widely distant and apparently unrelated places. In the same way, the seeds of a disease may be conserved over long periods from one epidemic to another.
That the carrying of pathogenic bacteria by either man or animals, together with the opportunity of their transmission to others, does not altogether explain the spread of disease is certain. A loss of virulence on the part of the virus or an acquisition of immunity by the population, or both of these occurrences, must be assumed to explain the gradual spontaneous termination of an outbreak, and, similarly, the converse of those phenomena must be regarded as playing a large part in the recrudescence of an epidemic.
The laws governing the loss or gain of virulence by bacteria are very imperfectly understood; even in the laboratory patho- genicity is largely beyond control; elsewhere it is entirely so. The two other factors concerned in the spread of disease are less elusive. Even though the carrier state is one which has so far shown itself recalcitrant to treatment, carriers can be, if circumstances warrant such a drastic step, segregated, kept under observation, and finally recommended to adopt a course of life not likely to favour infection of others. To hasten or forestall the immunity assumed to occur in a community during the course of an epidemic is the object of prophylactic inoculation, a procedure of which the success has been further demonstrated during the World War.
Prophylactic Inoculation. The compound anti-enteric vaccine, which includes all three typhoidal germs, B. typhosus, B. para- typhosus A and B, was universally employed in the British armies and was attended by excellent results, as witnessed by the following statistics.
Typhoid cases in the British Expeditionary Forces in France up to May 1915 numbered 827. It was found that the incidence was 14 times and the mortality 42 times greater among the uninoculated than among the inoculated; up to August 1916 508 uninoculated had a case mortality of 23-4 %, while 906 inoculated had one of 5-2 %. Similar good results attended the use of anti-typhoid vaccine in the armies of other belligerents. It clearly reduced the total number of cases and lowered the mortality rate. Only in Germany was doubt cast by any appreciable number of scientific workers on the efficacy of prophylactic inoculation. A small body of opinion there considers that only by the use of a living virus, as in smallpox vaccination, can a reasonable immunity be conferred. It has been suggested by their critics that the Kolle vaccine, which is used in Germany, is of in- ferior immunising power, and certain pre-war statistics, comparing the use of this vaccine with one prepared by Vincent's method, bear this criticism out.
Other prophylactic vaccines, the use of which has been attended more or less definitely by success, are those directed against cholera, plague, pneumonia, cerebrospinal meningitis and influenza. Tenta- tively used, because of its great toxicity, is anti-dysentery vaccine.
Vaccine Therapy. Other therapeutic employment of bacterial vaccines has been extensively adopted and has, according to some workers, justified itself in such widely different diseases as furunculo- sis, rheumatoid arthritis and whooping-cough. Much work without, unfortunately, corresponding success continues to be done with vaccine therapy in tuberculosis. It was hoped at one time that the administration of vaccines might be controlled by observations of the opsonic index, made during treatment, but the method has been discarded as not capable of furnishing a reliable guide to dosage, as was expected of it.
Serum Therapy. Treatment by inoculation with serum specific for the disease in question has made notable advances. Besides those long in use in diphtheria, tetanus and streptococcus infections, sera capable of neutralizing the toxins produced by B. welchii, B. oedematiens and V. septique, all these gas-gangrene bacilli, are now prepared. The efficiency of anti-meningococcus serum has been greatly increased by the recently acquired knowledge of the physiology of the meningococcus and by improvements in the manu- facture of anti-toxin. Thus it was possible, by the use of more effec- tive sera together with more rapid diagnosis generally, to lower the death-rate for cerebrospinal meningitis in the home forces from 65 % in 1914 to 353% in 1918, and even to less than 10% where the infection was due to that strain of the meningococcus known as Type I.; it is against this type that the most potent anti-toxin is preparable. Other sera the use of which has been attended by favour- able results are those directed against dysentery and pneumonia.
Anaphylaxis. In connexion with the administration of animal sera, the phenomenon of anaphylaxis has to be recognized. In animals this condition results after repeated inoculation with a protein foreign to the animal injected. A guinea-pig, for instance, if inoculated with even a very small quantity of, say, horse serum and then after at least five days reinoculated with the same type of protein, can in some cases suffer so severely that death ensues within a few minutes, and this although the total amount of protein ad- ministered on both occasions is very much less than that which could with perfect safety have been given on the first occasion. The first inoculation is regarded as rendering the animal " sensitive " to the particular protein employed and may, for an animal like a guinea- pig, be as little as 0-00005 of a milligramme. The second inoculation of O'l to 0-5 of a milligramme occasions the anaphylactic shock, which consists for the main part of convulsions, paralysis and cessation of respiration. The causative agent has been considered
to be a poison formed by the union of the antibodies, produced in the animal by the first inoculation, with the antigen (the protein) inoculated on the second occasion and has been called anaphylatoxin. A surprising feature is that, no matter what protein be employed, the symptoms are in all cases similar. It is for this reason that other investigators have thought anaphylaxis to be not a toxic but a col- loidal phenomenon, in which after the second inoculation an ex- tremely minute precipitation, a gel phase, occurs in the body, occasioning in the lungs mechanical interference with oxygen ab- sorption.
In man anaphylaxis is not so pronounced as in some animals, for instance rabbits and guinea-pigs, yet the danger is sufficiently grave to demand special care during serum treatment.
It has been found in animal experiments that if the second in- oculation of protein is survived, the anaphylactic condition dis- appears. In serum therapy, therefore, if any anaphylaxis is to be feared, a very small " desensitizing " inoculation is given before proceeding to the injection of the full amount. The anaphylactic state is met with in persons who have, on some previous occasion, had serum administered to them, or, more usually, it is encountered as a natural condition, as for instance in those individuals who show susceptibility to some particular foodstuff, such as white of egg.
Anaerobes and Gas Gangrene. A group of bacteria which the World War threw into great prominence is that of the anaerobes. A wide divergence exists among microorganisms as to the oxygen pressure under which growth is possible. The anaerobes require that oxygen be absent, or present in but minimal quantities', in their environment. The group is found widespread in nature; its chief breeding-ground being the intestinal tract of man and animals, distribution proceeds for the most part along with the manuring of the fields.
The importance of the group from a human point of view lies in the high toxicity possessed by several of its members. Its more special importance during the war lay in the fact that wounds inflicted by explosive force are usually extensive and earth-soiled, this in such highly cultivated lands as those of Flanders giving an opportunity for infection by* anaerobes and for the subsequent development of the very fatal gas gangrene that was, particularly in the first months of the war, such a frequent wound complication.
Knowledge of the anaerobes has been, until the last few years of intenser French, English and American work, in a chaotic con- dition, only B. botulinus, which occasions food-poisoning, and the bacillus of tetanus having been at all accurately studied and de- scribed. Of the remaining anaerobes little was known with cer- tainty; accounts were contradictory owing to non-recognition of the fact that the cultures with which work was carried out were not pure. In this way, besides there being great confusion in nomen- clature, the group acquired an undeserved reputation for remarkable variability; it was recorded how one species melted into another with the mere alteration of the media on which it was grown and the result was ascribed to an inconstancy of species. In reality, it was a second strain, long dormant in the impure culture, which was now, owing to a more congenial environment, able to assert itself.
The usual bacteriological methods for the establishment of pure cultures which hold good in the case of aerobes are unreliable when applied to the anaerobes, which appear to possess a special property of not readily growing, unless associated in some numbers. For this reason, the anaerobic cultures which " take " are far more likely to be impure, and the concealed impurity may pass undetected through a whole series of sub-cultures.
A more refined technique and a more meticulous criticism of results proved necessary and were applied during later investiga- tions.
In the group of spore-bearing anaerobic organisms concerned with wound infections and apart from B. tetanus^ already well studied, in spite of the fact that it also existed mainly in impure culture in the laboratories, three outstanding pathogenic species have been set up:
(i) B. welchii, the most frequently found of the gas-gangrene bacilli, previously described under a variety of names and in various conditions of impurity as B. aerogenes capsulatus, B. phlegmonis emphysematosae, B. perjringens, B. enteritidis sporogenes; (2) Vibrion septique (Pasteur), the B. oedematis maligni of Koch, and (3) B. oedematiens, a highly toxic organism discovered by Weinberg and Seguin in 1915.
For all three, potent antitoxic sera have been prepared and the treatment of cases has been greatly improved by their use. Certain slightly pathogenic anaerobes such as B. histolylicus are also con- cerned in the polymicrobic invasion of wounds, as well as a series of definitely non-pathogenic anaerobes, like B. sporogenes. Sonie of these may symbiotically assist infection; others appear only in the r61es of contaminating organisms, taking no part in the morbid processes.
Epidemic Influenza. To our knowledge of the aetiology of influenza the last world-wide epidemic of 1918, with its enormous incidence and with its appalling mortality returns, such as that of six millions for India alone, has brought but an increase of un- certainty. Discovered by Pfeiffer in 1892, the B. influenzae was, up till 1918, widely accepted as the cause of that disease. But the failure, during the last pandemic, of a large number of bacteriologists
