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Diphtheria

DIPHTHERIA (from , a skin or membrane), the term applied to an acute infectious disease, which is accompanied by a membranous exudation on a mucous surface, generally on the tonsils and back of the throat or pharynx.

In general the symptoms at the commencement of an attack of diphtheria are comparatively slight, being those commonly accompanying a cold, viz. chilliness and depression. Sometimes more severe phenomena usher in the attack, such as vomiting and diarrhoea. A slight feeling of uneasiness in the throat is experienced along with some stiffness of the back of the neck. When looked at the throat appears reddened and somewhat swollen, particularly in the neighbourhood of the tonsils, the soft palate and upper part of pharynx, while along with this there is tenderness and swelling of the glands at the angles of the jaws. The affection of the throat spreads rapidly, and soon the characteristic exudation appears on the inflamed surface in the form of greyish-white specks or patches, increasing in extent and thickness until a yellowish-looking false membrane is formed. This deposit is firmly adherent to the mucous membrane beneath or incorporated with it, and if removed leaves a raw, bleeding, ulcerated surface, upon which it is reproduced in a short period. The appearance of the exudation has been compared to wet parchment or washed leather, and it is more or less dense in texture. It may cover the whole of the back of the throat, the cavity of the mouth, and the posterior nares, and spread downwards into the air-passages on the one hand and into the alimentary canal on the other, while any wound on the surface of the body is liable to become covered with it. This membrane is apt to be detached spontaneously, and as it loosens it becomes decomposed, giving a most offensive and characteristic odour to the breath. There is pain and difficulty in swallowing, but unless the disease has affected the larynx no affection of the breathing. The voice acquires a snuffling character. When the disease invades the posterior nares an acrid, fetid discharge, and sometimes also copious bleeding, takes place from the nostrils. Along with these local phenomena there is evidence of constitutional disturbance of the most severe character. There may be no great amount of fever, but there is marked depression and loss of strength. The pulse becomes small and frequent, the countenance pale, the swelling of the glands of the neck increases, which, along with the presence of albumen in the urine, testifies to a condition of blood poisoning. Unless favourable symptoms emerge death takes place within three or four days or sooner, either from the rapid extension of the false membrane into the air-passage, giving rise to asphyxia, or from a condition of general collapse, which is sometimes remarkably sudden. In cases of recovery the change for the better is marked by an arrest in the extension of the false membrane, the detachment and expectoration of that already formed, and the healing of the ulcerated mucous membrane beneath. Along with this there is a general improvement in the symptoms, the power of swallowing returns, and the strength gradually increases, while the glandular enlargement of the neck diminishes, and the albumen disappears from the urine. Recovery, however, is generally slow, and it is many weeks before full convalescence is established. Even, however, where diphtheria ends thus favourably, the peculiar sequelae already mentioned are apt to follow, generally within a period of two or three weeks after all the local evidence of the disease has disappeared. These secondary affections may occur after mild as well as after severe attacks, and they are principally in the form of paralysis affecting the soft palate and pharynx, causing difficulty in swallowing with regurgitation of food through the nose, and giving a peculiar nasal character to the voice. There are, however, other forms of paralysis occurring after diphtheria, especially that affecting the muscles of the eye, which produces a loss of the power of accommodation and consequent impairment of vision. There may be, besides, paralysis of both legs, and occasionally also of one side of the body (hemiplegia). These symptoms, however, after continuing for a variable length of time, almost always ultimately disappear.

Under the name of the Malum Egyptiacum, Aretaeus in the 2nd century gives a minute description of a disease which in all its essential characteristics corresponds to diphtheria. In the 16th, 17th and 18th centuries epidemics of diphtheria appear to have frequently prevailed in many parts of Europe, particularly in Holland, Spain, Italy, France, as well as in England, and were described by physicians belonging to those countries under various titles; but it is probable that other diseases of a similar nature were included in their descriptions, and no accurate account of this affection had been published till M. Bretonneau of Tours in 1821 laid his celebrated treatise on the subject before the French Academy of Medicine. By him the term La Diphthérite was first given to the disease.

Great attention has been paid to diphtheria in recent years, with some striking results. Its cause and nature have been definitely ascertained, the conditions which influence its prevalence have been elucidated, and a specific "cure" has been found. In the last respect it occupies a unique position at the present time. In the case of several other zymotic diseases much has been done by way of prevention, little or nothing for treatment; in the case of diphtheria prevention has failed, but treatment has been revolutionized by the introduction of antitoxin, which constitutes the most important contribution to practical medicine as yet made by bacteriology.

Causation

The exciting cause of diphtheria is a micro-organism, identified by Klebs and Loffler in 1883 (see Parasitic Diseases). It has been shown by experiment that the symptoms of diphtheria, including the after-effects, are produced by a toxin derived from the micro-organisms which lodge in the air-passages and multiply in a susceptible subject. The natural history of the organism outside the body is not well understood, but there is some reason to believe that it lives in a dormant condition in suitable soils. Recent research does not favour the theory that it is derived from defective drains or "sewer gas," but these things, like damp and want of sunlight, probably promote its spread, by lowering the health of persons exposed to them, and particularly by causing an unhealthy condition of the throat, rendering it susceptible to the contagion. Defective drainage, or want of drainage, may also act, by polluting the ground, and so providing a favourable soil for the germ, though it is to be noted that "the steady increase in the diphtheria mortality has coincided, in point of time, with steady improvement in regard of such sanitary circumstances as water supply, sewerage, and drainage" (Thorne Thorne). Cats and cows are susceptible to the diphtheritic bacillus, and fowls, turkeys and other birds have been known to suffer from a disease like diphtheria, but other domestic animals appear to be more or less resistant or immune. In human beings the mere presence of the germ is not sufficient to cause disease; there must also be susceptibility, but it is not known in what that consists. Individuals exhibit all degrees of resistance up to complete immunity. Children are far more susceptible than adults, but even children may have the Klebs-Loffler bacillus in their throats without showing any symptoms of illness. Altogether there are many obscure points about this micro-organism, which is apt to assume a puzzling variety of forms. Nevertheless its identification has greatly facilitated the diagnosis of the disease, which was previously a very difficult matter, often determined in an arbitrary fashion on no particular principles.

Diphtheria, as at present understood, may be defined as sore throat in which the bacillus is found; if it cannot be found, the illness is regarded as something else, unless the clinical symptoms are quite unmistakable. One result of this is a large transference of registered mortality from other throat affections, and particularly from croup, to diphtheria. Croup, which never had a well-defined application, and is not recognized by the College of Physicians as a synonym for diphtheria, appears to be dying out from the medical vocabulary in Great Britain. In France the distinction has never been recognized.

Prevalence

Diphtheria is endemic in all European and American countries, and is apparently increasing, but the incidence varies greatly. It is far more prevalent on the continent than in England, and still more so in the United States and Canada. The following table, compiled from figures collected by Dr Newsholme, shows how London compares with some foreign cities. The figures give the mean death-rate from diphtheria and croup for the term of years during which records have been kept. The period varies in different cases, and therefore the comparison is only a rough one.

Mean Death-Rates from Diphtheria and Croup per Million living.

New York 1610 Munich 990
Chicago 1400 Milan 990
Buenos Aires 1360 Florence 830
Trieste 1300 Vienna 770
Dresden 1290 Stockholm 720
Berlin 1190 St Petersburg 650
Boston 1160 Moscow 640
Marseilles 1130 Paris 630
Christiania 1090 Hamburg 490
Budapest 1880 London 386

There is comparatively little diphtheria in India and Japan, but in Egypt, the Cape and Australasia it prevails very extensively among the urban populations. The mortality varies greatly from year to year in all countries and cities. In Berlin, for instance, it has oscillated between a maximum of 2420 in 1883 and a minimum of 340 in 1896; in New York between 2760 in 1877 and 680 in 1868; in Christiania between 3290 in 1887 and 170 in 1871. In some American cities still higher maxima have been recorded. In other words, diphtheria, though always endemic, exhibits at times a great increase of activity, and becomes epidemic or even pandemic. The following table for 1859-99 shows fairly well the periodical rise and fall in England and Wales. Diphtheria and croup are given both separately and together, showing the increasing transference from one to the other of late years. Diphtheria was first entered separately in the year 1859.

Deaths from Diphtheria and Croup per Million living in England and Wales.

Years. Diphtheria. Croup. Diphtheria
and Croup.
1859 517 286 803
1860 261 220 481
1861-70 185 246 431
1871-80 121 168 289
1881-90 163 144 307
1891-95 254 70 324
1896-97 269 43 312
1898 244 27 271
1899 293 32 325

The combined figures for diphtheria and croup in later years are: - (1900) 316; (1901) 296; (1902) 255; (1903) 195; (1904) 184; (1905) 174; (1906) 190; (1907) 175; (1908) 166.

Several facts are roughly indicated by the table. It begins with an extremely severe epidemic, which has not been approached since. Then follows a fall extending over twenty years. On the whole this diminution was progressive, though not in reality so steady as the decennial grouping makes it appear, being interrupted by smaller oscillations in single years and groups of years. Still the main fact holds good. After 1880 an opposite movement began, likewise interrupted by minor oscillations, but on the whole progressive, and culminating in the year 1893 with a death-rate of 389, the highest recorded since 1865. After 1896 a marked fall again took place. This is partly accounted for by the use of antitoxin, which only began on a considerable scale in 1895, and did not become general until a year or two later at least. Its effects were only then fully felt. The registrar-general's returns record mortality, not prevalence - that is to say, the number of deaths, not of cases.

On the whole, we get clear evidence of an epidemic rise and fall, which may serve to dispose of some erroneous conceptions. The belief, held until recently, that diphtheria is steadily increasing in Great Britain was obviously premature; it did rise over a series of years, but has now ebbed again. Moreover, the general prevalence during the last thirty years has been notably less than in the previous twelve years. Yet it is during years since 1870 that compulsory education has been in existence and main drainage chiefly carried out. It follows that neither school attendance nor sewer gas exercises such an important influence over the epidemicity of diphtheria as some other conditions. What are those conditions? Dr Newsholme has advanced the theory, based on an elaborate examination of statistics in various countries, that the activity of diphtheria is connected with the rainfall, and he lays down the following general induction from the facts: "Diphtheria only becomes epidemic in years in which the rainfall is deficient, and the epidemics are on the largest scale when three or more years of deficient rainfall follow each other." He points out that the comparative rarity of diphtheria in tropical climates, which are characterized by excessive rainfall, and its greater prevalence in continental than in insular countries, confirm his theory. His observations seem quite contrary to the view laid down by various authorities, and hitherto accepted, that wet weather favours diphtheria. The two, however, are not irreconcilable. The key to the problem - and possibly to many other epidemiological problems - may perhaps be found in the movements of the subsoil water. It has been suggested by different observers, and particularly by Mr M. A. Adams, who has for some years made a study of the subsoil water at Maidstone, that there is a definite connexion between it and diphtheria. In England the underground water normally reaches its lowest level at the end of the summer; then it gradually rises, fed by percolation from the winter rains, reaching a maximum level about the end of March, after which it gradually sinks. This maximum level Mr Adams calls the annual spring cleaning of the soil, and his observations go to show that when the normal movement is arrested or disturbed, diphtheria becomes active. Now that is what happens in periods of drought. The underground water does not rise to its usual level, and there is no spring cleaning. The hypothesis, then, is this: The diphtheria bacillus lives in the soil, but is "drowned out" in wet periods by the subsoil water. In droughty ones it lives and flourishes in the warm, dry soil; then when rain comes, it is driven out with the ground air into the houses. This process will continue for some time, so that epidemic outbreaks may well seem to be associated with wet. But they begin in drought, and are stopped by long-continued periods of copious rainfall. This is quite in keeping with the observed fact that diphtheria is a seasonal disease, always most prevalent in the last quarter of the year. The summer develops the poison in the soil, the autumnal rains bring it out. The fact that the same cause does not produce the same effect in tropical countries may perhaps be explained by the extreme violence of the alternations, which are too great to suit this particular micro-organism, or possibly the regularity of the rainfall prevents its development.

The foregoing hypothesis is supported by a good deal of evidence, and notably by the concurrence of the great epidemic or pandemic prevalence in Great Britain, culminating in 1859, with a prolonged period of exceptionally deficient rainfall. Again, the highest death-rate registered since 1865 was in 1893, a year of similarly exceptional drought. But it is no more than an hypothesis, and the fate of former theories is a warning against drawing conclusions from statistics and records extending over too short a period of time. The warning is particularly necessary in connexion with meteorological conditions, which are apt to upset all calculations. As it happens, a period of deficient rainfall even greater than that of 1854-1858 has recently been experienced. It began in 1893 and culminated in the extraordinary season of 1899. The dry years were 1893, 1895, 1896, 1898 and 1899, and the deficiency of rainfall was not made good by any considerable excess in 1894 and 1897. It surpassed all records at Greenwich; streams and wells ran dry all over the country, and the flow of the Thames and Lea was reduced to the lowest point ever recorded. There should be, according to the theory, at least a very large increase in the prevalence of diphtheria. To a certain extent it has held good. There was a marked rise in 1893-1896 over the preceding period, though not so large as might have been expected, but it was followed by a decided fall in 1897-1898. The experience of 1898 contradicts, that of 1899 supports, the theory. Further light is therefore required; but perhaps the failure of the recent drought to produce results at all comparable with the epidemic of the 'fifties may be due to variations in the resistance of the disease, which differs widely in different years. It may also be due in part to improved sanitation, to the notification of infectious diseases, the use of isolation hospitals, which have greatly developed in quite recent years, and, lastly, to the beneficial effects of antitoxin. If these be the real explanations, then scientific and administrative work has not been thrown away after all in combating this very painful and fatal enemy of the young.

Dissemination

The conditions governing the general prevalence of diphtheria, and its epidemic rise and fall, which have just been discussed, do not touch the question of actual dissemination. The contagion is spread by means which are in constant operation, whether the general amount of disease is great or small. Water, so important in some epidemic diseases, is believed not to be one of them, though a negative proof based on absence of evidence cannot be accepted as conclusive. On the other hand, milk is undoubtedly a means of dissemination. Several outbreaks of an almost explosive character, besides minor extensions of disease from one place to another, have been traced to this cause. Milk may be contaminated in various ways - at the dairy, for instance, or on the way to customers, - but several cases, investigated by the officers of the Local Government Board and others, have been thought to point to infection from cows suffering from a diphtheritic affection of the udder. The part played by aërial convection is undetermined, but there is no reason to suppose that the infecting material is conveyed any distance by wind or air currents. Instances which seem to point to the contrary may be explained in other ways, and particularly by the fact, now fully demonstrated, that persons suffering from minor sore throats, not recognized as diphtheria, may carry the disease about and introduce it into other localities. Human intercourse is the most important means of dissemination, the contagion passing from person to person either by actual contact, as in kissing, or by the use of the same utensils and articles, or by mere proximity. In the last case the germs must be supposed to be air-borne for short distances, and to enter with the breath. Rooms appear liable to become infected by the presence of diphtheritic cases, and so spread the disease among other persons using them. At a small outbreak which occurred at Darenth Asylum in 1898 the infection clung obstinately to a particular ward, in spite of the prompt removal of all cases, and fresh ones continued to occur until it had been thoroughly disinfected, after which there were no more. The part played by human intercourse in fostering the spread of the disease suggests that it would naturally be more prevalent in urban communities, where people congregate together more, than in rural ones. This is at variance with the conclusion laid down by some authorities, that in this country diphtheria used to affect chiefly the sparsely populated districts, and though tending to become more urban, is still rather a rural disease. That view is based upon an analysis of the distribution by counties in England and Wales from 1855 to 1880, and it has been generally accepted and repeated until it has become a sort of axiom. Of course the facts of distribution are facts, but the general inference drawn from them, that diphtheria peculiarly affects the country and is changing its habitat, may be erroneous. Dr Newsholme, by taking a wider basis of experience, has arrived at the opposite conclusion, and finds that diphtheria does not, in fact, flourish more in sparsely-peopled districts. "When a sufficiently long series of years is taken," he says, "it appears clear that there is more diphtheria in urban than in rural communities." The rate for London has always been in excess of that for the whole of England and Wales. Its distribution at any given time is determined by a number of circumstances, and by their incidental co-operation, not by any property or predilection for town or country inherent in the disease. There are the epidemic conditions of soil and rainfall, previously discussed, which vary widely in different localities at different times; there is the steady influence of regular intercourse, and the accidental element of special distribution by various means. These things may combine to alter the incidence. In short, accident plays too great a part to permit any general conclusion to be drawn from distribution, except from a very wide basis of experience. The variations are very great and sometimes very sudden. For instance, the county of London for some years headed the list, having a far higher death-rate than any other. In 1898 it dropped to the fifth place, and was surpassed by Rutland, a purely rural county, which had the lowest mortality of all in the previous year and very nearly the lowest for the previous ten years. Again, South Wales, which had had a low mortality for some years, suddenly came into prominence as a diphtheria district, and in 1898 had the highest death-rate in the country. Staffordshire and Bedfordshire show a similar rise, the one an urban, the other a rural, county. All the northern counties, both rural and urban, - namely, Northumberland, Durham, Cumberland, Westmorland, Lancashire, Yorkshire, Cheshire and Lincolnshire, - had a very high rate in 1861-1870, and a low one in 1896-1898. It is obviously unsafe to draw general conclusions from distribution data on a small scale. Diphtheria appears to creep about very slowly, as a rule, from place to place, and from one part of a large town to another; it forsakes one district and appears in another; occasionally it attacks a fresh locality with great energy, presumably because the local conditions are exceptionally favourable, which may be due to the soil or, possibly, to the susceptibility of the inhabitants, who are, so to speak, virgin ground. But through it all personal infection is the chief means of spread.

The acceptance of this doctrine has directed great attention to the practical question of school influence. There is no doubt whatever that it plays a very considerable part in spreading diphtheria. The incidence of the disease is chiefly on children, and nothing so often and regularly brings large numbers together in close contact under the same roof as school attendance. Nothing, in fact, furnishes such constant and extensive opportunities for personal infection. Many outbreaks have definitely been traced to schools. In London the subject has been very fully investigated by Sir Shirley Murphy, the medical officer of health to the London County Council, and by Dr W. R. Smith, formerly medical officer of health to the London School Board. Sir Shirley Murphy has shown that a special incidence on children of school age began to manifest itself after the adoption of compulsory education, and that the summer holidays are marked by a distinct diminution of cases, which is succeeded by an increase on the return to school. Dr W. R. Smith's observations are directed rather to minimizing the effect of school influence, and to showing that it is less important than other factors; which is doubtless true, as has been already remarked. It appears that the heaviest incidence falls upon infants under school age, and that liability diminishes progressively after school age is reached. But this by no means disposes of the importance of school influence, as the younger children at home may be infected by older ones, who have picked up the contagion at school, but, being less susceptible, are less severely affected and exhibit no worse symptoms than a sore throat. From a practical point of view the problem is a difficult one to deal with, as it is virtually impossible to ensure the exclusion of all infection, on account of the deceptively mild forms it may assume; but considering how very often outbreaks of diphtheria necessitate the closing of schools, it would probably be to the advantage of the authorities to discourage, rather than to compel, the attendance of children with sore throats. A fact of some interest revealed by statistics is that in the earliest years of life the incidence of diphtheria is greater upon male than upon female children, but from three years onwards the position is reversed, and with every succeeding year the relative female liability becomes greater. This is probably due to the habit of kissing maintained among females, but more and more abandoned by boys from babyhood onwards.

All these considerations suggest the importance of segregating the sick in isolation hospitals. Of late years this preventive measure has been carried out with increasing efficiency, owing to the better provision of such hospitals and the greater willingness of the public to make use of them; and probably the improvement so effected has had some share in keeping down the prevalence of the disease to comparatively moderate proportions. Unfortunately, the complete segregation of infected persons is hardly possible, because of the mild symptoms, and even absence of symptoms, exhibited by some individuals. A further difficulty arises with reference to the discharge of patients. It has been proved that the bacillus may persist almost indefinitely in the air-passages in certain cases, and in a considerable proportion it does persist for several weeks after convalescence. On returning home such cases may, and often do, infect others.

Treatment

Since the antitoxin treatment was introduced in 1894 it has overshadowed all other methods. We owe this drug originally to the Berlin school of bacteriologists, and particularly to Dr Behring. The idea of making use of serum arose about 1890, out of researches made in connexion with Mechnikov's theory of phagocytosis, by which is meant the action of the phagocytes or white corpuscles of the blood in destroying the bacteria of disease. It was shown by the German bacteriologists that the serum or liquid part of the blood plays an equally or more important part in resisting disease, and the idea of combating the toxins produced by pathogenic bacteria with resistant serum injected into the blood presented itself to several workers. The idea was followed up and worked out independently in France and Germany, so successfully that by the year 1894 the serum treatment had been tried on a considerable scale with most encouraging results. Some of these were published in Germany in the earlier part of that year, and at the International Hygienic Congress, held in Budapest a little later, Dr Roux, of the Institut Pasteur, whose experience was somewhat more extensive than that of his German colleagues, read a paper giving the result of several hundred cases treated in Paris. When all allowance for errors had been made, they showed a remarkable and even astonishing reduction of mortality, fully confirming the conclusions drawn from the German experiments. This consensus of independent opinion proved a great stimulus to further trial, and before long one clinique after another told the same tale. The evidence was so favourable that Professor Virchow - the last man to be carried away by a novelty - declared it "the imperative duty of medical men to use the new remedy" (The Times, 19th October 1894). Since then an enormous mass of facts has accumulated from all quarters of the globe, all testifying to the value of antitoxin in the treatment of diphtheria. The experience of the hospitals of the London Metropolitan Asylums Board for five years before and after antitoxin may be given as a particularly instructive illustration; but the subsequent reduction in the rate of mortality (12 in 1900, 11.3 in 1901, 10.8 in 1902, 9.3 in 1903, and an average of 9 in 1904-1908) added further confirmation.

Annual Case Mortality in Metropolitan Asylums Board's Hospitals.

Before Antitoxin. After Antitoxin.
Year. Mortality
per cent. Year. Mortality
per cent.
1890 33.55 1895 22.85
1891 30.61 1896 21.20
1892 29.51 1897 17.79
1893 30.42 1898 15.37
1894 29.29 1899 13.95

The number of cases dealt with in these five antitoxin years was 32,835, or an average of 6567 a year, and the broad result is a reduction of mortality by more than one-half. It is a fair inference that the treatment saves the lives of about 1000 children every year in London alone. This refers to all cases. Those which occur in the hospitals as a sequel to scarlet fever, and consequently come under treatment from the commencement, show very much more striking results. The case mortality, which was 46.8% in 1892 and 58.8% in 1893, has been reduced to 3.6% since the introduction of antitoxin. But the evidence is not from statistics alone. The beneficial effect of the treatment is equally attested by clinical observation. Dr Roux's original account has been confirmed by a cloud of witnesses year after year. "One may say," he wrote, "that the appearance of most of the patients is totally different from what it used to be. The pale and leaden faces are scarcely seen in the wards; the expression of the children is brighter and more lively." Adult patients have described the relief afforded by inoculation; it acts like a charm, and lifts the deadly feeling of oppression off like a cloud in the course of a few hours. Finally, the counteracting effect of antitoxin in preventing the disintegrating action of the diphtheritic toxin on the nervous tissues has been demonstrated pathologically. There are some who still affect scepticism as to the value of this drug. They cannot be acquainted with the evidence, for if the efficacy of antitoxin in the treatment of diphtheria has not been proved, then neither can the efficacy of any treatment for anything be said to be proved. Prophylactic properties are also claimed for the serum; but protection is necessarily more difficult to demonstrate than cure, and though there is some evidence to support the claim, it has not been fully made out.

AUTHORITIES - Adams, Public Health, vol. vii.; Thorne Thorne, Milroy Lectures (1891); Newsholme, Epidemic Diphtheria; W. R. Smith, Harben Lectures (1899); Murphy, Report to London County Council (1894); Sims Woodhead, Report to Metropolitan Asylums Board (1901).

Note - this article incorporates content from Encyclopaedia Britannica, Eleventh Edition, (1910-1911)

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