The Chlamydozoa

The name Chlamydozoa was proposed by Prowazek in 1907 for a number of minute, problematic organisms (fig. ) believed to be the causal agents of certain diseases in man and animals, such as vaccinia and variola, trachoma, inclusion blenorrhœa in infants, molluscum contagiosum, and bird epithelioma contagiosum. Other diseases possibly due to Chlamydozoa are hydrophobia, measles, scarlet fever, foot-and-mouth disease, the “Gelbsucht” disease of silkworms, and perhaps even typhus (Prowazek, 1913). The subject is difficult and controversial and can only be briefly discussed here. It is known that the viruses in all these diseases can pass through ordinary bacterial filters, that is, they belong to the group of “filterable viruses.” At such periods the organisms are extracellular or free. It is also known that in many of these cases the virus produces definite and characteristic reaction-products or cell-inclusions in the infected cells, during the intracellular phase of the life-history of the organism. As the organisms to be considered are problematic, it will be convenient to summarize their history:—

(1) Cell-inclusions, usually named after their discoverers, have been found in certain diseases, thus: In vaccinia Guarnieri’s bodies, in scarlet fever Mallory’s bodies, in hydrophobia Negri’s bodies, in trachoma Prowazek’s bodies occur.

(2) At first these characteristic cell-inclusions were considered to be actual parasitic organisms causing the diseases in question. The bodies received zoological names and attempts were made to work out their supposed development cycles. The supposed parasites of vaccinia and variola were referred to a so-called genus Cytoryctes, those of hydrophobia to Neuroryctes, of scarlet fever to Cyclasterium, while those of molluscum contagiosum were referred to the Coccidia. Calkins in 1904 studied in detail the cell-inclusions of vaccinia and small-pox, calling them Cytoryctes variolæ, Guarnieri. Calkins considered that in the stratified cells of the epidermis they passed through two cycles, the one cytoplasmic, the other intranuclear. The first is the vaccinia cycle, the second the pathogenic (intranuclear) variola cycle. It is hardly necessary to follow all Calkins’ stages here.

Negri (1909) described a cycle for Neuroryctes hydrophobiæ. Calkins refers both Cytoryctes variolæ and Neuroryctes hydrophobiæ to the Rhizopoda.

Siegel (1905) described quite different organisms under the name Cytorhyctes. He listed several species: C. vacciniæ; of vaccinia and small-pox, C. scarlatinæ of scarlet fever, C. luis of syphilis (this is probably the granule stage of Treponema pallidum), and C. aphtharum of foot-and-mouth disease.

(3) The afore-mentioned views were criticized, and the bodies were not considered to be living organisms but merely reaction products or cell-inclusions due to the effects of the virus on the host cells. Thus Guarnieri’s bodies were stated to consist of extruded nucleolar or plastin material, having no developmental cycle. It was further asserted that infection could be produced by lymph in which Guarnieri’s bodies had been destroyed. Similar assertions have been made regarding the Negri bodies, and others. The Cytoryctes, Neuroryctes, etc., are considered, according to these views, to be degeneration products of the nucleus or to be of a mucoid nature.

(4) More recently a positive belief has gained ground that there are true parasitic organisms causing these diseases, and that the parasites are very minute, being termed Chlamydozoa by Prowazek and Strongyloplasmata by Lipschütz.

The Chlamydozoa are characterized by (a) their very minute size, smaller than any bacteria, so that they can pass through bacterial filters; (b) they pass through intracellular stages, in the cytoplasm or the nucleus of the host cell, producing therein the reaction products or inclusions in the cell already recorded as characteristic or diagnostic of the diseases produced; (c) they pass through definite developmental cycles. Such a cycle consists essentially of growth and division. The mode of division of the Chlamydozoa resembles that of the centriole of a cell, by the formation of a dumb-bell-shaped figure. Two dots are observed connected by a fine line or strand which becomes drawn out and finally snaps across the middle. Prowazek and Aragão (1909) working on smallpox in Rio de Janeiro found that the chlamydozoal granules passed through a Berkefeld filter and that the filtrate was virulent. But if an “ultra-filter” were used, i.e., one coated with agar, then the granules were retained and the filtrate was no longer virulent. The surface of the ultra-filter was found to contain many granules.

The Chlamydozoa are parasites of epiblastic tissues (e.g., epidermal cells, nerve cells, conjunctival cells).

The life-history of a Chlamydozoön (fig. 119), such as that of vaccinia, is, according to Prowazek, Hartmann and their school, as follows:—

1. The infection begins with elementary bodies or elementary corpuscles which live at first extracellularly. An elementary body is a minute speck of chromatin, apparently devoid of cytoplasm, which can pass through a bacterial filter. It can enter a host cell, but the entry is not a process of phagocytosis.

2. Inside the host cell the elementary body grows in size, and becomes an initial body (fig. 119, a).

3. A reaction on the part of the host cell results, for nucleolar, plastin substance is extruded from the cell-nucleus and surrounds the parasitic initial body. The latter is thus enveloped in a mantle (hence the name Chlamydozoa, from χλαμὑς, a mantle), and the characteristic cell-inclusion (Guarnieri’s body, Negri’s body, etc.) is produced. The nucleolar, mantle substance probably represents the “cytoplasm” of Cytoryctes, described by Calkins.

4. The body next breaks up into a number of smaller bodies known as initial corpuscles. These, in their turn, divide by simple division (in the manner already described) into numerous elementary bodies (fig. 119). Thus, the life-cycle is completed.

The Chlamydozoa are, then, the minute granules inside the body of the Cytoryctes variolæ or the Neuroryctes hydrophobiæ, so that the whole body of the Cytoryctes or Neuroryctes corresponds to the mantle and parasite of the Chlamydozoön. The Cytoryctes group is said to cause destruction of the host cell. The Cytoöikon group (e.g., trachoma bodies) causes proliferation of the host cell.

In September, 1913, Noguchi described the cultivation of the parasite of rabies in an artificial medium, similar to that used by him for the cultivation of Spirochæta recurrentis. The cultures were stated to be infective to dogs, rabbits and guinea-pigs. Levaditi, in December, 1913, stated that he had succeeded in cultivating spinal ganglia of rabid monkeys in monkey plasma.

Noguchi and Cohen (November, 1913) have succeeded in cultivating the so-called trachoma bodies, or at any rate bodies very closely resembling them morphologically. The medium employed was Noguchi’s ascitic fluid and rabbit kidney medium, as used for spirochætes. The coarser cultural forms stained blue with Giemsa’s solution, the finer ones stained red. Attempts to infect monkeys from the culture tubes failed.

From their behaviour on treatment with such reagents as saponin, bile and sodium taurocholate, Prowazek considers that the Chlamydozoa approach the Protozoa.