easily worked with. This process of preparation may have to be continued for from six months to a year. The horse is then bled and from the clot the serum is separated, care being taken to determine by injection of the blood into mice that no living bacilli have by accident made their way into, and remained in, the horse’s blood. The serum is not considered to be sufficiently active until a drop and a half will protect the mouse against a dose of living bacilli fatal to a control mouse in from 48 to 60 hours. When this serum is injected in sufficiently large doses subcutaneously in mild cases, and subcutaneously and intravenously (Lancet, 1903, i. 1287) in more severe cases in doses of 150 to 300 cc. the results seem to be excellent, especially when the serum is injected into the tissues around the bubo or swellings formed in this disease. Calmette and Salimbeni used the serum in 142 cases in the Oporto outbreak. Amongst these they had a mortality of under 15%, whilst amongst 72 patients not so treated the death-rate was over 63%. This serum kills the bacilli and at the same time neutralizes the toxin formed during the course of the disease. The best results are obtained when large doses are given, and when the serum injected subcutaneously is thrown into the area in which the lymph flows towards the bubo. As in the case of the diphtheria antitoxic serum joint pains and rashes may follow its exhibition, but no other ill effects have been noted.
Pneumonia.—The case in favour of acute lobar pneumonia being an infective disease was a very strong one, even before it was possible to show that a special organism bore any aetiological relation to it. In 1880, Friedlander claimed that he had isolated such an organism, but the pneumo-bacillus then described appears to be inactive as compared with the pneumococcus isolated by Fraenkel and Talamon. This latter organism which is usually found in the sputum, is an encapsuled diplococcus. Grown on serum or agar over which sterile blood has been smeared, it occurs as minute, glistening, rather prominent points, almost like a fine spray of water or dew. When the organism is cultivated in broth the capsule disappears, and chains of diplococci are seen. It resembles the influenza bacillus in a most remarkable manner. It may be found, in almost every case of pneumonia, in the “rusty” or “prune-juice” sputum. Injected into rabbits, it produces death with very great certainty; and by passing the organism through these animals its virulence may be markedly increased. Like the influenza bacillus and even the diphtheria bacillus, this organism may be present in the mouth and lungs of perfectly healthy individuals, and it is only when the vitality of the system is lowered by cold or other depressing influences that pneumonia is induced; two factors, the presence of the bacillus and the lowered vitality, being both necessary for the production of this disease in the human subject. It is quite possible, however, that, as in the case of cholera, a slight inflammatory exudation may supply a nutrient medium in which the bacillus rapidly acquires greatly increased virulence, and so becomes a much more active agent of infection.
It is claimed by the brothers Klemperer, by Washbourn and by others, that they have been able to produce an anti-pneumococcic serum, by means of which they are able to treat successfully severe cases of pneumonia. The catarrhal pneumonia so frequently met with during the course of whooping-cough, measles and other specific infective fevers, is also in all probability due to the action of some organism of which the influenza bacillus and the Diplococcus pneumoniae are types.
Infective meningitis is, in most of the recent works on medicine, divided into four forms: (1) the acute epidemic cerebro-spinal form; (2) a posterior basic form, which, however, is closely allied to the first; (3) suppurative meningitis, usually associated with pneumonia, erysipelas, and pyaemia; and (4) tubercular meningitis, due to the specific tubercle bacillus.
1. The first form, acute infective or epidemic cerebro-spinal meningitis, is usually associated with Weichselbaum’s Diplococcus intracellularis meningitidis (two closely apposed disks), which is found in the exudate, especially in the leucocytes, of the meninges of the brain and cord. It grows, as transparent colonies, on blood-agar at the temperature of the body, but dies out very rapidly unless reinoculated, and has little pathogenetic effect on any of the lower animals, though under certain conditions it has been found to produce meningitis when injected under the dura mater.
More or less successful attempts have been made to treat acute epidemic cerebro-spinal meningitis by means of antisera obtained from different sources. Flexner uses the serum of horses that have been highly immunized against numerous strains of the meningococcus, the process of immunization extending over four or five months. Meister, Lucius and Brüning supply Ruppel’s antibacterial serum derived from animals immunized against several strains of meningococcus of high pathogenic activity. Both these sera may be looked upon as polyvalent sera. Ivy Mackenzie and Martin, pointing out that the cerebro-spinal fluid, even of patients who have recovered from this form of meningitis, contains no antibodies, tried and recommended injections of the patient’s own blood serum into the spinal canal. In all cases the action seems to be much the same. These sera contain immune body and complement, and are distinctly bactericidal, acting on the meningococcus and rendering it much more easily taken up and digested by the white blood corpuscles. It is possible that these sera may also exert some slight antitoxic action. The serum is injected directly into the spinal canal, a corresponding quantity of the cerebro-spinal fluid having first been withdrawn by lumbar puncture. The treatment thus resembles the treatment of lockjaw, where the antitetanus serum is brought as directly as possible into contact with the nerve centres. The dose of these sera ranges from 15 to 40 cc. according to the severity of the disease. Although the general mortality of the disease is from 50 to 80%, it is stated that where Flexner’s serum is used the mortality falls to 33%. The result corresponds somewhat closely to those obtained with antidiphtheria serum in diphtheria. In patients injected on the first day of the disease the mortality was only about 15%. on and from the fourth to the seventh day 22%, but after the seventh day 36%. From this it is evident that although the serum has a distinct effect in bringing about the phagocytosis of the meningococcus and the neutralization of the toxins produced, it cannot make good any damage already done to the tissues. Mackenzie and Martin treated 20 cases with the blood taken from patients suffering, or convalescent, from meningitis. Of 16 acute cases treated 14 received serum from patients who had already recovered from the disease, 8 of the patients recovered, 6 died, and 2 cases which received their own serum both recovered. In the presence of these anti-cerebro-spinal-fever sera the meningeal cocci become diminished in number and do not stain so readily, whilst, simultaneously, the polymorpho-nuclear leucocytes seem to be diminished in number. The serum should be given until the temperature becomes normal. Mackenzie and Martin' assert that even normal human blood contains substances which are bactericidal to the meningeal coccus, but that these substances increase “in amount and activity in the blood serum of patients suffering from an acute or chronic meningococcic infection, and the serum of a patient recently recovered from an infection shows the evidence of the presence of these substances in a still greater degree.” They were able to demonstrate, moreover, that the destructive action on the cocci depends on an immune body which requires the presence of a complement to complete the process. The cerebro-spinal fluid differs from the serum in that it does not contain substances which kill this meningeal coccus in vitro, nor are the immune body and complement present in the blood, found in this cerebro-spinal fluid. Hence the efficacy of the blood when it is called upon to replace the fluid in the cerebro-spinal canal.
2. Posterior basic meningitis, according to Dr Still, “is frequently seen during the first six months of life, a period at which tuberculous and epidemic cerebro-spinal meningitis are quite uncommon.” The organism found in this disease resembles the diplococcus intracellularis meningitidis very closely, but differs from it in that it remains alive without recultivation for a considerably longer period. It is less pathogenetic than that organism, of which possibly it is simply a more highly saprophytic form. This is a somewhat important point, as it would account for the great resemblance that exists between the sporadic and the epidemic forms of meningitis.
3. In suppurative meningitis these two organisms may still be found in a certain proportion of the cases, but their place may be taken by the pneumococcus or Diplococcus pneumoniae or Fraenkel’s pneumococcus—Diplococcus lanceolatus—which appears to grow in two forms. In the first it is an encapsulated organism, consisting of small oval cocci arranged in pairs or in short chains; the capsule is unstained. When the pneumococcus grows in chains—the second form—as when cultivated outside the body, on blood-serum or on agar over the surface of which a small quantity of sterile blood has been smeared, it produces very minute translucent colonies. Like Weichselbaum’s bacillus, it must be recultivated every three or four days, otherwise it soon dies out. Unlike the other forms previously described, it may, when passed through animals, become extremely virulent, very small quantities being sufficient to kill a rabbit. Although the pneumococcus is found in the majority of these cases, especially in children, suppurative
