INTRODUCTION.

The aim of the present volume is to give an account of the animal parasites of man, the number of which is very large. The Protozoa that infest man are very important, and the literature relating to them and to the treatment of the diseases that they produce is very extensive. All that can be done in this Appendix is to give a very brief outline of some of the more recent and approved methods of treatment, for further details of which the reader should refer to standard medical works, among which the following are noteworthy:-- Allbutt and Rolleston (1907): “System of Medicine,” vol. ii, part 2, “Tropical Diseases and Animal Parasites,” London. Castellani and Chalmers (1913): “Manual of Tropical Medicine” (second edition), London. Laveran and Mesnil (1912): “Trypanosomes et Trypanosomiases” (second edition), Paris. Manson (1914): “Tropical Diseases” (fifth edition), London. Mense (1905): “Handbuch der Tropenkrankheiten,” Leipzig. Ross (1911): “The Prevention of Malaria,” London. Scheube (1910): “Die Krankheiten der Warmen Länder,” Jena. References to the treatments tried in many parasitic diseases can be found in the _Sleeping Sickness Bulletin_ and _Kala-azar Bulletin_, both now superseded and greatly extended in scope in the _Tropical Diseases Bulletin_, published by the Tropical Diseases Bureau, Imperial Institute, London, S.W. The following diseases, due to protozoa and allied forms, are discussed:-- I. Amœbic Dysentery. II. Trypanosomiases. III. Flagellate Diarrhœa and Dysentery. IV. Leishmaniases--Kala-azar and Oriental Sore. V. Spirochætoses--Relapsing Fevers, Yaws, Syphilis and Bronchial. VI. Malaria. VII. Balantidian or Ciliate Dysentery. I.--AMŒBIC DYSENTERY. Amœbic dysentery, due to _Entamœba histolytica_ (see pp. 34–41), is present throughout the tropical world and also occurs in temperate zones. Walker and Sellards[429] (1913) conducted important experiments with amœbæ on prisoners in the Philippine Islands. They showed experimentally that cultural amœbæ are non-pathogenic. As regards experiments with _Entamœba coli_, after feeding to twenty individuals they concluded that _E. coli_ is a parasite of the human intestine but non-pathogenic and non-culturable. In a third series of experiments, after feeding with motile _Entamœba histolytica_, tetragena cysts were found in the stools later; when tetragena cysts were administered, motile _E. histolytica_ were present in the subsequent stools. Some of the histolytica cases developed dysentery after a time. They lay stress on the necessity for the frequent examination of stools in order to detect carriers. The incubation period of entamœbic dysentery is usually long. [429] _Philippine Journ. Sc._, B, viii, p. 253. With regard to the symptomatology of amœbic dysentery, Castellani and Chalmers distinguish four types--the acute, chronic, latent, and mixed types. The acute type has an abrupt onset; pain is felt in the lower part of the abdomen, and the motions, rarely exceeding thirty daily, are accompanied by much griping and straining. Blood and mucus are present in the motions, and occasionally greyish material, consisting of leucocytes, mucus, Charcot-Leyden crystals, amœbæ, and bacteria, sometimes with particles of tissue. Nausea and vomiting may occur. Digestion is usually deranged. The abdomen is sunken, the liver and spleen are normal, but tenderness is felt along the course of the large intestine. The urine may be diminished in quantity. The chronic type may succeed the acute, or appear like diarrhœa, the motions being fæculent and containing mucus. Between exacerbations, constipation may occur. The number of motions may only be twelve to fourteen per diem. Gangrenous complications may occur at any time, and chronic dysentery may persist for many years. The latent type is important, as the patients, though free from dysenteric symptoms, harbour amœbæ and act as parasite carriers. The latent condition may lead to acute attacks or to liver abscess. The mixed type occurs where amœbic and bacillary dysentery are combined. There is much fever, nausea, and vomiting. The motions are numerous and often very offensive. _Treatment._--The most modern method of treatment, due to Leonard Rogers, is by emetine. According to Castellani and Chalmers, it is well to relieve griping and straining by either a hypodermic injection of morphia or by small enemata of 40 minims of laudanum in 1 oz. of mucilage of starch or by using 1/4 gr. morphia or 1/4 gr. codeine suppository. A dose of castor oil (ʒiv to ʒvi) with or without a few minims of liquor opii sedativus or a few doses of saline may be given during the first twenty-four hours. After the castor oil has acted or simultaneously, emetine treatment should be commenced; 1/3 to 1/2 gr. of emetine hydrochloride, dissolved in sterile normal salt solution, is injected hypodermically three times a day for two or three days. If emetine cannot be obtained, 5 gr. doses of ipecacuanha every three to six hours in the form of membroids, or as pills coated with salol or keratin, can be substituted. After acute symptoms have disappeared, intestinal irrigations once or twice daily, on alternate days, are useful. A solution of tannic acid (3 to 5 per 1,000) or of quinine bihydrochloride varying in strength from 1 in 5,000 to 1 in 750 is very slowly injected in quantities of 1/2 to 3 pints by means of a long, soft, rectal tube. For gangrenous dysentery Castellani and Chalmers state that appendicostomy, with irrigation of the whole lower bowel with quinine lotion (1 in 1,000) or collargol (1 in 500), is the only chance. The use of emetine should be continued in smaller doses after the dysenteric symptoms have ceased, in order to prevent relapses and as a possible safeguard against the development of a liver abscess. Recently (July, 1914), Dr. W. E. Deeks[430] has given an account of his successful procedure in dealing with the dysenteries in the Ancon Hospital, Panama Canal Zone, of which medical clinic he is the chief. With regard to amœbic dysentery he advocates: (1) Rest, to increase the patient’s resistance; (2) a generous milk diet, which is practically all absorbed before it reaches the large bowel; (3) saline or plain water irrigations, one to three daily; (4) the administration of bismuth sub-nitrate in heroic doses; 180 gr. is given mechanically suspended in about a tumbler of plain or effervescent water every three hours, day and night in severe cases, only lessening the amount when improvement takes place. Mechanical suspension in a large quantity of water is essential. When the stools begin to decrease in number and the tongue becomes clean, the number of doses is reduced to three or four daily. In very chronic cases one or two doses daily for a month after convalescence are recommended. [430] _Annals Trop. Med. and Parasitol._, viii, pp. 321, 353. In exceptional cases of extreme emaciation and exhaustion, showing marked toxic symptoms, surgical treatment is necessary, and at Ancon a wide, open cæcostomy is performed. The treatment of dysentery with bismuth sub-nitrate has been in use for some years at Ancon. Latterly, a combined treatment by hypodermic injections of emetine and bismuth sub-nitrate by the mouth has been used, and the authorities there consider that it is better to combine the two drugs rather than use each singly. Emetine probably acts as a direct poison to the amœbæ, while the bismuth probably acts by destroying the symbiotic organisms necessary for their growth. With regard to preventive measures, all drinking water should be filtered and boiled, and uncooked vegetables and salads avoided. Scrupulous care with regard to personal cleanliness, and avoidance of touching the mouth or lips after contact with dysenteric patients, are essential. Isolation of parasite carriers is of great use in combating and controlling outbreaks of amœbic dysentery. The pollution of soil and water must be rigorously prevented. Liver abscess due to amœbæ must be localized by exploratory punctures, and then opened and drained. Intramuscular injections of emetine hydrochloride, 1/6 gr. to 1/2 gr. every day, will reduce the temperature and afford relief. Oral endamœbiasis has been recently investigated by Bass and Johns, Smith and Barrett and colleagues (see pp. 43, 733). It responds to treatment with emetine, and 1/2 gr. of emetine hydrochloride administered hypodermically each day is of service. Rinsing the mouth with a solution of fluid extract of ipecacuanha is also useful. Rogers[431] (1915) recommends a combined treatment of emetine and streptococcal vaccines for pyorrhœa alveolaris. [431] _Ind. Med. Gazette_, April, 1915, l, p. 121. II.--TRYPANOSOMIASES. The human trypanosomiases are those occurring in Africa, due to _Trypanosoma gambiense_ and _T. rhodesiense_ and spread by Glossinæ, and that due to _T. cruzi_, occurring in South America and spread by the Reduviid bugs, _Triatoma_ spp. These trypanosomiases present different clinical features and are best dealt with separately. African Sleeping Sickness. Sleeping sickness, due to _Trypanosoma gambiense_ or varieties thereof, was first reported from West Africa and is now present, not only along the West Coast and in Nigeria, but throughout the Congo basin into Uganda, north of which it exists in the Bahr-el-Ghazal province of the Sudan. In Nyasaland and Rhodesia a more virulent but less widely distributed disease is produced by _Trypanosoma rhodesiense_. There is a general similarity between the two diseases, and the symptoms as described by the leading authorities agree in the main. The malady due to _T. rhodesiense_ has been known only since 1910 and the differences between the malady due to it and to _T. gambiense_ will be indicated. The course of the disease may be roughly divided into three stages, the incubation, the febrile or glandular, and the cerebral stage. The exact incubation period is not known with certainty in man. Probably, in most cases, it does not exceed two to three weeks, but disease signs may not appear for months. The bite of the Glossina gives rise to local irritation, which may be overlooked. The irritation usually subsides in the course of a few days. The febrile, or glandular stage, is marked by attacks of fever of an intermittent type. An erythematous eruption is often found on Europeans. This rash begins as irregularly shaped pinkish patches which clear in the centre until a ring is produced. It may occur on any part of the body but is more frequent on the trunk. A typical symptom is the enlargement of one or more of the lymphatic glands, especially those of the neck. A general, deep hyperæsthesia, known as Kerandel’s sign, may be present, and if the patient strikes a limb against any hard object, a feeling of acute pain is felt, the sensation being slightly delayed. As repeated attacks of fever increase, the patient may become anæmic. The febrile stage may last for years, and cure may be brought about at this phase, but frequently, after the febrile stage has lasted some time, the cerebral stage is reached. Tachycardia is also a symptom. Auto-agglutination of the red blood corpuscles is another useful characteristic, as it is said to occur rarely in other tropical diseases, but some workers doubt its value. The cerebral, or true sleeping sickness stage is marked by a great change in the habits of the victim, who becomes apathetic and dull, careless and dirty in habits, and begins to experience difficulty in walking. Tremors of varying degrees of severity are common and the gait is peculiar. There is usually fever with rise of temperature from 100° F. to 104° F. in the evening, becoming subnormal in the morning. For some days before death, it often becomes permanently subnormal. Congestion and œdema of the lungs, with patches of pneumonia, are not infrequently observed before death. The torpor gradually deepens, and the patient loses flesh. Frequently the lips swell and saliva dribbles. The patient usually becomes comatose and death ensues. Mania and delusions, and psychical and physical symptoms resembling those found in general paralysis of the insane, sometimes occur, and death may arise from secondary complications such as pneumonia or dysentery. Pathologically, the disease seems to consist of a chronic inflammation of the lymphatic system. The trypanosomes reach the lymphatic glands which become inflamed, and gradually invade the blood and the cerebrospinal fluid. Sooner or later, as a result of the lymphatic disease, changes occur in the membranes and substances of the brain and spinal cord. There is round-celled perivascular infiltration of the pia-arachnoid of the brain and spinal cord. These changes cause compression of the blood-vessels, and so lessen the supply of blood to the brain and spinal cord. Further changes in the latter organs result in the production of the symptoms that have given the disease the name of “sleeping sickness.” The disease due to _Trypanosoma rhodesiense_ generally runs a more rapid course than that due to _T. gambiense_. The torpor and sleepiness may not be obvious or be very slight, and the enlargement of the lymphatic glands of the neck also may not be marked or may appear to be absent. The duration of the disease often appears to be from three to six months. Treatment is only of use if commenced in the earlier stages of the disease. The substances of most value so far are arsenic in the form of atoxyl (introduced by Wolferstan Thomas in 1905) and antimony in the form of tartar emetic. Castellani and Chalmers and Manson recommend treatment by combining the use of both substances. The combined treatment is recommended not only because both substances have been proved of service independently, but also because certain strains of trypanosomes resistant to arsenic are known, and trypanosomes can develop a resistance to arsenic. Such forms, that would not be affected by the atoxyl, are left open to attack by the antimony salt. Daniels also recommends combined arsenic and antimony treatment, and (1915) uses atoxyl and antiluetin. Atoxyl is best given intramuscularly in 10 per cent. solution in sterile normal saline solution. Galyl is also said to have given good results. Castellani and Chalmers recommend: (1) Manson’s method of administration of atoxyl, viz., 2 to 3 gr. of atoxyl are given by intramuscular injection every third day for at least two years; or (2) Broden and Rodhain’s method, 7-1/2 gr. of atoxyl by intramuscular injection every fifth day. For the combined therapy by atoxyl and antimony they recommend the following:--“An atoxyl injection (3 gr.) is given every third day or 7-1/2 gr. every fifth day, and sodiotartrate of antimony (Plimmer’s salt) is administered daily, 2 gr. dissolved in a large quantity of water (2 pints) by the mouth or by the rectum. Tartar emetic, however, is best given by intravenous injections, using solutions of 1 in 100 or 1 in 1,000. The dose of the drug to be given is 5 to 10 cg. per injection. It is important that none of the fluid of the injection should escape into the surrounding tissues, as a violent inflammation may result. These injections should be administered monthly on ten consecutive days for a long period.” Macfie and Gallagher (1914) injected 6 gr. of atoxyl intramuscularly every week in cases infected with _T. nigeriense_ in the Eket district of Southern Nigeria. Large doses of atoxyl were often said to cause distressing results such as optic atrophy, and when the onset of such occurred the drug was usually discontinued. However, Daniels[432] (July, 1915) points out that eye troubles, such as iridocyclitis, are symptoms of trypanosomiasis. [432] _Journ. Trop. Med. and Hyg._, xviii, p. 157. Other arsenical preparations such as soamin and arsenophenylglycin have been used, but less successfully than atoxyl. Fowler’s solution, well diluted, has been given by the mouth when treatment by injection was not possible, the doses commencing with 5 minims and increasing to 15 minims. Salvarsan and neo-salvarsan have also been tried for sleeping sickness. Plimmer recommended powdered antimony suspended in sterile olive oil. Ranken used precipitated metallic antimony in normal saline solution injected intravenously. Laveran and Thiroux have recommended a combined treatment of atoxyl and an inorganic salt of arsenic such as orpiment. The orpiment is given as pills, in doses of 2 gr. of orpiment two or three times daily. Opium is added to the orpiment to prevent diarrhœa. This treatment is said to have been used in man with good results. _Trypanosoma rhodesiense_ seems less amenable to treatment than _T. gambiense_. The main preventive measures seem to lie in segregation of the sick in areas not infested with Glossinæ, and in measures against these flies, such as bush clearing and destruction, to some extent, of _proved_ reservoirs in big game. South American Trypanosomiasis. The chief clinical features of the trypanosomiasis occurring in Brazil have already been indicated (see p. 87). With regard to treatment, according to Castellani and Chalmers the indications are the same as those for African trypanosomiasis, together with treatment for hypothyroidism. Preventive measures are directed against the Reduviid bug, _Triatoma megista_, that transmits the disease. The bugs occur in numbers in the cracks of the houses of the poor of Minas Geraes, and may be destroyed by sulphur fumigation, lime-washing or whitewashing. III.--FLAGELLATE DIARRHŒA AND DYSENTERY. The chief causal agents are _Trichomonas hominis_ (_T. intestinalis_), _Chilomastix_ (_Tetramitus_) _mesnili_ and allied organisms (see pp. 54 to 57), and _Lamblia intestinalis_ (see pp. 57 to 60 and Appendix pp. 734 to 736). These parasites and the associated diarrhœas occur in temperate as well as in warm climates. Probably some of the diarrhœas in India are thus caused. The same, or similar parasites occur in various Muridæ, especially rats and mice, which may act as reservoirs. (i) Mello-Leitao[433] (1913), writing from Rio de Janeiro, states that there is a primary flagellate dysentery, due to _Trichomonas intestinal_is (Leuckart) and to _Lamblia intestinalis_ (_Lambl_), either separately or in combination. He considers it a benign disease, and the most frequent form of dysentery in young children. Trichomonas and Lamblia were found to be pathogenic to children under 3 years of age. [433] _Brit. Journ. Children’s Diseases_, x, p. 60. Escomel[434] (1913) collected 152 cases of dysentery in Peru due solely to Trichomonas. Examination of the reservoirs containing the water used for drinking purposes showed the presence of Trichomonas. After the reservoirs were cleaned no more Trichomonas was found and the cases of dysentery ceased. [434] _Bull. Soc. Path. Exot._, vi, p. 120. Brumpt[435] (1912) described a colitis due to _Trichomonas intestinalis_ in a patient returned from Tonkin. [435] _Ibid._, v, p. 725. Cases of infection by _Chilomastix_ (_Tetramitus_) _mesnili_, with colitis or dysenteric symptoms, are recorded by Brumpt (1912) from France, and by Nattan-Larrier[436] (1912) from the Ivory Coast respectively. [436] _Ibid._, v, p. 495. Marques da Cunha and Torres[437] (1914) describe five cases of chronic diarrhœa in Brazilian children due to the _Chilomastix_ (_Tetramitus_). [437] _Brazil Medico_, xxviii, p. 269. Gäbel[438] (1914) described a case of seasonal diarrhœa contracted in Tunis and caused by a Tetramitid parasite which he named _Difämus tunensis_, as the discoverer considered that it lacked an undulating membrane in its large cytostome. [438] _Arch. f. Protistenkunde_, xxxiv, p. 1. Derrieu and Raynaud[439] (1914) record a case of chronic dysentery in Algeria due to a Trichomonad possessing an undulating membrane and five free flagella. The parasite was named _Hexamastix ardindelteili_, but the generic name _Hexamastix_ is pre-occupied. Chatterjee’s _Pentatrichomonas bengalensis_ (1915) is possibly the same organism. [439] _Bull. Soc. Path. Exot._, vii, p. 571. _Treatment._--Escomel (1913), finding ipecacuanha and calomel useless, recommends turpentine for Trichomonad dysentery. Two to 4 gr of essence of turpentine in an emulsion are given by the mouth, and enemata containing 15 to 20 drops of turpentine emulsified in the yolk of an egg to which is added a little water and tincture of opium. Derrieu and Raynaud found this treatment effective in Algeria. Smithies[440] (1912) reports two cures of cases of severe dyspepsia, in which Trichomonads were found in the stomach contents, after administration of a single dose of 50 to 60 gr. of thymol, given at bed-time, together with 2 gr. of calomel, and followed by an ounce of Carlsbad salts in the morning. The patients came from the Southern United States, and had been in the habit of drinking unfiltered surface water in the localities in which they lived. Mello-Leitao[441] used magnesium sulphate and water or milk diet. Sometimes enemata of collargol (1 per cent.) or electrargol were required. Rosenfeld recommended calomel. Methylene blue has also been tried. Recently, Escomel[442] (1914) recommends enemata of an aqueous solution of iodine (1 per 1,000) and farinaceous diet. Lynch[443] (1915), working in South Carolina, recommends a mouth wash of saturated solution of bicarbonate of soda three times daily in oral infections. A similar solution was used as a douche in vaginal trichomoniasis. [440] _Amer. Journ. Med. Sci._, cxliv, p. 82. [441] _Brit. Journ. Children’s Diseases_, x, p. 60. [442] _Bull. Soc. Path. Exot._, vii, p. 657. [443] _Amer. Journ. Trop. Dis. and Prevent. Med._, ii, p. 627. Stiles (1913) points out that when amœbæ or flagellates are found in a large percentage (10 to 40, or even 60) of the members of a community, means should be taken to improve the methods for the disposal of the dejecta, so that the food supply may be carefully protected against fæcal contamination. Cysts of the parasites may be air-borne or conveyed to food on the bodies of house-flies. (ii) _Lamblia intestinalis_ in man may cause diarrhœa with dysenteriform stools. The diarrhœa may be of a chronic recurrent character. The flagellate, or a variety of it, is fairly common in the digestive tract of rats and mice. Mathis[444] (1914) gives an interesting account of cases in Tonkin. In a child, aged 3, the stools were at first glairy and blood-stained, containing many encysted Lamblia. The child’s home was infested with mice. In another case, the house of the patient harboured numerous rats. [444] _Bull. Soc. Med. Chirurg. Indo-Chine_, v, p. 55. According to Mathis, prognosis is favourable, but emetine hydrochloride is without action on Lamblia. Prowazek and Werner[445] (1914), however, state that emetine will act upon the flagellates, but not upon the cysts. They recommend uzara (two tablets, three times daily) and extract of male fern as useful in certain cases. Martin Mayer (1914) found emetine hydrochloride successful in a case in the Hamburg Seamen’s Hospital, but Assmy (1914) points out that a suitable diet and daily doses of magnesium sulphate are sufficient, in his experience, to effect an improvement, and he doubts the specific action of emetine. Escomel (1914) recommends milk diet, then calomel succeeded by castor oil. [445] Beihefte z. _Arch. f. Schiffs- u. Tropen-Hyg._, xviii, 5, p. 155. According to Noc, Lamblia may also be water-borne. Healthy carriers of Lamblia cysts are known. Food should be protected from being soiled by rats and mice. IV.--LEISHMANIASES. A. *Kala-azar.* (i) _“Indian” Kala-azar due to_ Leishmania donovani. Indian kala-azar due to _Leishmania donovani_ is a very fatal disease with a rate of mortality varying from 70 to 98 per cent. of the cases. The incubation period is very variable and the early symptoms not well defined. The incubation period seems to range from three weeks to several months after exposure to infection. The onset seems to commence with a rigor and attack of irregular, remittent fever, which may show two remissions per day in a four-hourly temperature chart. Rogers considers the daily double remission almost diagnostic. The duration of this first attack is from two to six weeks. The spleen and liver enlarge, especially the former, and are painful and tender. Towards the end of the time the temperature declines and the first period of the disease ends. After this period an apyrexial interval occurs, which, after some weeks, ends in an attack of fever resembling the first. Periods of pyrexia and apyrexia alternate. Anæmia commences and asthenia appears and deepens steadily. The patient is now thin and wasted, the abdomen much swollen and protuberant, the ribs show clearly, the limbs are wasted and skin and tongue darker than normal. In Europeans the skin is of a remarkable earthy hue, and in natives of India darker than normal, approaching black. Intestinal disturbances, often in the form of very obstinate and intractable diarrhœa or dysenteric attacks, are common. Papular eruptions often appear, particularly on the thighs; hæmorrhages also may occur. The disease lasts for periods varying from seven months to two years, and usually ends fatally. Treatment, unfortunately, has not been very successful up to 1915. Manson has reported two cases of cure by intramuscular injections of atoxyl daily or every other day in doses of 3 gr. Rogers has advocated large doses of quinine, 60 to 90 gr. daily until the temperature falls and then 20 gr. daily. Castellani and Chalmers consider the best results are obtained by large doses of quinine given intramuscularly, supplemented by a course of quinine cacodylate injections or atoxyl injections. Tartar emetic should be tried (see pp. 627, 629), especially as L. Rogers (July, 1915) has had promising results in ten cases. Castellani (1914) and Mackie (1915), have also had successful results. Leishman states that the administration of red bone-marrow, either raw or in the form of tablets, may be beneficial. Good nursing and careful diet are essential, and diarrhœa or dysentery must receive the appropriate treatment. With regard to preventive measures, the extermination of bugs and other biting insects seems to be of most service. Domestic and personal cleanliness is of great importance. Patients should be segregated. It would probably be as well if houses in which many cases of kala-azar occurred were destroyed. Dodds Price, in Assam tea gardens, moves the coolie lines 300 to 800 yards from old infected ones, with satisfactory results. (ii) _Infantile Kala-azar due to_ Leishmania infantum. This malady is found among children, rarely in adults, along the Mediterranean littoral. The disease commences insidiously and is often unrecognized until some intestinal disturbance occurs. The spleen is then found to be somewhat enlarged, and the case has often been regarded as one of malaria. The child becomes anæmic, suffers from diarrhœa, alternating with constipation, and has attacks of irregular fever. The spleen continues to enlarge and protrudes from under the cover of the ribs. Hæmorrhages from the nose and gums and into the skin occur. Anæmia and wasting set in. The abdomen then becomes very enlarged. The child becomes much less active both physically and mentally, and looks prematurely old. Death often occurs from exhaustion, though some cases of spontaneous recovery are known. Treatment up till recently has been unsatisfactory. Some of the remedies tried, as quoted by Castellani and Chalmers, are 15 cg. doses of atoxyl, benzoate of mercury (2 to 4 mg. as a daily injection), thiarsol (5 to 15 mg. by subcutaneous injection), salvarsan, etc. Recently Cristina and Caronia (1915)[446] have given repeated intravenous injections of 1 per cent. aqueous solution of tartar emetic, the dose varying from 2 to 10 cg. The treatment in various cases has lasted from 15 to 40 days. [446] _Bull. Soc. Path. Exot._, viii, p. 63. Prophylactic measures seem to lie in the destruction of infected dogs and diminishing the breeding of fleas (see p. 111). B. *Oriental Sore, due to Leishmania tropica.* Oriental sore, known under many other names (see p. 107), is a local infection of the skin due to _Leishmania tropica_. The incubation period varies from a few days to some weeks, or even months, and then one or several small itching papules appear. Each spot becomes red and shotty, the papules increase slowly in size and the surface becomes covered with papery scales. After a variable time, usually not exceeding three to four months, ulceration occurs and a yellowish secretion is exuded that soon dries into a scab. Under the scab ulceration continues by erosion of the edges, and subsidiary sores arise around the parent ulcer and usually fuse with it. Healing commences after six to twelve months. Granulation begins at the centre and spreads outwards, and when healing is complete, a depressed, whitish or pinkish scar remains. Many treatments for Oriental sore have been devised but do not seem particularly satisfactory. Castellani and Chalmers state that the scabs should be removed by boracic acid fomentations, and the ulcers thoroughly disinfected once or twice daily with a 1 per 1,000 solution of perchloride of mercury, after which an ordinary antiseptic ointment is applied. The use of permanganate of potash has been advocated both by French and English doctors. Both large and small sores can be treated. The patient’s skin around the sore is protected by a thick layer of vaseline, and the surface of the ulcer powdered with potassium permanganate, which is kept in position by a pad of gauze and a bandage. The treatment is said to cause great pain for six to eight hours, but at the most, three treatments are necessary before the sore becomes a simple ulcer, well on the way to healing. The permanganate may also be used in ointment. Excision of the ulcer when small is advisable when the site of the ulcer permits of this. According to Manson, reports on treatment by radium, salvarsan and carbon dioxide snow are decidedly promising. Mitchell (1914)[447] reports favourably on the use of carbon dioxide snow in the form of a pencil, in India. In Brazil several workers (1914) record successful results from the intravenous injection of a 1 per cent. solution of tartar emetic in distilled water. Low (1915) has successfully treated a case by direct local application of tartar emetic. Row (1912) has treated cases of Oriental sore by inoculation of killed cultures of the causal organism. [447] _Journ. Roy. Army Med. Corps_, xxiii, pp. 440–446 (see _Trop. Dis. Bull._, v, No. 5, p. 276). As the disease is very contagious, the slightest wound, and any insect bite, should be thoroughly disinfected with 5 per cent. carbolic acid or iodine. Destruction of bugs, lice, and other biting insects should be enforced. As dogs may contract the disease (see p. 108), it is well not to allow them in the house and not to encourage undue contact with them. _Naso-oral Leishmaniasis_ (_Espundia_) _due to_ Leishmania tropica. This form of Leishmaniasis has been reported from South America and recently by Christopherson[448] (1914) from the Sudan. In South America it is often called Espundia, also Buba and Forestal Leishmaniasis. The primary lesion is found usually on the forearms, legs, chest or trunk. This ulcer is of the Oriental sore type, and after some months, or even as long as two years, heals up, leaving a thick scar. While the ulcer is open, or more often after it has healed, lesions appear on the mucosa of the mouth and nose. The hard and soft palate, gums and lips all may be attacked. The mucosa of the nose is usually attacked and the cartilages become destroyed, producing great deformity. In bad cases the pharynx and larynx may become infected. [448] _Annals Trop. Med. and Parasitol._, viii, p. 485. Till recently it was believed that treatment was of little use unless the case could be investigated early. Escomel considered that if the primary cutaneous lesion was excised or destroyed, further progress of the disease was prevented. When lesions have appeared on the mucosa of the mouth or nose, little could be done. The ulcers might be cauterized and mild antiseptic mouth washes used. In 1913 Vianna, working in Brazil, introduced treatment by tartar emetic, which is now becoming more widely known and proving efficacious. Carini[449] (1914) applies it thus. Tartar emetic (that is, potassium antimonyl tartrate) in 1 per cent. aqueous solution is introduced slowly into a vein, such as the vein at the bend of the elbow, in doses of 5 to 10 c.c. daily or on alternate days according to the tolerance of the patient to the drug. Eighteen to forty injections have been used. In some of the memoirs on the subject, the drug is referred to as antimony tartrate. [449] _Bull. Soc. Path. Exot._, vii, p. 277. The course of the disease is chronic and may last for twenty to thirty years, death usually resulting from some intercurrent disease. At present the actual transmitter of Espundia is not known with certainty. Various sand-flies (Simulidæ) have been suspected of transmitting the disease, though so far proof is wanting. It has also been suggested that the natural food sources of some Simulidæ known to bite man, namely, certain snakes[450] and lizards,[451] are possible reservoirs of the disease. [450] Lindsay (1914), _Trans. Soc. Trop. Med. and Hyg._, vii, p. 259. [451] Sergent (Ed. and Et.), Lemaire and Senevet (1914), _Bull. Soc. Path. Exot._, vii, p. 577. Prophylactic measures would seem to consist in the immediate disinfection of insect bites by tincture of iodine, and by avoidance of areas known to be infested with snakes and lizards, and insects that prey on them and man indifferently. The destruction of the primary lesion as soon as detected is essential, and the isolation of advanced cases of the disease seems advisable. V.--SPIROCHÆTOSES. A. *Relapsing Fevers.* The relapsing fevers of Europe and of America, due to _Spirochæta recurrentis_ and _S. novyi_ (probably a race of _S. recurrentis_), present much the same symptoms, which differ in some respects from those due to _S. duttoni_, the excitant of “tick” or “relapsing” fever in Africa (see pp. 116–122). The incubation period of _S. recurrentis_ varies from two to twelve days, during which time a very slight indisposition may be noticed. The onset is usually sudden, with severe headache, pains in the back, limbs and stomach and a feeling of weakness. There is a rise of temperature to 103° F. or 104° F., and the temperature continues high till about the sixth or seventh day. The skin is yellowish, hot and damp; a rash, disappearing on pressure, may occur on the trunk and legs, nausea is always present and thirst is usual. The liver and spleen both enlarge. The number of respirations and pulse-rate become increased. On the sixth or seventh day a crisis occurs. There is violent perspiration, with a rapid fall of temperature, pulse and respiration become normal and the patient sleeps and awakes better. Improvement continues for some days, and recovery may ensue, but usually about the fourteenth day relapse occurs, lasting usually three or four days. A second relapse is unusual. Numerous complications are known, _e.g._, bronchitis, pneumonia, diarrhœa and dysentery. With regard to treatment, the specific appears to be salvarsan. Castellani and Chalmers recommend salvarsan administered intravenously. Intramuscular inoculations (for example, into the buttock) of a suspension of “606” in oil can also be given. The drug is very efficacious, but large doses should not be given. An intravenous injection of 4 or 5 gr. does not give rise to unpleasant symptoms but is sufficient to effect a cure. The incubation period for the American form of the disease is at least five to seven days, and the first attack lasts about five to six days. The treatment is by salvarsan as detailed previously. As relapsing fever is spread by body lice and possibly by bugs, preventive measures are directed against these insects. Strict cleanliness of person, clothing, bedding and dwellings is essential. Furniture, _e.g._, wooden bedsteads, liable to harbour such insects should not be used. The principal and best-known relapsing fever of Africa is that excited by _Spirochæta duttoni_, and transmitted to man by ticks, chiefly _Ornithodorus moubata_. The incubation period is usually about seven days but may be longer. The patient is dull and lethargic, perspires freely and is often constipated. The temperature rises to 103° F. or 105° F., there is headache, pains in the back and limbs, general chilliness and great pain in the region of the spleen, which often enlarges. The symptoms become worse, there is a fall of temperature with improvement in the morning, and a rise, with increase of pain, in the evening. Spirochætes are now found in the blood in greater numbers. The symptoms last three to four days and end in a crisis with profuse sweating and fall of temperature below normal. The day before the crisis there is a pseudo-crisis, when the temperature falls but there is no improvement. The patient is left weak and tired. Recovery may follow, but more usually a relapse occurs. The intermission period varies; five to eight days is common. The symptoms of the relapses are like those of the first attack. The number of relapses varies, five to eleven may occur. The treatment recommended is by salvarsan, as for the European relapsing fever. With regard to prophylaxis, localities where ticks abound must be avoided and the parasites themselves destroyed. Native huts should be avoided. Mosquito nets, a bed well off the ground and the use of night lights are advised by Manson to avoid attacks by ticks, which are often nocturnal in their habits. In North Africa (Algeria, Tunis, Tripoli, Egypt), and sometimes in the Anglo-Egyptian Sudan, a spirochætosis due to _S. berbera_ occurs. According to Castellani and Chalmers, the incubation period varies somewhat. The fever reaches its height during the first twenty-four hours, and afterwards shows a morning remission. Jaundice is often absent, but there may be hepatic tenderness and splenic enlargement. One or two relapses usually occur. The treatment is on the same lines as for the other spirochætal fevers. Sergent and Gillot[452] (1911), working at the Institut Pasteur of Algeria, have had good results by using injections of salvarsan in doses of 0·75 to 1·0 cg. per kilogramme weight of the patient. The prophylactic measures are directed against lice and other biting insects. Personal cleanliness is most necessary. [452] _Bull. Soc. Path. Exot._, iv, p. 440. In Asia, a relapsing fever, due to the spirochæte named _S. carteri_ by Manson in 1907, producing a mortality of about 18 per cent., occurs. The symptoms have a general resemblance to those produced by _S. recurrentis_, but on the fall of temperature to subnormal on the sixth or seventh day, when profuse perspiration and polyuria occur, instead of improvement following, the patient often becomes collapsed, with a clammy skin and feeble pulse. Improvement is slow. The first relapse occurs about the fourteenth day of the attack, when the temperature may be higher than for the first attack. There are seldom more than four relapses. The treatment is by salvarsan, of which doses of not more than 5 gr. intravenously should be given. Sudden heart failure being common, Castellani and Chalmers state that cardiac stimulants should be given. Prophylaxis is the same as for European relapsing fever. B. *Yaws or Frambœsia tropica.* Yaws is essentially a tropical disease, though it is found in the tropical and subtropical zones in all parts of the world, except in the mountains and cold districts. In 1905, Castellani found the causal organism, _Treponema pertenue_ (sometimes called _Spirochæta pertennis_) (see p. 127). The disease shows three periods: (1) The primary stage, consisting of the development of the primary lesion or papule, which is usually extragenital. The papule dries into a crust beneath which an ulcer lies. (2) The secondary or granulomatous stage, which commences from one to three months after the primary lesion is first seen. It consists of a general eruption of small papules, some of which enlarge and become granulomatous nodules covered with a yellowish crust. They are common on the limbs and face. (3) The tertiary stage, in which deep ulcerations and gummatous nodules appear. Any of the tissues may be involved. Osseous lesions may occur. The disease does not appear to be hereditary; it is usually spread by contact. The best treatment appears to be by salvarsan or neo-salvarsan. Castellani and Chalmers recommend intramuscular and intravenous injections. For intramuscular injection an alkaline or neutral solution of the drug is preferable, or a suspension of the drug in oil may be used. The dose varies from 0·3 to 0·5 gr according to the age and sex of the patient. For use intravenously, a slightly smaller dose is required. Galyl is also being used. In countries where frambœsia is endemic, slight skin abrasions should be carefully treated with antiseptics. Yaws patients should be isolated till cured, and their dwellings and personal possessions disinfected. C. *Syphilis.* Syphilis, due to _Treponema pallidum_ (sometimes called _Spirochæta pallida_), is prevalent throughout the tropics as well as in temperate zones. The disease is amenable to treatment by salvarsan and neo-salvarsan, for administration of which see relapsing fever and yaws. Galyl is also being used with favourable results. Lambkin’s mercury cream has been found useful in treating numerous cases in Uganda. The life-history of the parasite is given on p. 124, and further medical details hardly come within the purview of this book. D. *Bronchial Spirochætosis.* Bronchial spirochætosis, due to _Spirochæta bronchialis_ (see pp. 122, 739) is probably of wide distribution in the tropics. The spirochætes have been found in cases of chest complaints, especially those with bronchitic symptoms. The disease may be suspected in atypical cases of pneumonia and bronchitis, and may be mistaken for incipient phthisis. Chalmers and O’Farrell[453] (1913), writing from Khartoum, recommended rest in bed, good food and ventilation, coupled with treatment by arsenic in some form, preferably associated with glycerophosphates. These may be given by the mouth, or intramuscularly as an injection of:-- Sodium cinnamate 0·05 grm. Sodium cacodylate 0·10 " Sodium glycerophosphate 0·10 " [453] _Journ. Trop. Med. and Hyg._, xvi, p. 329. Taylor[454] (1913–14), writing from Entebbe, Uganda, prescribes arsenious acid by the mouth in increasing doses. Creosote has been used in West Africa. [454] _Annual Med. and Sanit. Rept., Uganda_, for 1913, p. 80. 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. Stitt[455] (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. [455] “The Diagnostics and Treatment of Tropical Diseases.” London: H. K. Lewis. _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:-- Average mixture Crude carbolic acid (containing 15 per cent. phenol) 300 gallons Caustic soda 30 lb. Resin 200 lb. [456] “The Prevention of Malaria.” Second Edition (1911). London: John Murray. 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 Prowazek[457] (1913) and by Seifert. E. L. Walker[458] (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. Behrenroth[459] (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. [457] Beihefte z. _Arch. f. Schiffs- u. Tropen-Hyg._, xvii, 6, p. 371. [458] _Philippine Jl. Sc._, Sect. B, viii, pp. 1–15, 333–349. [459] _Arch. f. Verdauungs Krankheiten_, xix, p. 42. 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. ------------------------------------------------------------ |This section, except for minor corrections, is practically a| |translation of the original. | ------------------------------------------------------------ *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 Kermogant[460] states them to be of frequent occurrence in Tonkin[461]; 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] Bostroem[463] and Sagarra[464]) 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. [460] Kermogant, _Soc. méd. des Hôp._, February 7, 1905. [461] [The distomiasis of Tonkin is due to _Clonorchis sinensis_ and not to _F. hepatica_.--J. W. W. S.] [462] Bierner, _Schweiz. Zeitschr. f. Heilk._, 1863. [463] Bostroem, _Deutsch. Arch. f. klin. Med._, 1883. [464] Sagarra, quoted by Duffek. [465] Duffek, _Wien. klin. Wochenschr._, 1902, xxx. 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 Tappeiner[466] to discover an effective remedy against liver-fluke disease (liver rot), so prevalent among sheep, were unsuccessful. [466] Tappeiner, _Münch. med. Wochenschr._, 1900, l. 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] [467] Odhner, _Centrall l. f. Bakt._, 1902, xxxi. 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 (Katsurada[468]) is worthy of special attention. The onset of pulmonary paragonimiasis is generally insidious (Looss[469]); 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. [468] Katsurada, Ziegler’s _Beitr. z. path. Anat._, 1900, xxviii. [469] Looss, “Handb. d. Tropenkrankh.,” von Mense, 1905, i. Examination of the thorax frequently fails to reveal anything abnormal. Inouye[470] states that the most frequently observed changes consist in retraction of the thorax and in a contraction of its infrascapular portion. Scheube[471] 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. [470] Inouye, quoted by Looss. [471] Scheube, “Die Krankh. d. warm. Länder,” 1896. 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. [472] Otani, quoted by Looss. [473] Inouye, quoted by Looss. [474] Yamagiva, quoted by Looss [475] Taniguchi, _Arch. f. Psych. u. Nervenkrankh._, xxxviii. 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 Laspeyres[476] 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 Katsurada[477] 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. [476] Laspeyres, “Dissert. Kiel,” 1904. [477] Katsurada, Ziegler’s _Beitr. z. path. Anat._, 1900, xxviii. 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 (Stock[478]); 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; Kautsky[479] also called attention to the excessive degree of eosinophilia, whilst Goebel[480] expresses the opinion that a specific toxic action on the organism generally is not developed in bilharziasis. Kautsky[481] 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 Hardy[483]). 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. Goebel[484] 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, Kutner[485] 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 (Petrie[486]). [478] Stock, _Lancet_, September 29, 1906. [479] Kautsky, _Wien. klin. Rundschau_, 1903, xxxvi. [480] Goebel, _Arch. f. Schiffs- u. Tropen-Hyg._, 1903, vii. [481] Kautsky, _Wien. klin. Rundschau_, 1903, xxxv. [482] Balfour, _Lancet_, December, 1903. [483] Douglas and Hardy, _ibid._, October, 1903. [484] Goebel, _Centralbl. f. d. Krankh. d. Harn u. Sexualorgane_, xvii. [485] Kutner, _ibid._, xvi. [486] Petrie, _Brit. Med. Journ._, July, 1903. 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, Burfield[487] found in the excised vermiform appendix ova of _Schistosoma hæmatobium_; he assumed this to be a gradual secondary infection of the appendix, whilst Kelly[488] 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 Symmers[489] 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. [487] Burfield, _Lancet_, February 10, 1906. [488] Kelly, quoted by Burfield. [489] Symmers, _Lancet_, January 7, 1905. 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] Horwood[491] 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. [490] Milton, quoted by Looss, “Handb. d. Tropenkrankh.,” v. Mense, 1905, i, p. 95. [491] Horwood, _Brit. Med. Journ._, March 10, 1906. 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 (Brock[492]), or the latter alone and santonin given in small doses for a week at a time, in the morning, are said by Petrie[493] to be of value. Sandwith[494] and Harley[495] 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. [492] Brock, _Journ. of Path. and Bact._, 1893. [493] Petrie, _loc. cit._ [494] Sandwith, _Annal. of Surgery_, 1904, xxxix. [495] Harley, _Lancet_, 1870. 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. 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. [496] Reyher, _Deutsch. Arch. f. klin. Med._, 1886, xxxix. [497] von Shapiro, _Zeitschr. f. klin. Med._, 1888. [498] Podwissotsky, _Jahrb. f. Kinderkrankh._, 1889. [499] Pariser, _Deutsch. med. Wochenschr._, 1892. [500] Schaumann, Berlin, 1894, and _Deutsch. med. Wochenschr._, 1898. [501] Müller, _Charité-Annal._, xiv. [502] Kurimoto, _Zeitschr. f. klin. Med._, xl, and _Kongr. f. inn. Med._, Karlsbad, 1899. [503] Meyer, _Mount Sinai Hosp. Reports_, 1903 and 1904, iv. [504] Rosenquist, _Verein f. innere Med. in Berlin_, May 6, 1901; and _Zeitschr. f. klin. Med._ xlix. [505] Bendix, _Deutsch. Aerzte Zeitg._, 1904, i. [506] Zinn, _Deutsch. med. Wochenschr._, 1903. [507] Isaac and van den Velden, _Deutsch. med. Wochenschr._, 1904, xxvii. [508] Galli-Valerio, _Therap. Monatsh._, 1905. [509] Tallqvist, _Zeitschr. f. klin. Med._, 1907, lxi. [510] Leichtenstern, “Handb. d. Therap. v. Pentzoldt-Stintzing,” 1898, 2nd edition, iv. [511] Lenhartz, _ibid._, 1903, 3rd edition, iv, p. 607. 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. [512] Leichtenstern, _Deutsch. med. Wochenschr._, 1899. [513] Lussana, _Rivista Clin. Arch. ital. di clin. Med._, 1890. [514] Arslan, _Rev. mens. des Mal. de l’Enfance_, 1892. [515] Fischer, _Versamml. d. ophthal. Gesellsch._, 1892. [516] Samelsohn, _ibid._ [517] Zappert, _Wien. klin. Wochenschr._, 1892. [518] Müller and Rieder, _Deutsch. Arch. f. klin. Med._, xcviii. [519] Bücklers, _Münch. med. Wochenschr._, 1894. [520] Neusser, _Wien. klin. Wochenschr._, 1892. [521] Bohland, _Münch. med. Wochenschr._, 1894. [522] Daniels, _Lancet_, No. 3,725. [523] Looss, _Centralbl. f. Bakt._, 1897. 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. [524] Scheube, “Die Krankh. der warm. Länder,” 1896. [525] v. Jaksch, _Münch. med. Wochenschr._, 1902. [526] Galvagno, _Arch. di Patol. e Clin. inf._, 1902–1904. [527] Loeb and Smith, _Centralbl. f. Bakt._, xxxvii. [528] Bauer, _Wien. klin. Wochenschr._, 1904. [529] Allessandrini, _Policlinica_, 1904. [530] Hynek, _Klin. Chron._, 1904. [531] Goldmann, _Wien. klin. Rundschau_, 1905. [532] Romani, _Gaz. d. Osp._, 1904. [533] Liefmann, _Zeitschr. f. Hyg._, 1905, l. 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. [534] Berti, _Gaz. d. Osp._, 1906. [535] Peiper, _Deutsch. med. Wochenschr._, 1897. [536] Löbker and Bruns, _Arb. aus dem kaiserl. Reichsgesundheitsamt_, 1906, xxiii. [537] Cao, _Riforma Med._, 1901. [538] Messineo and Calmida, _Centralbl. f. Bakt._, xxx. [539] Jammes and Mandoul, _Acad. des Sciences_, 1904. [540] Messineo, _Giorn. med. del regio eserc._, 1903. [541] Pereira, _Lancet_, September, 1903. [542] Barnabo, _Sperimentale_, 1906, v. [543] Gagnoni, _Pediatric._, 1903. [544] Dirksen, _Deutsch. med. Wochenschr._, 1903. [545] Brandt, quoted by Pollak in _Centralbl. f. Bakt._, 1889, v. [546] Peiper, _vide_ Seifert, “Lehrb. d. Kinderkrankh.,” 1897, p. 243. 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_. [547] Demme, _vide_ Seifert, _ibid._ [548] Kutner, _Berl. klin. Wochenschr._, 1865. [549] Lutz, _Centralbl. f. Bakt._ [550] Drouillard, _Journ. de Méd._, 1900. xi. [551] Annaratone, _Giorn. med. del regio eserc._, 1900. [552] Delille, _Journ. de Méd._, May 10, 1907. [553] Mériel, _Annal. de Méd. et Chir. inf._, 1900. [554] Papi, _Gaz. d. Osp._, 1901. [555] Taillens, _Arch. de méd. d’Enf._, 1906. [556] Máreo, _Allg. Wien. med. Zeitg._, 1902. 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. [557] Schupfer, _Gaz. d. Osp._, 1901. [558] Duprey, _Lancet_, 1903. [559] Naab, _Münch. med. Wochenschr._, 1902. [560] Hammiss, _Wien. med. Wochenschr._, 1904, iii. [561] Koneff, quoted by Liesen, “Dissert. Bonn,” 1904. [562] Buchholz, _Norsk. Mag. for Läge_, 1903. [563] Rose, Billroth and Pitha, “Chirurgie.” [564] Cattaneo, _Arch. f. Kinderheilk._, xliv. [565] Messineo, _Giorn. med. del regio eserc._, 1905. [566] Huber, _Deutsch. Arch. f. klin. Med._, 1870, vii. 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. [567] Barth, reported by Valleix, Paris, 1845. [568] Gibson, _Lancet_, 1862. [569] Pascal, quoted by Kahane, _Korrespondenzbl. f. Schweizer_ Aerzte, 1907, viii. [570] Burchhardt, _Deutsch. med. Wochenschr._, 1880. [571] Rippe, _St. Petersb. med. Wochenschr._, 1907, i. [572] Moosbrugger, _Med. Correspondenzbl. f. Württemberg_, 1890. [573] Morsasca, abstract in _Centralbl. f. innere Med._, 1897. [574] Becker, _Deutsch. med. Wochenschr._, 1902. [575] Sandler, _ibid._, 1905. [576] Girard, _Annal. de l’Inst. Pasteur_, 1901. [577] Schiller, _Beitr. z. klin. Chir._, 1902, xxxiv. [578] Hausmann, _St. Petersb. med. Wochenschr._, 1900. 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. Silvester[580] and Valdes[581] report on giddiness, headache and anuria in cases observed by them; whether the eosinophilia recorded by Bücklers[582] and Bruns[583] is due to the toxin of Strongyloides must remain an open question. [579] Hartmann, _Naturforschervers._, Köln, 1889. [580] Silvester, quoted by Schlüter, “Dissert. Kiel,” 1905. [581] Valdes, quoted by Schlüter, _op. cit._ [582] Bücklers, _Münch. med. Wochenschr._, 1894. [583] Bruns, _Münch. med. Wochenschr._, 1907. 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. Müller[584] has collected nine such cases out of the literature, to which may be added six cases of Finsen[585] 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 Caffarena[586] 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 Spada[587] 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 Bindi[588] 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. [584] Müller, D., “Dissert. Würzburg,” 1885. [585] Finsen, quoted by D. Müller. [586] Caffarena, _Convers. clin. Genova_, 1902. [587] La Spada, _Gaz. d. Osp._, 1904. [588] Bindi, _ibid._, 1907. [589] Santucci, “Clinica moderna,” 1905. [590] Welsh and Barling, _Scot. Med. and Surg. Journ._, 1907. 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 Merling[591] (1836), Zebert[592] (1859), Platonor[593] (1853), and Schachtinger[594] (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. Bergmann[595] records a case in which an Ascaris perforated the appendix and got into the peritoneal cavity. [591] quoted by Rostowzeff, _Bobritsch. Gaz. Botkina_, 1902. [592] quoted by Rostowzeff, _Bobritsch. Gaz. Botkina_, 1902. [593] quoted by Rostowzeff, _Bobritsch. Gaz. Botkina_, 1902. [594] quoted by Rostowzeff, _Bobritsch. Gaz. Botkina_, 1902. [595] Bergmann, _Prag. med. Wochenschr._, 1890. Strümpell[596] reckons among the symptoms of Trichocephalus the possibility of a “typhlitis.” On account of the marked sensitiveness of the ileo-cæcal region, Boas[597] mentions the possibility of confusing it with appendicitis. Still[598] regards Oxyuris as a principal cause of catarrhal affections of the appendix. Arboré-Rally[599] regarded severe symptoms of appendicitis in a boy, aged 10, as due to Ascarides. In all cases of appendicitis Metschnikoff[600] 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. Matignon[601] 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 Barres[602] expresses himself in similar fashion. Out of twenty-one cases of appendicitis Kirmisson[603] 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. Moty[604] considers Oxyuris to be the sole cause in his three cases of appendicitis. Girard[605] 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 Triboulet[606] describes a case of appendicitis which he considers was due to Ascaris. In Morkowitin’s[607] case numerous Oxyuris had clearly caused the appendicitis. von Genser[608] 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 Schiller[609] 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 Kaposi[611] 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, Schwankhaus[612] found that an Ascaris had perforated the appendix. Ramstedt[613] 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. Rostowzeff[614] ascribes only a minimal direct etiological significance to intestinal worms in the origin of appendicitis; in 163 cases he found worms in three instances. Wirsaladze[615] expresses himself in a similar fashion. Oppe[616] 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 Hanau[617] Oxyuris was undoubtedly the etiological starting-point; in a case of Galli-Vallerio[618] Oxyuris and Trichocephalus. In the opinion of Ssaweljews[619] in some cases of appendicitis, in addition to other causes, intestinal parasites play a prominent part. The case recorded by Nason[620] is an interesting one; in this an Ascaris in the appendix became twisted with it round a coil of gut, causing obstruction. Spieler[621] 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 Bégonin[622] fifteen Oxyuris were found in the excised appendix (the mucosa showed some ulceration), and in another recorded by Putnam[623] twenty Oxyuris were present in the appendix, in which there was no evidence of any change. The standpoint Schilling[624] 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. Blanchard[625] assumes the possibility of a secondary infection arising from lesions of the mucosa produced by helminthes (Ascaris and Oxyuris). Moore[626] considers Trichocephalus the excitant of the appendicitis in his case. In a second case of appendicitis recorded by Auley[627] operation became unnecessary owing to the passage of the _Ascaridæ_. Page’s[628] 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. Schoeppler[629] states that there is the danger of an appendicitis even after the death of an Oxyuris that has found its way into the appendix. Oui[630] met with two specimens of Trichocephalus which had become embedded by their thin ends deep in the mucosa. Frangenheim[631] 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 Kahane[632] many Trichocephali were found partly free in the appendix and partly embedded in the mucosa; microscopically appendicitis was diagnosed. At a laparotomy for salpingitis Heekes[633] found the appendix elongated, thickened, and containing about eleven Oxyuris without the mucosa being in any way changed. In one case Andrews[634] 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 Bremser[641] 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] Rokitansky[644] considers perforation of the gut by Ascaris as at least a rare occurrence. Gerhardt[645] does not doubt that the worms can actively perforate the intestine. Cases like those of Abrault,[646] Apostolides,[647] Marcus[648] (recorded by Perls as a valid example of “ascaridophagous” gut perforation), Wischnewsky,[649] Galvagno,[650] Salieri[651] 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’s[652] case (fifty-six Ascarides escaped from the umbilicus of a girl, aged 7), in Gräffe’s[653] (eighty Ascarides escaped from an inguinal tumour), in Nicolino’s[654] (perforation of the intestinal wall with strangulated hernia), in Liesen’s[655] (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 Boloff[656] the Ascarides appear to have produced, by forming a tight coil, necrosis of the gut with perforative peritonitis. In a case recorded by Lutz[657] the perforative peritonitis was without doubt provoked by Ascaris, and in one by Schiller[658] the Ascaris had clearly gained access to the peritoneal cavity through a gunshot wound opening. In a case observed by Rehn[659] the worm probably entered through a gangrenous portion of the intestine in a hernial sac. Broca[660] 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 Lutz[661] 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. Froelich[662] assumes that in his case (a boy, aged 11) the Oxyuris were able to penetrate the whole intestinal wall, but Vuillemin[663] 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 (Marro[664]), and perhaps causing a parasitic endometritis (Simons[665]), 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 Kolb[666] (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 Chiari[667] (adult Oxyuris in Douglas’s pouch) and by Schneider[668] (an Oxyuris encapsuled in the pelvic peritoneum). Sehrt’s[669] 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-Dufresne[670]) and within three years 5,126 worms. In the case recorded by Tschernomikow[671] 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 Black[681] and Parkinson[682] the intestinal obstruction was caused by a coil of tapeworms. [596] Strümpell, “Lehrb. d. spez. Path. u. Therap.,” 1894. [597] Boas, _Deutsch. med. Wochenschr._, 1895. [598] Still, _Brit. Med. Journ._, 1899. [599] Arboré-Rally, _Arch. de Méd. des Enf._, 1900. [600] Metschnikoff, _Bull. méd._, 1901. [601] Matignon (abstract), _Münch. med. Wochenschr._, 1901. [602] Des Barres, _Gaz. des Hôp._, 1903. [603] Kirmisson, _Annal. de Méd. et Chir. des Enf._, 1901. [604] Moty (abstract), _Münch. med. Wochenschr._, 1901, p. 910. [605] Girard, _Annal. de l’Inst. Pasteur_, 1901. [606] Triboulet, _Soc. méd. des Hôp. de Paris_, 1901. [607] Morkowitin (abstract), _Centralbl. f. d. Grenzgebiete_, 1902. [608] v. Genser, _Wien. med. Wochenschr._, 1901. [609] Schiller, _Beitr. z. klin. Chir._, 1902, xxxiv. [610] Czerny and Heddäus, _ibid._, xxi. [611] Kaposi, _ibid._, xxviii. [612] Schwankhaus, _Amer. Pract._, 1901. [613] Ramstedt, _Deutsch. med. Wochenschr._, 1902. [614] Rostowzeff, _Russ. med. Rundschau_, 1903. [615] Wirsaladze, _Bobritsch. Gaz. Botkina_, 1902. [616] Oppe, _Münch. med. Wochenschr._, 1903. [617] Hanau, _ibid._, 1903. [618] Galli-Vallerio, _Centralbl. f. Bakt._, 1903, p. 1094. [619] Ssaweljews, _Deutsch. med. Zeitg._, 1903. [620] Nason, _Journ. Amer. Med. Assoc._, 1904. [621] Spieler, _Wien. klin. Wochenschr._, 1904. [622] Bégonin, _Journ. de Méd. de Bordeaux_, July, 1902. [623] Putnam, quoted by Spieler. [624] Schilling, “Würzb. Abhandl.,” 1905. v. [625] Blanchard, _Acad. de Méd._, July 3, 1904. [626] Moore, _Brit. Med. Journ._, August 18, 1906. [627] Auley, _ibid._, 1906. [628] Page, _New York Med. Journ._, January 20, 1906. [629] Schoeppler, _Centralbl. f. Bakt._, 1906. [630] Oui, _Rev. prat. d’Obstét. et de Paed._, 1906. [631] Frangenheim, _Samml. klin. Vortr._, 1906, No. 424. [632] Kahane, _Schweiz. Korrespondenzbl._, 1907, viii. [633] Heekes, _Brit. Med. Journ._, March 16, 1907. [634] Andrews, _ibid._, 1906. [635] Leuckart, “Die Parasiten des Menschen.” [636] Heller, “Handb. d. spez. Path.,” v. Ziemssen, vii. [637] Mosler and Peiper, “Spez. Path. u. Ther.,” v. Nothnagel, vi. [638] Henoch, “Vorlesungen über Kinderkrankheiten.” [639] Davaine, “Traité des Entozoaires.” [640] Küchenmeister and Zürn, “Die Parasiten des Menschen.” [641] Bremser, “Lebende Würmer im lebenden Menschen.” [642] Mondière, _Schmidt’s Jahrb._, 1840. [643] v. Siebold, “Parasiten” in Wagner’s “Handwörterbuch,” 1845. [644] Rokitansky, “Path. Anat.” [645] Gerhardt, quoted by Liesen, “Dissert. Bonn.” [646] Abrault, quoted by Seifert, “Lehrb. d. Kinderkrankh.” [647] Apostolides, _Lancet_, 1898. [648] Marcus, quoted by Seifert, “Lehrb. d. Kinderkrankh.” [649] Wischnewsky, quoted by Seifert, _ibid._ [650] Galvagno, _Arch. de Patol. et Clin., inf._, 1902. [651] Salieri, _Rif. med._, 1902. [652] Lini, _Schmidt’s Jahrb._, 1838. [653] Gräffe, _Protokoll d. Ges. f. Natur u. Heilkunde_, Dresden, 1853. [654] Nicolino, _Clin. mod._, 1902. [655] Liesen, “Dissert. Bonn.” 1904. [656] Boloff, quoted by Seifert, “Lehrb. d. Kinderkrankh.” [657] Lutz, _Centralbl. f. Bakt._ [658] Schiller, _Beitr. z. klin. Chir._, xxxiv, p. 200. [659] Rehn, _see_ Schiller, _loc. cit._, p. 201. [660] Broca, _Rev. mens. des Mal. de l’Enf._, 1904. [661] Lutz, _Wien. klin. Wochenschr._, 1905, xv. [662] Froelich, _Rev. mens. des Mal. de l’Enf._, 1897. [663] Vuillemin, _Centralbl. f. Bakt._, 1902. [664] Marro, _Arch. per le Sci. med._, 1901. [665] Simons, _Centralbl. f. Gynäk._, 1899. [666] Kolb, _Centralbl. f. Bakt._, 1902. [667] Chiari, _Prag. med. Wochenschr._, 1902. [668] Schneider, _Centralbl. f. Bakt._, 1904. [669] Sehrt, _Beitr. z. klin. Chir._, li. [670] Fauconneau-Dufresne, quoted by Seifert. [671] Tschernomikow, quoted by Seifert. [672] Mosler and Peiper, _loc. cit._ [673] Raie, _Lancet_, 1899. [674] Schulhof, _Münch. med. Wochenschr._, 1903. [675] Rehberg, “Dissert. Königsberg,” 1907. [676] Rocheblave, _Gaz. des Hôp._, 1898. [677] Heller, _loc. cit._ [678] Leichtenstern, “Ziemssen’s Handb.,” vii. [679] Huber, quoted by Rehberg. [680] Wilms, _Deutsch. Zeitschr. f. Chir._, xlvi. [681] Black, _Brit. Med. Journ._, 1872. [682] Parkinson, quoted by Rehberg. In the earlier history of medicine the helminthes played a great part as the excitants of many intestinal diseases and of enteric as well. Even if to-day they no longer be regarded as such, the conception that they represent the predisposing factor in typhoid infection through the injury they inflict on the mucosa (Guiart,[683] Blanchard,[684] Vivaldi and Tonello[685]) must not be summarily rejected. Vivaldi and Tonello found helminthes in 80 per cent. of their typhoid patients, numbering among these _Trichocephalus dispar_, _Oxyuris vermicularis_, _Ancylostoma duodenale_, and _Ascaridæ_. The report of Leuckart[686] is here worth citing, to the effect that Thiebault never failed to find Trichocephalus in his cholera patients at Naples. Blanchard[687] goes so far as to express the desire that in every febrile affection of the intestine an anthelmintic treatment with thymol should be undertaken as early as possible, even before learning the results of serum diagnosis. [683] Guiart, _Compt. rend. Soc. de Biol._, Paris, March 16, 1901. [684] Blanchard, _Arch. d. Par._, 1901. [685] Vivaldi and Tonello, _Gaz. d. Osp._, October 29, 1905. [686] Leuckart, quoted by Kahane. [687] Blanchard, _Acad. de Méd._, October 18, 1904. The lesions of the liver and pancreas due to _Ascaridæ_ are briefly discussed in the chapter on Ascariasis (p. 687). A discussion of the intestinal helminthes from the clinical and therapeutical point of view follows these general considerations. Dibothriocephalus latus. From what is known as to the development of _Dibothriocephalus latus_, the way by which man is infected is self-evident: infection can only take place through the ingestion of insufficiently cooked fresh-water fish (pike, burbot, perch, grayling and vendace); what degree of temperature is necessary to kill the larval forms is still unknown. _Dibothriocephalus latus_ lives in the small intestine of man, alone or in some numbers, frequently also together with _Tænia solium_. The proglottides are passed always united in large pieces, the ova are deposited through the uterine pore, while the worm is still in the intestine, so that they are easily found in the fæces. The proglottides are so characteristic that they cannot be confused with those of other species. In reference to whether age or sex is spared by _D. latus_, it is not possible to make any definite statement, especially so far as the endemic area is concerned, whether a person resides in it continuously or visits it, so long as his habit of life is in accordance with those of the country. Bendix[688] certainly emphasizes the fact that early childhood is as a rule immune: his case was that of a child, aged 4-1/2 years. [688] Bendix, _Verein f. innere Med._, Berlin, June 16, 1902. Sparganum mansoni. According to our present knowledge (Miyake[689]) the disease occurs almost exclusively in China and Japan. On the main island it occurs in all districts, though rarely under observation. It is especially frequent in the neighbourhood of Kioto and Osaka; these places are very near together, and between them there is mutually active intercourse, so that taken together they may be regarded as one district infested by this worm disease. As regards localization in the body, there appears to exist a certain predisposition for definite regions, for instance, the eye and genito-urinary tract. In some cases the parasite manifested the peculiarity of wandering about the body and of appearing at certain favourite points (musc. quadriceps femoris) (Hashimoto[690]). Most patients complain more or less of the onset of attacks of pain and of sensitiveness to pressure. In those cases in which the patients evacuated the worm during micturition, the symptoms were variable; sometimes there was tenesmus of the bladder, sometimes pains in the inguinal region, sometimes hæmaturia. None of these troubles is characteristic of the disease, and does no more than represent the symptoms that follow a mechanical irritation that any kind of foreign body may produce. Besides the onset of attacks of pain, swelling of the regions affected, if superficial, may often be recognized, when a superficial diffuse soft tumour can be felt which often gives pseudo-fluctuation. Sometimes a peculiar crackling can be detected internally, as in the making of a snowball. During the further course an abscess not infrequently forms around the worm. When the situation of the worm is superficial, “an inflammatory tumour with a tendency to migrate” is stated by Omi[691] to be an important diagnostic sign. That, however, is not always the case, as the observation made by Inoye[692] shows. It would be better to add to this sign the onset of paroxysmal pain and the temporary change in volume of the tumour. When once the parasite is removed, the wound heals just as satisfactorily as any other fresh wounds made at operation. [689] Miyake, _Mitteil. aus d. Grenzgebiete_, 1904, xiii. [690] Hashimoto, quoted by Miyake. [691] Omi, _Iji-Shinshi_, Tokio, 1898. [692] Inoye, _ibid._, 1897. *Dipylidium caninum* (_Tænia cucumerina_). This species belongs to parasites of rare occurrence. Up to the year 1905 Bollinger[693] collected thirty-six cases from the literature, twenty-nine of which were children and seven adults. Since then some further cases have come to light, so that the number now observed amounts to ninety, and among them only eight adults. The youngest child was 6 weeks old (Köhl[694]), in which the first proglottides were passed when the child was 40 days old. This preponderating occurrence in children is clearly connected with the close intercourse between children and dogs, and also cats. Bollinger believes that _D. caninum_ in reality occurs more frequently in adults than has hitherto been supposed. In addition, it must be mentioned that this species is quite unknown to many physicians, and is occasionally confused with _Tænia solium_. One notices almost daily a large quantity of cucumber-seed-like bodies, reddish or whitish-grey, about 1 cm. long and 2 mm. broad, discharged with the stools. Lindblad[695] remarks that these bodies have lively movements, that they perish rapidly in fresh water, and become white and smooth. These Cestodes, in isolated cases, are parasitic in the intestine in large numbers. Sonnenschein[696] expelled four fragments in the case of a boy, aged 4 months; Asam[697] three fragments in the case of a child, aged 19 months; and Zschokke[698] as many as five or six in that of a boy, aged