CHAPTER XXI

ANCYLOSTOMIASIS

HISTORY AND GEOGRAPHICAL DISTRIBUTION

=History.=—It is very probable that hookworm disease existed in Egypt in the remote past and it has been claimed that a disease mentioned in the Ebers Papyrus was of that nature.

Goeze found a hookworm in a badger in 1782. He named the parasite _Ascaris criniformis_. Froelich, in 1789, found hookworms in the fox and named them hookworms from the hook-like ribs of the copulatory bursa. He proposed the generic name _Uncinaria_. Therefore _Uncinaria_ belongs to the hookworms of the fox and is not valid for any human species.

In 1838, Dubini noted that these worms were generally found in very anaemic cases and that the mucosa of the duodenum or jejunum frequently showed punctate haemorrhages. On account of the four ventral teeth projecting from the mouth he gave it the name _Agchylostoma_ or correctly _Ancylostoma_.

In 1854 Griesinger, as a result of frequently noting the lesions produced by the worms, stated that they were the cause of Egyptian chlorosis. In 1866, Wucherer connected hookworms with a disease of Brazil called opilacao. In 1878 Grassi noted that the disease could be diagnosed by the finding of the characteristic eggs in the stools of patients.

It was the prevalence of a severe anaemia among the workmen employed in the construction of the St. Gothard tunnel, which Perroncito proved to be due to hookworm infection, that established the great importance of this parasitic disease as the cause of a severe and fatal anaemia (1879). About the same time it became generally considered that the anaemias which affected workmen in mines were of a similar nature.

That the disease was very prevalent in the Southern States of the U. S., as long ago as 1849, is shown by the writings of Duncan, who noted the frequency of anaemia, often associated with dirt eating, among the slaves. He described the oedematous legs, the protuberant belly and cardiac palpitation. There were several cases reported in the U. S. from 1893-1897 but they were mainly in foreigners.

From 1895 to 1901, Stiles kept insisting that hookworm disease should be of frequent occurrence in the U. S.

A. J. Smith found several cases in persons living in Texas and recognized the fact that these hookworms were different from those of Europe. It was from a study of material from Smith and Claytor in the U. S. and, later on, from Ashford in Porto Rico, that Stiles, in 1902, reported a new genus of hookworm as existing in man. It was first named _Uncinaria americana_ but _Uncinaria_, belonging to the hookworm of the fox, was not valid, so he changed the name to _Necator americanus_.

[Illustration: FIG. 88.—Geographical distribution of Ancylostomiasis. Stars show where disease is widely prevalent. Triangles, where less so.]

=Geographical Distribution.=—The disease is rare outside the tropical and subtropical countries except in mines or tunnels where suitable conditions of warmth and moisture exist.

It is extremely prevalent in India and Egypt as well as in China and other parts of the East. It is a very important infection in Porto Rico and the Philippine Islands. It is extensively distributed in South America, especially Brazil, as well as in Central America, Mexico and the Southern States of the U. S. The inhabitants of many of the islands of the Pacific are heavily infested. Hookworm disease is common in southern Europe.

ETIOLOGY AND EPIDEMIOLOGY

=Etiology.=—The hookworm infections of man come almost entirely from two parasites, _Ancylostoma duodenale_, the Old World species, and _Necator americanus_, which is generally called the New World species from its having first been reported from the U. S. by Stiles. Hookworms belong to the class Nematoda and family Strongylidae.

Quite recently Lane has reported a new species, _A. ceylanicum_, as having been obtained from 3 men in Bengal, after treatment. This species is the one that infects the civet cat in Ceylon. So far as we know the other human species belong solely to man.

The male hookworms are a little more than ⅓ of an inch (9 mm.) long and the females a little more than ½ inch (13 mm.) in length. The males can readily be distinguished by their posterior, umbrella-like expansion or copulatory bursa. The tail of the female is pointed. The vulva of _A. duodenale_ is located in lower half of the ventral surface; that of _N. americanus_ in upper half. The large, oval mouth of the Old World hookworm has four claw-like teeth on the ventral side of the buccal cavity and two knob-like teeth on the dorsal aspect. It also has a pair of ventral lancets below the four ventral teeth. One cannot make out a dorso-median tooth. In _N. americanus_ the buccal capsule is round, smaller and the ventral teeth are replaced by chitinous plates. Dorsally there are two similar but only slightly developed lips or plates. A very prominent, conical dorso-median tooth projects into the buccal cavity. Through it passes the duct of the dorsal oesophageal gland. There are also 4 buccal lancets. The copulatory bursa of the _Necator americanus_ is also different, being terminally bipartite and deeply cleft in the division of the dorsal ray, rather than tripartite and shallow, as with _A. duodenale_.

The anterior extremity of _Ancylostoma_ bends in the same direction as the general body curve while that of _Necator_ hooks back in an opposite direction to the body curve.

By dropping the worms, while still alive, into hot 70% alcohol they readily assume the attitudes noted above.

In general, _Ancylostoma_ is larger and thicker than _Necator_.

The name hookworm was given to these nematodes from the hook-like processes of the ribs of the rays of the copulatory bursa. Dubini called the Old World parasite _Agchylostoma_, properly _Ancylostoma_, on account of the 4 formidable hook- or claw-like ventral teeth of the buccal capsule. (αγχὶλος, hook, and στομα, mouth.)

_A. ceylanicum_ is somewhat smaller than _A. duodenale_ and in the copulatory bursa of the male we have a deeper cleft in the dorsal ray and 2 rather long tips to each branch instead of the shallow cleft and 3 stumpy processes of the 2 branches as in _A. duodenale_.

=Life History.=—The delicate-shelled eggs pass out in the faeces, and in one or two days a rhabditiform embryo (200 × 14 microns) is produced. The mouth cavity of the embryo is about as deep as the diameter of the embryo at the posterior end of the mouth cavity; that of _Strongyloides_ is only about one-half as deep as the diameter.

[Illustration: FIG. 89.—1a, Copulatory bursa of _Necator americanus_, showing the deep cleft dividing the branches of the dorsal ray and the bipartite tips of the branches; also showing the fusion of the spicules to terminate in a single barb. Scale 1/10 mm. 1b, Branches of dorsal ray magnified. 2a, The buccal capsule of _N. americanus_. 2b, The same magnified. 3a, Copulatory bursa of _Ancylostoma duodenale_, showing shallow clefts between branches of the dorsal ray and the tridigitate termination. Spicules hair-like. 3b, The dorsal ray magnified. 4a, The buccal capsule of _A. duodenale_, showing the much larger mouth opening and the prominent hook-like ventral teeth. 4b, The same magnified. 5a, Egg of _N. americanus_. 5b, Egg of _A. duodenale_. 6a, Rhabditiform larva of _Strongyloides_ as seen in fresh faeces. 6b, Rhabditiform larva of hookworm in faeces eight to twelve hours after passage of stool. From Stitt.]

As a practical point, the anaerobic conditions in the intestines seem to prevent development of the hookworm ova or at any rate the absence of the oxygen, so necessary for the segmentations preliminary to the formation of the embryo, prevents it. Therefore hookworm ova in freshly passed faeces never show other than commencing segmentation while development of the larvae of _Strongyloides_ takes place in the intestines, so that in freshly passed faeces we find, generally, actively moving larvae or at least eggs containing fully developed embryos. Hookworm ova very rarely show more than 4 segments or exceptionally 8 segments in the freshly passed egg.

In the presence of oxygen these ova rapidly develop into larvae,

## particularly at a temperature of about 27°C. Beyond 37°C. and below

14°C. development does not seem to take place.

The rhabditiform larvae grow rapidly and by the 3rd day are about 300 microns long and undergo a primary moulting. By the 5th day the bulb-like swellings disappear and the larva becomes possessed of a straight oesophagus, thereby becoming a strongyloid larva. It then undergoes a 2nd ecdysis or moulting, but instead of casting off this old covering, it retains it as a protecting sheath. The full grown larva is about 550 by 24 microns. At this time it ceases to take food but can move actively in its sheath so that it can crawl up blades of grass or vertical sides of mines. They can live in this state for months, when moisture and shade are present, but are rapidly killed by drying. Before becoming encysted hookworm larvae are readily destroyed by the action of the sun or chemicals or even by dilution of the faeces, especially with urine. Cort and others have found it a common occurrence for mature larvae to lose their sheaths while living in the soil, and to continue their lives in the unsheathed state. The proportion losing their sheaths varies from 52 to 98%.

This is the _infecting stage_ in which the larvae bore their way into the skin, which is the usual method of infection, or, occasionally, by entering the mouth on vegetables or otherwise.

Looss thought that they entered the skin by way of the hair follicles but the idea now is that they can bore into any part of the skin. It only requires a few minutes for the larvae to enter the skin. From the subcutaneous tissues they effect an entrance into lymphatics or veins, go to the right heart, thence to lungs. From the alveolar capillaries they pass into the pulmonary alveoli, thence up the bronchi and trachea, to pass out of the larynx and then down the oesophagus to the stomach. The larva loses its protecting sheath in the stomach and in a few days develops a provisional buccal capsule.

By the end of the 2nd week, after another ecdysis, the larvae have grown to be about 2 mm. long and 130 microns broad and in about 4 weeks become adults, usually in the jejunum, where, after fertilization of the females by the males, the giving off of eggs begins. The adults attach themselves to the mucosa of the intestine, feeding on the deeper structures of the mucosa, or on the tissues of the submucosa. Sambon believes that the larvae can work their way into the jejunum without going there by way of the trachea and oesophagus.

By providing an exit to the trachea, Fülleborn demonstrated that in dogs, infected with the dog hookworm, great numbers of larvae poured out of the trachea. In other dogs he stitched the oesophagus to the skin and noted larvae coming out of these openings. In these dogs, with the ordinary channel obstructed, infection did occur with, however, only a few worms, thus showing the truth of Sambon’s views but at the same time demonstrating the unimportance of such a route of infection.

The mouth cavity of the embryo is about as deep as the diameter of the embryo at the posterior end of the mouth cavity, that of _Strongyloides_ is only about one-half as deep as the diameter. The genital anlage of _Strongyloides_ is much larger than that of _Ancylostoma_.

=Epidemiology.=—When faeces containing hookworm eggs are deposited where conditions of moisture, warmth and shade exist, they develop into the infecting stage, which is the nonfeeding but motile larva inside the cuticle formed by the second moulting. While eggs and younger larvae are killed rapidly, the encysted larvae withstand drying for considerable periods.

[Illustration: FIG. 90.—_Ancylostoma duodenale_ (life size). Shows some worms adherent to the intestinal mucosa and some free. (From Jefferys and Maxwell.)]

Stiles notes that the more favorable conditions for development are in a porous, sandy soil rather than in a clay one. Where a sewerage system exists there is very little danger of the spread of hookworm disease and the same is true where there is proper disposal of the faeces by burning, boiling or treatment in a septic tank. In rural districts, however, where the stool is often deposited in the shade and retirement of a clump of trees, the soil becomes infested with myriads of larvae, so that one standing with bare feet on such a spot easily becomes infected. It is for this reason that shoes are of protective value. In infected mines with temperatures below 22°C. infection is rare (6%); from 22°C. to 25°C. more common (16.6%), and above 25°C., it may reach high figures (61%).

Those of the negro race do not suffer from the infection as do the whites. They appear to have an immunity but serve as carriers of the disease. There is difference of opinion as to the length of time the parasites may live in man in the absence of reinfection. Some consider this period one of a few months, others of two or three years. We can certainly consider that a case leaving an infested region will get rid of his parasites within seven years.

PATHOLOGY

The site of entrance of the larvae is characterized by a dermatitis which is often called “ground itch” or “foot itch” by reason of its frequent location in the foot which has come in contact with the faeces-polluted soil. The dermatitis disappears in about two weeks unless some secondary infection occurs. There are reports of pulmonary irritation which may be explained by the wandering of the larvae through the lungs.

[Illustration: FIG. 91.—Longitudinal section through a hookworm attached to the intestinal mucosa, about 6 hours after the death of the carrier. A portion of the submucous coat is drawn into the buccal cavity and trails along cord-like into the oesophagus, in which 4 small tissue nuclei are still discernible. Section 0.01 mm. thick. (From Mense.)]

Pronounced anaemia with yellow, wax-like skin is a feature of severe cases but emaciation is rare, the subcutaneous fat still remaining. There is frequently oedema about the ankles. In the jejunum we find small haemorrhagic spots from the size of a pea to that of a half dollar. A worm may be found in the center of this spot. In sections from the tissues injured by the bite we note an infiltration of eosinophiles. The heart often shows fatty degeneration with dilatation. The liver and kidneys usually show fatty change while the spleen is generally shrunken. Sandwith noted splenic enlargement in many of his autopsies but such enlargement must have been due to other causes.

There are many views as to the manner in which the damage due to the hookworm is brought about. Some think it by bacterial infections occurring through the wounds made by the worms, others that it is due to a haemolytic toxic material excreted by the worms, while Stiles considers the ingestion of the patient’s blood important. Looss thinks it due to the gradual destruction of the intestinal mucosa from the feeding on this, and especially of the submucosa, by the worms. In their feeding the worms move from site to site. When they leave a point bleeding continues and this may account for much of the anaemia.

On the side of the blood we have at first a moderate leucocytosis which disappears with the anaemia. Eosinophilia and Hb. percentage reduction are often observed. In 3 cases I have known a fatal pernicious anaemia to develop.

SYMPTOMATOLOGY

In a secondary anaemia, with early and marked cardiac palpitation together with epigastric tenderness and a tendency to mental retardation and physical deterioration, one should always examine the stools for hookworm eggs.

The course of the disease is decidedly insidious and indefinite and the clinical diagnosis notoriously uncertain, as shown by many reports where physicians of experience, after examining a number of persons in a mill or school and only diagnosing 2 or 3% as infected, have been astonished, upon examination of the faeces of the group, to obtain positive evidence of infection in 70 to 80% of the number examined.

For convenience, it is well to divide hookworm cases into 3 groups; 1. Where the person infected fails to show any special evidence of abnormality, the diagnosis resting almost entirely on the finding of ova in the faeces.

Such cases may show very slight reduction in haemoglobin and only admit of a certain lack of energy. The best indication that hookworm infection is doing the host injury is that after treatment they gain in weight and energy and show improvement in mental concentration.

2. Mild cases with moderate degrees of anaemia, the Hb. percentage ranging from 55 to 75. In these cases there is rather marked epigastric tenderness with frequent attacks of acid eructations. Cardiac palpitation and a tendency to shortness of breath may be quite noticeable. Headache and vertigo may be present.

3. Severe cases. In such cases we may find extreme anaemia with Hb. percentages around 35 or even as low as 15. I have always felt that one was only approximating when recording percentages of 10 or lower.

These cases are very weak and show marked cardiac palpitation and dyspnoea upon the slightest exertion. There is often dilatation of the stomach and a protuberant abdomen. The red cells may fall below 1,000,000. There is also oedema, especially about the feet and ankles. Tinnitus aurium is rather frequent.

Such cases often show depravity of appetite, the best-known craving being that for earth. Other patients crave chalk, wood, cotton, etc.

[Illustration: FIG. 92.—Fatal case of ancylostomiasis. Red cells 810,000. Hb. 15%. White count 6400. Eosinophiles absent. Upper part of small intestines lined with hookworms. (From U. S. Naval Medical Bulletin.)]

It is in children that we have the most serious effects of the disease, there being marked stunting of the growth with a corresponding mental backwardness. Such children show marked retardation and delay in answering the question asked them and often repeat it in a drawling manner. Tested by the Binet-Simon method we may find a sixteen year old child to have the mental development of a ten year old one, but at the same time we would note that from a standpoint of physical development the child only seemed ten years old.

As the child approaches adult age we note a striking lack of sexual development and the lack of pubic hair. In girls there is delay in the onset of the menstrual periods or these may never appear.

In from 80 to 90% of cases there is a history of dermatitis,

## particularly of toes or feet, which is commonly called “ground itch,”

“foot itch,” or “dew itch.” This is most frequent between the toes or on the inner side of the sole of the foot. The irritation is due to the penetration into the cutaneous tissues of the hookworm larvae. The itching is intense and secondary infections often occur as the result of scratching. Vesicles appear about the second day and are often ruptured by the scratching with a resulting pustular or impetiginous conditions. The skin and hair generally are dry.

As a rule the temperature is normal throughout the course of an uncomplicated case of hookworm disease. During the first week or so following a heavy infection there may be pulmonary manifestations when the larvae are migrating by way of the lungs.

In the diagnosis of a case Stiles attaches much importance to a tallow-yellow color of the alae of the nose and the forehead, as well as to the eye characteristics which are like those seen in the eye of a fish or that of an intoxicated person.

He also notes that the pupil tends to dilate instead of to contract when the patient looks at a bright light. It has seemed to me that the condition is rather one of hippus. In severe cases retinal haemorrhages may occur. There may be night blindness. Ascites may be present in advanced cases.

Symptoms in Detail

_Skin Manifestations._—The dermatitis following the penetration of the larvae is most often about the toes or inner side of the sole of the foot. The skin is very dry and often a pale earthy color. A tallow-yellow tinting of the alae of the nose may be observed. The hair is dry and scanty or absent in pubic and beard regions. Oedema, especially of ankles or feet, is common.

_Circulatory and Respiratory Systems._—Palpitation of the heart is early and marked. Functional murmurs are frequent in the advanced stages. Pulsation of the neck veins is also common. The pulse rate averages about 110 and the blood pressure is low. There is frequently some right side dilatation of the heart. A high pulse pressure is common in severe cases. Shortness of breath on slight exertion is the most common respiratory symptom. There are at times cough and bronchitis, probably induced by the irritation of the larvae in the pulmonary alveoli.

_Digestive System._—Epigastric tenderness going to the right is very characteristic. The stomach is often dilated and the gastric juice hyperacid. As the anaemia increases the acidity diminishes. It has been suggested that the desire to neutralize this acidity with an alkali is the explanation of the desire for alkali-containing earth on the part of “dirt eaters.”

Patients often are pot-bellied. Constipation is rather a common feature and the stools very rarely show macroscopic blood.

_Nervous System._—Hookworm patients are not only physically tired but, as well, mentally tired. The infection in children leads to a backward mental state. Patients have very little energy or initiative and are often considered stupid and lazy. Hypochondriasis is at times noted and some severe cases become melancholic.

_The Blood._—The red cell count averages in marked cases 2,500,000 to 3,000,000 red cells per cu. mm. The Hb. percentage is down in such cases to between 30 and 50. The color index is well below 1, except in certain rare cases, when the color index is that of pernicious anaemia, being above 1. These latter cases are very resistant to treatment and often show very few infecting worms notwithstanding the severity of the symptoms.

There is at times a moderate leucocytosis but as a rule the white count is approximately normal.

Eosinophilia is quite characteristic and usually ranges from 15 to 35% of the leucocytes. Eosinophilia tends to disappear as the cases become advanced.

The spleen and liver very rarely give rise to any symptoms and while albuminuria is rather common in advanced cases with oedema about the feet, yet casts are but rarely found.

DIAGNOSIS

=Clinical Diagnosis.=—The diseases with which it is most likely to be confused are beriberi, chronic nephritis and malarial cachexia. Stiles notes that heavy _Ascaris_ infections may give rather similar symptoms.

The signs of a multiple neuritis should differentiate beriberi, and the presence of casts or high blood pressure, chronic nephritis. Recently, there has been a great deal written about the danger of confusing hookworm disease and malarial cachexia, the statement being often made that splenic enlargement is a feature of ancylostomiasis. Most authorities, however, state that the spleen of ancylostomiasis is not enlarged, this point being of diagnostic value in differentiating it from malaria and kala-azar.

=Laboratory Diagnosis.=—As a matter of fact the diagnosis is almost invariably made by finding hookworm ova in the faeces. The eggs are oval and thin-shelled with a wide, clear, glassy zone separating the more or less segmented, granular central portion from the shell.

Formed stools are more satisfactory for examination than the liquid ones resulting from a dose of salts. Put about 2 drops of water or 1% trikresol solution in the centre of a glass slide and emulsify in it as much of the faeces as is held by the spatulate end of a wooden toothpick. A small piece of wood or a match stick will answer. These preparations can be readily examined without a cover-glass, using a ⅔ inch objective, with a 1-inch ocular.

Cultural methods give a higher percentage of success than looking for ova in the stools. Put a pile of 2 inch filter papers in the center of a Petri dish. Fill the dish with water to the level of the paper island. Smear a thick layer of faeces on the paper. The larvae hatch out and can be found by centrifuging the water.

It is usually stated that about 500 worms must be present for several months to produce symptoms. Grassi has thought that the presence of 150 eggs in 0.01 gm. faeces indicates the presence of 1,000 worms, of which 25% would be males.

There may be as many as 4,000,000 eggs in a stool. Bass has proposed the following method for the examination of faeces for ova: The faeces, which have been made fluid, should be centrifuged and the supernatant fluid containing vegetable débris poured off. The sediment contains hookworm eggs. Then pour on sediment a calcium chloride solution of sp. gr. 1.050. Again centrifuge and decant. Next add calcium chloride solution of a sp. gr. of 1.250 and centrifuge. This brings to the surface the hookworm eggs which may be pipetted off. As a rule, the finding of hookworm eggs is very easy without such a technique.

[Illustration: FIG. 93.—Ovum of _Ancylostoma duodenale_. By J. A. Thomson. (Jefferys and Maxwell.)]

Recently we have been using Barber’s technique. Emulsify the faeces in equal parts of glycerine and saturated salt solution on a slide. The eggs rise to the surface and are easily discovered with the ⅔-inch objective. As a centrifuge method, Barber emulsifies faeces in this same mixture which brings the eggs to the surface. A wisp of cotton is placed on the surface and 3 or 4 drops of melted agar dropped on the cotton. The disc of agar is removed with the cotton, deposited on a slide and examined for entangled eggs. With operculated eggs this method does not seem to be satisfactory as the salt solution loosens the operculum and floods the contents of the shell,—thus altering the specific gravity of the egg and preventing flotation.

_Lane Levitation Method._—Clayton Lane recommends a technique which he designates as the levitation method. In this procedure the concentrated sediment of a centrifuged specimen is transferred to a glass slide, where it is mixed with one cc. of water. The slide is allowed to stand for five minutes and is then immersed in water and manipulated until all coarse matter has floated free. The hookworm ova stick firmly to the slide and are not washed away. Lane reports that on an average this method results in a ten-fold concentration of ova.

In certain cases, where a microscope is not available, the diagnosis may be made by finding the worms in the stool following a thymol treatment.

Whyte has recommended the phenolphthalein test for occult blood as of value in determining the cure of ancylostomiasis. This test is so delicate that the least trace of blood from the mucosal lesion will be detected.

The presence of eosinophilia is of great assistance in diagnosis but it should be remembered that not rarely severe cases of the disease fail to show any excess of eosinophiles.

Charcot-Leyden crystals are often present in hookworm stools.

PROGNOSIS

The disease is more serious in children than in adults, on account of its interfering with physical and mental development. The dark races do not seem to suffer as much as the white ones. Treatment is usually most successful, but in those who are debilitated by other diseases or, in those in whom the disease has assumed a pernicious anaemia tendency, the outlook is not good.

The presence of eosinophilia is of good prognostic significance as the absence of eosinophiles indicates an exhaustion of the haemopoietic system.

The disease shortens the life of the people in an infected district and makes them readily fall victims to intercurrent diseases. Various statistics give the mortality as from less than one-half of 1% to figures approximating 7%.

PROPHYLAXIS AND TREATMENT

=Prophylaxis.=—The first measure is to diagnose infections in carriers and to insist upon the treatment of such persons. The proper disposal of the fecal material from hookworm patients is the objective point in prophylaxis.

The use of some type of properly constructed privy is essential as there is nothing more favorable to the development of the hookworm larvae from eggs to infecting stage than the practice of defecating on the ground where conditions of porous, sandy soil, shade and moisture exist. Later on, such a spot teems with infecting larvae and the person stepping there with bare feet is almost sure to become infected. For this reason the wearing of shoes is an important prophylactic measure. At the same time shoes are not a sure protection, as Ashford has noted infections in soldiers who wore good shoes. The fecal material, collected in a pail or tub, should preferably be burned or boiled. Otherwise it should be buried not less than 300 feet from the water supply and down hill from the same.

The best method is to use some septic tank process as the anaerobic processes of fermentation destroy the eggs.

The use of an amount of compound cresol solution equaling the fecal mass, plus urine, is of value.

Hookworm disease tends to disappear in towns or cities where there is an efficient sewerage system.

Hookworm disease is one of the most conspicuous examples of soil pollution disease.

Some authors think _Ancylostoma_ more difficult to expel than _Necator_.

=Treatment.=—The drugs best known in treatment are thymol and chenopodium but carbon tetrachloride offers the greatest promise.

_The Thymol Treatment._—Bozzolo introduced this drug in the treatment of hookworm disease in 1879. Thymol has an aromatic, thyme-like odor and a pungent taste and, while soluble in about an equal amount of alcohol, is only soluble in water in the proportion of 1 to 1100.

It is usual to prescribe the drug in 5-grain capsules or preferably in cachets, one part of thymol being triturated with an equal amount of sugar of milk. If the cachet is moistened with a little water it may be swallowed like a raw oyster.

Stiles prefers giving the treatment on Sunday so that the working days of the patient may not be lessened. By giving the patient bicarbonate of soda for a few days before the treatment it is thought that the mucus lining of the jejunum is cleared away so that the worms are more readily affected by the drug. At any rate one should give about 1 or 2 ounces of a 50% solution of Epsom salts on Saturday evening. Sodium sulphate is preferred by some.

The following morning at 6 A.M. the patient takes one-half the dose of thymol proper for his age and at 8 A.M. he takes the remaining half of the dose. At 10 A.M. he takes another dose of Epsom salts. The reason for dividing the dose of thymol is that should untoward symptoms occur after the first portion of the dose we do not give the second. Stiles now prefers to divide his dose into three portions, one to be given at 6 A.M., one at 7 A.M. and the remaining third portion at 8 A.M., followed by salts at 10 A.M. The patient should lie on the right side while taking the treatment to facilitate the passage of the drug from the often dilated stomach.

The patient should remain in bed until 12 o’clock when he may take some coffee, without milk, and crackers.

Patients must be warned to avoid anything containing fats or alcohol while undergoing treatment as fats and alcohol dissolve the thymol and tend to cause poisoning. Under no circumstances should castor oil be used. People are apt to forget that butter, milk, etc., contain the dangerous fats.

Seidell has shown that about one-third of the thymol dosage is excreted in the urine and very little by faeces. This shows absorption of the drug. It is thought some of the drug may be excreted by the lungs. Congestion of the lungs has been reported in fatal cases of thymol poisoning.

Mild symptoms of poisoning are burning in the pit of the stomach and tingling sensations of the body. More severe symptoms are those associated with cardiac weakness and respiratory distress. Coffee and strychnine are the usual remedies for thymol poisoning. Inhalation, but not swallowing, of aromatic spirits of ammonia is often of value.

The thymol dosage recommended according to the age, or rather the apparent age of the patient, is:

Under 5 years old 7½ grains. From 5 to 9 years old 15 grains. From 10 to 14 years old 30 grains. From 15 to 19 years old 45 grains. From 20 to 59 years old 60 grains. Above 60 years old 30 to 45 grains.

Total dose to be divided into 2 or 3 portions. The patient is allowed to eat only a light luncheon and supper the day of the treatment but the next day he may resume his regular meals.

As a rule most of the worms expelled by the treatment will have been passed by night of the day of treatment, although an occasional one may be passed for four or five days.

In from 25 to 50% of cases all the worms may be expelled in one treatment but it is usually necessary to give as many as 3 treatments, one on each of three Sundays.

_Thymol and Beta-naphthol._—Nicol in a comparison of the efficacy of various drugs, noted that thymol in 90-grain doses, taken in 3 portions of 30 grains each, at 6, 8, and 10 A.M. expelled 98% of the worms at the first treatment and the remaining worms at the second treatment a week later. With this rather large dose he frequently observed a tendency to syncope. He used Epsom salts as a purgative.

On the other hand, while using 60 grains of beta-naphthol, given in two portions at 6 and 8 A.M., followed by salts, 86% of the worms were expelled at the first treatment and 14% with the second one. He did not observe any bad effects from beta-naphthol.

The great objection to beta-naphthol is that it is a renal irritant and may damage a kidney already diseased.

Nicol found the treatment with eucalyptus oil, 2 cc., chloroform, 3 cc. and castor oil, 30 cc. vastly inferior in anthelminthic effect to the other two treatments and liable to cause severe manifestations of nausea and syncope.

It is better to divide the dose as just stated into two portions, the second half to be given about one-half hour after the first portion. This reduces the danger from the chloroform.

Schüffner tried male fern and only obtained 7 hookworms while the next day, using thymol, 1253 hookworms were expelled. He notes that thymol is dangerous when administered to patients with acute or subacute dysentery.

In Brazil a tabloid of 5 grains beta-naphthol combined with 1 grain of phenolphthalein has been generally employed. Using phenolphthalein in this way enables them to dispense with purgation.

_Oil of Chenopodium Treatment._—As the result of comparing the relative efficiency of thymol and oil of chenopodium the International Health Board Commission reported in favor of oil of chenopodium. In only 7.6% of the cases treated with chenopodium was there failure to eradicate the parasites while there was noted 23.6% of failures with thymol. The dose of oil of chenopodium recommended was 1.5 cc. given in three divided doses of O.5 cc. at 7, 8, and 9 o’clock in the morning. Two such treatments will remove 99% of worms present in a case. The Commission found the oil more efficient than an emulsion of the oil.

The low diet and preliminary dose of salts, as noted under thymol treatment, are to be recommended although the commission found various purges to have little effect on the results of treatment. At 11 o’clock give a purgative dose of magnesium sulphate.

The maximum dose of oil of chenopodium is usually given as 3 cc. but a number of deaths have followed the administration of doses of from 2 to 3 cc., so that it is better to keep within 1.5 cc.

After effects of treatment, such as dizziness, depression, unsteady gait, partial loss of consciousness, tingling of hands and feet, burning sensation in the epigastric region and nausea are more frequent with chenopodium than following thymol. The toxic symptoms may be greatly delayed and even be postponed for a day or so. A large dose of castor oil seems to be the most important measure in treating a case of chenopodium poisoning. The same methods of stimulation as noted under thymol poisoning are also indicated.

Kantor has treated a large number of cases with oil of chenopodium administered through the duodenal tube. After the bucket had passed the pylorus he introduced into the duodenum about 2 cc. of oil of chenopodium and followed this in six minutes with two (2) ounces of a warm saturated solution of magnesium sulphate. The tube is withdrawn after introducing the salts. Several copious watery stools follow in a short time.

_Carbon tetrachloride_ in a dose of 3 cc. administered in hard gelatine capsules, is recommended by Hall for the removal of hookworms and ascarids. The drug is cheaper, more effective, and, when chemically pure, safer than thymol or chenopodium. It does not depress unstriated musculature or lessen peristalsis, thus eliminating the use of purgatives, which is an item of expense in extensive hookworm campaigns. The drug is of no value in treatment of tapeworms and is as unreliable as other anthelminthics for the removal of whip-worms.

There is a rapidly growing mass of reports concerning the clinical use of carbon tetrachloride, all of which agree in confirming experimental observations regarding its effectiveness, and indicate that a standard dosage as high as 10 to 12 cc. may be safely employed.

After expelling the worms it is advisable to give the patient a tonic containing iron or arsenic. In those cases with a tendency to pernicious anaemia the arsenic treatment is better than that with iron.

In the treatment of ground itch the usual application is a zinc oxide ointment containing 10 grains of salicylic acid to the ounce.

Barlow recommends a 3% salicylic acid solution in alcohol.

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