# Tropical Diseases/Chapter 28

Section III.— ABDOMINAL DISEASES
CHAPTER XXVIII
CHOLERA
Definition.— An acute, infectious, epidemic disease, characterized by profuse purging and vomiting of a colourless serous material, muscular cramps, suppression of urine, algidity and collapse, the presence of a special bacterium in the intestine and intestinal discharges, and a high mortality.
History and geographical distribution.— It is probable that from remotest antiquity cholera has been endemic in Lower Bengal,* and that thence, from time to time, it has spread as an epidemic over the rest of India. European physicians observed it there in the sixteenth, seventeenth, and eighteenth centuries, but it was not until the great epidemic extension of 1817 that the disease seriously attracted the attention of the profession in Europe. In that year cholera began to spread all over Asia, extending eastwards as far as Pekin and Japan, southwards to Mauritius, and westwards to Syria and the eastern shores of the Caspian. Stopping short at Astrakhan in 1825, it did not on that occasion invade Europe.
European epidemics.— In 1830 cholera visited Europe for the first time. Advancing through Afghanistan and Persia, it entered by way of Russia, and swept as an epidemic over nearly the entire continent, reaching Britain at the beginning ​of 1832. During the same summer it crossed the Atlantic to Canada and the United States. This epidemic did not die out in Europe till 1839. Since that time there have been at least five European epidemics— 1848-51, 1851-55, 1865-74, 1884-86, and 1892-95. Minor epidemics have occurred in Europe since, but they have been restricted in area. During the Balkan War of 1913, and in the course of the European War, especially in the Balkans and in Mesopotamia, there have been many outbreaks of cholera, but up to the present the disease has not extended as an epidemic beyond the seat of war.
Great Britain has been seriously involved in four only of these epidemics— namely, in 1832, 1848, 1854-55, and in 1866. On the occasion of the last two European epidemics, although the disease was frequently imported, it did not spread in Britain. America has not been so fortunate, for, although the 1870-73 epidemic practically spared Great Britain, it crossed the Atlantic and, entering by way of Jamaica nd New Orleans, raged for a time in the United States.
From a study of the march of these various epidemics, it is to be concluded that cholera reaches Europe by three distinct routes: (1) via Afghanistan, Persia, the Caspian Sea, and the Volga valley; (2) via the Persian Gulf, Syria, Asia Minor, Turkey in Europe, and the Mediterranean; (3) via the Red Sea, Egypt, and the Mediterranean.
With certain exceptions, hereafter to be mentioned, there is hardly an important country in the world which has not, at one time or another, been visited by cholera in the course of some of its pandemic extensions.
Etiology.— The disease is carried by man.— A study of the various epidemics shows that in its spread cholera follows the great routes of human intercourse, and that it is conveyed chiefly by man—probably in its principal extensions by man alone —from place to place. In Britain and the United States, for example, the places first attacked have been invariably seaports in direct and active com​munication with other ports already infected. In India, although the problem is much more difficult to unravel, in certain instances the influence of human intercourse in diffusing the disease can be distinctly traced. Thus the extensive pilgrimages, so frequent in that country, are a fruitful source of its rapid spread. During these gatherings hundreds of thousands of human beings are collected together under highly insanitary conditions— as at the Hurdwar and Mecca pilgrimages. Cholera breaks out among the devotees, who, when they separate, carry the disease along with them as they proceed towards their homes, infecting the people of the places they pass through. Cholera never travels faster than a man can travel; but in modern times, owing to the increased speed of locomotion and the increased amount of travel, epidemics advance more rapidly and pursue a more erratic course than they did sixty years ago.
Isolation secures immunity.— In the case of isolated countries the absence of active and frequent intercourse with the outer world favours immunity, even during approximately pandemic extensions. Thus, though so near to the reputed home of cholera the Andaman Islands have never been visited by that disease. Similarly, Australia and New Zealand hitherto have enjoyed practical exemption. The same can be said of the Pacific Islands, the Cape of Good Hope, the West Coast of Africa, Orkney and Shetland, Iceland, the Faroe Islands, and many of the islands of the Atlantic.
Unequal diffusion in the endemic and epidemic areas.— Although cholera is always present in some part of the endemic area in Bengal, it is not equally diffused there, nor is it equally common at all seasons and every year. Thus, even within this area there are places which enjoy an absolute or a relative immunity, and there are seasons and years of special prevalence. It has also to be remarked that the season of immunity for one place may be the season for prevalence in another place, and vice versa. The same observations apply to the areas of epidemic extension. ​When cholera extends as an epidemic, its course is often singularly erratic. Some places, apparently in the direct line of advance, are passed over, to be attacked, perhaps, at a later period. Similarly, certain districts of a town may be spared, while other parts of the same town are ravaged by the disease.
Local conditions favouring the presence of cholera.— On the whole, it may be said that low-lying districts, particularly those along river banks, are more subject to the disease than high and dry situations; and that overcrowding and unhygienic conditions generally conduce to its prevalence. The principal and special element, however, which determines the diffusion of cholera is, undoubtedly, the character of the water supply.
Cholera in the main a water-borne disease, entering by the stomach.— From time to time many theories of the cause and nature of cholera have been put forward, most of them very absurd and manifestly incorrect. Most of these have now been definitely abandoned in favour of the theory that the cause of cholera is a specific germ which, for the most part, is water-borne. The evidence in favour of this view may be regarded as being almost conclusive, although there Is still some room for doubting whether the germ itself has really been discovered.
The earliest, and still one of the most telling pieces of evidence in favour of the water-borne theory of the diffusion of cholera, we owe to the late Dr. Snow. In August, 1854, cholera was epidemic in parts of London, notably in the neighbourhood of Golden Square, Soho. A child, after an illness of three or four days, died of the disease at 40, Broad Street, on the 2nd of September. The discharges from the patient had been thrown into a leaky cesspool which, as was subsequently discovered, drained into a well only three feet away. This well supplied the neighbourhood with drinking-water. On the night of the 31st of August cholera broke out among those who used the water of this particular well, very few escaping an attack. On the 2nd of September a lady died of cholera at Hampstead ​Attention was specially called to this lady's case, as hitherto the disease had not been seen in that district. On inquiry it was found that she had been habitually supplied with drinking-water from the Broad Street well referred to, as she had formerly resided in Broad Street, and had retained a liking for the water from this particular well. She drank some of the water which had been procured on the 31st of August, both on that day and again on the 1st of September. On the latter day she was seized with cholera. A niece, on a visit to this lady, also drank some of the same water; she, too, was attacked by cholera, and died. A servant also drank the water; although she suffered to some extent, she recovered. So far as could be ascertained by careful inquiry, these people had had no connection whatever with the cholera district except through the water fetched from this particular Broad Street well. Cholera, as mentioned, was not epidemic at Hampstead at the time. The inference that 'the germ had been conveyed in the polluted water is difficult to avoid.
Another remarkable illustration of the diffusion of the cholera germ by water is supplied by a recent epidemic in Hamburg. At the time the sanitary conditions under which the inhabitants of the contiguous cities of Hamburg, Altona, and Wandsbeck lived were practically identical, save in the matter of water supply. Hamburg and Altona both drew their water from the Elbe; but, whereas the water distributed to the people of Altona was most carefully filtered, that supplied to the people of Hamburg was simply pumped up from the river and passed directly into the mains without filtration or purification of any description. The Wandsbeck water came from a lake, and was filtered. In Hamburg, during the epidemic, there were 8,605 deaths from cholera, equal to 13.4 per thousand; whereas in Altona only 328 deaths occurred, equal to 2.1 per thousand. The death-rate in Wandsbeck was similar to that of Altona. Hamburg and Altona are contiguous, and practically one city. At one part a street forms the boundary between the municipalities. On one side of this ​street, the Hamburg side, there were numerous cases of cholera; on the Altona side there were no cases. The houses on both sides of the street were of the same character and occupied by the same class of people. The only difference, so far as could be ascertained, was in the water supply: the houses on the healthy side of the street received Altona water; those on the cholera-stricken side, Hamburg water. It was remarked that a certain group of houses on the Hamburg side remained free from the disease. On investigation it was found that, unlike the other houses on the same side, these houses derived their water supply from an Altona main.
As regards its relation to the water supply, this Hamburg epidemic is the exact counterpart of what happened in South London in 1854. Formerly this district was supplied with water by two companies— the Southwark and Vauxhall Company and the Lambeth Company. Both companies drew their water from the Thames— the latter from near Hungerford Bridge, the former from near Battersea Fields. The epidemic of cholera which visited London in 1849 was especially severe in South London. Subsequently the Lambeth Company removed its intake higher up the river to Thames Ditton, and consequently the water it supplied at the time of the 1854 epidemic had improved in quality. The Southwark and Vauxhall Company did not change their intake, and in 1854 they were still drawing their supply from the river near Battersea Fields. When cholera visited London in that year the death-rate from the disease in the houses supplied by the Southwark and Vauxhall Company amounted to 153 per 10,000 inhabitants, whereas that in houses supplied by the Lambeth Company was only 26 per 10,000. The mains of the two companies ran side by side, some houses receiving the water of one company, some that of the other.
During the Hamburg epidemic it was also found that the incidence of cholera was three times greater among those who used the town water than among those who got their supplies from wells.
These and many similar facts which might be ​adduced clearly point to water as a principal medium for the diffusion of the cholera germ.
The virus contained in the dejecta.— Evidence equally conclusive tends to show that the germ on being swallowed by man multiplies in his alimentary canal, and, on being voided in the dejecta, subsequently finds its way by a route more or less direct to water again, in which, under favourable conditions, it continues still further to multiply. An illustration, amounting almost to proof, of the fact that the germ of cholera is contained in the stools of cholera patients is supplied by Macnamara. Some of the characteristic rice-water discharge from a cholera patient got mixed accidentally with a few gallons of water. This was exposed to the sun for twelve hours. Early the following morning 19 persons each drank about an ounce of the mixture. Within thirty-six hours 5 of these 19 persons were seized with cholera.
Conditions of infection are complex.— It is evident that the ingestion of the germ is a necessary condition for the production of the disease, but there are many facts which render it equally evident that this is not the only condition. Were it the only condition, then every one of those individuals referred to by Macnamara would have sickened. What the other necessary conditions may be it is, in the present state of knowledge, impossible to say.
There is reason to believe that not only are the conditions complicated as regards the susceptibility of the individual, but also that they are equally complex as regards the germ itself in relation to its pathogenic, proliferating, and diffusing properties.
The germ of cholera.— Early views.— Since European pathologists first directed their attention to the subject, many views have been entertained as to the exact nature of the cause of cholera. Some of these views were of the most fantastic description. Mysterious atmospheric and telluric conditions were invoked, and only a very few years ago superstitious notions worthy of the Middle Ages were freely ventilated, even in high places and by educated minds. ​Among those who ventured to formulate definite and more reasonable hypotheses, some considered that cholera, like the more familiar exanthematous fevers, was directly contagious. Others thought that it was not directly contagious, but that it was communicated by the evacuations of the sick after these evacuations had undergone some peculiar fermentation process outside the human body. Others again, as von Pettenkofer, regarded the virus as a chemical ferment which developed in the soil under certain unknown epidemic conditions.
Discovery of the comma bacillus*— Since the rise of the germ theory of infective disease most of these speculations have been definitely abandoned, or have received more precise expression in the view that cholera is caused by a certain bacterium, known as the comma bacillus or cholera vibrio, which Koch found to be present, practically invariably, in the stools and intestinal contents of cholera patients. This bacterium Koch first discovered in Egypt in 1883. Believing in its importance, he afterwards proceeded to India on a special mission, and there, in Calcutta, in 1884, he found the same bacterium in the intestinal contents of 42 fatal cases, and in the stools of 30 other cholera patients; in fact, he found it in every case of the disease examined. Moreover, he entirely failed to find it in any other disease or in healthy discharges. These observations, so far as they concern the presence of the comma bacillus in cholera stools, have been abundantly confirmed by many other workers; so that the presence or absence of this bacterium is now regarded as a trustworthy and valuable practical test of the choleraic or non-choleraic nature of any given case of intestinal flux; and this even by the opponents of Koch's special view as to the nature of the relationship of the bacterium in question to the disease with which it is so intimately associated. If only on account of its diagnostic value, the comma bacillus, therefore, is an organism of importance; but as many ​high authorities regard it as a necessary concomitant and even as the actual germ and true cause of Asiatic cholera, the vibrio acquires an importance of the first rank.
Description of the comma bacillus.—The comma bacillus (Fig. 77) is a very minute organism, 1.5 to 2 μ in length by 0·5 to 0·6 μ in diameter—about half the length and twice the thickness of the tubercle bacillus. It is generally slightly curved, like a comma; hence its name. After appropriate
Fig. 77.—Cholera bacillus. Agar culture: 24 hours' growth. x 1,000. (Muir and Ritchie.)
staining, at each end, or at one end only, flagella can be distinguished—sometimes one, sometimes (though less frequently) two. These flagella, though of considerable length—from one to five times that of the body of the bacterium—owing to their extreme tenuity are difficult to see in ordinary preparations. They are not always present during the entire life of the parasite. In virtue of this appendage the bacillus exhibits very active spirillum-like movements. The individual bacilli when stained show darker parts at the ends or at the centre, suggesting spore formation. Sometimes in ​tions two or more bacilli are united, in which case an S-shaped body is the result; or it may happen that several bacilli are thus united together, producing a spirillar appearance.
The comma bacillus is easily stained by watery solutions of fuchsin, or by Loffler's method, dried cover-glass films being used. It is decolorized by Gram. Dilute solution of methyl violet mixed with the intestinal contents and placed on a slide suffices for partial staining.
The bacillus grows best in alkaline media at a temperature of from 30° to 40° C. Growth is arrested below 15°, or above 42° C.; a temperature over 50° C. kills the bacillus. Meat broth, blood serum, nutrient gelatin, and potato are all suitable culture media. It multiplies rapidly without curdling in milk. It dies rapidly in distilled water; it survives longer if salt be added to the water.* For diagnostic purposes nutrient gelatin and potato are the most convenient culture media.
In gelatin plate cultivations minute white points appear; around these the gelatin liquefies, and the colonies of bacilli sink into funnel- or bubble-shaped depressions. By the end of the second or third day the culture is besprinkled with such depressions, liquefaction spreading peripherally until it involves the entire surface of the gelatin. The colonies are white or yellowish, very irregular in shape, granular, and shining like so many particles of ground glass. Later they assume a peculiar roseate hue, said to be absolutely characteristic.
In gelatin stab cultures the growth at first is most active near the surface; later, the colony sinking, liquefaction advances most below the surface of the gelatin, so that a bubble-shaped appearance is produced. Later still, as growth proceeds along the needle track, a finger-shaped liquefaction results, which in time extends to the sides of the tube. At the bottom of the liquefied area there is an accumu​lation of a white mass of bacteria; at the top a scum of bacteria in various stages of degeneration. The cultures may die after five or six weeks.
Agar is not liquefied, and in it the cultivations retain their vitality longer. On potato, at 20 to 30 C., the culture appears as a thin, brownish, porcelain-like film. In broth some of the bacilli form a scum on the surface ; others, falling in masses to the bottom, leave the body of the liquid clear.*
Although, taken together and in conjunction with the morphological appearances, these culture characters are fairly distinctive, nevertheless certain other bacteria, such as Tinkler's spirillum, behave very similarly ; and, as the microscopic features of those other bacteria in some instances are very much like those of the cholera vibrio, a mistake is easily made. The production of what is known as " cholera red " by the addition of pure sulphuric acid to a culture in peptonized broth is also not quite distinctive of the cholera vibrio, for a similar reaction (indol reaction) is produced by some other bacilli.
In careful and practised hands the diagnosis of cholera by the microscopic and cultural characters of the vibrio may be made with practical certainty.
Is the comma bacillus the germ of cholera? —Although it may be safely asserted that cholera is intimately associated with the comma bacillus, it does not necessarily follow that this organism is the cause of cholera. Many attempts have been and are being made to establish such a relationship. Nevertheless, what may be considered as absolute proof is still wanting— such proofs as alone can be afforded by the production in man, or in the lower animals, of a disease in every respect like cholera by the administration of pure cultures of the comma bacillus. Short of this the proof may be said to be almost complete; indeed, by not a few the causal relationship of the bacillus to the disease is considered as established. ​Since Koch first announced his discovery many facts having a bearing on the subject have been brought to light, some in favour of his views, some apparently militating against them.
1. It has been found that there are several bacilli with morphological and cultural characters closely resembling those of the cholera comma, notably the Finkler-Prior bacillus of cholera nostras, Lewis's saliva comma bacillus, many of the commashaped bacilli discovered by Cunningham, and certain species found in river-water. Koch and others maintain that, though morphologically similar, as these various bacilli behave so differently from that of cholera in culture media, they must be considered as biologically specifically distinct from the latter.
2. Cultures of pure bacilli have many times been swallowed by way of experiment; yet, although in some instances diarrhœa with comma bacilli in the stools has resulted, in only a very few instances has true cholera been produced. On this account it is held by some that the comma bacillus cannot be regarded as the germ of cholera. Against this it is advanced that other factors must be present to ensure the induction of cholera by such experiments; for example, a suitable and peculiar condition of the body, possibly, as Buchner suggests, some second and as yet unknown micro-organism. Buchner accordingly regards cholera as the result of a mixed infection. It is to be presumed, therefore, that in the two or three instances in which cholera followed on the intentional or accidental ingestion of cultures of the cholera vibrio, these secondary but essential conditions were present. It must be remembered also, in assessing the value of negative feeding experiments, that the cholera vibrio, like other pathogenic bacteria, may lose through cultivation, or otherwise, its virulence while retaining its morphological and cultural qualities.
3. A few cases of what, from a clinical point of view, appears to be true cholera have been observed in which the most careful and prolonged bacterio-logical examinations failed to detect the comma bacil​lus. Therefore, it has been advanced, as cholera can occur without the comma bacillus, the comma bacillus cannot be the cause of cholera. Against this it has been said that these observations were defective; that although the bacillus was not found, it by no means follows that the bacillus was not present at some time in the case.
4. The comma bacillus has been observed in the stools of individuals who did not at the time or afterwards suffer from cholera. To this it is answered that although one of the necessary conditions for the production of cholera was present, others, equally necessary, were absent. Possibly, as Pettenkofer remarked, for the production of an attack of cholera three things may be necessary, X, Y, and Z. The comma bacillus may be the X, but in the absence of the Y, certain local, and of the Z, certain personal conditions, disease does not result.
5. It has been found impossible by the administration of comma bacilli to produce in the lower animals true cholera, or any condition with clinical symptoms closely resembling cholera. Koch and others, in certain experiments on guineapigs, acting on the supposition that the acid in the stomach killed the bacillus, neutralized this by the administration of sodium carbonate, and paralysed the intestine by intraperitoneal injections of tincture of opium. In this way they claim to have succeeded in killing guineapigs with symptoms to a certain extent like those of cholera. There are many sources of fallacy in this experiment, as has been pointed out by Klein and others. Exactly similar results can be got by using the Finkler-Prior and other bacilli. The most promising experiments in this direction are those by Jablotny on the ground squirrel, Spermophilus guttatus. By administering to this animal comma cultures in alkaline media a disease in many respects like cholera was produced; and, in the intestines and discharges of the animals experimented on, cholera-like pathological changes were found, as well as comma bacilli.
Variability of the cholera microbe.— Bacterio-logical studies, always difficult, are extremely so in ​the case of the cholera microbe owing to its special liability to variation, both in its morphological and in its pathogenic characters. On this subject Haffkine remarks: " When the cholera bacillus was first discovered its properties were described with extreme precision, which helped in concentrating for a long time all studies on well-defined and carefully chosen specimens. Little by little, as the field of observation grew larger, a number of varieties have been found with characteristics differing so largely as to annihilate almost completely the original description. When we open the intestine of deceased cholera patients and investigate the microbes there, the adopted methods will bring to the surface vibrios in which the external forms, instead of the characteristic comma or spirillum, will vary between a coccus and a straight thread; the number and disposition of the cilia, the secretion of acids, the form of growth in broth, will vary; instead of giving in gelatin a discrete and well-defined figure of liquefaction, the variation will extend from the complete loss of this property to a rapid dissolution of the whole medium; there will be varieties which grow luxuriantly in given media, and others which do not grow there at all; some will be phosphorescent in the dark, and others not; some will give the indol reaction, and others will be deprived of this property, —and so on. The first thing to be done is to select carefully among these the most typical specimens, rejecting the others, and then to try their pathogenic power. We shall find such a divergence in strength that the extreme forms will not be believed to be the cholera species. There will be commas deprived of any virulence demonstrable on animals, and others which will kill the most resistant species. Some will be fatal to a guineapig at a dose of 1/100 of a culture tube, and others harmless in doses 500 times stronger. The average comma dies out when introduced under the skin of an adult animal; others will spread in the system and give rise to a fatal septicaemia. The ordinary comma will be without effect on birds; but several specimens have been isolated, and believed to be typical, which easily killed pigeons by hypodermic ​or intramuscular injection. I believe to be of great value the method worked out by Pfeiffer for comparing all such varieties with one selected as typical, which he employed for the preparation of an antitoxic serum. This method will be found of efficient help in distinguishing specimens of the greatest affinity with the average cholera comma. But once such specimens are selected and their particular properties studied, they begin to change from the first day they are introduced into the laboratory, and no calculation based on these studies is possible. In a case quoted by Metchnikoff, the proportion of the initial power of the microbe, and the strength it showed at a later trial, was as 75 to 1, the microbe having gradually sunk to 1/75 of its initial virulence." These remarks, by so great a master of the subject, whilst they indicate a way of reconciling many apparent discrepancies in matters of fact and differences in the conclusions arrived at by different bacteriologists, and whilst they indicate a key to many of the clinical features of cholera, teach us caution in accepting as proved the causal relationship of the cholera vibrio to the disease with which it is so invariably associated.
Symptoms.— An attack of cholera commences in one of two ways: either it may supervene in the course of what appears to be an ordinary case of diarrhœa, or it may come on suddenly and without any well-marked prodromal stage. During cholera epidemics diarrhœa is unusually prevalent. It is a common observation that at such times an attack of this latter nature, after a day or two, may assume the characters of true cholera. The preliminary looseness in such cases is called the "premonitory diarrhœa." Whether this looseness is specifically related to the subsequent attack, or is of an ordinary catarrhal or bilious type and acts simply by predisposing to the specific disease, has not been determined. Possibly, owing to a catarrhal condition— in itself non-specific —the resisting power of the mucous membrane is impaired; possibly, in diarrhœa, the large amount of fluid in the gut affords a favourable medium ​for the cholera germ to multiply in. Besides diarrhœa, other prodromata, such as languor, depression of spirits, noises in the ears, etc., are sometimes noted.
When true cholera sets in, profuse watery stools, painless or associated with griping, and at first fæcal in character, pour, one after the other, from the patient. Quickly the stools lose their fæcal character, becoming colourless or, rather, like thin rice-water containing small white flocculi in suspension. Enormous quantities— pints— of this material are generally passed by the patient. Presently vomiting, also profuse, at first perhaps of food, but very soon of the same rice-water description, supervenes. Cramps of an agonizing character attack the extremities and abdomen; the implicated muscles stand out like rigid bars, or are thrown into lumps from the violence of the contractions. The patient may rapidly pass into a state of collapse. In consequence principally of the loss of fluid by the diarrhœa and vomiting, the soft parts shrink, the cheeks fall in, the nose becomes pinched and thin, the eyes sunken, and the skin of the fingers shrivelled like a washerwoman's. The surface of the body becomes cold, livid,and bedewed with a clammy sweat; the urine and bile are suppressed; respiration is rapid and shallow; the breath is cold and the voice is sunk to a whisper. The pulse soon becomes thready, weak, and rapid, and then, after coming and. going and feebly fluttering, may disappear entirely. The surface temperature sinks several degrees below normal to 93° or 94° F.; whilst that in the rectum may be several degrees above normal— 101° to 105° F. The patient is now restless, tossing about uneasily,' throwing his arms from side to side, feebly complaining of intense thirst and of a burning feeling in the chest, and racked with cramps. Although apathetic, the mind generally remains clear. In other instances the patient may wander or may pass into a comatose state.
This, the "algide stage" of cholera, may terminate in one of three ways— in death, in rapid convalescence, or in febrile reaction. ​When death from collapse supervenes, it may do so at any time from two to thirty hours from the commencement of the seizure, usually in from ten to twelve. On the other hand, the gradual cessation of vomiting and purging, the reappearance of the pulse at the wrist, and the return of some warmth to the surface may herald convalescence. In such a case, after many hours' absence, the secretion of urine returns, and in a few days the patient may be practically well again. Usually, however, a condition, known as the " stage of reaction," gradually supervenes on the algide stage.
Reaction; cholera typhoid.— When the patient enters on this stage the surface of the body becomes warmer, the pulse returns, the face fills out, restlessness disappears, urine may be secreted, and the motions diminish in number and amount, becoming bilious at the same time. Coincidently with the subsidence of the more urgent symptoms of the algide stage and this general improvement in the appearance of the patient, a febrile condition of greater or less severity may develop. Minor degrees of this reaction generally subside in a few hours; but in more severe cases the febrile state becomes aggravated, and a condition in many respects closely resembling typhoid fever, " cholera typhoid," ensues. This febrile or possibly typhoid state may last from four or five days to perhaps a fortnight or even longer. In severe cases the face is flushed, the tongue brown and dry, and there may be delirium of a low typhoid character with tremor and subsultus; or the patient may sink into a peculiar torpid condition. The motions are now either greenish or like pea-soup, and may contain a larger or smaller amount of blood; at the same time they are very offensive. The reappearance of urine may be delayed from two to six days; at first scanty, high-coloured, cloudy, albuminous, and containing casts, it gradually becomes more profuse, paler, and with less albumin. Though at first the urine is very deficient in urea, in uric acid, and in salts, later the quantity of these substances may exceed for a time the normal ​During the stage of reaction death may occur from a variety of complications; from pneumonia, from enteritis and diarrhœa, from asthenia, or from such effects of uræmic poisoning as coma and convulsions.
In cholera there is a considerable variety in the character of the symptoms and in their severity, both as regards individual cases and as regards different epidemics. It is generally stated that during an epidemic the earlier cases are the more severe, those occurring towards the end of the epidemic being on the whole milder.
Ambulatory cases occur during all epidemics. Such cases are characterized by diarrhœa and malaise merely; there is never complete suppression of urine, the diarrhœa never loses its bilious character, and it is not accompanied by cramps. The attack gradually subsides without developing a subsequent stage of reaction.
Cholerine.— In another set of cases the diarrhœa may be somewhat more acute, and the stools assume the well-known rice-water appearance; but the looseness soon ceases without leading to suppression of urine, or to algide symptoms, or even to very severe cramps, and without being followed by a stage of reaction. Such cases are sometimes designated "choleraic diarrhœa" or "cholerine."
Cholera sicca.— A very fatal type is that known as " cholera sicca." In these cases, though there is no, or very little, diarrhœa or vomiting, collapse sets in so rapidly that the patient is quickly overpowered as by an overwhelming dose of some poison, and dies in a few hours without purging or any attempt at reaction. At the post-mortem examination the rice-water material, so characteristic of cholera, though it may not have been voided during life, is found in abundance in the bowel. Other cases die suddenly from apnœa caused, apparently, either by coagula in the right heart, or by spasm of the pulmonary arterioles, the lungs refusing to transmit the thickened blood. In certain cases, after temporary improvement relapse may occur and is nearly always fatal. ​Hyperpyrexia is an occasional though rare occurrence in cholera. In such the axillary temperature may rise to 107° F., the rectal temperature perhaps to 109° F. These cases also are almost invariably fatal.
Sequelœ.— Cholera is apt to be followed by a variety of more or less important sequelæ, such as anæmia, mental and physical debility, insomnia, pyretic conditions, chronic enterocolitis, nephritis, different forms of pulmonary inflammation, parotitis apt to end in abscess, ulceraticn of the corneæ, bedsores, and gangrene of different parts of the body. Jaundice occurs at times, and is said to be of the gravest import. Pregnant women almost invariably miscarry, the fœtus showing evidences of cholera.
Morbid anatomy and pathology.— Rigor mortis occurs early and persists for a considerable time. Curious movements of the limbs may take place in consequence of post-mortem muscular contractions. On dissection the most characteristic pathological appearances in cholera are those connected with the circulation and with the intestinal tract.
If death have occurred during the algide stage, the surface presents the shrunken and livid appearance already described. On opening the body all the tissues are found to be abnormally dry. The muscles are dark and firm; sometimes one or more of them are discovered to be ruptured— evidently from the violence of the cramps during life. The right side of the heart and systemic veins are full of dark, thick, and imperfectly coagulated blood, which tends to cling to the inner surface of the vessels. Fibrinous clots, extending into the vessels, may be found in the right heart. The lungs are usually anæmic, dry, and shrunken; occasionally they may be congested and œdematous. The pulmonary arteries are distended with blood, the pulmonary veins empty. The liver is generally loaded with blood; the gall-bladder full of bile; the spleen small. Like all the other serous cavities, the peritoneum contains no fluid, its surface being dry and sticky. The outer surface of the bowel has generally a diffuse rosy red. occasionally ​an injected appearance. On opening the bowel it is found to contain a larger or smaller amount of the characteristic rice-water material, occasionally blood. The mucous membrane of the stomach and intestine is generally pinkish from congestion, or there may be irregularly congested or arborescent patches of injection here and there throughout its extent. In addition, there may be seen smaller or larger points of ecchymosis in or under the mucous membrane. The changes in the alimentary canal are most marked at the lower end of the ileum, where Peyer's patches and the solitary glands may be seen to be congested and swollen. In some instances the bowel is pale throughout; in many the mucous membrane has a sodden, pulpy appearance from exfoliation of epithelium— possibly a post-mortem change; occasionally, especially towards the lower end of the ileum, a croupous exudation is met with. Greig has shown that the gall-bladder and biliary passages are frequently invaded by the cholera vibrio, and in a proportion of instances are, consequently, more or less inflamed. He also found that in a proportion of cases (8 in 55) the vibrio is present in the urine. The mesenteric glands are congested. The superficial veins of the kidneys are full; the medullary portion is much congested, the cortical portion less so; the tubules are filled with granular matter; the epithelium is cloudy, granular, or fatty, and, at a later stage, may be shed. The bladder is empty and contracted. Nothing special is to be noted in the nervous system .
If death have occurred during the stage of reaction, the tissues are moist; the venous system is less congested; the lungs are probably congested and œdematous, perhaps inflamed. Very probably there are evidences of extensive enteritis.
Microscopical examination of the contents of the bowel during the acute stage of the disease discovers, in most instances, the comma bacillus. Usually it is in great abundance; occasionally in what is almost a pure culture. Sections of the intestine show the bacillus lying on and between the epithelial cells of ​the villi and glands. As the comma bacillus does not occur in the blood, and assuming that it is the cause of cholera, we must conclude that the clinical phenomena are not the result of a septicæmia, but that they arise either from a local intestinal irritation produced by the bacillus, or from some toxin which it generates in the bowel and which is absorbed; or from a combination of these factors.*
That the cholera vibrio is a powerful irritant is shown by the effect produced locally by a hypodermic injection of a virulent culture. When so injected, not only does it give rise to local œdema, but, unless precautions are taken, it causes in certain animals necrosis of the tissues and ulceration at the seat of injection. It is conceivable, therefore, that when in the course of the naturally acquired disease the bacilli proliferate in the bowel they or their products act as an irritant to the mucous membrane, and so provoke the hypercatharsis and the consequent dehydration of the tissues which are the dominating features of the disease. On the other hand, the hypodermic injection of cholera vibrio cultures is followed by smart febrile movement lasting from one to three days, evidencing the presence of a febrogenic toxin capable of producing constitutional symptoms. This fact, together with the rapid and intense prostration which, in some instances of natural cholera, appears to be out of all proportion to the amount of catharsis present, suggests that the lethal effects of the vibrio are attributable not alone to the drain of fluid from the blood and tissues but also to the absorption of a cholera toxin from the intestine. It is somewhat strange, however, if this toxin be anything more than a subsidiary element in the production of the symptoms in most instances of the naturally acquired disease, that catharsis is not one of the effects of the hypodermic introduction of the vibrio, and that fever is not an earlier and more prominent symptom in ​natural cholera. The modern tendency is to regard the clinical phenomena as the result partly of local irritation and partly of toxæmia; variation in the proportional intensities of the different clinical elements depending on the degree of virulence of the particular strain of microbe introduced, and on the circumstances and idiosyncrasy of the patient.*
Diagnosis.— During the height of an epidemic the diagnosis of cholera is generally an easy matter; the profuse rice-water discharges, the collapse, the cold clammy skin, the cyanosis, the shrunken features the shrivelled fingers and toes, the feeble, husky, hollow voice, the cold breath, the cramps, and the suppression of urine, together with the high rate of mortality, are generally sufficiently distinctive. But in the first cases of some outbreak of diarrhœa, which may or may not turn out to be cholera, and the true nature of which for obvious reasons it is of importance to determine, correct diagnosis, though urgently required, may not be so easily attained.
Symptoms resembling true cholera may supervene in the course of an ordinary severe diarrhœa, and are very usual in cholera nostras, in mushroom poisoning, in ptomaine poisoning, in the early stages of trichinosis, and in a certain type of pernicious malarial fever. In none of these, however, is the mortality so high as in cholera. It may be laid down, therefore, that epidemic diarrhœa attended by a case- mortality of over 50 per cent, is cholera.
In other forms of diarrhœa it is rare for the stools to be persistently so absolutely devoid of biliary colouring matter as they are in cholera. A careful inspection of the stools sometimes yields valuable information in other ways. Thus, in mushroom poisoning fragments of the mushrooms which caused the catharsis may be seen; in trichinosis the microscope may detect the adult trichina. In choleraic malarial attacks the presence of the malaria parasite ​in the blood, the periodicity of the symptoms, their amenability to quinine, together with the character of the prevailing epidemic, generally combine to guide to a correct diagnosis.
The detection of the comma bacillus in the stools is now regarded as a positive indication of cholera. It would be rash, however, to affirm that a negative result from bacteriological examination of a single case is conclusive against its being cholera. Moreover, such" examinations to be trustworthy have to be made by a skilled bacteriologist. According to Kanthack and Stephens, the following were the methods of bacteriological diagnosis practised by Klein during the threatened epidemic in 1893:—
Method 1.— A. flake from the dejecta is placed in peptone broth and incubated at 37° C. In twenty-four hours an abundant crop of vibrios is found in the superficial layers of the broth. This pellicle consists of a practically pure culture, or, at any rate, is a culture which easily allows of pure subcultures being obtained.
Method 2.— A flake is placed in sterile salt solution or broth; it is shaken up, and from this gelatin or agar tubes are inoculated, and plates are made. In agar plates incubated at 37° C. numerous colonies may be found in twenty to thirty hours. In the gelatin plates, after two to three days' incubation at 20° to 22° C., numerous typical colonies can be got. (A more modern method which is very efficacious is Dieudonne's blood-alkali agar. Equal parts of defibrinated ox-blood and normal caustic soda solution are mixed with 70 c.c. of neutral peptone agar. On this medium few organisms other than the cholera vibrio develop.)*
Method 3.— A flake is placed directly into Dunham's peptone salt solution (1 per cent, peptone, 0.5 per cent, sodium chloride), or the Dunham's solution is inoculated after previous dilution of the material. The peptone solution, after six, eight, to ten hours' incubation at 37° C., shows a definite turbidity, due to the rapid growth of the comma bacilli; and the cholera-red reaction may be obtained, although not absolutely specific. For speedy diagnosis this method is most valuable; in six to twelve hours, or, at latest, in sixteen hours, comma bacilli can be found in the superficial layers of the ​peptone solution, so that in twenty-four hours pure cultures and the cholera-red reaction can be obtained in secondary peptone tubes. Also, a positive result may be obtained by this method in cases in which the microscopical examination has failed to give definite evidence of the presence of vibrios.
In addition to these methods the agglutination test is frequently employed. The serum of a rabbit immunized against a known cholera vibrio by frequent and massive intraperitoneal injections, and therefore having a high agglutinating power, affords a very rapid means of differentiation of pathogenic from non-pathogenic vibrios.
In case of doubt as to the identity of a suspected cholera vibrio, Pfeiffer's reaction might be employed with advantage. An emulsion of the organism, to which a small amount of the patient's serum had been added, is injected into the peritoneal cavity of a normal guineapig. Half to one hour later the peritoneal fluid is examined. If the case be one of cholera the bacteria will be found to be degenerated and mostly spherular.
The first two methods are applicable to those instances in which microscopical examination of the stools shows crowds of comma bacilli. Method 3 is specially applicable to those stools in which comma bacilli are in very small numbers.
As an agglutination reaction is not obtainable from the blood serum during the acute stage of the disease, this means of diagnosis is not available in cholera.
Mortality.— The average case-mortality in cholera amounts to about 50 per cent. Some epidemics are more deadly than others. As already mentioned, the mortality is greater at the earlier than at the later stages of an epidemic. To the old, the very young, the pregnant, the subjects of grave organic disease— particularly of the liver, kidneys, and heart —the dissipated, the underfed, and the feeble, the danger is very great.
Quarantine prevention.— Theoretically, quarantine should be "an efficient protection against the introduction of cholera into a community; practically, it has proved a failure. Unless they are stringent and thoroughly carried out, quarantine regulations can be of little use. Unfortunately, the temptation to evade such regulations is in proportion to their stringency. It is impossible to secure the absolute honesty and efficiency of every individual in a large ​body of men charged with the details of any system entailing great personal inconvenience and loss to travellers and merchants. Therefore, if the strength of the quarantine chain is to be measured by that of its weakest link, the chain must be weak indeed, as a very slight knowledge of human nature will lead us to suspect, and a very slight acquaintance with the working of quarantine as ordinarily practised will attest. Even if the utmost care, intelligence, and honesty succeed in excluding individuals actually suffering from cholera, or likely within a reasonable time to suffer from cholera, there is yet no guarantee that the germ of the disease may not be introduced. Koch and others have shown that sometimes the dejecta even of individuals apparently in good health and who have not suffered, or who may not subsequently suffer from choleraic disease, may yet contain, and for some time continue to contain, the cholera vibrio. In 271 fatal cases Greig found the vibrio in the gall-bladder, a situation favouring persistence in the event of recovery. During the epidemic of 1911, in Naples, 10 per cent, of healthy contacts had cholera vibrios in their stools and continued to pass them for three to five days. If the cholera vibrio be the germ of cholera, then such healthy, vibrio-bearing individuals may well suffice to start an epidemic. It is impossible, short of absolute and complete isolation, for any practicable system of quarantine to deal efficiently with such cases.
So far from ordinary quarantine proving a defence against cholera, it may actually increase the risk of an epidemic. This it does by fostering a false sense of security, and so leading to neglect of those well-proved guarantors of the public health— domestic, municipal, and personal cleanliness, and a pure water and food supply.
The system to which Great Britain apparently owed her immunity during recent epidemics on the continent of Europe is a practicable and, in civilized conditions, an efficient one. Under this system only ships which were carrying or which had recently carried cholera patients were detained; and even ​these merely till they could be thoroughly disinfected. Thus inconvenience and loss to travellers and merchants were small, and the temptation to conceal cases of the disease or to evade regulations was proportionately minimized. Any cholera cases were isolated in suitable hospitals, the rest of the crew and passengers, although supervised for a time, being given free pratique. At the same time, attention was not diverted from the sanitation of towns, especially of seaports; this was the measure mainly relied on. Suspicious cases occurring on shore were at once reported to the sanitary authorities and promptly dealt with, fomites being destroyed or disinfected at as little cost and inconvenience to individuals as possible. Every endeavour was made to prevent fæcal contamination of the public water supply.
Of late years in India effort is being directed much 011 the same lines, attention being given to sanitation rather than to quarantine. During the great religious festivals the sanitary condition of the devotees is looked after so far as practicable, special care being given to provide them with good drinking and bathing- water. Many of the large Indian towns now enjoy an abundant and pure water supply; and civilized systems of night-soil conservancy and other important sanitary measures are being gradually introduced, and, in the case of more than one great city, with the most gratifying results.
Among the troops in India, on the appearance of cholera in their neighbourhood, special protective measures are promptly instituted, elaborate directions having been drawn up for the guidance of medical officers. For an account of these regulations the reader is referred to the Annual Report of the Sanitary Commissioner with the Government of India for 1895, Appendix, p. 189.
Incubation period.— All quarantine and protective systems must take cognizance of the fact that, although cholera may declare itself within a few hours of exposure to infection, it may also do so at any time up to ten days thereafter; three to six days may be set down as the usual duration of the incubation period. ​Anti-choleraic inoculations.— During an epidemic of cholera in Spain, in 1885, Ferran instituted a system of prophylactic inoculation. He injected hypodermically ordinary laboratory cultures of the cholera vibrio obtained directly from cholera corpses. No attempt was made to regulate or standardize in any way the virulence of the cultures. The results were not encouraging. As accidents were frequent, the Government put a stop to the practice.
In 1893 Haffkine, after elaborate experiments on the lower animals, commenced a system of anticholera vaccinations, using a pure virus of a fixed and known strength. This virus he prepared by passing the cholera vibrio through a series of guineapigs by means of intraperitoneal injections. In this way the microbes were increased in toxicity to a definite point beyond which their virulence could not be exalted. Cultures so prepared gave rise, when injected hypodermically, not only to a general but also to a local reaction, the latter being so severe that it ordinarily ended in extensive sloughing and ulceration. To avoid this undesirable result, a milder vaccine was prepared by cultivating the strong vaccine in artificial media at a temperature of 39° C., and in an atmosphere kept constantly renewed. By first injecting under the skin of animals this milder vaccine it was found that such a measure of protection was conferred that subsequent injection of the strong virus was no longer followed by violent local reaction. Having satisfied himself that the subcutaneous injection of these two vaccines conferred immunity against the cholera vibrio in the lower animals, Haffkine, with the approval and aid of the Government, proceeded to use them in man on a large scale in India. Up to 1895,70,000 injections of living cholera bacilli had been made in 43,179 individuals. In no instance did any bad result ensue. While admitting that the value of his method has not been fully proved, Haffkine claims that the results are sufficiently encouraging to justify a continuation of these inoculations on a larger scale.
The symptoms which these injections produce are ​fever, transient œdema and tenderness at the seat of injection, the first evidence of constitutional disturbance appearing from two to three hours after the injection is made. The fever and general indisposition last from twenty-four to thirty-six hours, the local symptoms gradually disappearing in from three to four days. The symptoms following the second injection— made from three to four days after the first— are generally more marked, but of shprter duration. The microbes injected die; it is the substances set free on their death which confer the immunity. It is found that carbolized cultures— that is, dead vibrios— produce the same immunizing and constitutional effects, though in a somewhat milder and probably less permanent degree. How long the immunity conferred by these injections endures has not been definitely settled.*
In consequence of an experiment on himself, Haffkine found that, although the virulent comma bacillus produced necrotic effects at the site of inoculation in guineapigs, it did not do so in man. Accordingly, he has abandoned his original method of a primary inoculation with an attenuated virus, and has since countenanced immediate inoculation with virulent, recently-isolated vibrios, without further preparation. According to Powell, the method is as follows:—
" The whole surface of agar in a sloped tube is inoculated with the comma and cultivated for twenty-four to thirty-six hours at a temperature of 40° C. The whole surface should then be covered with a uniform layer of growth. Sterilized water is then added to one-third the height of the agar, and the growth washed off and suspended in the water by rapidly rotating or shaking, till the surface of the agar is quite clear. Half a cubic centimetre, about nine minims, is the dose for an average adult."
Powell's results are highly favourable— namely, 198 cases of cholera with 124 deaths among 6,549 non-inoculated tea-garden coolies in Assam, against 27 cases and 14 deaths among 5,778 inoculated coolies. ​Had the incidence of cholera been the same in both classes, the inoculated would have had 174 instead of 27 cases, and 109 instead of 14 deaths. In 1912, 8,000 Europeans were inoculated in Batavia, and among these there was only one death from cholera as against 15 deaths amongst 2,700 uninoculated.
Subsequent experience, particularly that obtained during the Balkan War of 1913 and the European War, has gone far to confirm these earlier impressions of the value of Haffkine's vaccinations. Recently Castellani has advocated, and practised with promising results, the use of a " tetra vaccine " of combined cholera, typhoid, and paratyphoid A and B strains.
Personal prophylaxis.— During cholera epidemics great care should be exercised to preserve the general health; at the same time, anything like panic or apprehension must be sedulously discouraged. Fatigue, chill, excess— particularly dietetic or alcoholic excess— are to be carefully avoided. Visits to cholera districts should be postponed if possible, seeing that the new-corner is specially liable to contract the disease. Unripe fruit, over-ripe fruit, shell-fish, food in a state of decomposition, and everything tending to upset the digestive organs and to cause intestinal catarrh are dangerous. Melons, cucumbers, and the like deserve the evil reputation they have acquired. Purgatives— particularly saline purgatives— unless very specially indicated, should never be taken at these times. All drinking-water, and all water in which dishes and everything used in the preparation and serving of food are washed, should be boiled. Filters— except perhaps the Pasteur-Chamberland filter— are not for the most part to be relied on; in many instances they are more likely to contaminate the water passed through them than to purify it. A good plan in a household, or in public institutions, is to provide for drinking purposes an abundant supply of weak tea or lemon decoction, the supply being renewed daily; such a plan ensures that the water used in the preparation of the drink has been boiled. All food should be protected from flies. ​Diarrhœa occurring during cholera epidemics should be promptly and vigorously treated.
Treatment.— During cholera epidemics it is customary to establish depôts where sedative and astringent remedies for the treatment of diarrhœa are dispensed gratuitously. Experience seems to encourage the belief that by such means incipient cholera may be aborted during the stage of premonitory diarrhœa. Of the various drugs used with this view, chlorodyne, or chlorodyne with brandy, is the most popular. Lead and opium pill; chalk, catechu, and opium mixture; compound kino powder; aromatic powder of chalk and opium; a pill of opium, asafœtida, and black pepper; dilute sulphuric acid and laudanum, are among the drugs more commonly employed for this purpose. Whether true cholera can be cut short in this way or not, it is certainly in the highest degree advisable at such a time to neglect no case of diarrhœa, but to insist on rest, warmth, and the greatest prudence in feeding in all cases of intestinal catarrh or irritation.
Many plans of treatment, based on theoretical considerations, have been advocated from time to time. The eliminative treatment advocated by Dr. George Johnson; the spinal ice-bag recommended by Chapman; various antiseptic methods directed to the destruction of the vibrio in the intestinal canal; drugs designed to counteract the physiological effects of the cholera toxins, as chloroform, atropine, nitrite of amyl, and nitro-glycerine, may be mentioned as belonging to this category of remedies.
Until recently, the only treatment of proved value in cholera was the purely symptomatic and expectant one. If our efforts have failed to counteract the premonitory diarrhœa, attention should be given to maintaining the patient in as favourable a condition as possible to struggle against the poison of the disease. He should be kept strictly in the horizontal position, in a warm bed, and in a well-ventilated but not too cold room. His thirst should be treated by sips of iced water or of soda-water, or champagne, or brandy and water. Copious draughts, ​as they are likely to provoke vomiting, are usually condemned. It does not follow from this that they are harmful; the emesis contributes to the elimination of germ and toxin. Cramps may be relieved by gentle frictions with the hand or with ginger-root, by a small hypodermic injection of morphia, or, these failing, by short chloroform inhalations. The surface of the body should be kept dry by wiping it with warm dry cloths, and the surface heat maintained by hot- water bottles or warmed bricks placed about the feet, legs, and flanks. The patient must not be allowed to get up to pass his stools; a warmed bed -pan should be provided for this purpose. All food should be withheld while the disease is active.
If the pulse fail or disappear at the wrist, stimulants by the mouth, or, if there is much vomiting and these do not appear to be absorbed, hypodermic injections of ether or brandy, may be given. No improvement ensuing, intravenous or subcutaneous injection of normal, or hypertonic, saline fluid may be had recourse to. As regards the former, a suitable injection may be quickly prepared of common salt 60 gr., carbonate of soda 60 gr., boiled water 1 quart. Of this, from one to three quarts at a temperature of 100° F. may be slowly introduced by gravitation into a vein, the effect being carefully watched. The pulse can generally be quickly restored temporarily by this means and life prolonged, possibly in a few instances saved; too often, however, the fluid so introduced rapidly escapes by the bowel, and collapse once more sets in. Dr. Cox, of Shanghai, has had some encouraging results from continuous, prolonged, slow, intravenous injection of saline fluid, the fluid gravitating from a vessel placed 2½ ft. above the level of the patient's arm. The flow is kept up for several hours, and as long as it is deemed that there is any risk of collapse.
Rogers has recently introduced a method of treating cholera by intravenous injection of hypertonic saline solution, which promises well. He claims that since the introduction of his method the case-mortality from this disease in the Calcutta Medical ​College Hospital has been greatly reduced; and others, who have practised his methods, have in most instances had equally good results. The principle of the treatment is based on the fact that not only is the water content of the blood reduced by one-third to two thirds, according to the severity of the case, but in addition there is a loss of the saline constituents. Hence the necessity for supplying the latter. His hypertonic solution is composed as follows: Sodium chloride, 120 gr.; potassium chloride, 6 gr.; calcium chloride, 4 gr.; sterilized water, 1 pint. This he introduces by means of a special stop-cocked cannula and transfusion bulb at the rate of not more than 4 oz. a minute, the flow being slowed down to 1 oz. if distress or headache supervene. At the same time he gives permanganate of potassium in solution or in pill by mouth up to 50 gr. a day 2 gr. every quarter of an hour for two hours, then every half -hour till the stools are coloured green. In suppression of urine, if the blood pressure is normal, isotonic solution should be used. As the injections may have to be repeated several times, the cannula, suitably secured and protected, should be left in the vein till symptoms indicate that the acute stage is subsiding.
With the intravenous saline Rogers combines hypodermic injections of atropine.
Rogers considers that the occurrence of uræmia in cholera is the result of the development of an acidosis. In such cases he recommends the injection subcutaneously or per rectum of a 2- to 3-per-cent. solution of sodium bicarbonate if the specific gravity of the blood is low; if the specific gravity of the blood is high or normal, it should be given intravenously at first, and subsequently by rectum.
Other Indian practitioners claim to have got better results in suppression of urine from permanganate in adrenalin solution, the dose of the latter being 10 minims of a l-in-10,000 solution every three hours.
During the stage of reaction, should purging persist, large doses of salicylate of bismuth with a little opium may prove of service. In these circum​stances massive rectal injections of tannin 1 oz., gum arabic 1 oz., warm water 1 quart, are of use. If the secretion of urine is not quickly restored, large hot poultices over the loins, dry-cupping of the same region, and the judicious use of bland diluents should be had recourse to. Stimulating diuretics are dangerous. Retention of urine must be inquired about, and the region of the bladder frequently examined, and, if necessary, the catheter employed. In the event of constipation, purgatives must be eschewed and simple enemata alone used.
In cholera convalescents the diet for a time must be of the simplest and most digestible nature— diluted milk, barley-water or rice-water, thin broths, meat juice, and so forth— the return to ordinary food being effected with the greatest circumspection.
Cholera typhoid must be treated much as ordinary enteric fever.
Precautions.— It must never be forgotten by those responsible for the management of cholera cases that through their discharges such patients are a danger to the community, and that those discharges may contain the vibrio in some instances up to fifty days after the attack. The Bordet-Gengou reaction,*a complicated serum reaction, has been advantageously employed in the detection of these cholera carriers. Further, that though the germ dies in a few hours if dried, it preserves its vitality for many days if kept moist, as, for example, in damp, soiled linen; that it may live for months as a saprophyte in water or ​damp soil; and that it is not killed by ordinary cold. Therefore, all discharge and soiled linen from cholera cases should be immediately disinfected or destroyed, and every precaution must be taken during convalescence, as well as during the acute stage, to prevent contamination of wells, public water supply, drinking and table vessels, and food. The domestic fly and other vermin as vectors of the germ must not be overlooked.
* ↑ * Though it is customary to speak of Lower Bengal as the home of cholera, it is by no means certain that other Eastern localities have not some claim to a similar distinction— Bangkok, Canton, and Shanghai, for example. Dr. Henderson, in his health reports, indicates that the disease is rarely absent during the summer months from the last-named city; the same may be said of Bangkok and of Canton.
* ↑ * "Bacillus" is a bad term for this organism, which is really a spirillum.
* ↑ * Gelarie found that cultures of the vibrio lived for at least 285 days in sterilized sea-water; whilst they died in less than one day in sterilized tap-water.
* ↑ * Opinions differ as to whether or not the cholera vibrio is hæmolytic to a suspension of sheep's corpuscles. Strong, in the Philippines, found that all vibrios which agglutinated with a cholera serum were genuine cholera vibrios, and that none of them were hæmolytic.
* ↑ * Greig, although he failed to recover the vibrio from the blood during life, nevertheless found it widely distributed in the organs after death, and concludes that it is distributed in these by the lymphatic system.
* ↑ * Metchnikoff, Roux, and Salembeni demonstrated the existence of a soluble cholera toxin by introducing collodion sacs (2-3 c.c. capacity) filled with cholera cultures into the peritoneal cavity of guineapigs. Macfadyen obtained a virulent endotoxin by triturating cultures in liquid air.
* ↑ * The cholera vibrio forms indol very rapidly and in considerable amount, reducing nitrates to nitrites, especially in peptone water. A few drops of pure sulphuric acid added to a peptone-water culture eight to twelve days old gives a pinkish colour, more intense according to the age of the culture. The coli group and other bacteria produce indol, but do not reduce nitrates to nitrites so readily; the presence of the latter is essential for the reaction.
* ↑ * For details of Haffkine's original methods and technique see the Brit. Med. Journ., Feb. 4, 1893, and the Indian Med. Gaz., Nov., 1896.
* ↑ * The Bordet-Gengou reaction is based on the fixation of the complement, using a culture of the vibrio as an antigen. The following mixtures are prepared in three test tubes: Nos. 1 and 2 contain 0.2 c.c. suspension of cholera vibrio, and 0.6 c.c. suspected person's serum (heated to 56° F. for half an hour), and 0.1 c.c. complement (guineapig's serum); tube 3, a similar mixture with the substitution of normal person's serum. These tubes are shaken and incubated for half an hour. Then 1 c.c. of mixture of a serum hæmolytic to sheep's corpuscles (heated to 56° F. for half an hour) and one volume of washed sheep's corpuscles. To tube 2 is added 0.1 c.c. of a mixture of two volumes of normal saline and one volume of washed sheep's corpuscles. Should the suspected serum be that of a cholera carrier, the complement in tube 1 will be fixed and no hæmolysis occur, whereas in tube 3 it will be free and hæmolysis will take place.