It seems advisable to preface the section on the Cestodes with some general observations on the symptoms of disease provoked by tapeworms, especially so far as they relate to the question of toxic effects, and to include the Nematodes in this discussion. After this will follow a brief exposition of the most important intestinal lesions causally connected with intestinal parasites.
It is known to every experienced practitioner that the different intestinal parasites can give rise to a series of nervous symptoms, slight or severe, and produce, above all, blood changes—anæmia of the most varied nature, to the extent of severe progressive anæmia. These symptoms are regarded by many authors as reflex, or, as in the case of ancylostomiasis, the main feature from the loss of blood caused by the habit of life of the intestinal parasites. More frequently, however, they are regarded as toxic conditions produced by the parasites. In view of this divergence of opinion there appears to be some advantage in defining clearly the present position as to the toxic action of parasites. Most interesting in this respect are Dibothriocephalus latus and Ancylostoma duodenale.
We are indebted to the clinic at Helsingfors for our most detailed knowledge of bothriocephalus anæmia. Reyher[496] was the first to demonstrate that this parasite under certain circumstances can produce a severe, progressive and sometimes fatal anæmia, which can be cured, generally in a surprisingly short time, by expulsion of the worm. Among the various hypotheses which have been advanced as to the mode of origin of bothriocephalus anæmia, the greatest importance has been attached to the assumption already mentioned by Reyher, but definitely expressed by von Shapiro,[497] to the effect that Bothriocephalus latus produces a poison which is absorbed by the intestine and exercises a deleterious influence on the composition of the blood, especially on the erythrocytes, perhaps also on the blood-forming organs. This assumption is supported by no slight number of clinical and experimental investigations. Podwissotsky[498] observed severe blood changes in a child, aged 4 1/2, affected with B. latus. In the case reported by Pariser[499] the severe anæmia in a girl disappeared fairly soon after expulsion of the worm. In that reported by Schaumann[500] high fever accompanied the bothriocephalus anæmia; he also proved the hæmolytic properties of the broad tapeworm. The case reported by F. Müller[501] was one of severe anæmia. Also, in the first of the cases described by Kurimoto[502] of Diplogonoporus grandis there were present the same symptoms of anæmia as in the case of B. latus. Meyer[503] observed severe anæmia in two youths caused by B. latus. Rosenquist[504] has discussed the proteid metabolism in anæmia. The presence of B. latus produces in the majority of cases an increased proteid consumption, to which the blood change generally corresponds—toxic anæmia; in a further communication he reports on twenty cases of bothriocephalus anæmia, nineteen of which were cured by expulsion of the worms, while one case proved fatal, and he again emphasizes the toxic properties of the intestinal parasites. In the case reported by Bendix,[505] that of a girl, aged 4 1/2, the anæmia was moderate, whilst in the case of Zinn[506] (a woman, aged 30) the anæmia was so excessive that the patient succumbed five days after expulsion of six bothriocephalus heads. Isaac and van den Velden[507] have established that in the serum of patients who suffer from anæmia due to B. latus, parasitic products are dissolved, as shown by a distinct precipitin reaction. Galli-Valerio[508] considers it likely that toxic substances are secreted by the living helminthes which produce a lowering or raising of the body temperature, nervous disturbances and hæmolysis. Tallqvist[509] succeeded in extracting from B. latus a lipoid-like body which had a strong hæmolytic action. The experimental anæmia thereby produced differed in no respect from the severe chronic bothriocephalus anæmia of man. The question as to under what special conditions severe, and sometimes fatal bothriocephalus anæmia is developed is answered by Leichtenstern[510] and by Lenhartz,[511] by the assumption that among the Bothriocephali some are toxic, that is, manufacture a poison which, when absorbed by the host, produces a severe anæmia.
Certain factors lead him to conclude that an accumulation of poison, dependent on time and place, occurs in the Bothriocephali.
In the case of ancylostome anæmia, experience so far, according to Leichtenstern,[512] by no means supports the hypothesis of a difference in virulence of the worms according to time and locality, ancylostome anæmia being rather, so far as is known at present, in all races of man, everywhere and at all times, simply and solely dependent on the number of ancylostomes, the duration of the disease and—within certain narrow limits—on the individual capability of resisting the loss of blood and the toxic effect of the parasites. As is shown by a short historical résumé of the toxic action that has to be considered in ancylostome anæmia, we must admit that doubtless here, as in the case of bothriocephalus anæmia, the toxins secreted by the parasites exercise a hæmolytic action, even while admitting Leichtenstern’s contention that the significance of the loss of blood due to ancylostomes must not be underrated. The toxic hypothesis acquired a definite standing through a series of experiments of Lussana[513] on rabbits, where he succeeded in producing anæmia by injecting urinary extracts of ancylostome patients. Arslan[514] extracted toxins from the urine of two ancylostome patients and injected them into rabbits, which thereupon sickened and showed the same blood changes as the ancylostome patients. Retinal hæmorrhages, so frequent in ancylostome anæmia, which, according to Fischer[515] and Samelsohn,[516] are not due to direct loss of blood, must also be ascribed to a parasitic toxin. A further argument in favour of the toxic hypothesis is furnished by the blood changes recorded by Zappert,[517] Müller and Rieder,[518] Bücklers,[519] and Neusser,[520] which must be regarded as the expression of toxic action, especially with reference to eosinophilia. The striking increase in proteid destruction in ancylostomiasis observed by Bohland,[521] and which ceased after the parasites had been expelled, also gives additional support to the assumption of toxic action. The observation of Daniels[522] also deserves consideration in this connection, according to which the presence of yellow pigment in the liver and kidney cells is to be attributed to blood destruction by a verminous toxin absorbed from the gut. Looss[523] considers it not at all improbable—in fact, almost certain—that Ancylostoma, in addition to withdrawing blood, exert a kind of toxic action on their host.
Scheube[524] attributes almost equal importance to the loss of blood, the digestive disturbances, and the intoxication induced by certain metabolic products of the parasites. According to v. Jaksch[525] ancylostome anæmia is not induced solely by loss of blood, but by the fact that the parasites produce a ferment which has a toxic action and produces stimulation in those organs in which the eosinophile cells arise. The hæmolytic action of ancylostomes has frequently been observed by Galvagno[526] in men employed in sulphur mines. According to Loeb and Smith[527] the anterior half of the body of ancylostomes contains a substance which probably causes anæmia. Bauer[528] found in the urine of ancylostome patients glycuronic acid, which he considers to be a sign of metabolic disturbance due to parasitic toxins. As has been demonstrated by Allessandrini,[529] the secretion of glands in the anterior part of the body has a distinct hæmolytic effect on the erythrocytes. While the worm attaches itself to the mucosa by means of its teeth, these glands discharge their secretion, producing hyperæmia. The extravasated blood is acted on by this secretion, so that it can serve as food for the parasites. Hynek[530] attributes eosinophilia (up to 20 per cent.) to a toxic action. Goldmann[531] expresses a similar opinion, though he assumes that the anæmia is secondary, as the toxin of the cephalic glands, as the parasites bite, penetrates the mucosa and thence into the blood, where it dissolves the red blood corpuscles. Romani[532] discusses the agglutinating hæmolytic action of the serum of ancylostome patients. Whether Ancylostoma produce toxins and what is their nature, or whether the loss of blood causes the anæmia, Liefmann[533] was unable definitely to determine; hæmolytic substances do not appear to take any part in it.
Berti[534] also is inclined to attribute the anæmia to metabolic products of the ancylostomes; he found, in fact, that a serum obtained from a sheep (after subcutaneous injections of the culture fluid of ancylostome larvæ) was efficacious in the treatment of ancylostome anæmia. Peiper[535] likewise assumes that the parasite secretes a cell toxin. Löbker[536] at the present day still maintains that the cause of the disease must be looked for really, if not perhaps entirely, in the continued withdrawal of blood by the parasites; the secretion of toxins by ancylostomes has not yet, in his opinion, been conclusively proved. Except in the case of Bothriocephalus latus, referred to previously, toxic action appears to be of quite subordinate importance for the other Cestodes occurring in man—especially Tænia solium and T. saginata, which are most frequently found; thus Cao[537] flatly denies the presence of toxins in the body of Tæniæ, while others, such as Messineo and Calmida,[538] Jammes and Mandoul,[539] consider they are justified from their investigations in concluding that Tæniæ contain a specific toxin. Messineo[540] injected, with all bacteriological precautions, extracts of Tænia, dissolved in physiological salt solution. He invariably obtained severe motor disturbances and frequently death. The observation by Pereira[541] of a case of chorea in which rheumatic and cardiac symptoms were absent and which after expulsion of a Tænia was quickly cured, also favours the view of a toxic action. Barnabo,[542] however, was unable to obtain a toxin from Tænia saginata. Gagnoni,[543] on account of a marked eosinophilia which, after expulsion of a Tænia saginata, fell within fourteen days to 1 per cent., assumes the formation of a Tænia toxin. Dirksen’s[544] observation has reference to a sailor affected with serious anæmia, who, after expulsion of twelve pieces of Tænia solium, was rapidly cured. A portion of the worm was already breaking down, the absorption introducing into the body highly toxic hæmolytic products, to which the anæmia must be ascribed. How far the serious disturbances of the nervous system, frequently to be observed in cases of Hymenolepis nana, are to be considered as of purely reflex nature or toxic must remain an open question; the same applies to Dipylidium caninum, in which case Brandt[545] observed serious central nervous symptoms. Caution is necessary in judging as to any connection between worm stimulus and nervous symptoms in cases of Ascaris infection. Peiper[546] is inclined to regard such nervous symptoms not as reflex, but rather as due to a toxin contained in the helminthes, or metabolic in origin.
In cases of pernicious anæmia when the symptoms disappear after expulsion of Ascaridæ a toxic action must be assumed (Demme[547]). Additional clinical observations do not, indeed, lead to any definite conclusion as to the question whether Ascaridæ produce a toxin which is capable of causing more or less injury either to the nervous system or to the blood, yet it may be worth while to give a brief review of this question. In a case of Kutner’s,[548] that of a girl, aged 12, there was a hæmolysis which was cured after expulsion of twenty-four Ascaridæ. Attacks of opisthotonos in a girl, aged 16, ceased after seventy-eight Ascaridæ had been expelled (Lutz[549]). Unusually serious disturbances were observed in a man, aged 26, who was rapidly cured by Drouillard[550] by the removal of a great number of Ascaridæ. The observations on pseudomeningitis are of especial interest; they are evidently toxic in origin as in the case of Annaratone,[551] of a man who was taken ill with gastro-intestinal symptoms and who died with meningitic symptoms. Post mortem the brain was normal, but the stomach contained a great coil of Ascaridæ. The cases of Delille,[552] Mériel,[553] Papi[554] (the occurrence of Cheyne-Stokes respiration has been ascribed to the action upon the centre in the medulla oblongata of the products of the Ascaridæ), and Taillens[555] related to children in which the meningitic symptoms (meningismus), partly serious, disappeared with the removal of the Ascaridæ. Máreo[556] designates this disease helminthiasis meningitiformis, which exhibits all the symptoms of meningitis, but which is caused by the metabolic products of Ascaridæ.
Schupfer,[557] Duprey[558] (observations in the West Indies, where such symptoms are said to be of very frequent occurrence), Naab[559] (the flow of water from the mouth at night is mentioned as a remarkable fact), and Hammiss[560] assume the action of an Ascaris toxin in the clinical observations made by them, mostly children with fever and intestinal symptoms. Schupfer assumes in such cases, as he observed it once in a man, aged 23, that the disease termed Lombricoise à forme typhoïde by Chauffard was due to B. coli of marked virulence due to the action of the Ascaridæ. The Widal reaction was negative. Koneff[561] reports a case in which acute attacks of cramp, trismus, and rigidity of the pupil disappeared after expulsion of seven Ascaridæ. Tetanus, as observed by Buchholz[562] in a girl, aged 17, and rapidly cured after expulsion of sixteen Ascaridæ, is manifestly rare, since only Rose[563] mentions this as a cause in his article on Tetanus. Only a few experimental data exist. Cattaneo[564] could detect only a very weak toxin in Ascaris, while Messineo,[565] by injecting into animals extracts in physiological salt solution, invariably succeeded in producing serious motor disturbances and frequently death. Interesting also are the observations of Huber,[566] who, after working with Ascaridæ, suffered from itching of the head and neck, blisters, swelling of the ear, conjunctivitis, ecchymosis and troublesome palpitation in the head. He consequently assumes that Ascaridæ can induce irritation by chemical (toxic) means.
In the case of Trichocephalus dispar no more than in the case of Ascaris lumbricoides can we speak with certainty of a toxic effect, even though a number of observations are available which might justify such an assumption as regards these intestinal parasites. Barth[567] found the brain normal in a man who had died with meningitic symptoms, but the intestines were full of Trichocephalus dispar; Gibson[568] records the rapid cure of serious cerebral symptoms after expulsion of Trichocephalus, so also Pascal,[569] Burchhardt[570] and Rippe.[571] Moosbrugger[572] was the first to draw attention to grave anæmic conditions induced by Trichocephalus, Morsasca[573] and Becker[574] to progressive grave anæmia (trichocephalus anæmia is accompanied by marked reduction of the number of red blood corpuscles, of the specific gravity and of the hæmoglobin, well-marked morphological changes of the red cell, micro-, macro-, and poikilocytosis and nucleated red cells). Sandler,[575] in his case of a boy, aged 11, who died of anæmia, assumes a trichocephalus toxin to be the cause of the disease, and Kahane also reports on anæmic conditions induced by Trichocephalus. Girard,[576] in addition to symptoms in the gastro-intestinal tract, calls attention to those arising in the blood—anæmia and its sequelæ—and also to nervous symptoms: cerebral phenomena, headache, giddiness, aphonia, symptoms of meningitis. In a case of Schiller’s[577] high fever was present, which probably set in when the Trichocephali present in the gut in great numbers commenced their parasitic activity. Hausmann,[578] in order to explain the adaptability of Trichocephalus, assumes that according to the locus minoris resistentiæ, at one time the reflex at another the toxic action is effective, now on one organ, then on another; anæmia being present in most cases, frequently general and local neuroses and cerebral symptoms of various kinds.