Pseudotuberculosis

PSEUDOTUBERCULOSIS, a concept introduced in 1885 by Eberth, which unites an aetiologically very heterogeneous group of diseases, for which the formation of nodules in organs, externally resembling tuberculous ones, is characteristic. Pseudotuberculosis has no relation to tuberculosis. There were attempts to replace the term Pseudotuberculosis with another for clarification. Thus, Baumgarten proposed instead of Pseudotuberculosis the designation "infectiose miliare Leucocytombildung" or "granulosis micrococcica", Pfeiffer - "acute miliare Leucocytombildung", but the name Pseudotuberculosis nevertheless persisted. It is more correct, as will be seen from the following, to consider Pseudotuberculosis a variety of septicaemia, observed especially often in the animal kingdom. Cases of Pseudotuberculosis caused by bacteria, fungi (Blastomycetes, Streptothrix, Aspergillus, etc.), animal parasites (helminths), and even foreign bodies are distinguished. The name Pseudotuberculosis is most commonly used in relation to processes of bacterial origin. Among the bacteria causing pseudotuberculous changes in animals and humans, one must name Bac. pseudotuberculosis rodentium (Pfeiffer), Bac. pseudo-tuberc. ovis (Preisz-Nocard), Bac. pseudotuberc-murium (Kutscher), and others. In individual cases of Pseudotuberculosis, streptococci, paratyphoid bacteria, and others were detected. The bacillus of Pseudotuberculosis of rodents (Bac. pseudotub. rodentium) deserves the greatest attention, often causing severe epizoo-

Figure 1. Imprints from colonies of variants of Bac. pseudotuberculosis rodentium. Morphology of the bacteria of the variants: smooth (S) and rough (R₁ and R₂). R₁-periphery, R₂-central colonies, where larger forms predominate.

-otics among guinea pigs, rabbits, and other rodents; it has also been isolated in human diseases. It is also of interest due to its similarity to the causative agent of plague (Bact. pestis). This microbe was first isolated in 1883 (Malassez and Vignal); in 1889, it was described in detail by Pfeiffer. Bac. pseudotuberculosis rodentium in smears from organs and broth cultures is a short, clumsy, bipolar, ovoid-shaped bacillus that stains Gram-negative. It is non-motile, does not form capsules or spores, and grows on ordinary nutrient media. In liquid media, it forms chains. According to the latest research, Bac. pseudotub. rod. exhibits a characteristic phenomenon of dissociation, consisting of the splitting of the culture into a number of variants: 1) "smooth variant" - forms smooth, discoid colonies on agar with a shiny surface, with even edges, translucent with a bluish tint; the bacterial mass is viscous and emulsifies well; morphology of the bacteria - thin bacilli 1.5–3μ long, occasionally filaments (Fig. 1 S). In broth - homogeneous turbidity. 2) "Rough variant" - forms colonies on agar with a convex, granular center, sharply demarcated from the lacy peripheral zone, turbid with a brownish tint; the bacterial mass is dense and does not produce a homogeneous emulsion; morphology - shortened bipolar bacilli 0.8–1μ long with an admixture of coarse forms (4–8μ long) of bizarre outlines (Fig. 1 R). In broth, flocculent growth without turbidity. Besides the described extreme variants, a number of "intermediate" forms are observed. The smooth variant is more virulent than the rough one. In laboratory cultures, the microbe is usually encountered in the form of the rough variant. - The biochemical properties of the variants are identical. The microbe does not liquefy gelatin; does not coagulate milk; does not form indole; decomposes glucose, levulose, maltose, and mannitol with the formation of acid without gas; does not change lactose and sucrose. The reaction of the microbe to certain carbohydrates (rhamnose, adonitol) and experimental infection of laboratory animals is significant for distinguishing the Pseudotuberculosis bacillus from the plague bacillus (Bact. pestis). However, in practice, differentiation may encounter significant difficulties, and even immune reactions in this case do not present a completely reliable criterion. At present, one can rely on the following distinguishing features between these microbes: 1. White rats are resistant to infection with Bac. pseudotuberculosis, while being highly sensitive to Bact. pestis. This sign is fairly reliable but relative. Cases of increased virulence of the Pseudotuberculosis bacillus towards white rats are known; the plague microbe, conversely, may lose its virulence during storage in the laboratory. 2. A characteristic unequal change in the concentration of hydrogen ions (pH) in cultures of these microbes: Bac. pseudotuberculosis alkalizes the medium faster than Bact. pestis. 3. In relation to certain carbohydrates, these microbes also show different activity, with the most reliable results given by media with rhamnose and adonitol, towards which the plague microbe proves inactive, in contrast to the Pseudotuberculosis bacillus. Epizootics of Pseudotuberculosis are most often observed among guinea pigs; rabbits are affected less frequently. Besides these rodents, according to a summary collected by Yurkevich, Bac. pseudotuberculosis was found several times in hares, then in cattle, pigs, horses, cats, chickens, and songbirds. Cases of its detection in grey rats have also been described. The prevalence of this microbe in the external environment is noted - it has been found in drinking and sewage water, in the air, in soil, milk, and spoiled oats. Infection under natural conditions apparently occurs most often through the digestive tract, as well as through the respiratory tract. The epidemiological role of insects has not been studied. Clinic. The disease in guinea pigs proceeds in three forms. In the septic form, which kills the animal in 1–2 days, nodules do not have time to develop, and phenomena of haemorrhagic septicaemia (haemorrhages on serous membranes, etc.) come to the fore. The most characteristic and common is the tuberculosis-like form, lasting about 5–15 days and causing the death of the animal with phenomena of exhaustion with the picture described below. The third form is cachectic, in which the animal dies in 2–4 weeks without characteristic pathological-anatomical changes. In experimental infection of guinea pigs, cases of recovery are sometimes observed (see Pathology of laboratory animals). - For the pathological-anatomical picture of Pseudotuberculosis, the following changes are characteristic: in the abdominal and thoracic cavities - semi-liquid, viscous exudate; internal organs are hyperaemic. The spleen is enlarged, dark red in color, permeated with greyish-white nodules slightly protruding above the surface of the organ, ranging in size from a millet seed to a small pea; nodules are also frequent in the liver, lungs, omentum, intestines, and in the mesenteric lymph nodes. Pseudotuberculous nodule (Fig. 2)

Figure 2. Pseudotuberculous nodule of the liver. (According to Roger.)

initially represents a miliary tissue necrosis (death of parenchymal cells around bacterial accumulations) and in acute course (which is generally observed in cases of P. in humans) reactive phenomena from the surrounding tissue are usually absent. In more prolonged course (more often in rodents) exudative processes develop due to lymphoid and polymorphonuclear cells. Giant and epithelioid cells are usually absent, although this by no means can be considered a rule. With the development of the process, the nodule consists mainly of caseous necrotic mass, often with softening in the center. No calcification of caseous masses is observed. For some rodents, characteristic features of the lesion are noted. Thus, for example, in rabbits, in addition to the above-described changes, characteristic changes in the vermiform appendix are observed. The appendix is enlarged, has the appearance of a dense tube, completely studded with nodules the size of a mustard seed. Bacteria in the developed nodules are rarely found microscopically (evidently as a result of loss of the ability to be stained). In more acute cases, on the contrary, accumulations of bacteria ('zoogloeae') are found, from which the French name 'tuberculose zoogleique' is derived. The culture of the causative agent, both from organs and from blood, is isolated without difficulty. From a differential-diagnostic point of view, it is important to mention that the similarity, more significant than with a tuberculous nodule, exists with nodules observed in glanders and in the subacute form of plague. It is also noteworthy to note that with intraperitoneal infection in guinea pigs, orchitis can develop, analogous to that of glanders (Ramon and others). Cases of bacterial P. in humans to the present time have been described in a very small number. A significant part of them should be considered doubtful, since the culture of the causative agent was not isolated directly from humans, but through inoculation to experimental animals, in which spontaneous P. cannot be excluded. In a review of the literature up to 1927, Poppe (Porre) cites 10 such doubtful cases and 11 cases, the etiology of which is undoubtedly associated with infection by Bac. pseudotuberculosis rodentium or closely related microbes. Diseases were observed in newborn children (in the first days of life) and in adults. The course is as a rule very acute, rapidly ending in death. In adults, a typhoid-like picture is observed, with high temperature, sometimes with jaundice. There are no characteristic diagnostic signs in the clinical picture. In the described cases, the diagnosis was made on the basis of bacteriological examination, and the culture of the causative agent was obtained either during life - from blood, or at autopsy - by sowing from internal organs affected by a characteristic patho-anatomical process. Several cases of localized lesions of a pseudotuberculous nature have also been described, which upon bacteriological examination gave cultures of microbes similar to the P. bacillus, for example, a case of inflammation of the middle ear, cases of conjunctivitis resembling Parino's disease, a case of appendicitis, in which the culture was obtained from ulcers and suppurating follicles of the removed segment of the intestine and lymph glands, and the isolated microbe agglutinated up to a dilution of 1:1280 with the patient's serum, etc. In newborn children, infection is assumed to occur during passage through the lower birth canal, and the infection apparently enters through the mouth, from where it enters the intestine and the portal vein system. Children die within 1-2 days. At autopsy, as a rule, lesions of the lymphatic apparatus of the intestine and mesenteric glands and multiple necrotic nodules in the liver and spleen are noted. Bacteriologically, among the strains of the P. bacillus isolated from humans, a division into two varieties is observed: one identical or almost identical with the microbe isolated from rodents, and the second, differing from it in its relation to Gram staining (Gram-positive). This second variety was as a rule observed in diseases of newborn children. Undoubtedly, the problem of P. deserves more attention than has been paid to it to date, and requires further study and accumulation of facts. This is especially true of the bacteriology, epidemiology, and clinic of bacterial P. in humans.