After three or four hours there Is noticeable swelling and some pain;
and after ten hours a rise in temperature, usually not very marked,
occurs. These signs soon disappear, and at the end of three or four
days the second injection is made, usually on the opposite side.
This is also followed by a rise of temperature, by swelling, pain and
local redness: these, however, as before, soon pass off, and leave no
ill effects behind. A guinea-pig treated in this fashion is now imrnune
against some eight or ten times the lethal dose of cholera poison,
and, from all statistics that can be obtained, a similar protection is
conferred upon the human being.
Pfeiffer found that when a small (quantity of the cholera vibrio is injected into the peritoneal cavity of a guinea-pig highly immunized against cholera by Haffkine's or a similar method, these vibrios rapidly become motionless and granular, then very much swollen and finally " dissolve." This is known as Pfeiffer's reaction. A similar reaction may be obtained when a quantity of a culture of the cholera vibrio mixed with the serum derived from a guinea-pig immunized against the cholera vibrio, or from a patient convalescent from the disease, is injected into the peritoneal cavity of a guinea-pig not subjected to any preliminary treatment; and, going a step further, it was found that the dissolution of the cholera vibrio is brought about even when the mixture of vibrio and serum is made in a test tube. On this series of experiments as a foundation, the theory of acquired immunity has been reared.
Evidence has been collected that spirilla, almost identical in appearance with the cholera bacillus, may be present in water and in healthy stools, and that it is in many cases almost impossible to diagnose between these and the cholera bacillus; but although these spirilla may interfere with the diagnosis, they do not invalidate Koch's main contention, that a special form of the comma bacillus, which gives a cotnplete group of reactions, is the cause of this disease, especially when these reactions are met with in an organism that comes from the human intestine.
Typhoid Fever. — Our information concerning the aetiology of typhoid fever was largely increased during the last twenty years of the 19th century. In 1880 Eberth and Klebs independently, and in 1882 Coats, described a bacillus which has since been found to be intimately associated with typhoid fever. This organism (Plate II. fig. 4) usually appears in the form of a short bacillus from 2 to Sfiin length and 0-3 to O' 5^1 in breadth; it has shghtly rounded ends and is stained at the poles; it may also occur as a somewhat longer rod more equally stained throughout. Surrounding the young organism are numerous long and well-formed flagella, which give it a very characteristic appearance under the microscope. At present there is no evidence that the typhoid bacUlus forms spores. These bacilli are found in the adenoid follicles or lymphatic tissues of the intestine, in the mesenteric glands, in the spleen, liver and kidneys, and may also be detected even in the small lymphoid masses in the lung and in the post-typhoid abscesses formed in the bones, kidneys, or other parts of the body; indeed, it is probable that they were first seen by von Recklinghausen in 1871 in such abscesses. They undoubtedly occur in the dejecta of patients suffering from typhoid fever, whilst in recent years it has been demonstrated that they may also be found in the urine. It is evident, therefore, that the urine, as well as the faeces, may be the vehicle by means of which the disease has been unwittingly spread in certain otherwise inexplicable outbreaks of typhoid fever, especially as the baciUus may be present in the urine when the acute stage of the disease has gone by, and when it has been assumed that, as the patient is convalescent, he is no longer a focus from which the infection may be spread. Easton and Knox found typhoid bacilli in the urine of 21% of a series of their typhoid patients.
In 1906 Kayser demonstrated what had previously been suspected, that the typhoid bacilli may persist for considerable periods in the bile duct and gall bladder, whence they pass into the intestinal tract and are discharged with the evacuations. Patients in whom this occurs are spoken of as " typhoid carriers." They become convalescent and except that now and again they suffer from slight attacks of diarrhoea they appear to be perfectly healthy. It has been observed, however, especially during these attacks of diarrhoea, that typhoid bacilli may be found in the faeces. Curiously enough the bacilli are as virulent as are those isolated when the disease is at its height. Hence these typhoid carriers are exceedingly dangerous centres of infection, and as women act as " carriers " much more frequently than do men, although, as is well known, typhoid fever attacks men much more frequently than women, the facilities
for the distribution of the disease are great, as women so frequently act as laundresses, cooks, housemaids, nurses and the like. Frosch states that out of 6708 typhoid patients 310 excreted bacilli for more than 10 weeks after convalescence; 144 of these were no longer infective at the end of three months; 64 had ceased to be infective at the end of a year, and 102 at the end of three and a-half years; further back than this no authentic records could be obtained, but from a critical examination of the histories of 25 such carrier cases he was convinced that 14 had been continuously infective for from four to nine years. Dr Donald Greig, in 1908, reported a case in which the patient appears to have been a typhoid carrier for fiftytwo years from the time of convalescence. Frosch pointed out, what has now been fully confirmed, that the bacilli in these cases though often present in the faeces in enormous numbers may disappear and again reappear from time to time, and that a continuous series' of examinations is necessary before a convalescent patient can be acquitted of being a " typhoid carrier." In this connexion it is interesting to note that Blumenthal and Kayser have discovered typhoid bacilli in the interior of gall-stones. Drs Ale.xander and J. C. G. Ledingham, examining the 90 female patients and attendants in a Scottish asylum in which, during some four or five years, 31 cases of typhoid had occurred in small groups in which the source of infection could not be traced to any recognized channel, found amongst them three " typhoid carriers." The importance of such a discovery amongst asylum patients may be readily understood when the careless and uncleanly habits of insane patients are borne in mind. As it has been demonstrated that the typhoid bacillus is found, not merely in the lymphatic tissue but, in 75 % of the cases, actually circulatmg in the blood, the appearance of the bacillus in the secretions and excretions may be readily understood.
There can be little doubt that typhoid bacilli are not, as is very frequently assumed, present merely in the lymphatic glands and in the spleen (see Plate II. fig. 5): they may be found in almost any part of the lymphatic system, in lymph spaces, in the connective tissues, where they appear to give rise to marked proliferation of the endothelial cells, and especially in the various secreting organs. It is probable that the proliferation often noticed in the minute portal spaces in the liver, in cases of typhoid fever, is simply a type of a similar proliferation going on in other parts and tissues of the body. It was for long assumed that the typhoid bacillus could multiply freely in water, but recent experiments appear to indicate that this is not the case, unless a much larger quantity of soluble organic matter is present than is usually met with in water. The fact, however, that the organism may remain alive in water is of great importance; and, as in the case of cholera, it must be recognized that certain of the great epidemics of typhoid or enteric fever have been the result of " water-borne infection." The bacillus, a facultative parasite, grows outside the body, with somewhat characteristic appearances and reactions: it flourishes specially well on a slightly acid medium; in the presence of putrefactive organisms which develop strongly alkaline products it may gradually die out, but it appears to retain its vitality longer in the presence of acid-forming organisms. It may, however, be stated generally that after a time the typhoid bacillus becomes weakened, and may even die out, in the presence of rapidly growing putrefactive organisms. In distilled water it may remain alive for a considerable period — five or six weeks, or even longer. It grows on all the ordinary nutrient media. It does not coagulate milk; hence it may grow luxuriantly in that medium without giving rise to any alteration in its physical characters; contaminated milk, therefore, is specially dangerous affording as it does an excellent vehicle for the dissemination of the typhoid bacillus which may also be conveyed by food and even by water. To food the bacillus is readily conveyed by flies, on their limbs or by the proboscis, which become infected by the excrement on which they crawl and feed. The observations of physicians working amongst the British troops in South Africa afford abundant evidence that the typhoid bacillus may also be carried along with dust from excreta to fresh patients, for although these bacilli die very rapidly when they are desiccated, they remain alive sufficiently long to enable them to multiply and flourish when again brought into contact with moist food, milk, &c.
When inoculated on potato, careful examination will reveal the fact that certain almost invisible moist patches are present; these are made up of rapidly multiplying typhoid bacilli. The typhoid bacillus grows in gelatin, especially on the surface.
