experiments conducted at the Rockefeller Institute have shown that anti-pneumococcic serum is protective and curative, only when the specific serum against the type of organism

causing the infection is used. It has been demonstrated that pneumococcus serum prepared by the injection of Type I pneumococcus is highly effective in the treatment of cases of pneumonia due to the same type of organism. The serum of Type II has given less favorable results and it has not yet been clearly demonstrated whether it has any curative value or not. Type III serum has given such slight protective power to laboratory animals that therapeutic application has not seemed justifiable. There are so many different types of pneumococci belonging to Group IV that the difficulty in preparing a serum against this group is obvious.

In general the sera now in use are prepared by injecting healthy horses with gradually increasing doses first of dead and then living pneumococci. When the serum of the horse has been found to possess sufficient protective power the animal is bled under strictly aseptic

technic. The blood is allowed to clot and the resulting serum is stored in the refrigerator for two months. After it has been tested for sterility and toxicity it is ready for dispensing. In administering the serum the patient first must be tested for sensitiveness with horse serum. If the intradermal skin test is positive, the patient should be desensitized by injecting extremely small amounts of serum subcutaneously at one-half hour intervals, doubling the size of dose at each injection. Experience has shown that anti-pneumococcic serum, to be effective, must be given in large doses and intravenously. As a rule doses of ninety to one hundred cubic centimeters are given at eight hour intervals,

the total amount averaging about 250 cubic centimeters.

Keys in the Journal of Medical Research for July, 1918, reports that he has produced a powerful anti-pneumococcic serum by injecting massive doses of virulent cultures into domestic fowl intraperitoneally. He found that intravenous doses of two and one-half cubic centimeters of the immune serum, on an average of three injections, gave beneficial results. Polyvalent and univalent sera were used. In a group of patients who were inoculated the death rate was 20.8 percent while 45.3 percent of the non-inoculated die.

Serum treatment has been practiced extensively in our Army hospitals during the past year. Reports as to the results of this treatment have been made to the

Surgeon General, but as yet they have not been made public. No doubt these reports will shed considerable light upon the value of serum therapy in the treatment of pneumonia.

Stewart in the Medical Record for August, 1918, states that, in the opinion of Army surgeons with whom he has talked, the use of polyvalent serum possessing antibodies for Types I, II, and III, serves a better purpose than the employment of Type I alone. because it produces more or less immunity to reinfection.

As a measure of prophylaxis, vaccination, although it has not as yet been given a fair trial, promises to be particularly valuable. Lister, of the South Africa Institute of Medical Research, has been the first to report successful vaccination. His researches were conducted among the diamond workers at Kimberly, where pneumonia is prevalent. He reports