351 THE COMPLEX NATURE OF TYPHOID ETIOLOGY, AND THE … · typhoid fever. The next bacterium, and...

351

THE COMPLEX NATURE OF TYPHOID ETIOLOGY, AND THE ROLE PLAYED BY ANIMALS AND MAN IN THE SPREAD OF THE TYPHOID GROUP OF DISEASES.!

By MAJOR J. C. B. STATHAM. Royal Army Medical Corps.

THE question of the etiology of enteric or typhoid fever covers so wide a field of thought and conjecture, work and knowledge, that it would be unprofitable, even impossible, for me to attempt to deal with its every phase. It may be thought, and I have more than once heard it suggested, that the subject has been overdiscussed and is consequently ill-chosen; but the more I work at typhoid etiology the greater is my conviction that much work must be done, and many present-day theories be modified, ere the true nature of typhoid etiology stands revealed, and its truths are generally understood and accepted.

Before we can profitably discuss the question of typhoid or enteric etiology, it is necessary to clearly realise what these words mean both in their clinical and bacteriological senses. Typhoid means typhus-like, and was used to represent the clinical picture of prolonged fever-abdominal symptoms, exhaustion, and mental apathy-often present in this disease. The word "enteric" was introduced owing to the prevailing idea that intestinal lesions and symptoms were always present in typhoid. Now these terms " typhoid" and "enteric" have the sanction of long usage, and will stay in consequence, but unless we are careful this nomenclature is liable to lead us into diagnostic error, and has possibly even helped to keep alive and spread endemic and epidemic typhoid. The clinical symptoms which give rise to the term "typhoid" accompany only one of the phases of a disease in which at another time none of the clinical manifestations of the typhoid state may be present. The term "enteric" is applied to a disease in which intestinal lesions and symptoms may be conspicuous by their absence.

Pathological conditions of such varied nature as hepatitis, sore throat, general adenitis, bronchitis, pneumonia, cholecystitis, or

1 A paper read before the Public Health Section of the South African Medical Congress, October 14th, 1907.

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352 The Oomplew Nature of T:/jphoid Etiology

localised purulent affections, such as abscesses, middle-ear diseases, &c., may be induced by micro-organisms similar to those which cause typical typhoid fever (Mya,l Bersenius,2 Besan(jon,8 Philibet 4). The micro-organisms which produce these widely varying pathological conditions themselves vary considerably. Fifteen, even ten years ago, it might have been confidently stated that in the Bacillus typhosus of Eberth had been found the unique causal agent of the dangerous and widespread disease, typhoid fever. The knowledge of recent years has forced us to realise that there are quite a number of allied but distinct species of bacteria, anyone of which is capable of originating typhoidal disease-that, in fact, the etiology of this condition is as complex as its symptomatology. Further, we now also know that this group of bacteria, while at one time originating a disease with all the clinical symptoms of typhoid fever. may, at another, cause pathological conditions utterly unlike it. Typhoid is, in fact, a group disease, produced by a group of organisms.

It will be my endeavour in the first part of this paper to prove the complex etiological nature of this paradoxical disease, and in doing so I shall endeavour to limit references and technical details as much as possible, as I am aware how tedious a paper such as this must be in any case. In the appended table are given the bacteria which produce the typhoid group of diseases, along with their cultural reactions, pathogenic effects, and variety of animal hosts. The first column of the table gives the names of these various bacteria; the second, the pathogenic effects they produce on man. The third and fourth columns briefly specify the morphological and cultural characters and the specific agglutinative reaction of these bacteria. In the fifth column are enumerated their animal hosts. The first part of my paper refers to the complex nature of typhoid etiology, and while discussing this question I shall largely refer to the information in the first three columns of the table. The last column, dealing with various animal hosts of this group of bacteria, I shall refer to chiefly in the second part of this paper, which mentions the rOle played by animals and man in the spread of typhoid disease.

By looking at the table it will be seen that six species of bacteria, more accurately sub-groups of bacteria, are mentioned as capable of originating disease in man indistinguishable from typhoid

1 Gent. f. Bakt., Ref., May 23rd, 1905. 2 Ibid.

3 Journ. de Phy. et. Path. gen., t. vi., 1904. 4 Iibd.

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J. O. B. Statham 353

fever, and to show that this paper represents no mere academic discussion, I may mention that bacteria of all the groups but one mentioned in this table have been isolated from typhoid cases admitted to the Military Hospital at Roberts' Heights, Pretoria, during the last few months. The bacteria were isolated from the blood of these cases by a new and simple method, originated by Conradi1 and Kayser.2 I shall presently discuss these various bacteria in turn, but think it advisable at this stage to explain what are the morphological and cultural characters of the bacteria of this large group and on what they depend for individual differentiation.

Morphologically, all the bacteria of this group are short motile rods. The paratyphoids are more motile than the typhoids, and these latter than the colon bacteria. All the bacteria of this group named in the table are readily stained by solutions of aniline dyes, and all of them have the peculiarity that, when stained by one of these dyes (aniline gentian-violet) and subsequently treated with a solution of iodine, they are rapidly decolorised by washing with alcohol. This staining peculiarity is known by the name of Gram's reaction.

A general characteristic is the power possessed by these bacteria of fermenting sugars, and the measure of their individual activity in fermenting these sugars is one of the best means we have at present of differentiating, culturally, between the individual members of this great group. For the sake of simplicity, I have limited the various reactions of these bacteria to their action on the two sugars, glucose (grape sugar), lactose (milk sugar), and a body closely allied to a sugar, mannite. The production of acidity and the formation of gas generally represent, the one in a lesser and the other a greater degree, the fermenting power of a bacterium of this group.

To allow of the growth of the bacterium, some nutrient medium, such as jelly (agar), broth, &c., is associated with the sugar, and to illustrate the production of acidity or alkalinity from a sugar medium various colouring reagents, like litmus, neutral red, and others, are added, which indicate any change of reaction by a change of colour. The production of gas is made evident, in a solid medium like agar, by the production of gas bubbles which are imprisoned in its substance. In a fluid medium, an inverted glass capsule collects and shows any gas that may be formed.

1 Miinch. mea. Wochenschr., 1906. • Cent. f. Bakt., Orig. xlii., September 1st.

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354 The Oomplex Naiu1'e of Typhoid Etiology

The three media are: (1) An agar medium containing grape sugar (glucose), and an indicator (neutral red); (2) milk, which of course contains milk sugar or lactose, and to which the indicator litmus has been added; (3) a nutrient solution containing mannite, to which litmus has also been added.

Bacillus coli communis is the most active sugar fermenter, for it first acidifies and then coagulates litmus milk, produces both fluorescence and gas abundantly in the neutral red glucose-agar (note the gas bubbles and yellow colour), and also markedly affects the mannite medium, producing great acidity and abundant gas in the inverted capsule in the tube. The paratyphoid bacillus named "B" approaches, though it does not equal, the colon bacillus in its sugar-fermenting power. It produces first acid and then alkali in milk sugar; the medium is first turned pink, and later (six days) blue; the milk is, however, not coagulated. In neutral red agar and in mannite broth there is acid and gas production, but to a less degree than with B. coli. The paratyphoid bacillus termed " A" is a less powerful ferment er of sugar again than the type "B." Milk sugar is slightly but permanently acidified, while the production of acid and gas is less pronounced in the neutral red agar (less yellow) and mannite media (very little gas produced). The typhoid bacillus produces such slight changes in milk sugar and grape sugar neutral red that these media remain practically unaltered, while the mannite medium is turned from blue to red, but contains no gas in its gas capsule. The B. fcecalis alcaligenes is unable to ferment sugars, consequently these media are not affected by its presence. The litmus milk alone will turn a deeper blue, owing to alkali formation.

No. 1 on the list of these bacterial groups in the table is the B. imcalis alcaligenes. Not much is known regarding the animal distribution of the bacillus whose cultural reaction I have just given, but it has been isolated in some instances from the dejecta of man, both in health and disease, and has been supposed on more than one occasion to have originated a condition simulating typhoid fever. The next bacterium, and the most important of the group associated with typhoid disease, is No. 2 in the table, the B. typhosus of Eberth. While producing the classical clinical picture of typhoid fever more frequently than any other of the typhoid-colon group of bacteria, the typhoid bacillus cannot now be considered, as was the case a few years ago, the sole producer of the disease. Furthermore, it may induce diseases of a type utterly unlike typhoid. Mya, Bursenius, Besanyon, Philibet and

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others have reported cases proved, bacteriologically, to be of typhoid nature, where the clinical symptoms were limited to sore throat, bronchitis, pneumonia, perityphlitis, nephritis, influenza, hepatitis or general adenitis; or, again, to local purulent affections, such as abscesses or middle-ear disease. Even when fever is present other symptoms, like rash, abdominal symptoms, &c., may be absent; further, the duration of the fever may be anything from two days to two months.

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FIG. I.-Photographs of seven temperature charts from cases of typhoid aisease The first three and the last two charts are from patients who suffered from fever caused by the B. typh08t~S. These charts represent a type of typhoid frequently met with in Pretoria. The chart marked orange is from a case from whose blood the B, paratyphous, type "B," was isolated (orange had been twice inocnlated against typhoid). The remaining chart is taken from a woman who suffered from fever, jaundice and pain over the gall, bladder, and whose blood serum gave a markedly positive Widal reaction. The case was, I think, one of typhoid cholecystitis.

The above are temperature charts of cases proved, bacteriologically, to be due to the typhoid bacillus (see fig. 1). These cases were in hospital (1907) during what we call the typhoid season. It will be perceived how greatly the type of disease varies. One of these temperature charts comes from a woman who suffered from pain over the liver, accompanied by jaundice. She gave a positive

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356 The Oomplex Nature of Typhoid Etiology

Widal reaction to typhoid, and I believe the case was one of typhoid cholecystitis. The woman had never suffered from what we could clinically call typhoid fever.

Post-mortem examinations of cases of typhoid fever show that while the swelling and ulceration of Peyer's patches is usually a marked feature in adults, it may be absent. We had such a case this year. In children the patches of Peyer are frequently left unchanged. (Brion and Kayser.):

While, as I have already stated, the B. typhosus is morphologically identica1 2 with the six others of the typhoid-colon group, it is sharply differentiated from most of them by its cultural characters, particulars of which have already been given. There is another way in which the typhoid bacillus may be distinguished from the others of its group. I refer to its specific agglutination reactions. There are many bacteria which are agglutinated by the serum of the man or animal suffering from the disease they have produced. The specific property of such a serum may be retained even when it is diluted hundreds, even thousands of times, so delicate is the reaction. This reaction is named after Widal, who first recorded it. The serum of an animal or man suffering from disease produced by the B. typhosus may also agglutinate allied bacteria, such as the individuals of the typhoid-colon group; but this group agglutination reaction only takes place, as a rule, in a low dilution of the serum, and never in the high dilutions in which it will agglutinate its own causative organism (specific agglutination). I will not refer to other methods of differentiation, such as immunity reactions and inoculation experiments, which are too technical.

The third bacterium which may produce a disease indistinguishable from typhoid fever is the B. paratyphosus (A). This is by far the rarer of the two varieties of paratyphoid bacteria, of which much has been said and written during the last ten years. I do not know of more than a dozen or so of strains of this organism which have been isolated. I have had the rare good fortune to isolate bacteria of this group from the blood of four cases of typhoid fever at the Military Hospital, Pretoria. Fig. 2 represents the temperature charts of these cases, from which it is evident that, clinically, they could not be distinguished from the conditions produced by the B. typhosus.

1 DtJutsches Archiv f. klin. Med., lxxx., 1906. 2 The question of differentiation of the members of the typhoid-colon group

by the number and position of their flagelhe was not introduced.

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J; O. B. Statharn 357

To those who may not have closely followed the question of paratyphoid affections, I will briefly mention the facts concerning their discovery and subsequent history. Ever since Widal introduced his now well-known method of diagnosis by means of agglutination tests, it had been remarked that a small percentage of cases, clinically like typhoid, never gave the expected serum reaction. The mystery was cleared up when, in 1896, Achard and Bensaude 1 isolated two atypical typhoid bacilli, one from a post-

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FIG. 2.-Photographs of six temperature charts from cases of paratyphoid fever. From the first four cases a bacillus of the type paratyphosus "A " was isolated, while from the patient whose temperature chart comes last on the plate a bacillus closely resembling the B. coli communis was recovered by hremoculture.

typhoid abscess, and the other from a case of cystitis. These bacteria differed from the typhoid bacillus in certain cultural characters, to which I have already referred, as well as by the fact that the serum of patients affected did not agglutinate the typhoid bacillus except in low dilutions (group agglutination). Achard and Bensaude's discovery was quickly followed by those of Widal and

I Soc. Med. de8 Hopt. de Paris, 1896.

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Noblecourt,I Gwyn,2 Cushing,3 and many others. Finally SchOtmuller,' Brion and Kayser,5 in 1902, classified the paratyphoids by dividing them into two groups, which they called "A" and "B." " A" is distinctly a rare organism, while the bacteria which resemble B. paratyphosus "B" are found in many domestic and other animals, and have caused numerous epidemics of disease among men.

After seeing the temperature charts of the four cases of paratyphoid "A" disease previously referred to, it will be seen how difficult is a clinical diagnosis between these cases and the similar condition produced by the allied micro-organism, the B. typhosus. In the few cases of paratyphoid affections which have been examined post mortem, it has been found that in some Peyer's patches are not ulcerated (Jochman,6 Sion and Negel,)7 but this condition of the intestine may also be found, as I have already stated, in disease caused by B. iyphosus. The cultural reactions of the B. paratypkosus "A" have already been pointed out. Its fermenting power on sugars is greater than that of the B. typhosus, while not so marked as those of the paratyphoid group "B." The blood sera of patients suffering from the paratyphoid " A" affection, specifically agglutinate the B. paratyphosus "A," which fact further differentiates this organism from others of the typhoidcolon group.

I now come to a large and important group of very closely allied, probably identical, organisms, anyone of which may produce typhoid disease in man. This group includes the B. paratyphosus "B," the two groups of meat-poisoning bacteria, and various bacteria known by the disease they cause in animals, viz., hogcholera group, B. morbificans bovis, bacillus of calf septicremia, B. psittacosis, and B. typhi murium. It is not necessary at present to discuss the striking connection between human typhoid and the disease of domestic animals, because I shall deal specially with this subject in the latter part of this paper.

It is probable that under the variously named bacteria in this group we often refer to one and the same organism. No clear morphological or cultural distinctions have yet been discovered Which can serve to distinguish one from another (Trantman,8 Kolle,9 Wasserman).lO All the bacteria in this great group produce

1 Semaine Medicale, 1897. 2 Johns Hopkins Hosp. Bull., 1898 and 1900. 3 Ibid. 4 Zeit. f. Hyg. u. Inj., Bd. xxxvi., 1900. I> Munch. med. Wochen8chr., 1902. 6 Cent. f. Bakt., Re£., February, 1903. 7 Cent. f. Bukt., Orig., 1903. 8 Zeit. f. Hyg. u. Inj., Bd. xii., 1903.

9 Ibid., lii., 1906. 10 Ibid.

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gas and fluorescence in the neutral red glucose-agar medium, and form acid and gas in the mannite-litmus solution. Their action on litmus-milk is especially characteristic, the medium being first turned reddish and then, through subsequent alkalisation, into a deep blue colour (Kutscher and Meinicke)l. Further, except for the second group of meat-poisoning bacteria, which are closely allied, curiously enough, by their agglutination reactions with E. typhosus, all the other bacteria in this group appear to interagglutinate. As there are, however, minor differences in the degree of pathogenicity of these bacteria to experimental animals, and as further differences may yet be discovered between them, it is at present advisable to retain ~he distinctive names of the bacteria of this group.

The diseases produced by this type of organism, whether derived from a previous case in man (E. paratyphosus B), eating the meat of diseased pigs (hog cholera), cattle (B. morbificans bovis), bacillus of calf septicremia, or handling parrots (B. psittacosis), may be either indistinguishable from ordinary typhoid fever, or an acute gastro-enteritis, formerly known as meat or ptomaine poisoning (Kutscher,2 Vagede,3 Ulrich,4 Uhlenhuth5 • The acute gastroenteritis type of disease is frequently found in epidemic form in Germany, and is due to eating ill-cooked meat derived usually from animals diseased by bacteria of this group. Some twenty such epidemics have occurred, and in most of these epidemics bacteria of this group have been isolated from the suspected meat, and from the patients who suffered after partaking of it. Along with the cases of acute gastro-enteritis, with diarrhcea, vomiting, headache, occasional rashes, and possibly two or three days fever, there may be present cases indistinguishable from classical typhoid, and from such cases also micro-organisms of this bacterial gr oup have been isolated and proved to have originated the disease (L e vy6 and Fornet, Heller,7 Vagede8).

The factor deciding the question whether acute gastro-enteritis or typhoid fever will be produced after eating infected llleat may possibly be the amount of bacterial toxin already present in the meat eaten_ This toxin acts as a gastro-intestinal irritant, vomiting and peristalsis are set up, and the obnoxious bacterja are got

I Meinicke, Zeit. f. Hyg. u. Inf. Bd., !ii., 1906 (drittes Heft). 9 Ibid., Bd. Iv., 1906. 3 Klin. Jahrb, 1905. 4 Zeit. f. Hyg., 1903. 5 Cent. f. Bakt., April 10th, 1906. 6 Cent. f. Bakt., May, 1906. 7 Ibid., xliii., January, 1907.

8 Klin. Jahrb., 1905. 25

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360 The Oomplem Nature of Typhoid Etiology

rid of. If few or no toxins are present in the diseased meat, the infecting bacteria are not got rid of by vomiting and purging, and if the body resistance is impaired at the time, typhoid fever may be induced (Levy and Fornet). Meat poisoning epidemics were at one time considered to be due to the ingestion of substances called ptomaines, obscure products of meat decomposition. There is no doubt that nearly all these cases of epidemic gastro-enteritis are due either to infection by bacteria of the typhoid-coli group, or to a saprophytic anaerobic organism, the B. botulinus. Botulism is the condition produced by the latter organism, and is characterised by acute disease of the central nervous system, including paralysis of the ocular muscles, larynx, pharynx, &c., and is readily distinguishable from the condition set up by the paratyphoid B group of bacteria. I shall refer again to this group of bacteria when dealing with the part played by animals in the spread of typhoid diseases, and shall now deal with the last group of organisms mentioned in the table, viz., the group B. coli communis.

I have already described the cultural reactions of B. coli communis, or at least one strain of it, for unfortunately there are at least five varieties of this group, some of which approach in cultural characters more closely to the B. typhosus. The strain, the reactions of which I have described, is the most active fermenter of sugars in the typhoid-coli group of bacteria.

As regards pathogenicity, B. coli has been isolated from cases indistinguishable from typhoid fever (Montier I). Such a case occurred at the Military Hospital at Roberts' Heights this year. B. coli is largely responsible for the feverish diarrhooa of infants, and has caused at least one epidemic of enteritis, the infection being water-borne in this instance (Levi della Vide,2 Vicenzi).3

This closes the first part of my paper, which refers to the question of the complex nature of typhoid etiology, and I hope I have succeeded in my endeavour to point out that in typhoid we have a disease of protean nature, which may be induced by anyone of several groups of allied but distinct bacteria. I shall now take up the question of the part which animals and man play in disseminating typhoid.

I Cent. f. Bakt., :\Iay 16th, 1907. 2 Cent. f. Bakt., February 21st, 1907. 3 Ibid.

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J. o. B. Statham 361

THE PART PLAYED BY ANIMALS AND MAN IN THE SPREAD OF·

THE TYPHOID GROUP OF DISEASES.

In the fifth column of the table will be seen tbe beading, "Various Animal Hosts." Closer examination of the contents of this column will make it evident that practically all of the bacteria of the typhoid-colon group play an important part in the life and diseases of many animals besides man. The names of several diseases of the bacteria of the fourth group are, indeed, derived from the animal diseases which they have produced; for instance, the bacteria of hog cholera and of cattle disease, B. psittacosis, &c.

The belief is gaining ground, especially in Germany, that the direct spread of enteric from man to man, or from animal to man, accounts for more of the endemic form of this disease than has hitherto been suspected, and, if this widespread disease is to be stamped out, far greater attention must in future be paid to these avenues of infection than has been the case heretofore. We have bacteria in this group which may produce disease in a domestic animal or typhoid in man, and this human typhoid may be due to eating the flesh of the animal so diseased. These facts cast, I think, a new light on the question of typhoid etiology, and, in order to further study them, I will now deal with the animal distribution of each of the organisms of the typhoid-colon group in turn.

The B. typhosus has not yet been proved to have a widespread distribution in animals. Typhoid bacilli, however, have been found in the spleen abscess of a cow, and in a few instances in the tissues of cattle (Levy and Fornet). Though milk has been proved to have conveyed typhoid fever, I do not know of an instance where the typhoid bacteria were proved to have been derived from a diseased cow. But this question has scarcely yet been seriously investigated, as it is only lately that the possibility of typhoid spread through the agency of diseased animals has been realised. The next bacterium is B. paratyphus "A." This producer of typhoid disease in man has been isolated from the intestines of many domestic and other animals-dogs, pigs and guinea-pigs (Morgan1). The bacillus has, up to the present, been so rarely isolated from disease in man that the question of its transmissibility to the human body from animals can only be decided by future research. The last group but one of bacte.ria I shall

I Briti8h Medical Journal, January 10th, 1905.

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deal with, the B. para typhus "B," is peculiarly interesting; here we have six species of bacteria, which are apparently identical as regards their cultural reactions, and with one exception (the second meat-poisoning group) as regards their agglutination reactions also. Of this group of bacteria the first isolated from disease in man was called Gartner's bacillus, after its discoverer, who isolated it from patients suffering from meat poisoning. When similar organisms are isolated nowadays from human typhoid or meat poisoning they are usually spoken of as bacteria of the paratyphoid "B" group. Practically identIcal organisms have been found associated with hog cholera, enteritis in oxen, and septicrnmia in calves (B. morbificans bovis bacillus of calf septicrnmia). A bacillus of this type has also been isolated, which is believed to cause an enteritis in horses (Tromsdorf,I Kiitscher and Meinicke,2 Bohme,3 Wasserman 4).

Through eating the imperfectly-cooked flesh of much-diseased domestic animals frequent epidemics of meat poisoning have occurred in man, the disease induced being generally an acute gastro-enteritis, occasionally typhoid fever. Bacteria of the B.paratyphosus "B" type have been isolated from the suspected meat and from the affected persons, and the blood sera of the patients have been found to agglutinate these bacteria, proving the source of the disease to be the infected meat (Frome 5, Heller 6). The bestknown epidemics of meat poisoning are those named in the table, and so called either from the place of origin or name of the discoverer. The bacteria isolated from all these epidemics are identical in cultural reactions with any and all of the others of this group, but owing to differences in agglutination reactions they have been divided into two groups (Kutscher and Meinicke).

The first group includes the epidemics named after Aertyck, Meirelbeck, Gunther, Calmphout, Smith and Serault). The bacteria isolated from the diseased flesh and the human patients in these epidemics were found to have similar agglutination reactions with B. paratyphosus " B," and the bacilli of hog-cholera, cattle disease, B. psittacosis and mouse typhoid; it is probable that all these bacteria are of one and the same species. The bacteria isolated from the epidemics named after Gartner, Moorceilli, Brussel, Gent, Rumfieth and Haustadt, while culturally identical with the other

1 Congress in Meran, 1905. 3 Ibid. (erstes Heft). 5 Cent. f. Bakt., April, 1907.

2 Zeit. f. Hyg. u. Inj., Bd. Hi., 1906. 4 Zeit. j. Hyg. ~~. In!, lii., 1906 (zweites Heft). 6 Ibid., January 17th, 1907.

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J O. B. Statham 363

species in group 4, are allied, curiously enough, through agglutination reactions to the B. typhosus (Kiitscher and Meinicke). The psittacosis bacillus, a bacterium indistinguishable from all those of group 4 in cultural characters, and from all but the second meatpoisoning group of bacteria in agglutination reactions, has caused g-astro-enteritis, and even typhoid fever, among dealers in parrots. Similar bacteria have also been isolated from dogs, guinea-pigs and mice (B. typhi murium) , animals closely associated with man (Smallman,l Klimenko,2 Tromsdorf,3 Morgan4

• The last member of the typhoid-colon group of bacteria I shall deal with is the B. coli communis. This common and widespread organism is present in the intestinal tract of most animals. It occasionally produces gastro-enteritis and a disease like typhoid in man.

I have called attention to the fact that bacteria similar to those which cause typhoid disease in man are the common producers of animal disease also; further, that man may be affected by attacks of gastro-enteritis or typhoid fever by partaking of the meat of such diseased animals. I have also shown that animals closely in association with man, such as farm animals, horses, dogs, parrots, mice, &c., are all liable, either normally or when diseased, to harbour bacteria in their intestinal tract or tissues, which may set up typhoid disease in the human subject.

THE PART PLAYED BY MAN IN THE DISSEMINATION OF TYPHOID.

As I have already shown, man is liable to infection from any one of these groups of bacteria, the disease produced being either a localised affection, or, what is more usual, a septicremia.

Wherever the typhoid bacillus obtains an entry into the circulation, it is carried along, among other directions, to the liver and gall-bladder. In bile, the bacteria of the typhoid-colon group find a medium so suitable for their continued existence that t.hey will often survive here when they have perished elsewhere in the tissues. These facts have been established both by post-mortem findings in man and by experiments in animals. Doer,5 Foster and Kayser,6 and others have found that, when bacteria of the typhoidcolon group are injected into laboratory animals, the gall-bladder

1 JOURNAL OF THE ROYAL ARMY MEDICAL CORPS, July, 1905. 2 Cent. f. Bakt., July, 1906. 3 Congress in Meran, 1905. 4 British Medical Journal, January 10th, 1905. 5 Cent f. Bakt., xxxix., October, 1905. 6 Ibid., Ref. June.

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364 The Oomplex N'2tu1°e of Typhoid Etiology

is early affected and remains affected long after other portions of their tissues. In post-moTtem examinations on typhoid disease in man, a pure culture of typhoid can usually be isolated from the bile, and Foster and Kayser have found the gall-bladder infected by typhoid bacilli in persons long recovered from typhoid, even in people who give no history of a typhoid attack. A typhoidinfected gall-bladder may constantly reinfect an intestinal tract free from the germ. While this fact is of little importance from the affected person's point of view, it is a serious business for that person's neighbours (Foster and Kayser).

We have long known that during the acute stage of typhoid fever the stools and urine are infective. The danger to nurses and neighbouring patients of this source of infection has long been recognised in military hospitals, where enteric patients are kept in enteric wards, and their excreta carefully sterilised. What is less known is that, largely through typhoid-infected gall-bladders, the stools of recovered typhoid patients may be infective for months, even years. It has been estimated that typhoid bacilli may be isolated from enteric stools in 25 to 30 per cent. of the cases in the first three weeks, 10 to 15 per cent. in the next two months, 4 or 5 per cent. after the third month, and finally that some 1'5 per cent. of the cases become regular carriers (Dregalski, Brion and Kayser) . Working on typhoid stools in the Army Headquarters Laboratory, Pretoria, I have had similar results. The latest period, however, at which I have isolated the B. typhOS1£S from stools, has been the third month of convalescence from typhoid fever. Some healthy persons who appear never to have had typhoid, pass bacilli of the typhoid group in their stools. It is difficult, however, to be certain that they have never had typhoid, because many of the manifestations of the disease are so utterly unlike the clinical picture. Typhoid bacilli are present in the urine in some 30 or 40 per cent. of severe cases, and in about 15 per cent. of all diagnosed cases of typhoid fever. The bacilluria may last for months and form a very serious source of infection (Vas,I Lesseur,2 \Vassiljef).3 Now, when we come to think of the large number of people who suffer from recognised typhoid, and then remember how great the chances of typhoid being unrecognised are, owing to its protean character, we must be

I Cent. f. Bakt., February, 1907. 2 Ibid., Ref. March, 1907. 3 Zeit f. Hyg. i. Inf., Bd. Iv., 1907.

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impressed by the potentiality of man as a typhoid distributor. I do not now refer to the infection of a water supply by typhoid patients or bacilli-carriers, but to the direct communication of the disease from one man to another (Minelli,I Netter and Liefman,2 Klinger, Levy and Weekes3). In Germany especially, this factor in the spread of typhoid is receiving the attention it deserves. Endemic typhoid is looked upon as contracted from infected" Typhushiiuser" and " Typhnstrager" -" typhoid houses" and "typhoid carriers." Cases are constantly coming to light of a bacilli-carrier in a house infecting the other inmates of that house. In a recent and specially remarkable case, a woman confectioner, who had been a bacilli-carrier since an attack of typhoid twenty-four years before, infected all the assistants in the shop (nine) who used the same water-closet. In domestic life or on campaigns, think of the possibilities of typhoid spread from the handling of bread alone; and the origin of more than one epidemic of typhoid can be traced to milk, infected through a bacilli-carrying cow-milker (Klein,4 Conradi,5 and Kayser). There is also one other way in which, in my opinion, a person may be infected by typhoid, i.e., by auto-infection. ,TV e know that there are often in the intestinal tract of healthy people, bacteria capable of causing typhoid. Why should not such a person, ;yhen for some reason his vitality is lowered, contract the disease? Diphtheria, pneumonia, boils and abscesses, are largely due to auto-infection following lowered bodily vitality; why not enteric? I throw this possibility out as a suggestion.

SUMMARY.

(1) Typhoid fever must be looked upon as a group disease. The classical symptoms of typhoid are but one of the manifestations of a disease which may at other times simulate pathological conditions utterly unlike it.

(2) The etiology of this disease is as complex as its symptomatology, for there are a number of allied but distinct species of bacteria which may produce disease indistinguishable from typhoid fever.

1 Cent. f. Bakt., xli. 2 Ibid., February 21st, 1906. 3 Cent. f. Bakt., xliii., March 5th, 1907. 4 Cent. f. Bakt., Orig., xxxviii., March 29th, 1906. 5 Ibid., November, 1905.

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366 The Oomplem Nature of Typhoid Etiology

(3) Most of the varieties of bacteria composing the typhoidcolon group are found in apparently healthy animals, and many diseases among domestic and other animals are caused by bacteria which may produce typhoid in man. Further, typhoid has been induced in human beings by eating the improperly-cooked flesh of such diseased animals.

(4) The danger of typhoid being spread by direct infection through the contaminated excretions of unrecognised typhoid cases is a real one. A certain percentage of those convalescent or even recovered from typhoid become bacilli-carriers, and cause endemic typhoid by infecting houses, food, &c.

The conclusions to be drawn from these facts are, I think:The technique of cultures from the blood in disease has been so much simplified that this method may be adopted with advantage in all cases of doubtful pyrexia. The other method of serum (Widal) diagnosis, though still very useful, has many drawbacks. Agglutinins may not be formed in typhoid blood till late in the disease; they may be transient or even altogether absent. Much confusion may also arise if the serum under examination is taken from a patient suffering from disease caused by organisms allied to the B. typhosus. I am heretic enough to believe that endemic typhoid is as largely produced by house infection or transferred from man to man, or animal to man, as epidemic typhoid is due to infected water. There is never epidemic without endemic typhoid, and the way to prevent the first is to remove the second. This is the method in which the present campaign against typhoid in Germany is being conducted, and it is also the method we adopt in the Army. Animals may play such a large part in the transference of typhoid that the segregation and destruction of diseased animals on farms, and the close supervision of abattoirs, must be undertaken more energetically than ever before.

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Name of Organism

TABLE SHOWING THE CHARACTERISTICS OF THE TYPHOID-COLON GROUP.

Pathogenic Effects upon Man

Morphology Litmus

milk

CULTURAL RE.!.CTION.

Neutral Mannite red glucose solution

Agglutination

Various Animal Hosts

------------------------------------------------- ------ - ---------------Bacillus fcBcalis alcaU-

genes.. .. ..

B. typhosus . . . .

B. paratyphosus A

B. paratyphosus B .. Meat poisoning bacilli

Group A. Aertyck, Meirelbeck,

Serault, Gunther, Calmphout, Smith

Group B. Gartner, Morceilli,

Brussel, Gent, Brugge, Rumfleth, Haustadt

Hog-cholera Group: B. morbificans bovis

(calf septicoomia) B. typhi murium B. psittacosis

B. para-coli

B. coli

Has induced conditions indistinguishable from classical typhoid

Most commonly induces typhoid fever. May cause abdominal symptoms without fever or vice versa. Has induced conditions simulating sore throat, bronchitis, pneumonia, hepatitis, cholecystitis, appendicitis, meningitis, general local affections, such as abscesses, middle-ear diseases, adenoids, &c.

May induce a condition chemically indistinguishable from typhoid fever. The cases, however, are mild. Post mortems show the patches of Peyer not affected, and mesenteric glandR and spleen less enlarged than in typhoid

Produce either an acute gastro-enteritis or a condition clinically indistinguishable from typhoid fever

Both varieties may occur in the same epidemic

May produce typhoid fever or enteritis

Blue ..

Unchanged or but slightly altered

Turned a permanent pinkish

Turned first red (acidity), later a deep blue (alkalinity)

Unchanged.. Unchanged ••

Unchanged ..

Gas is evolved and slight fluorescence; disappear. ing in a few days

Much gas and marked permanent fluorescence

Acid, no gas ..

Acid, little or no gas

Acid and gas

Turned red Verymuchgas Acid andmuoh and

coagulated and marked gas fluorescenoe

Man

Has been found in splenic abscesses in cows also in tissues of men, oxen and cattle.

Man, cattle, sheep, dogs and pigs.

Man, cattle, sheep, dogs and pigs.

Found in the meat of pigs, oxen, sheep, &c.

Man, most mammals.

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351 THE COMPLEX NATURE OF TYPHOID ETIOLOGY, AND THE … · typhoid fever. The next bacterium, and...

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