Man is one of those organisms in on on which a whole host of parasites find conditions suitable for their existence: Protozoa, Platyhelminthes, Nematoda, Acanthocephala, Hirudinea, and a large number of Arthropoda (Arachnida as well as Insects) all include members which are parasites of man. These animals either live on the external surface of the body or within the intestine and its appendages. Other organs and systems are not quite free from foreign organisms—we are acquainted with parasites in the skeletal system, in the circulatory system, in the brain, in the muscles, in the excretory and genital organs, and even in the organs of sense.

It is possible, and perhaps might be advantageous, to arrange and describe the parasites of man according to the situations in which they are found (parasites of the skin, intestinal parasites, etc.). Their description in the various stages of development would, however, be disturbed when, as is generally the case, the different stages are passed in different organs, and a work which treats more fully of the natural history of the parasites than of the local disorders to which they give rise would suffer thereby. It is, therefore, preferable to describe the parasites of man in their systematic order, and to mention their different situations in man in describing each species.

All those animal organisms which throughout their entire life never rise above the unicellular stage, or merely form simple, loose colonies of similar unicellular animals, are grouped under the term Protozoa (Goldfuss, 1820), as the simplest types of animal life. All the vital functions of these, the lowest forms of animals, are carried out by their body substance, the protoplasm (sarcode). Often particular parts possess special functions, but the limits of a cell are never over-stepped thereby. These special parts of the cell are called “cell-organs”; recently they have been termed “organellæ.”

The living protoplasm has the appearance of a finely granular, viscid substance which, as a rule, when not surrounded by dense investing membranes or skeletons, exhibits a distinct kind of movement, which has been termed amœboid. According to the species, processes of different forms and varying numbers called pseudopodia are protruded and withdrawn, and with their assistance these tiny organisms glide along—it might almost be said flow along—over the surface. In most Protozoa two layers of cytoplasm may be recognised, and distinguished by their appearance and structure, namely, the superficially situated, viscid, and quite hyaline ectosarc or ectoplasm, and the more fluid and always granular endosarc or endoplasm, which is entirely enveloped by the ectoplasm. The two layers have different functions; the movements originate from the ectoplasm, which also undoubtedly fulfils the functions of breathing, introduction of food and excretion. The endoplasm, which in some forms (Radiolaria) is separated from the ectoplasm by a membrane, undertakes the digestion of the food. To this distribution of functions between the various layers of cytoplasm is due the development of particular cellular organs, such as the appearance of cilia, flagella, suctorial tubules (in the Suctoria) and the myophan striations, which are contractile parts of the ectoplasm in Infusoria and Gregarines. In many cases (Flagellata, Ciliata), an area is differentiated for the ingestion of food (oral part, cytostome) to which there is often added a straight or curved opening (cytopharynx), through which the food reaches the endoplasm. The indigestible residue is either cast off through the oral part or excreted by a special anal part (cytopyge). In rare cases, structures sensitive to light, the so-called pigment or eye spots are developed, e.g., Euglena. In the case of Infusoria the endoplasm circulates slowly, and agglomerations of fluids (food vacuoles) sometimes appear around each bolus of food; in these vacuoles the food is digested under the action of certain materials (ferments). Even in the lowliest Protozoa fluids to be excreted are, as a rule, gathered into one, or, more rarely, several contractile vacuoles, which regularly discharge their contents. This action, however, is to a certain extent governed by the temperature of the surrounding medium. In some Infusoria a tube-like channel in the cytoplasm is joined to the contractile vacuole which usually occupies a certain position; this forms a sort of excretory duct, and there are also supply-canals leading to these organellæ.

Very frequently various substances are deposited in the endoplasm, such as fatty granules, drops of oil, pigment granules, bubbles of gas or crystals. More solid skeletal substances are secreted in or on the ectoplasm. To the latter belong the cuticle of the Sporozoa and Infusoria, the chalky shells containing one or several chambers of the Foraminifera, the siliceous and very ornamental framework of the Radiolaria, and the chitinous coat of many Flagellata, Infusoria, etc. Some forms make use of foreign bodies found in their surroundings, such as grains of sand, to construct their protective coverings.

The food often consists of small animal or vegetable organisms and of organic waste; it is usually introduced in toto into the endoplasm. On the other hand, the Suctoria extract nourishment from their prey by means of their tentacles. Many parasitic species also ingest solid food, others feed by endosmosis.

In all cases one nucleus at least is present. It is true that the existence of non-nucleated Protozoa, the so-called Monera, is still insisted upon, but some of these have already proved to be nucleated, and the presence of nuclei in the others will no doubt be established. Very often the number of nuclei increases considerably, but these multinucleate stages are always preceded by uninucleate stages. In the Infusoria, in addition to the larger or principal nucleus (macronucleus) there is usually a smaller reproductive nucleus (micronucleus). This dualism of the nuclear apparatus is considered by some to be general, and usually to appear first at the onset of reproduction.

The form and structure of the nucleus vary greatly in different species. There are elongate, kidney-shaped, or even branched nuclei as well as spherical or oval ones. In addition to vesicular nuclei with a distinct karyosome and incidentally also with a nuclear membrane, homogeneous and more solid formations are frequently encountered. The nuclei are always differentiated from the protoplasm by their reactions, particularly in regard to certain stains.

In many Protozoa an extra-nuclear mass, sometimes compact, sometimes diffuse, arises from or near the nucleus. This mass, whose staining reactions resemble those of the nucleus, is termed the chromidial apparatus. On the dualistic hypothesis, two varieties of chromidia occur, one originating from the vegetative nucleus (macronucleus), being chromidia in the restricted sense, the other derived from the reproductive or micronucleus being termed sporetia. Chromidia consist of altered (? katabolic) nuclear material.

The nucleus plays the same part in the life of the single celled organisms as it does in the cells of the Metazoa and Metaphyta. It appears to influence in a certain manner all, or at least most, of the processes of life, such as motility, regeneration, growth, and generally also digestion. Its principal influence, however, is exercised in the propagation of the cells, as this is always brought about by the nucleus.

The PROPAGATION of the Protozoa is effected either by division or by means of direct budding. In division, which is preceded by direct or indirect (mitotic) division of the nucleus, the body separates into two, several, or even a great many segments. In this process the entire substance of the body is involved, or a small residual fragment may be left, which does not undergo further division and finally perishes. In the budding method of multiplication a large number of buds are formed, either on the surface or in the interior of the organism. Where divisions or buddings follow one another rapidly, without the segments separating immediately after their production, numerous forms develop, which are often unlike the parental forms, and these are termed swarm spores or spores. Divisions imperfectly accomplished lead to the formation of protozoal colonies.

Sometimes encystment9 takes place previous to division. Frequently, also, sexual processes appear, such as the union of two similar (isogamous) or dissimilar (anisogamous) individuals. In the latter case sexual dimorphism occurs, with the formation of males (microgametes) and of females (macrogametes). The union may be permanent (copulation), the process being comparable with the fertilisation of the ovum by a spermatozoon. On the other hand, attachment may be transient (conjugation) when, after the exchange of portions of the nucleus, the couple separate, to multiply independently of each other. Sometimes there is an ALTERNATION OF GENERATIONS, as there may be several methods of propagation combined in the same species, either direct multiplication, conjugation, or copulation being practised; the different generations may thus, in certain cases, be unlike morphologically.

Protozoa inhabit salt water as well as fresh water; they are also found on land in very damp places, and invade animals as parasites.

Class I.—Sarcodina (Rhizopoda). Protozoa, the body substance of which forms pseudopodia; many of them are capable of developing chitinous, chalky, or siliceous coverings or skeletal structures, which, however, permit the protrusion of the pseudopodia either over the entire periphery or at certain points. They possess one nucleus or several.

Class II.—Mastigophora (Flagellata). Protozoa with one or several long flagella used for locomotion and for acquiring food; in stationary forms their only function is to take in food. Cytostome and contractile vacuole may be present. May be either naked or provided with protective coverings; one or more nuclei. They live either in fresh or salt water, or may be parasitic.

This class is again divided into several sub-classes and orders, of which only the Euflagellata, with the Protomonadina and Polymastigoda are of interest here.

Class III.—Sporozoa. Protozoa that only live parasitically in the cells, tissues, or organs of other animals. They ingest liquid food by osmosis; the surface of the body is covered with an ectoplasmic layer, or cuticle; they have no cilia in the adult state, but may form pseudopodia. Flagella occur, but only on the male propagating individuals. There may be one or numerous nuclei, but no contractile vacuole. Propagation by means of spores, mostly provided with sporocysts, is characteristic.

Sub-class 1.—Telosporidia. These are usually of constant form, rarely amœboid; they are uninucleate in the mature state; they live within host cells in the first stage. Spore-formation occurs at the end of the life-cycle.

Sub-class 2.—Neosporidia. They are multinucleate when adult, and the form of the body varies exceedingly (often amœboid); spore-formation commences before the completion of growth.

Class IV.—Infusoria (Ciliata). The body is generally uniform in shape, with cilia and contractile vacuole, frequently also with cytostome; usually has macro- and micro-nucleus; live free in water and also parasitically.

The orders Holotricha, Heterotricha, Oligotricha, Hypotricha and Peritricha are classified according to the arrangement of the cilia.

Class V.—Suctoria. Bodies with suctorial tubes, contractile vacuoles, macro- and micro-nucleus, no cytostome. They generally invade aquatic animals as cavity parasites, yet also attack plants; early stage ciliated. Live sometimes as parasites on Infusoria. [The Suctoria are frequently regarded as a sub-class of the Infusoria.]

The Protozoa and Protophyta are sometimes united under the term Protista (Haeckel, 1866). The Spirochætes are Protists (see pp. 114–128).

The first record of the occurrence of amœba-like organisms in the human intestine, that is, in intestinal evacuations, was that of Lambl (1859); nevertheless, the case was not quite conclusive, as the occurrence of testaceous amœbæ of fresh water (Arcella, Difflugia) was also reported. In 1870 Lewis found amœbæ associated with disorders of the large intestine in patients in Calcutta. A year later Cunningham reported from the same locality that he had observed on eighteen occasions, in one hundred examinations of dejecta from cholera patients, colourless bodies with amœboid movements, which became encysted and multiplied by fission. The daughter forms were said to be capable of dividing again, but they might also remain in contact. Contractile vacuoles were not noticed. The same bodies were observed also in simple diarrhœa (twenty-eight cases out of one hundred.)

The case reported by Lösch in 1875 attracted more attention. It was that of a peasant, aged 24, who came from the province of Archangel. He was admitted into Eichwald’s clinic at Petrograd with symptoms of dysentery. In the discharges containing blood and pus, Lösch found amœbæ in large numbers. When at rest these amœbæ measured from 20 µ to 35 µ; in a state of movement their length might extend up to 60 µ (fig. 1). The pseudopodia appeared only singly, and, since they were hyaline (ectoplasmic), were thus distinguished from the markedly granular endoplasm that enclosed a spherical nucleus of from 5 µ to 7 µ in diameter. One or more non-contractile vacuoles were present. Quinine enemata had the effect of making the amœbæ disappear from the fæces and thus causing the diarrhœa to abate. Four months after admission the patient died from the results of intercurrent pneumonia. At the autopsy ulceration of the large intestine was found, especially in the lower parts. Lösch connected the amœbæ with the ulcerations by experiments made on four dogs by injecting them with recently passed stools (per os et anum). Eight days after the last injection numerous amœbæ were found in the fæces of one of these dogs; eighteen days after the injection the animal was killed. The mucosa of the rectum was inflamed, covered with blood-stained mucus and ulcerated in three places. Numbers of amœbæ were found both in the pus of the ulcers and in the mucus. The three other dogs remained healthy. From these observations Lösch concluded that the species of amœba described by him as Amœba coli could not be regarded as the primary cause of the disease, but that it was certainly capable of increasing a lesion of the large intestine already present, or at least of preventing its healing.

B. Grassi (1879) found in the stools of healthy as well as in those of diarrhœic patients from various localities in Northern Italy, amœbæ similar to those discovered by Lösch. As this was of frequent occurrence, the pathogenicity could not be definitely established. Normand, formerly naval surgeon at Hong-Kong, observed numerous amœbæ in the dejecta of two patients suffering from colitis.

Many further investigations, which cannot be quoted in detail, showed not only that intestinal amœbæ were widely distributed in man, but indicated with greater certainty their rôle as agents of dysentery. The Commission sent out by the German Government in the year 1883 to investigate cholera in India and Egypt—whose members discovered the cholera bacillus—also collected information with regard to dysentery. In five cases of dysentery examined post mortem at Alexandria, with the exception of one case in which ulceration of the colon had already cicatrized or was approaching cicatrization, R. Koch found amœbæ as well as bacteria in sections from the base of the ulcers, although such had previously escaped notice in examination of the dejecta. Encouraged by these results, Kartulis (1885), who had discovered amœba-like bodies in the stools of patients suffering from intestinal complaints at Alexandria, continued his investigations. The results, obtained from more than 500 cases, gave rise to the theory that typical dysentery was caused by amœbæ as were also the liver-abscesses that often accompany it. Kartulis supported his theory not only by the regular occurrence of amœbæ in the stools of dysenteric patients and their absence in other diseases, and by the occurrence of the parasites in ulcers of the large intestine and in the pus from liver-abscesses, but also by experiments which he performed on cats. These were infected by injection per anum of stool material rich in amœbæ from subjects of dysentery. The infection took place also when amœba-containing, but bacteria-free, pus from liver-abscesses was used. It has been objected that the infection of man with Amœba coli, as the dysenteric amœbæ were then generally designated, does not take place per anum but per os. This difficulty, however, diminished in proportion as the encysted states of amœbæ (fig. 2), long known in the case of other Protozoa, became understood. The infection of man (Calandruccio, 1890) and of cats (Quincke and Roos) succeeded solely when material containing such stages was used. Amœbæ introduced into the intestine multiply there by fission (Harris, 1894). However, this theory, to which various other authors gave support on the grounds of their own observations, encountered opposition. Thus it was established that amœbæ were not found in patients in every place where dysentery was endemic, or else they were much rarer than was expected. Further, amœbæ were present in the most varied kinds of intestinal diseases, both of infective and non-infective characters. Also they were present in quite healthy persons.

Moreover, for various reasons, infection experiments on animals failed to supply proof, and finally a bacterium was discovered (Shiga, 1898) to be the excitant of one form of dysentery. Agglutination attested the specific part played by this organism, as it was produced by the blood serum of a person suffering from or recovered from dysentery, but not by the serum of one who was uninfected. Bacillary dysentery consequently was a distinct entity. The final step to be taken was to decide whether there was a specific amœbic enteritis (amœbic dysentery or amœbiasis, according to Musgrave).

This question should decidedly be regarded from the positive point of view. It is intimately connected with another, namely, whether there are not several species of intestinal amœbæ. The possibility of this had already been recognized. In addition to the Amœba coli Lösch, R. Blanchard distinguished yet another, Amœba intestinalis, and designated thereby the large amœbæ described in the first communication made by Kartulis; later on he stated the distinction between the species. Councilman and Lafleur10 (1891) considered the amœba of dysentery to be Amœba coli Lösch and so re-named the species Amœba dysenteriæ. Kruse and Pasquale (1893) employed the same nomenclature, but retained the old name Amœba coli Lösch for the non-infectious species. Quincke and Roos (1893) set forth three species: a smaller species (25 µ) finely granular, pathogenic for men and cats (Amœba coli Lösch); a larger species (40 µ) coarsely granular, pathogenic for men but not for cats (A. coli mitis); and a similar species non-pathogenic either for man or cat (A. intestini vulgaris). Celli and Fiocca (1894–6) went still further, they distinguished:

(1) Amœba lobosa variety guttula (= A. guttula Duj), variety oblonga (= A. oblonga Schm.) and variety coli (= A. coli Lösch).

(2) Amœba spinosa n. sp. occurring in the vagina as well as in the intestine of human patients suffering from diarrhœa and dysentery.

(3) Amœba diaphana n. sp. found in the human intestine in cases of dysentery.

(4) Amœba vermicularis Weisse, present in the vagina and in dysentery; and

(5) Amœba reticularis n. sp. in dysentery.

Shiga distinguished two species; a larger pathogenic species with a somewhat active movement, and a small harmless species with a somewhat sluggish movement. Bowman mentions two varieties, Strong and Musgrave (1900) two species—the pathogenic Amœba dysenteriæ and the non-pathogenic Amœba coli; Jäger (1902) and Jürgens (1902) mention at least two species. In the following year (1903) a work by Schaudinn was published which marked a real advance. This, in conjunction with the establishing of a special genus (Endamœba or Entamœba) for human intestinal amœbæ first by Leidy11 and then by Casagrandi and Barbagallo,12 for the time cleared up the confused nomenclature, the old name Amœba coli being retained for the harmless intestinal amœbæ of man, whereas the pathogenic species was designated Entamœba histolytica. The history of more recent work is incorporated in the accounts of the entamœbæ given below.

There are varying accounts of the details of the life-cycle of Entamœba coli in its different stages. Thus, regarding schizogony or multiple fission it was formerly stated that the nucleus of the parent amœba divided into eight portions, which after dissolution of the nuclear membrane, passed outwards into the cytoplasm, which segregated around each. Eight merozoites were thus produced. More recently the process of schizogony has been considered to consist in the repeated division of the nucleus into two, four, and finally eight nuclei (fig. 3, A-D), and the formation of eight merozoites or amœbulæ.

The process of encystment is initiated by the extrusion of all liquid and foreign bodies from the protoplasm, which assumes a spherical form (fig. 4, A). The rounded uninucleate amœba then secretes a soft gelatinous coat, which finally differentiates into a double contoured cyst wall in older cysts. According to Casagrandi and Barbagallo, the size of the cyst varies from 8 µ to 30 µ, and averages about 15 µ. According to Schaudinn (1903) the cytological changes during cyst formation are as follows. The nucleus of a rounded uninucleate form divides into two (fig. 4, B). Each of these nuclei fragments into chromidia (fig. 4, C), some of which are absorbed, while others reunite so that the cell becomes binucleate again. Each of these nuclei, by a twice repeated division, produces three nuclei (fig. 4, D), the smaller two of which degenerate and were regarded as reduction nuclei. There is a clear zone or vacuole in the middle of the cyst during these maturation processes, dividing the cyst into two halves. After the nuclear reduction the clear space disappears, and each nucleus (termed by some a gamete nucleus) divides into two pronuclei (fig. 4, E). The pronuclei of the pairs were said by Schaudinn to differ slightly. Copulation occurs between pairs of unlike pronuclei, and is an example of autogamy (fig. 4, F). When complete, each of the fusion nuclei (synkarya) divides twice, giving rise first to four and finally to eight nuclei. Eight amœbulæ are thus formed within the cyst.

According to Hartmann and Whitmore (1911)13, however, autogamy does not occur within the cysts of E. coli. They consider that eight small amœbulæ are formed (fig. 3, 2-10) which escape from the cyst and then conjugate in pairs (fig. 3, 10-12), afterwards growing into a new generation of trophozoites.

Only some 10 to 20 per cent. of the cysts evacuated with the fæces undergo the full course of development, the majority perish previously. In old dry fæces, only cysts with eight nuclei are found, and it is these alone that cause the infection.

Entamœba williamsi, E. bütschlii, E. hartmanni and E. poleki (Prowazek) are probably only varieties of E. coli.

In the large intestine of infected cats the amœbæ creep over the epithelium, and here and there they force the epithelial cells apart, as well as removing them or pushing them in front of them; the amœbæ thus insert themselves into the narrowest fissures. They penetrate also into the glands through the epithelium, and thence into the connective tissue of the mucosa. Intestinal and glandular epithelia perish under the influence of these parasites: the cells are pushed aside, fall to pieces or are absorbed by the amœbæ. In the connective tissue of the mucosa the amœbæ migrate further, and often accumulate above the muscles. Finally they rupture this and force their way into the submucosa. In cats, apparently, the penetration is not so great as in men, according to Kruse and Pasquale. During their migration the parasites also gain access to the lymph-follicles of the wall of the intestine, which become swollen and commence to suppurate; follicular abscesses arise and after their rupture follicular ulcers. The diseased patches in the mucosa are markedly hyperæmic and numerous hæmorrhages are set up. Roos and Harris state that the amœbæ also penetrate into the blood-vessels (fig. 7) and this explains the occurrence of metastatic abscesses.15 The whole submucosa is severely swollen at the diseased spot and undergoes small-celled infiltration in the neighbourhood of the colonies of amœbæ. From these findings Jürgens (1902) draws the conclusion16 which is followed here, that the amœbæ are causative agents of the enteritis of cats, which disease is well defined, both pathologically and anatomically. Subsequent researches confirm the experience of earlier authors; great precautions were taken to exclude errors, hence, as with Gross and Harris, no exception can be taken to their results. The inoculation material was derived from soldiers who suffered from amœbic enteritis in China and who were admitted into the garrison hospital at Berlin. In order to be independent of the patients themselves, transmission experiments from cat to cat were performed, after the first experiments on cats yielded positive results. This was also effected by rectal feeding as employed by earlier workers. Such appeared necessary in order to prevent the evacuation of the inoculation material per anum, as well as to avoid the employment of morphia and ether narcosis. Forty-six cats were used for the experiments. Ten cats received tested stools containing motile amœbæ from soldiers suffering from amœbic enteritis contracted in China. Sixteen other cats received stools from cats infected by inoculation. All the animals sickened and suffered from the disease. Five cats received dejecta from human amœbic enteritis in which, however, no motile amœbæ were present. Thirteen cats received stools from soldiers who suffered from bacillary dysentery. None of the latter cats took the complaint and none showed changes in the large intestine upon sectioning. The injection of various bacteria, obtained from a stool of amœbic enteritis pathogenic to cats, remained without result in both the cats employed for this experiment. Lastly, two cats, which had been kept with those artificially infected, were taken ill spontaneously and suffered from the disease. In the opinion of Harris, who ascertained the harmless nature of bacteria derived from the intestinal flora containing dysenteric amœbæ, young dogs are capable of being infected.

Within the large intestine an active increase of Entamœba histolytica must occur. Nevertheless, Jürgens did not definitely find changes that might be interpreted in this sense. Schaudinn (1903) observed division and gemmation in vivo. Both processes, in which the nucleus divides by amitosis, can only be distinguished by the fact that the daughter individuals are similar in binary fission but dissimilar in gemmation, whether they make their appearance singly or in greater numbers. Schizogony, resulting in the formation of eight individuals, which is so characteristic for Entamœba coli, was not observed. (But schizogony, into four merozoites, is now known to occur. Gemmation processes are apparently degenerative.)

Resistant stages, which serve for transmission to other hosts, are according to Schaudinn17 first formed when the diseased portions commence to heal, or more accurately, the recovery commences when the vegetative increase of the amœbæ in the intestine discontinues. The so-called spores of E. histolytica were distinguished very definitely from those of E. coli; they were said to consist of spheres of only 3 to 7 µ in diameter, which were surrounded by a double membrane, at first colourless, but becoming a light brownish yellow colour after a few hours, and possessing a protoplasmic content containing chromidia. They were said to arise by fragments of chromatin passing outwards from the nucleus of the amœba into the surrounding cytoplasm (fig. 9, a) and undergoing so marked an increase that finally the whole cytoplasm became filled with chromidia. The remainder of the nucleus underwent degeneration and became extruded. On the surface of the cytoplasm there then arose small protuberances containing chromidia. These processes had been observed in the living organisms. They gradually divided and separated from membranes which later became yellow. The remainder of the amœba perished. Craig18 had also seen phases of this process of development. It must be remarked that, according to recent researches, these processes of exogenous sporulation are degenerative in character (see p. 41). The small spores may be fungi. The “sporulation” processes are only mentioned here as a warning. They are now only of historic interest. By means of an experiment made on a cat, Schaudinn ascertained that ingestion of permanent cysts, which resist desiccation, is the cause of the infection. The animal took food containing dry fæces with amœba cysts; these fæces came from a patient suffering from amœbic enteritis in China. On the evening of the third day the cat evacuated blood-stained mucous fæces which contained large numbers of typical Entamœba histolytica. On the fourth day after the infection the animal experimented upon died, and the large intestine showed the changes previously stated.

E. histolytica also is found in the large intestine. This was originally shown to be the case by Kartulis, and the fact has recently been confirmed from many quarters. It is also present in the metastatic abscesses of which it is the cause (cf. among other authors, Rogers, Brit. Med. Journ., 1902, ii, No. 2,177, p. 844; and 1903, i, No. 2,214, p. 1315).

It should lastly be pointed out in this connection that mixed infections also take place. For instance, in addition to E. histolytica, E. coli, and, under certain circumstances, flagellates may be found together. In the same way E. coli may come under observation even in bacillary dysentery. On the other hand, Schaudinn stated that in cases of dysentery endemic in Istria, Entamœba coli, if it had hitherto been present, disappeared, to return again after recovery from the illness.