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(316) The Middlesborough Epidemic.

To these examples may be added the Middlesborough epidemic,1 investigated by Dr. Ballard. Middlesborough itself has a population of about 69,000, and the adjacent sanitary districts of Ormesby, Normanby, and Eston, are something in the aggregate about 28,000. The epidemic period extended over twenty-four weeks from January 20th to July 14th, 1888, during which time there were 369 fatal cases of pneumonia; this, probably, represented some 1,000 cases, for the mortality of 762 known cases was 231 per cent. There was an exceptional mortality among males, and an exceptional incidence on certain age periods. On each 10,000 males the incidence was 64, on each 10,000 females, 16. The rate of mortality in the group under 15 years of age was about the average, but above 15 about 5 times that of the mean annual mortality for corresponding periods. In the age group, 15 to 45 years, the rate of the mortality was 46 times that of the mean of eight years, and at ages above 45 it was 54 times that of the Dr. Ballard gives a clear account of the symptoms, and also of the post-mortem appearances, these differ but little from the acute pleuro-pneumonia that any one who has practised in rural districts is quite familiar with. There was ample evidence of its infective character.

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(317) Etiology of Pneumonia.

Gamaléia's Views.

Gamaléia has carefully worked out the bacteriology of pneumonia, and his views are as follows:

He considers that the streptococcus lanceolatus is the cause of pneumonia. This same micro-organism under the name of the diplococcus lanceolatus is, according to Professor Pio Poa and Dr. Guido Bordoni Ufferduzzi, the cause of epidemic cerebro-spinal meningitis (see Public Health, vol. i. p. 85). Its presence is constant in pneumonia. This is proved not alone from the clinical experience of others, but from his own observations on twelve autopsies. "I have studied," says Gamaléia, "these post mortems

1 Supplement to Eighteenth Annual Report of the Local Government Board, 1888-89.

2 "The Etiology of Fibrinous Pneumonia in Man." by N. M. Gamaléia. (Annales de l'Institut Pasteur. No. 8, August, 1888.) Public Health, vol. ii.

without choice, and in the order in which they presented themselves on the dissecting table. Some cases had been erroneously diagnosed as those of typhoid fever or miliary tuberculosis, but I only accepted the diagnosis revealed by the corpse. Thus I have collected varied forms of pneumonia-simple pneumonia of a single lobe, double pneumonia, pneumonia complicated with cerebro-spinal meningitis and endocarditis. The duration of the malady was also variable, and I had under observation the different anatomical forms of the sick lung, the initial hyperæmia, the red hepatisation, grey hepatisation, and abscess. Each case has served

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(a) To make cultures on gelatin.

(b) To make stained microscopical preparations of the juice of different organs.

"(c) To inoculate animals sensible to the pneumonic virus.

The first method rarely succeeded, because the autopsies were made long after death, and the culture of our microbe on solid media is very difficult. A small number of foreign germs prevents the specific culture. The second process has on the contrary always given me positive results, and I have always been able to recognize as cause of the evil the streptococcus lanceolatus, that is to say the double lanceolate coccus surrounded by a clear or coloured coccus, retaining the violet coloration of Gram. But on this subject there are important remarks to make. The lanceolate coccus has not always its typical form and aspect. It sometimes happens that in a rabbit or mouse dead of septic pneumonia that the microbes in the blood and even in the spleen present themselves under the form of simple cocci without capsule, whilst the liver and kidneys are full of typical diplococci. Nevertheless, it has only happened to me in three lungs out of the twelve not to find typical forms, but even in these the specific microbe appeared with all its distinctive characters in other parts of the same body (fibrinous pleuritic exudation, spleen, dura mater of spinal cord). Besides, in the human lung (likewise in the sheep), the pneumonic coccus has often its capsule coloured, and as this coloured capsule may be elongated and tortuous, it singularly disfigures the appearance of the microbe. On the contrary, the cocci absorbed by the leucocytes, as is the rule in the first period of the pneumonic affection in the man and the dog often remain as colourless as their

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capsules, and are only distinguished as little regular vacuoles in the bodies of cells. Lastly, the same thing may happen which has been observed in the spleen in anthrax, and especially in the oedema of anthrax-that is, the soluble products excreted by the virulent microbes render every preparation too confused to allow the typical form of the microbe to be distinguished. This may be remedied by washing the preparation with alcohol after passing it through the flame.

"These reserves made, I affirm I have always seen the microbe of Pasteur in the pneumonic corpse."

Gamaléia next speaks of the success of his inoculations. He finds the mouse more sensitive than the rabbit. The mouse "inoculated under the skin with an emulsion of pneumonic sputa, dies in twentytwo hours, and presents at the autopsy a mass of typical microbes in the blood and organs." He next deals with the objection made against the etiological unity of fibrinous pneumonia, especially on behalf of Friedlander's microbe. This last microbe is found normally in saliva. It is a good saprophyte, and invades sometimes the diseased or dead lung. Weichselbaum found it in 70 per cent. of his cases, but, with the exception of three cases, always mixed with other microbes. As to the researches of authors preceding Frankel, it is certain the microbe they called Friedlander, which they found, was no other than that of Pasteur, since it was stained by the method of Gram which decolourises the bacillus of Friedlander. As to the experimental production of pneumonia by cultures of Friedlander's microbe, there is no doubt several bacteria will produce pneumonia. Such for instance which determine at the seat of inoculation a sero-fibrinous exudation, as the microbe of fowl cholera, and the bacteria of charbon.

(318) Pathogenic Role of the Streptococcus Lanceolatus.

Contrary to general belief, this microbe does produce typical pneumonia in the dog and sheep. The experiments which follow were made with virulent pneumonic virus, that is with the Pasteur microbe taken from the human corpse, or isolated from pneumonic sputa, and its virulence increased by several passages through rabbits. The successive passages through the organism of the rabbit, especially if the inoculation has been intravenous, augments

manifestly the virulence of the pneumonic streptococcus. The time elapsing between infection and death becomes progressively shorter from twenty-four hours to twelve, and even to five hours. The character of the disease is also changed; instead of the prolonged febrile affection with meningitic complications, produced by the ordinary virus, a sort of poisoning appears, which commences. with the infection, and leads to a tranquil death, preceded by a progressive and continuous loss of strength. This excessively virulent matter no longer leaves in the body the hyperæmia and hypertrophy of the spleen typical of the ordinary virus-the animal succumbs without resisting. The blood of the heart is full of streptococci which have in this case often coloured capsules. It is this blood, or cultures from it, with which the experiments were made.

Animals may be placed in relation to their resistance to the pneumonic virus, on a scale, the bottom of which is occupied by the pigeon with its absolute resistance, and the successive stages by the dog, the sheep, and the rat; the rabbit and the mouse are at the top of the scale. The mouse is the animal most sensitive to pneumonia, it always dies after a subcutaneous injection of a few drops of a virulent culture within an interval of from twelve to twenty-four hours, with all the symptoms of subacute septicemia. At the autopsy is found a slight gelatinous oedema at the seat of inoculation, the spleen more or less hyperæmic, and an enormous quantity of microbes in the blood and in all the organs. The virulence of the microbe increases in its passage through the body of the animal. M. Gamaléia's experiments were made on thirty mice. The disease in the rabbit has the same characters, The attenuated virus produces a fibrino-granulous infiltration at the seat of inoculation, a pneumonia, a sero-fibrinous pleurisy with fibrinous peritonitis. The virus sterilized by heat (120° C.), produces a persistent granular tumour which has no tendency to be absorbed. The same tumour is produced by the virulent virus in the rabbit rendered refractory to the virus. The virulence is considerably increased by passing through the rabbit; Gamaléia has made as many as twenty-four transmissions from animal to animal, and has caused pneumonia in 200 rabbits.

The white and grey rat are also very sensitive, and similar lesions are found, but the local effect is greater. The sheep is

more refractory, and requires large doses; here again, the local symptoms are considerable. Death takes place in from the third to the fifth day of the disease. Gamaléia has experimented on twelve dogs. The dog is still more refractory, he is cured generally in from ten to fifteen days, after having passed through all the stages of red and grey hepatisation as in man. The squirrel and the cat occupy in the scale of susceptibility an intermediate place between the rabbit and the rat. All these facts lead to the following conclusion:

(1) There exists variable degrees of receptivity for the pneumonic virus. These degrees may be measured by the abundance of the microbes of the blood and by the extent of the local reaction. The less an animal resists, the less the inflammatory pneumonia at the place of inoculation, the greater the abundance of microbes in the blood of the corpse. The type of the local reaction varies according to the degree of receptivity. The local reaction absent in the mouse, becomes a restricted hæmorrhagic cedema in the rabbit; the rat presents an extended cedema of a yellow amber tint, and gelatinous consistence; in the sheep and the dog, the ædema is greater, and is composed of sero-fibrinous parts mixed with harder granulations having a grey tint constituted by an abundant cellular infiltration.

(2) The animals little sensitive to the pneumonic virus offer a very pronounced local resistance, followed by a typical fibrinous pneumonia. Pneumonia, then, is not a general infection localizing itself in the lung as its place of predilection, but the local reaction has the place of the virulent inoculation. The animals extremely susceptible, as the rabbit, and mouse, have no pneumonia because there is no local action, and the virus generalizes itself within them and slays them by acute septicemia.

(3) Man belongs, in relation to the pneumonic virus, to the category of resistant animals. Hence the feeble mortality from pneumonia (10.8 per cent.)-hence the extended local reaction in the form of inflammation of the lungs, and the paucity of microbes in his blood. It is clear that the results obtained in the dog and sheep, animals little susceptible, are specially applicable to the elucidation of human pathology. It may be affirmed that an inoculation into the pulmonary tissue of animals partially refractory (e.g., dogs, sheep) of the streptococcus lanceolatus,

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