Syphilitic Lesions Research Articles

Limited protection of rabbits against infection with Treponema pallidum by immune rabbit sera.

After intradermal infection of rabbits with 3 x 10(6) Treponema pallidum (Melbourne 1 strain) samples of serum were taken at one, two, three, four, and six months after infection. Normal rabbits were passively immunised with these sera, challenged with intradermal doses (10(4), 10(3), 10(2), 10) of T. pallidum, and the latent periods of infection, lesion diameters, and the number of inoculation sites developing into lesions were observed. The sera taken at three, four, and six months reduced the number of intradermal inoculation sites that developed into syphilitic lesions after challenge with 10 T. pallidum. These same three sera also increased the latent period of infection after challenge with 10(4) T. pallidum. The transfer of 50 ml of immune serum per rabbit over a nine-day period before challenge had very little effect on the course of the challenge infection. Only a low level of immunity in rabbits to this strain of T. pallidum appears to be mediated by immune serum but this small degree of protection did increase with time after infection. Enhanced growth of T. pallidum in the serum-recipient rabbits did not occur, thus suggesting that none of the sera was immunosuppressive.

Susceptibility of rabbits to Treponema pallidum after infection with Mycobacterium bovis.

Rabbits stimulated with Mycobacterium bovis (strain BCG) one month before challenge with Treponema pallidum (Nichols) did not show any modification in their development of syphilitic lesions. A second infection with BCG given at the same time and at the same intradermal site as the T. pallidum challenge also failed to protect the rabbits against syphilis. Thus the non-specific activation of cell-mediated immunity by BCG does not appear to protect rabbits against T. pallidum infection even when both activation and challenge take place in the dermis. The role of the macrophage in syphilis remains obscure.

Macrophages in immunity to syphilis: suppressive effect of concurrent infection with Mycobacterium bovis BCG on the development of syphilitic lesions and growth of Treponema pallidum in tuberculin-positive rabbits

Paired groups of male rabbits were challenged with Treponema pallidum and Mycobacterium bovis BCG. One group had been sensitized to BCG by inoculation 3 weeks before challenge. All animals were challenged intradermally at multiple sites with T. pallidum alone, BCG alone, and both organisms into the same sites. The resulting lesions were followed clinically and histologically. BCG lesions enlarged more rapidly in sensitized rabbits, but they were otherwise no different from those in the controls. T. pallidum lesions enlarged and regressed simultaneously in both groups, but in the BCG-sensitized animals they became twice as large as those in the unsensitized rabbits. Mixed BCG-T. pallidum lesions showed the greatest differences in the two groups of animals. Like the pure BCG lesions, they enlarged more rapidly in the sensitized rabbits but began to recede after 1 week. The corresponding lesions in the controls enlarged more slowly and reached their maximum size after 3 weeks when the receding lesions in the sensitized animals were much smaller. The most marked histological-histochemical difference between the two groups of animals was in the number and activation of macrophages. These cells were more numerous in the mixed lesions of BCG-sensitized animals than in similar lesions of the controls and more activated as determined by beta-galactosidase staining. Although sparsely distributed, activated macrophages were more numerous in the pur T. pallidum lesions of sensitized animals than in those of control animals. Silver-stained sections revealed fewer treponemes in mixed lesions of sensitized animals than in the mixed lesions of control animals. Quantitation of treponemes in pure T. pallidum versus mixed lesions was determined in two groups of rabbits challenged intratesticularly. The total number of treponemes per testis in the mixed lesions of BCG-sensitized rabbits was significantly less than the number in the mixed lesions of control animals, and also less than the number in pure T. pallidum lesions of both groups of animals.

Surface Mucopolysaccharides of Treponema pallidum

The viscous mucoid fluid that accumulates within syphilitic lesions may be due to breakdown of host tissue during infection, or may be synthesized by Treponema pallidum. Experiments were performed to investigate the acidic mucopolysaccharides that occur at the surface of T. pallidum (Nichols strain). These mucopolysaccharides were demonstrated by reaction with acidified bovine serum albumin and by agglutination with wheat germ agglutinin and soybean agglutinin. The polycations ruthenium red and toluidine blue influenced treponemal survival. Concentrations of both compounds at 200 mug/ml inhibited survival, whereas concentrations at 0.1mug/ml enhanced survival. The mucopolysaccharide concentration within the mucoid fluid that accumulates during intratesticular infection was determined by reaction with acidified bovine serum albumin; it ranged from 10,000 mug/ml to less than 8 mug/ml. The addition of this mucoid fluid to treponemal suspensions resulted in differing effects on T. pallidum survival. Some preparations were inhibitory, and others were stimulatory. Commercial preparations of hyaluronic acid and chondroitin sulfate at 400, 200, 100, and 50 mug/ml were detrimental to treponemal survival. The organisms exhibited pronounced clumping in the presence of the higher concentrations of hyaluronic acid. These clumps of treponemes were comprised of mucopolysaccharides as shown by acidified bovine serum albumin and toluidine blue reactions and by hyaluronidase degradation. Results are discussed in terms of the derivation and potential role of acidic mucopolysaccharides at the surface of T. pallidum.

The Demonstration of Spirochetes in Syphilitic Lesions by F. Schaudin and E. Hoffman

The Demonstration of Spirochetes in Syphilitic Lesions by F. Schaudin and E. Hoffman

Attachment of virulent Treponema pallidum to human mononuclear phagocytes.

The predominant phagocyte in established human syphilitic lesions is the mononuclear phagocyte. As these leucocytes may be important in immunity to Treponema pallidum, the initial interaction between human phagocytes and pathogenic T. pallidum (Nichols strain) was studied in vitro. Motile, virulent T. pallidum attach to the surface membrane of phagocytes but are not ingested by these cells. Heated, non-motile treponemes are not cell-associated but are observed free in the extracellular medium. Attachment is polar, at one or both terminal portions of the treponeme, and is neither serum- nor complement-dependent. Ingestion of virulent treponemes was not observed by phase-contrast or by electron microscopy in the presence of normal human or rabbit serum and complement. Techniques were chosen to preserve both the fragile surface constituents of the treponeme and the phagocytic function of mononuclear cells. Unfixed preparations were observed by phase-contrast microscopical examination during incubation to differentiate motile from non-motile organisms and fixed preparations were used for quantitation of attachment. This model should be useful for studying humoral and cell-mediated immunity in syphilis.

Demonstration by Labeled Treponemal Antigen of Specific Antibodies in The Tissue Infiltrates of Secondary Syphilis

Specific antitreponemal antibodies have been demonstrated by immunofluorescence techniques in the lymphoplasmocytic infiltrates which characterize early symphilitic lesions. A purified suspension of Nichols strain Treponema pallidum was sonified and labeled with fluorescein isothiocyanate and applied to cryostat sections of 12 biopsy specimens from the cutaneous lesions of 11 patients with proven secondary syphilis, using a modified direct immunofluorescence procedure. Specimens from various inflammatory dermatoses processed similarly served as controls. Granular fluorescence was noted in the dermis in 9 of the 12 specimens corresponding to areas of heavy plasma cell infiltration and some fluorescence was found directly on plasma cells which were identified by subsequent hematoxylin and eosin staining. This fluorescence could be blocked by prior incubation of the sections with unlabeled sonified treponemal suspension. Control slides did not reveal any fluorescence. The use of labeled treponemal antigen may aid the tissue diagnosis of early syphilitic lesions which can mimic a variety of dermatological disorders.

Treponema pallidum in early syphilitic lesions in humans during high-dosage penicillin therapy. An electron microscopical study.

The alterations of early syphilitic infection occuring in the course of high dosage penicillin (120 mega IU, 36 h) as clinical experimental trial has been studied both from the clinical and the electron microscopical views. By electron microscopical studies, findings revealing the localization and the status of treponemes before and during penicillin treatment could be established. Before treatment started, the majority of treponemes was of intercellular localization. In the course of treatment various forms of destruction could be differentiated. The most striking change in the host tissue after 7-8 h of penicillin therapy was an elimination of treponemes by penetrating phagocytes. 24 h after the beginning of treatment, treponemes could not be demonstrated any more. The clinical and serological findings after the high dosage penicilline will produce results comparable to those of conventional therapie.

Effect of pretreatment with Mycobacterium bovis (strain BCG) and immune syphilitic serum on rabbit resistance to Treponema pallidum

Stimulation of the rabbit reticuloendothelial system with viable Mycobacterium bovis (strain BCG), and other agents, had no effect on the development of syphilitic lesions after intradermal or intravenous inoculation with graded doses of Treponema pallidum (virulent Nichol's strain; mean infective doses less than 10). The simultaneous administration of immune syphilitic rabbit serum retarded the development of lesions, but this appeared to be due solely to the immune serum, suggesting no synergism between the activated reticuloendothelial system and the anti-T. pallidum antibodies. The administration of two doses of BCG enhanced syphilitic lesion development in the rabbit.

Effect macrophage activation on infection with Treponema pallidum.

Infection of rabbits with Treponema pallidum induces nonspecific acquired cellular resistance (ACR) to Listeria monocytogenes. This resistance can be adoptively transferred using thymus-dependent lymphocytes. Since infections that induce ACR are usually brought under control by cellular mechanisms, we sought to determine whether induction of ACR in rabbits stimulates resistance to challenge with T. pallidum. When BCG-infected rabbits which suppressed the growth of Listeria were challenged intravenously with T. pallidum, lesions appeared at the same time and progressed in a fashion similar to that in non-BCG-infected controls. There was a tendency for syphilitic lesions to disseminate more widely in BCG-infected animals and for the lesions to necrose more rapidly in controls. T. pallidum may resist phagocytosis by macrophages, as has been suggested previously, or macrophages may fail to be activated locally in the dermis. Although syphilitic infeciton appears to stimulate ACR, activation of the macrophages may not contribute significantly to the ability of the host to suppress T. pallidum.

Isolation and purification of Treponema pallidum from syphilitic lesions in rabbits.

Treponema pallidum were extracted from testicular syphilomas of corticosteroid-treated rabbits and purified by differential centrifugation. The steroid therapy allowed a longer holding time for infected rabbits, which produced greater treponeme yields, averaging 1.58 x 10(10) treponemes per rabbit. The treatment, which also diminished cellular infiltration and increased the extracellular mucoid material in lesions, produced much cleaner suspensions than preparations from nontreated animals. Most of the treponemes in the purified suspensions were still motile, and none carried demonstrable host immunoglobulin. The preparations were free of recognizable host tissue debris and they contained, on the average, 1.9 x 10(-7) mug of protein per treponeme.

Intracellular Treponema pallidum in cells of a syphilitic lesion of the uterine cervix

In an electron microscopic study of biopsy tissue from an ulcer of the human cervix uteri, organisms morphologically identical to T. pallidum were observed. Large numbers of the organisms were seen lying among collagen fibrils and between cells. T. pallidum was seen within vacuoles of some fibroblasts and epithelial cells. Within the nucleoplasm of several cells, treponemes were observed, surrounded by a clear zone which might represent a mucopolysaccharide outer layer. The diameter of the organisms was 171 nm., and the diameter of the external axial filaments was 25 nm., dimensions similar to those reported by others for T. pallidum.

Solitary papular lesions on the penis in insufficiently treated early syphilis. A report of two cases.

Two cases of insufficiently treated early syphilis with solitary papular lesions on the penis are described. There seems to be a close resemblance between these cases and descriptions from the Salvarsan era concerning the occurrence of solitary papules located on or near the place of the healed primary syphilitic lesion, after insufficient treatment with Salvarsan. Problems in diagnosing these cases are discussed.

Comparison of Fluorescent and Conventional Darkfield Methods for the Detection of Treponema Pallidum in Syphilitic Lesions

Comparison of Fluorescent and Conventional Darkfield Methods for the Detection of Treponema Pallidum in Syphilitic Lesions

Further observations on penicillinase.

THE APPLICATION of the enzyme penicillinase (Neutrapen) as a therapeutic agent in the treatment of penicillin reactions has been reassuring to the patient as well as the physician harassed by penicillin reactions. It has been previously demonstrated that parenteral injection of penicillinase in experimental animals and human subjects given penicillin resulted in rapid disappearance of detectable circulating penicillin.1However, clinical studies on the therapeutic value of the enzyme are often inconclusive since they frequently rely on improvement of subjective symptoms as their criterion. A more objective clinical analysis of penicillinase may be made by determining spirochetal protection when penicillin and penicillinase are injected concurrently into syphilitic patients with darkfield positive lesions. It was reasoned that if penicillinase destroys all penicillin, thenTreponema pallidumwill continue to survive in their chancres or moist eruptions. Materials and Methods Patients with early syphilitic lesions luxuriant inT. pallidumwere selected for this

Erythromycin in treatment of early syphilis.

While the treponemicidal properties of erythromycin were first described in 1953 by Keller and Morton,¹it is only recently that adequate clinical information has become available. Keller and Morton, as well as Turner and Schaeffer,²were able to demonstrate Treponema pallidum more susceptible to the action of erythromycin than other antibiotics with the exception of penicillin. Later, Kolmer³reported similar treponemicidal properties to erythromycin but obtained superior results with several other antibiotics. In 1954 Alexander and Schoch⁴treated 4 patients with syphilitic lesions with erythromycin and observed rapid disappearance of Treponema pallidum from the lesions. In 1956 Montero⁵presented 27 patients with early syphilis treated with a total of 9 to 12 gm. of erythromycin with satisfactory results. In 1959 Montgomery and Knox⁶reported on 40 darkfield-positive cases of early syphilis treated with 9 to 10 gm. of erythromycin stearate over a period of

Cervicitis resulting from turpentine irritation

Two cases demonstrating similar characteristic lesions of the cervix caused by turpentine used in douche preparations are described.Lesions of this nature must be differentiated from carcinoma of the cervix, syphilitic lesions of the cervix, and tuberculosis of the cervix.A careful review of the literature failed to reveal any reports of lesions of a like nature.

SYPHILIS as an occupational hazard to physicians.

Although accidentally acquired syphilis should be uncommon in physicians, a recent survey conducted by Epstein¹suggests that it would be a mistake to ignore the possibility of innocently acquiring syphilis from patients. A total of 51 cases of extragenital chancres in physicians were reported by 32 of 125 dermatologists who answered questionnaires. In 35 instances the syphilitic lesions occurred on the fingers, in 6 instances in the nasal cavity, in 1 on an eyelid, and in 1 on an arm. Otolaryngologists were more frequently affected than any other well-defined group, and in six of them lesions developed. In addition, six cases of accidentally acquired syphilis were observed in interns, residents, and medical students; five cases occurred in general practitioners; and two were detected in pathologists. Routine clinical examination of patients produced infection in seven physicians, while in five physicians syphilis was acquired during obstetric procedures or during pelvic examination

Sarcoid-like granulomata of the pituitary gland; a cause of pituitary insufficiency.

DESTRUCTION of the pituitary gland by giant-cell granulomata is a poorly understood, seldom recognized cause of pituitary insufficiency. While these granulomata are readily apparent pathologically, their cause is obscure. They have been considered to be sarcoid or tuberculosis. 1 A syphilitic causation has often been questioned. 2 Some have considered these lesions to be a distinct, specific disease of unknown origin. 3 It is probable that four etiological processes are involved in the reported cases of this disease. In the literature 16 cases have been associated with typical uveoparotid fever, osteitis multiplex cystica, lupus pernio, hyperglobulinemia, or other characteristics of Besnier-Boeck-Schaumann sarcoidosis. In some of these cases, furthermore, the asteroid and Schaumann bodies which are so suggestive of sarcoidosis have been demonstrated. 4 Occasional reported cases may represent a healed syphilitic process: In the case of Oelbaum and Wainwright the association of pituitary granulomata with the almost pathognomonic syphilitic lesions of interstitial keratitis and

SYPHILITIC DISEASE OF THE LONG BONES IN THE BANTU

Although syphilitic lesions in bone have become increasingly rare in European communities, syphilis is still a common cause of bone pathology in the South African Bantu. Syphilis entirely accounts for, or complicates, 90 per cent of all bone lesions-apart from fractures-seen in the Baragwanath Hospital. Syphilis is notorious for the diverse ways in which it may present itself, and an attempt is made here to illustrate by typical examples its usual manifestations in the bones of the Bantu. The disease is usually classified according to the age at which it manifests itself-that is, in infancy, in adolescence and in the adult-and according to whether it is congenital or acquired. In establishing a diagnosis of syphilis we have relied upon the following criteria in addition to a positive \Vassermann or Eagle reaction. 1) Multiplicity of the bone lesions. 2) Typical radiographic appearances in other parts-for example, an associated gumma of the clavicle, or a “ moth-eaten “ appearance of the skull-besides the lesion in the long bones. 3) Rapid resolution of the lesion, or of the symptoms, in response to anti-syphilitic treatment, which in most cases consisted of penicillin 600,000 units daily. 4) When necessary, biopsy of the bone to exclude any other bone pathology. Pain in the affected limb was the most common symptom, although often a lesion was discovered during routine radiography in other conditions. Pain always subsided rapidly with anti-syphilitic treatment. Sometimes there was also a marked improvement in the radiographic appearance of the bone lesion, especially with gummata and with the disease in infants. In differentiating these lesions from other conditions, it might be asked how syphilis is distinguished from yaws ; but yaws does not occur in the South African Bantu. It does not extend southwards beyond Northern Rhodesia (Hackett 1946) and it is unknown in the Union of South Africa, whence all these cases are drawn. Moreover yaws does not occur as a congenital affection, and the extensive scarring and pigmentation seen in yaws were not present in these cases. Finally in the large dermatological out-patient department of Baragwanath Hospital no skin manifestations of yaws have been seen. Goldmann and Smith (1943), in discussing the radiographic features of the two diseases, stated that it is unusual for syphilis to attack the bone and leave the periosteum unscathed. The opposite occurs in yaws, which regularly attacks the compact bone of the shaft and only affects the periosteum if the lesion is superficial. Helfet (1944) emphasised the acute onset of yaws in shafts of long bones, which simulates that of pyogenic osteomyelitis, with intense pain and swelling. For these reasons, in none of these cases did yaws cloud the diagnosis.