Taylor454 (1913–14), writing from Entebbe, Uganda, prescribes arsenious acid by the mouth in increasing doses. Creosote has been used in West Africa.

VI.—MALARIA.

Malaria, known also under the names of ague, paludism, marsh fever, remittent fever, intermittent fever and climatic fever, among others, is a very widely spread disease. It is most prevalent in the equatorial regions and gradually diminishes north and south of the equator. The various malarial parasites (see pp. 155 to 172) are spread by species of Anophelines, and hence malaria is present in districts favourable to these intermediate hosts, that is, in places where there is a considerable amount of atmospheric moisture and rain, as well as heat.

The principal malarial parasites are: Plasmodium vivax, the agent of simple tertian fever; Plasmodium malariæ, the parasite of quartan malaria, and Laverania malariæ or Plasmodium falciparum, producing malignant tertian or sub-tertian malaria (and quotidian, see p. 167). These various malarial fevers present certain clinical features in common, which will be stated here (see also pp. 155 to 157). For further particulars regarding malaria in all its aspects the reader is referred to the book by Sir Ronald Ross on “The Prevention of Malaria,” to the “Manual of Tropical Medicine,” by Drs. Castellani and Chalmers, and to the “Tropical Diseases” of Sir Patrick Manson.

Typical malarial fevers consist of a series of pyrexial attacks which recur at definite intervals of twenty-four (quotidian), forty-eight or seventy-two hours, according to the parasite present in the patient’s blood. Each attack shows three stages, a stage of rigor, a heat stage and a stage of profuse perspiration. Following on these three stages, there is an interval relatively or actually without pyrexia. Then the fever returns again. A rise of temperature, often accompanied by a general feeling of malaise, may precede the initial stage of rigor. When the latter sets in, the patient feels intensely cold, shivers violently, the skin becomes cold and the features pinched. There may be violent vomiting and convulsive attacks in young children. The temperature, however, is really above the normal, and continues to rise. After about an hour, the shivering abates and the heat stage succeeds it. The temperature rises rapidly, even to 106° F. The patient becomes very flushed, the pulse is rapid, headache may be intense and the skin dry and burning. This stage, that causes acute distress to the patient, may last for one or often three to four hours, and then the patient commences to perspire profusely, the clothing and bedding often being saturated with sweat. After this, the fever rapidly declines, and when the sweating ceases, the patient may feel almost well although somewhat languid. The sweating stage persists from two to four hours, so that the attack lasts as a rule from six to ten hours. After an interval of one, two or three days, a recurrence takes place. During the early part of the attack, especially at the stage of rigor, there is great splenic enlargement. At first the enlargement disappears in the interval, but in the case of repeated attacks the spleen tends to become permanently enlarged. During malarial attacks and during the intermission period, there is a great increase in the amount of nitrogen excreted by the kidneys, while the excretion of iron and bile in the fæces is increased.

Stitt455 (1914) points out that it is characteristic of malignant tertian paroxysms that they set in with chilly sensations rather than a frank, definite chill, and that the fever is of the remittent type.

Plasmodium malariæ and P. vivax rarely produce marked lesions in the bodies of their hosts, as they sporulate in the circulating blood and so do not accumulate in any one organ. On the other hand, Laverania malariæ (Plasmodium falciparum) multiplies within the internal organs of its host, and consequently aggregates or clusters of the parasites occur therein. The organ in which most sporulation occurs suffers most. The liver is generally enlarged, soft and congested. The capsule of the spleen is tense, but the splenic consistency is less than normal. The bone-marrow is often dark and congested in the spongy bones and brownish-red in long bones. The blood-capillaries of the brain and spinal cord are often filled or blocked with sporulating parasites and large quantities of pigment are found in these organs. Even if the parasites are absent, the pigment is present in the endothelial cells. Pigment is found in most organs of the body.

Atypical forms of malaria may occur in which some or all of the symptoms are much modified. Irregular fevers also may be produced by successive infections by the same parasite, or by the presence of two different malarial parasites.

As regards the diagnosis of malaria, according to Manson the three pathognomonic signs are—periodicity, the effect of quinine, and the presence of the malarial parasite.

Treatment.—The great specific for malaria is quinine. It attacks the merozoites or asexual generation. The drug can be administered by the mouth, by the rectum, by intramuscular injections or by intravenous injections, the two latter methods being adopted in serious infections or where gastric complications are present. When quinine is taken by the mouth, the more soluble acid salts, e.g., quinine bihydrochloride and bisulphate, are better than the sulphate, the form in which quinine is usually sold. Tablets, pills and capsules are convenient means of taking quinine but must not be old or hard, or they may pass unchanged through the body. In the case of mild tertian or quartan malaria, Castellani and Chalmers recommend the administration of a dose of quinine four hours before the sporulation of the parasite is due. Another modification is to give 10 gr. of quinine by the mouth in the morning and a second dose of 10 gr. as above. In many cases they give 5 to 10 gr. of the drug three times a day. Administration of quinine per rectum may be useful but they recommend intramuscular inoculation. The solutions used must be sterile, and the “sterilettes,” small, hermetically sealed vials, containing 1 grm.) or  1/2 grm. (7 1/2 grm.) of quinine in solution, are recommended. A deep injection into the deltoid or gluteus muscle is usual.

For pernicious infections, intravenous inoculation with not less than 1 grm. at a time is recommended.

After the fever has subsided, the administration of quinine in smaller doses must be continued for some time, in order to avoid relapses.

Stitt (1914) writes that “there now seems to be a tendency to use the alkaloid itself instead of its salts, it having been found that the alkaloid and its very insoluble tannate are absorbed from the digestive tract equally as well as the soluble salts.” Euquinine or ethylcarbonate of quinine contains 81 per cent. of quinine, but is expensive.

During malarial attacks, constipation must not be allowed. Headache can be relieved by cold applications, and perspiration must be encouraged in the early stage by hot tea, warm lime drinks, etc. After bad attacks, a change to a cooler climate is desirable, but the quinine treatment must not be discontinued.

Preventive measures take two main forms, directed respectively against the malarial parasites in man, and against the mosquitoes that convey the parasite from man to man.

With regard to man, houses should be built away from low-lying marshy ground, and kept free from vegetation such as grass or brush which furnishes shelter to the mosquitoes. In the tropics, the chief reservoirs of the malarial parasites are the native children, hence European quarters should be away from native dwellings as far as possible. Mosquito nets, having twenty to twenty-four meshes per square inch, should be used invariably, and houses should be screened. Malaria-conveying mosquitoes bite chiefly towards evening. Quinine treatment for preventive purposes is important. A dose of 5 gr. of quinine daily, with a dose of 10 gr. on the seventh day (Castellani), is efficacious. Some workers, however, recommend a large dose (15 gr.) on two consecutive days every eight or ten days for three months, while others recommend 10 gr. twice a week. Celli administered 3 gr. of quinine morning and evening.

The second line of attack is directed against mosquitoes, especially Anophelines, on the lines so well set forth by Sir Ronald Ross.456 The accumulation of small quantities of water in various vessels, many of them unnecessary, should be prevented, as Stegomyia (Culicines) breed in such receptacles. Anophelines breed in small pools. All drinking water and household vessels, water-butts and cisterns must be effectively screened with wire gauze. Cesspools, etc., must also be screened, and they, and all collections of water, should be oiled with crude petroleum sprays every week or ten days, or fortnight according to some workers. The petroleum is a good larvicide and suffocates the Anopheline larvæ, while its presence renders the site obnoxious to the adult mosquitoes. The amount of crude petroleum or kerosene will vary according to the locality concerned, due regard being paid to its powers of spreading on the surface treated. Different authorities have used different quantities, such as 1 oz. of oil to 1 square yard or to 15 square feet. Others have used 1 pint of the petroleum to a circle of 20 feet in diameter, while  1/2 pint for every 100 square feet of surface has also been recommended. The larvicide used so successfully in Panama consisted of:—

One part of this mixture in 5,000 parts of water containing mosquito larvæ destroys them within five minutes; 1 part in 8,000 of water kills larvæ in thirty minutes. Small fish, such as the “millions” fish, that feed on the larvæ, can be introduced into collections of water and are of local service. Ducks may also act as destroyers of larvæ. The growth of water-weeds and rank vegetation, that affords shelter to the larvae, must be prevented as far as possible.

Wherever possible hollows should be filled up, swamps and roads should be well drained. Much good has followed the use of such measures in Panama, Egypt, British Guiana and other places. The ideal conditions for malaria reduction appear to consist in a combination of general quinine prophylaxis with anti-mosquito measures.

VII.—BALANTIDIAN DYSENTERY.

This disease is also known as ciliate or ciliary dysentery. The chief causal agent is Balantidium coli. Others are Balantidium minutum, Nyctotherus faba, etc. (see pp. 200–206).

Balantidiasis is insidious and is marked by alternate attacks of diarrhœa and constipation with vomiting, while mucus is passed in the motions, which are foul smelling. There may be chronic ulceration of the colon. Œdema of the face and limbs and anæmia may occur.

Treatment is at present rather unsatisfactory. Castellani and Chalmers state that “the symptomatic treatment for entamœbic dysentery may be tried.” Various treatments, more or less empirical, by calomel, quinine, carbolic acid in pill form, salicylic acid, extract of male fern, methylene blue, iodine solution, rice water and tannin enemata are mentioned by Prowazek457 (1913) and by Seifert. E. L. Walker458 (1913) found, from experimental work, that organic compounds of silver, e.g., protargol, were most effective. Local treatment by large enemata of collargol or protargol seems to be indicated. Behrenroth459 (1913) successfully treated a Prussian case with thymol, given in 4 grm. doses every two days, followed at the end of a fortnight by de-emetinized ipecacuanha, given in pills containing 6 cg. each, to the number of thirty a day. In about another fortnight the symptoms had subsided. The thymol checked the diarrhœa, but it was necessary to give the de-emetinized ipecacuanha to kill off the balantidia still present. Phillips (1915) also recommends thymol. Ardin-Delteil, Raynaud, Coudray and Derrieu (1914) found neither emetine hydrochloride nor protargol of use.

As regards prophylaxis Walker states that pigs “should be confined and not allowed to run in yards and dwellings.” Behrenroth considers that dirty hands, for example, those of farm workers brought into contact with pigs, are probably the medium of infection. The personal cleanliness of such persons is, then, of the greatest importance.

PLATHELMINTHES (Flat Worms).
BY
J. W. W. STEPHENS, M.D., B.C., D.P.H.

FASCIOLIASIS.

Fasciola hepatica.

The symptoms of disease evoked by Fasciola hepatica are rarely observed in our part of the world, whereas Kermogant460 states them to be of frequent occurrence in Tonkin461; the parasites are there called “Douves.” In our experience they are only accidentally found post mortem in a certain number of cases, as no changes are manifested during life which would permit of any conclusion being drawn as to the presence of these parasites. In three cases (Bierner,462 Bostroem463 and Sagarra464) icterus was present; in a fourth case, recorded by Duffek,465 the parasites had led to a severe and acute distomiasis of the liver, combined with chronic purulent and ulcerative cholecystitis, with purulent cholangitis and dilation of the bile-ducts and numerous small abscesses of the liver. The total number of flukes found in these cases amounted to about fifty. The parasites passed from the duodenum into the bile-ducts, and first obstructed the flow of bile and then set up icterus, followed by cholecystitis and cholangitis.

As regards localization of the liver fluke in the pharynx, see p. 242.

The treatment must be directed to the principal symptoms; prophylaxis is especially important in districts where distomiasis is of frequent occurrence. As the embryos live in water, only boiled or filtered water should be drunk. The attempts of Tappeiner466 to discover an effective remedy against liver-fluke disease (liver rot), so prevalent among sheep, were unsuccessful.

Fasciolopsis buski.

This parasite lives in the intestine, not in the liver of man; it produces bloody stools and typical symptoms—high fever and a condition of apathy (Odhner).467

PARAGONIMIASIS.

Paragonimus ringeri.

The disease produced by the lung fluke is specially endemic in Japan, also in isolated parts of China, Formosa and Korea. The fact that the lung-fluke disease is most frequently found in mountainous districts (Katsurada468) is worthy of special attention. The onset of pulmonary paragonimiasis is generally insidious (Looss469); generally the only symptom is a slight cough, occurring at first at longer, and later at shorter intervals; it is accompanied by the expectoration of discoloured sputum, frequently blood-stained. Though now and then severe hæmorrhages result, up to the present no case has been established in which they have been the direct cause of death.

Examination of the thorax frequently fails to reveal anything abnormal. Inouye470 states that the most frequently observed changes consist in retraction of the thorax and in a contraction of its infrascapular portion. Scheube471 repeatedly observed that the one side, presumably that which harboured the worm, moved less freely than the other. The physical changes are not uniformly spread over the whole lung, but are localized. The disease may come to a standstill for long intervals and then set in again, lasting on the whole from ten to twenty years. In addition to paragonimiasis of the lungs, cysts are frequently found on the eyelids, which occasionally extend deeply into the orbit and hinder the movements of the eyes. Post mortem, cysts the size of hazel nuts containing one, two, or three adult worms are found in the lungs, and in addition, not uncommonly there exist pulmonary emphysema and bronchiectasis. Besides being present in the lungs and in the eyelids, the parasites have also been found in the pleura, the liver, the intestinal wall, the peritoneum, the cervical glands, and in the scrotum, without actually occasioning any actual symptoms in these tracts.

The most dangerous locality is in the brain. Otani,472 Inouye,473 Yamagiva,474 and recently also Taniguchi,475 have found post mortem the worms and their ova in tumours of the brain, or, in areas of softening in cases of Jacksonian epilepsy; in Taniguchi’s case the eggs were found in masses in the inflammatory areas of softening. In the nineteen cases of paragonimiasis of the brain collected by Inouye, the following symptoms were observed: general convulsions on eight occasions, unilateral convulsions on six occasions, convulsions with paralysis on the same side and hemiplegia, five times each; in Taniguchi’s case, attacks of cortical epilepsy, choreiform twitchings in the right extremities, which gradually become athetotic. The following were symptoms of rarer occurrence: paresis of the right upper extremity, vertigo, dementia, and amnesic aphasia, disturbances of vision. Paragonimiasis of the brain appears to arise by embolism from a primary pulmonary lesion.

The diagnosis depends upon the finding of ova in the sputa; if together with ova in the sputa, cerebral disturbances make their appearance, in all probability the cause is the presence of worms or ova in the brain.

The prognosis of pulmonary paragonimiasis is favourable; on the other hand, that of cerebral paragonimiasis is very doubtful.

The treatment of the pulmonary lesion consists only in paying attention to the general condition (good food, rest, cough remedies), as all attempts to destroy the worms in the lungs by means of vermicidal drugs administered internally or by way of inhalation have so far been without result. The treatment of the cerebral lesion is entirely hopeless. Trephining has been proposed for cases the condition of which is more favourable, but it has not reached the stage of performance.

Prophylaxis consists in general management: cleansing and if need be boiling of everything that is eaten or drunk.

Clonorchis sinensis.

According to our present knowledge Clonorchis sinensis is only found in China and Japan; even the post-mortem case reported by Laspeyres476 was that of an Asiatic sailor who was admitted into the General Hospital St. George, Hamburg, in a moribund condition with the clinical diagnosis of beri-beri. The bile-ducts are the usual site of the parasite, though Katsurada477 has found them also in the pancreatic ducts. In addition, it is found not uncommonly in the upper portion of the small intestine, especially in the duodenum, also, though decidedly rarely, in the stomach. As these sites, however, do not afford the conditions necessary to life, they are only found here on their way out of the body of the host.

The initial stage of infection with this fluke generally runs a symptomless course; in proportion as the worms multiply the following symptoms are manifested: First there is a morbid sense of hunger and irregularity in defæcation; at the same time the patient experiences a feeling of pressure and pain in the epigastrium and right hypochondrium, or just a dull pain. Pressure increases the pain considerably. The liver appears to be enlarged, sometimes the enlargement is specially perceptible over the left lobe of the liver. The patients maintain a proportionately good general state of health in this state for a long time and may hope to recover. In severe cases there occurs copious and generally bloody diarrhœa, also icterus. The next stages are anæmia, emaciation, epistaxis, ascites, enlarged spleen, and cachexia, to which the patient finally succumbs. In general the course of the disease is very chronic and irregular; in winter and spring there is generally improvement, in the summer and autumn the patient gets worse. At post-mortem the bile-ducts are enlarged and thickened, there is interstitial hepatitis with enlargement of the liver, but not to such an extent as in hypertrophic cirrhosis. After the initial enlargement contraction of the liver sets in, the peritoneal coat and capsule proper of the liver become more or less thickened in places. In the pancreas also dilatation and thickening of the ducts occur, as well as interstitial inflammatory processes. Obstructions in the portal circulation may lead to catarrhal changes in the stomach.

The diagnosis is based on the demonstration of ova in the fæces.

As a radical treatment is still unknown, consequently it can only be purely symptomatic. Prophylaxis consists in the prohibition of drinking unboiled water or eating uncooked molluscs, fish, etc., of canal water. Leaving the epidemic region may bring about gradual recovery.

BILHARZIASIS.

Schistosoma hæmatobium.

The symptoms of bilharziasis are manifested chiefly in the urinary apparatus, and above all as hæmaturia, at the outset without any special troubles. Later, however, it is accompanied by subjective symptoms in the shape of feelings of pain, and of vague pains in the perinæum and lumbar region, and of burning in the urethra during the passing of urine. All the symptoms are usually aggravated after excesses in eating and drinking, and after considerable bodily exertion. Another condition found, but not often mentioned, is lipuria (Stock478); the highest amount has been 2 per cent. fat in the urine. Stock found 6 to 20 per cent. of eosinophile cells in ten cases examined by him. They appear to be increased, especially in the early cases; Kautsky479 also called attention to the excessive degree of eosinophilia, whilst Goebel480 expresses the opinion that a specific toxic action on the organism generally is not developed in bilharziasis. Kautsky481 assumes a toxic anæmia as in the case of ancylostomiasis. English authors also have called attention to the eosinophilia and to a considerable amount of leucocytosis (Balfour,482 Douglas and Hardy483). The severe forms occur almost exclusively in men; symptoms of catarrh of the bladder make their appearance, vesical calculi are frequently found, whilst the formation of stone in the kidneys and ureters is rare. Urethral fistula occurs in bilharziasis, often without stricture, and if granulations occur the fistula is distal to them. Goebel484 regards the bilharzia fistula as a chronic burrowing of pus, caused by the irritation set up by the ova as foreign bodies and consecutive restricted suppuration; and secondly as due to the passage of urine through the defect in the epithelium or the wall of the urethra. The fistulæ, which are generally situated at the neck of the bladder and at the membranous portion, are very tortuous and frequently very numerous; they often lie embedded in well-marked tumours—in fact, in granulation tumours with marked inclination to excessive formation of cicatricial tissue. The opening generally is in the perineal and scrotal regions. In the case of a patient, aged 21, from the Transvaal, Kutner485 found by cystoscopic examinations the whole summit and walls of the bladder covered with large and small tumours. In addition to smooth glistening tumours, others were more or less disintegrated, and scattered large and small cauliflower-like growths occurred. Like malignant growths, the tumours were inclined to break down, the process extending from within outwards towards the surface. Whether the hydrocele so frequent in Egypt has any connection with bilharzia is not known. A frequent sequela of bilharziasis is complete sexual impotence (Petrie486).

Bilharziasis of the rectum is manifested by symptoms of dysentery; the repeated violent attempts at defæcation lead in time to prolapse of the rectum, which sooner or later induces septic infection and so death. In the mucosa of the rectum, polypoid growths similar to those in the bladder are met with, due to the ova of the parasites in the mucosa and submucosa. In the case of a man, aged 36, who had lived for a long time in South Africa, Burfield487 found in the excised vermiform appendix ova of Schistosoma hæmatobium; he assumed this to be a gradual secondary infection of the appendix, whilst Kelly488 mentions a case of primary bilharziasis of the appendix; the eggs lay in the submucosa directly above the muscularis. Tumours containing numerous ova are frequently found in the region of the genitalia, thighs and scrotum. In one case Symmers489 found numerous male schistosomes in the portal blood and a copulating pair in the left lung. Though schistosome eggs have been found by some observers in the lung tissue, this is nevertheless the first case in which living parasites have been found in the lesser circulation. Perhaps they got there by way of the external iliac vein from the veins of the bladder and rectum.

In the female sex bilharziasis is incomparably rarer than in the male and is generally limited to hæmaturia. Bilharziasis of the vagina, which takes the form of an acute vaginitis, is frequent according to Milton.490 Horwood491 found in one case a polypoid tumour of the cervix uteri, and in the connective tissue of the tumour Schistosoma ova, both in masses and singly. It could not be established whether the ova reached the vagina and thence the cervix directly, or through the urine from the bladder.

The course of the disease is chronic, and in slight cases, provided fresh infections do not occur, is not unfavourable; in severe cases the cachexia caused by loss of blood, or intercurrent diseases to which the patients easily succumb—e.g., pyelitis, pyelonephritis, pyæmia, or uræmia—lead to a fatal issue.

In regions in which Schistosoma hæmatobium is endemic, or in patients from such regions, the diagnosis is easy by microscopically finding the eggs in the urine.

As regards the treatment of the affection this much must be said, that so far there is in existence no certain remedy. In countries where bilharziasis is endemic copaiva balsam is considered a specific. Kutner (loc. cit.), however, in the case of his patient who for a long time had taken no inconsiderable amounts of copaiva, had no success worth speaking of to record. Urotropin (three times daily, 1 grm.) has similarly failed, salol (0·75 grm. several times daily) perhaps affords relief in affection of the bladder (Milton). Methylene blue, oil of turpentine with extract of male fern (Brock492), or the latter alone and santonin given in small doses for a week at a time, in the morning, are said by Petrie493 to be of value. Sandwith494 and Harley495 were not very successful. By way of experiment Kutner for some time used collargol per rectum, proceeding on the assumption that this preparation, which has proved of such remarkable service in bacterial infection, would perhaps render a continuance of life difficult for the bilharzia worms. But this hope proved illusory. In order so far as possible to limit the loss of blood, Kutner regularly employed stypticin for long periods (three times daily, two tabloids of 0·01 grm.) with undoubted success, in so far that the hæmorrhages became considerably less in amount. As two patients in the course of enteric fever lost their hæmaturia, Stock accordingly recommends subcutaneous injections of Wright’s typhoid vaccine. In the early stages of the rectal lesion suppositories of iodoform, ichthyol, or narcotics might possibly be of use. In the case of urethral fistulæ, division, excision and scraping out of the granulation tissue are recommended; in cystitis with formation of tumours high resection with curetting of the tumours or their destruction with the cautery; in the case of vesical calculi, high resection, curetting the bladder, and then drainage. Tumours of the rectum must also be removed by operation.

Prophylaxis is important; it should be extended to all modes of using water, only filtered water being drunk, and only boiled water being used for washing. This advice should be given to tourists who travel through the infected districts, and is also recommended to soldiers and officials who are despatched to the Colonies. The favourable influence of change of climate can only show itself where fresh infections are avoided.

CESTODES.

GENERAL.

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. Reyher496 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. Podwissotsky498 observed severe blood changes in a child, aged 4 1/2, affected with B. latus. In the case reported by Pariser499 the severe anæmia in a girl disappeared fairly soon after expulsion of the worm. In that reported by Schaumann500 high fever accompanied the bothriocephalus anæmia; he also proved the hæmolytic properties of the broad tapeworm. The case reported by F. Müller501 was one of severe anæmia. Also, in the first of the cases described by Kurimoto502 of Diplogonoporus grandis there were present the same symptoms of anæmia as in the case of B. latus. Meyer503 observed severe anæmia in two youths caused by B. latus. Rosenquist504 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 Zinn506 (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 Velden507 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-Valerio508 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. Tallqvist509 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 Leichtenstern510 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 Lussana513 on rabbits, where he succeeded in producing anæmia by injecting urinary extracts of ancylostome patients. Arslan514 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 Fischer515 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 Daniels522 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. Looss523 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.

Scheube524 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. Jaksch525 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 Galvagno526 in men employed in sulphur mines. According to Loeb and Smith527 the anterior half of the body of ancylostomes contains a substance which probably causes anæmia. Bauer528 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. Hynek530 attributes eosinophilia (up to 20 per cent.) to a toxic action. Goldmann531 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. Romani532 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, Liefmann533 was unable definitely to determine; hæmolytic substances do not appear to take any part in it.

Berti534 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. Peiper535 likewise assumes that the parasite secretes a cell toxin. Löbker536 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 Cao537 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. Messineo540 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 Pereira541 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’s544 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 Brandt545 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. Peiper546 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 (Demme547). 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 (Lutz549). Unusually serious disturbances were observed in a man, aged 26, who was rapidly cured by Drouillard550 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 Papi554 (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 Taillens555 related to children in which the meningitic symptoms (meningismus), partly serious, disappeared with the removal of the Ascaridæ. Máreo556 designates this disease helminthiasis meningitiformis, which exhibits all the symptoms of meningitis, but which is caused by the metabolic products of Ascaridæ.

Schupfer,557 Duprey558 (observations in the West Indies, where such symptoms are said to be of very frequent occurrence), Naab559 (the flow of water from the mouth at night is mentioned as a remarkable fact), and Hammiss560 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. Koneff561 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 Buchholz562 in a girl, aged 17, and rapidly cured after expulsion of sixteen Ascaridæ, is manifestly rare, since only Rose563 mentions this as a cause in his article on Tetanus. Only a few experimental data exist. Cattaneo564 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. Barth567 found the brain normal in a man who had died with meningitic symptoms, but the intestines were full of Trichocephalus dispar; Gibson568 records the rapid cure of serious cerebral symptoms after expulsion of Trichocephalus, so also Pascal,569 Burchhardt570 and Rippe.571 Moosbrugger572 was the first to draw attention to grave anæmic conditions induced by Trichocephalus, Morsasca573 and Becker574 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’s577 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.

With regard to the toxic action of Oxyuris there is only the single record of Hartmann,579 who noticed the disappearance of epileptic fits and psychic disturbances in a girl, aged 13, after the removal of Oxyuris. Nervous disturbances and blood changes can but rarely be attributed to Strongyloides. Silvester580 and Valdes581 report on giddiness, headache and anuria in cases observed by them; whether the eosinophilia recorded by Bücklers582 and Bruns583 is due to the toxin of Strongyloides must remain an open question.

Reference has already been made to the possibility that intestinal ciliates (Balantidium coli) can also produce toxins.

The contents of echinococcus cysts appear to contain a substance only moderately toxic, giving rise to urticaria, in a series of cases where the fluid has escaped into the abdominal cavity (during puncture). D. Müller584 has collected nine such cases out of the literature, to which may be added six cases of Finsen585 in which the escape of fluid into the peritoneal cavity led to severely itching urticaria, which usually disappeared again after one or two days. On one occasion, indeed, urticaria occurred after rupture into the pleural cavity. In the case recorded by Caffarena586 of echinococcus of the right lobe of the liver, widespread urticaria developed as the result of the exploratory puncture. In the case of an echinococcus of the liver rupturing into the abdominal cavity La Spada587 ascribed the symptoms leading to death to toxic influence while the peritoneal symptoms were less marked. Eosinophilia in hydatid disease is slight according to the investigations of Bindi588 and Santucci,589 and is, according to Welsh and Barling,590 no certain sign of echinococcus; it is independent of the age, sex and temperature of the patient, but upon rupture of the cyst eosinophilia invariably sets in.

The question as to the importance of helminthes in relation to certain diseases of the gut requires special discussion, but it concerns only Ascaris lumbricoides, Oxyuris vermicularis, and Trichocephalus dispar, and the question of appendicitis first of all. The entrance of intestinal parasites into the vermiform appendix was already known to medical men in the fifties of last century, as is shown by the works of Merling591 (1836), Zebert592 (1859), Platonor593 (1853), and Schachtinger594 (1861). Most of these authors have considered intestinal worms, together with other foreign bodies, to be the cause of appendicitis. As regards the part played by these intestinal parasites in the etiology of appendicitis, so much discussion has taken place during the last few years that it is worth while to give a résumé of the later views on this question, even though at the outset it must be admitted that the matter is not cleared up. Bergmann595 records a case in which an Ascaris perforated the appendix and got into the peritoneal cavity.

Strümpell596 reckons among the symptoms of Trichocephalus the possibility of a “typhlitis.” On account of the marked sensitiveness of the ileo-cæcal region, Boas597 mentions the possibility of confusing it with appendicitis. Still598 regards Oxyuris as a principal cause of catarrhal affections of the appendix. Arboré-Rally599 regarded severe symptoms of appendicitis in a boy, aged 10, as due to Ascarides. In all cases of appendicitis Metschnikoff600 requires a microscopical examination to be made for eggs, and considers treatment for worms carried out otherwise as a cause of the frequency of perityphlitis. Matignon601 does not agree with this opinion, as in spite of the extraordinary frequency of intestinal worms in China, he has only seen one case of appendicitis in four and a half years, and Des Barres602 expresses himself in similar fashion. Out of twenty-one cases of appendicitis Kirmisson603 discovered the ova of Trichocephalus eighteen times and the ova of Ascarides in three of these cases; in twelve cases of enteric fever the examination for eggs was negative nine times. Moty604 considers Oxyuris to be the sole cause in his three cases of appendicitis. Girard605 ascribes to Trichocephali the rôle of more or less septic foreign bodies which may bring about the entry of intestinal bacteria into the appendix, and Triboulet606 describes a case of appendicitis which he considers was due to Ascaris. In Morkowitin’s607 case numerous Oxyuris had clearly caused the appendicitis. von Genser608 records the case of a boy, aged 5, who was operated on for appendicitis, and who passed through the operation wound a living Ascaris on the eighteenth day after the operation. In the first case communicated by Schiller609 the disappearance of the typhlitic swelling after the discharge of the Ascarides pointed to the etiological significance of the parasites, and the same obtained in a further case published at an earlier date by Czerny and Heddäus.610 In a case abstracted by Kaposi611 Trichocephali appear to have been a contributory cause in the production of the appendicitis. In a further case reported by Schiller, where the appendix was removed, it was shown that Oxyuris had given rise to a pronounced appendicular colic. In a girl, aged 13, who died from diffuse peritonitis, Schwankhaus612 found that an Ascaris had perforated the appendix. Ramstedt613 found in an extirpated appendix a whole “tangle” of Oxyuris, and believes in the possibility of their having provoked the inflammation; he recommends an examination for entozoa before the operation, without, however, after Metschnikoff’s example, substituting worm treatment for the operation. Rostowzeff614 ascribes only a minimal direct etiological significance to intestinal worms in the origin of appendicitis; in 163 cases he found worms in three instances. Wirsaladze615 expresses himself in a similar fashion. Oppe616 observed Oxyuris six times in excised appendices, and emphasizes the opinion that in appendicitis the question of a worm cure ought to be taken into consideration. Ascaris and Oxyuris, if no contra-indication exists, may be expelled, but in the case of Trichocephalus, which frequently defies all expulsive treatment, no attempt should be made, but operation proceeded to forthwith. In a case briefly reported by Hanau617 Oxyuris was undoubtedly the etiological starting-point; in a case of Galli-Vallerio618 Oxyuris and Trichocephalus. In the opinion of Ssaweljews619 in some cases of appendicitis, in addition to other causes, intestinal parasites play a prominent part. The case recorded by Nason620 is an interesting one; in this an Ascaris in the appendix became twisted with it round a coil of gut, causing obstruction. Spieler621 argues against the underestimation by many authors as to the part played by intestinal worms in producing appendicitis, although he also does not regard them as a frequent, to say nothing of an exclusive, cause of the disease. In a case recorded by Bégonin622 fifteen Oxyuris were found in the excised appendix (the mucosa showed some ulceration), and in another recorded by Putnam623 twenty Oxyuris were present in the appendix, in which there was no evidence of any change. The standpoint Schilling624 takes is to the effect that entozoa irritate the mucosa and can increase an already existing inflammation, but he considers it very questionable whether they can produce appendicitis. Blanchard625 assumes the possibility of a secondary infection arising from lesions of the mucosa produced by helminthes (Ascaris and Oxyuris). Moore626 considers Trichocephalus the excitant of the appendicitis in his case. In a second case of appendicitis recorded by Auley627 operation became unnecessary owing to the passage of the Ascaridæ. Page’s628 case is an interesting one; it was that of a man who came up for operation with a diagnosis of appendicitis. On incising the abdominal wall numerous Ascarides were found at the base of the wound, lying in cavities; even after eight days Ascarides escaped from the wound. The author assumes there was a perforation of the gut wall; it is strange that the worms were able to exist a proportionately long time in the muscular tissue. Schoeppler629 states that there is the danger of an appendicitis even after the death of an Oxyuris that has found its way into the appendix. Oui630 met with two specimens of Trichocephalus which had become embedded by their thin ends deep in the mucosa. Frangenheim631 is not in a position to pronounce any opinion as to what part intestinal parasites play in the etiology of appendicitis. In a case recorded by Kahane632 many Trichocephali were found partly free in the appendix and partly embedded in the mucosa; microscopically appendicitis was diagnosed. At a laparotomy for salpingitis Heekes633 found the appendix elongated, thickened, and containing about eleven Oxyuris without the mucosa being in any way changed. In one case Andrews634 claims Ascarides to have been the direct cause of the appendicitis. The literature dealing with this question, so important in our time, has been collected almost without any omissions, but, unfortunately, no decisive opinion as to the significance of parasites in appendicitis can be inferred from it. The vexed question whether intestinal parasites, especially Ascaris, are able to penetrate the intestinal wall is just as little finally decided. Leuckart,635 Heller,636 Mosler and Peiper,637 Henoch,638 Davaine,639 Küchenmeister,640 and Bremser641 are opposed to the idea that the healthy intestinal wall can be penetrated by intestinal worms, especially Ascarides, whilst a whole series of other authors are of the opinion that even the healthy intestinal mucosa can be perforated. Among these is numbered Mondière,642 who is of the opinion that Ascaris, by violent pressure against the mucosa, forces it so much apart that it is enabled to escape through the gap thus formed into the peritoneal cavity; this opinion is shared by v. Siebold.643 Rokitansky644 considers perforation of the gut by Ascaris as at least a rare occurrence. Gerhardt645 does not doubt that the worms can actively perforate the intestine. Cases like those of Abrault,646 Apostolides,647 Marcus648 (recorded by Perls as a valid example of “ascaridophagous” gut perforation), Wischnewsky,649 Galvagno,650 Salieri651 certainly show that perforation of the healthy gut wall cannot be denied, but at the same time that this occurrence, compared with the frequency of Ascaridæ, should be regarded as exceedingly rare. It is another matter as to whether it is possible for the worms to penetrate an intestinal wall already diseased, especially when ulcerated; a whole series of observations are in favour of this. In Lini’s652 case (fifty-six Ascarides escaped from the umbilicus of a girl, aged 7), in Gräffe’s653 (eighty Ascarides escaped from an inguinal tumour), in Nicolino’s654 (perforation of the intestinal wall with strangulated hernia), in Liesen’s655 (a living Ascaris in the peritoneal cavity in a woman suffering from a peritoneal abscess)—in these it is clear that disease processes in the intestine preceded the exit of the worms. In a case described by Boloff656 the Ascarides appear to have produced, by forming a tight coil, necrosis of the gut with perforative peritonitis. In a case recorded by Lutz657 the perforative peritonitis was without doubt provoked by Ascaris, and in one by Schiller658 the Ascaris had clearly gained access to the peritoneal cavity through a gunshot wound opening. In a case observed by Rehn659 the worm probably entered through a gangrenous portion of the intestine in a hernial sac. Broca660 is unable to determine whether in his case the intestinal perforation was primary (a worm escaped from the abdominal wound about two months after a laparotomy for suppurative peritonitis). The case reported by Lutz661 is of special interest: it was that of a young man who had shot himself in the region of the abdomen, and who died after fifteen days. At the post-mortem two Ascarides were found in the pulmonary artery; they had probably escaped from the intestine, and had gained access to the inferior vena cava. Froelich662 assumes that in his case (a boy, aged 11) the Oxyuris were able to penetrate the whole intestinal wall, but Vuillemin663 considers this improbable, and is more inclined to think that the Oxyurides penetrated the rectum at small ulcerated points, and thus gained access to the perirectal connective tissue. In females Oxyuris not only have the power of penetrating far into the sexual organs (Marro664), and perhaps causing a parasitic endometritis (Simons665), but also clearly of gaining access to the peritoneal cavity by way of the tubes, as is to be assumed in the case recorded by Kolb666 (that of a woman, aged 42, in whom post mortem nodules were found over the peritoneum of Douglas’s pouch, in which the pressure of encapsuled Oxyuris could be demonstrated), in that reported by Chiari667 (adult Oxyuris in Douglas’s pouch) and by Schneider668 (an Oxyuris encapsuled in the pelvic peritoneum). Sehrt’s669 case is worthy of attention; in this an abscess was found in the omentum with numerous Ascaris ova in the pus and a nodular lesion of the peritoneum, with Ascaris ova encapsuled in the nodules. Massive accumulation of Ascarides may give rise to a complete occlusion of the gut. Such an occurrence is not so surprising as might be thought when one reflects that the number of Ascarides in one individual may amount to several hundreds. For instance, one boy evacuated within a single day 600 Ascarides (Fauconneau-Dufresne670) and within three years 5,126 worms. In the case recorded by Tschernomikow671 a boy, aged 2 1/2, evacuated during a day 208 worms, partly through the stomach, partly through the intestine. Coil-formation of such masses of Ascarides renders possible not only constipation, but also complete obstruction with symptoms of ileus, as shown by the five cases quoted by Mosler and Peiper,672 as well as from observations made by Raie,673 Schulhof,674 Rehberg,675 Rocheblave,676 Heller,677 Leichtenstern,678 Huber,679 and Wilms.680 In two cases of Black681 and Parkinson682 the intestinal obstruction was caused by a coil of tapeworms.