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[Survival and humoral response of mice infected with Treponema pallidum (author's transl)].

To judge the pathogenicity of Treponema palllidum in mice, we inoculated two groups of animals. 1) One with a normal immune system : adult Swiss mice. 2) The other with an immune system presenting a defect in T cells : athymic Nude mice. No lesions appeared at the points of inoculation and the survival of these animals was not modified compared with control animals. We have also carried out a study of antitreponema antibodies in adult and new-born Swiss mice, using, for the adults, various concentrations of treponema pallidum and various routes of inoculation. In adult mice, the search for antibodies by fluorescence, showed, firstly, that the intradermal route permits a more rapid humoral response than the intraperitoneal route, with higher antibody titers. Furthermore, an inoculum of 8,6 X 10(6) per mice, gives earlier results and higher titers than those obtained with an inoculum twice lower. The earliness of the positive Nelson test is independent of the route of inoculation but related to the injected dose. On the other hand, the Kline reaction remained negative for all groups of mice throughout the whole period of our study. In new-born mice, 76% only became positive on fluorescence and Nelson test.

Animals↗

Development of of macrophage migration inhibition in rabbits infected with virulent Treponema pallidum.

Peritoneal exudate cells from rabbits infected with Treponema pallidum Nichols were used as indicators of macrophage migration inhibitory factor activity. Between 3 and 15 weeks after infection, the migration of peritoneal exudate cells was inhibited in the presence of 3 to 25 microgram of T. phagedenis biovar Reiter protein per ml. Before this period, the migration patterns of peritoneal exudate cells from infected animals were uninhibited and similar to those from noninfected control rabbits. These observations were correlated with the development of active cell-mediated immunity during experimental T. pallidum infection.

Animals↗

Suppression of lymphocyte response to concanavalin A by mucopolysaccharide material from Treponema pallidum-infected rabbits.

The testicular fluid and serum from rabbits infected intratesticularly with Treponema pallidum inhibited the mitogenic response of normal rabbit peripheral blood lymphocytes to concanavalin A. Mucopolysaccharide material present in the testicular fluid and serum was associated with the lymphocyte-inhibitory activity. Degradation of the mucopolysaccharide material with hyaluronidase resulted in the loss of the inhibitory activity of testicular fluid and serum of T. pallidu-infected rabbits.

Animals↗

Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimer's disease.

The purpose of this investigation was to use molecular and immunological techniques to determine whether oral Treponema infected the human brain. Pieces of frontal lobe cortex from 34 subjects were analyzed with species-specific PCR and monoclonal antibodies. PCR detected Treponema in 14/16 Alzheimer's disease (AD) and 4/18 non-AD donors (P < 0.001), and AD specimens had more Treponema species than controls (P < 0.001). PCR also detected Treponema in trigeminal ganglia from three AD and two control donors. Cortex from 15/16 AD subjects and 6/18 controls contained Treponema pectinovorum and/or Treponema socranskii species-specific antigens (P < 0.01). T. pectinovorum and/or T. socranskii antigens were also found in trigeminal ganglia and pons from four embalmed cadavers, and 2/4 cadavers also had Treponema in the hippocampus. These findings suggest that oral Treponema may infect the brain via branches of the trigeminal nerve.

Adult↗

Gene conversion: a mechanism for generation of heterogeneity in the tprK gene of Treponema pallidum during infection.

The tprK gene sequence of Treponema pallidum subspecies pallidum (T. pallidum) is heterogeneous within and among isolates. Heterogeneity in the tprK open reading frame is localized in seven discrete variable (V) regions, and variability results from apparent base changes, insertions or deletions. The TprK V regions are the focus of anti-TprK antibodies arising during infection. To test our hypothesis that V region sequences change during infection and passage, we developed a clonal isolate from the Chicago strain of T. pallidum and confirmed V region diversification during passage of this isolate. We describe the sequence anatomy of the seven V regions of tprK and the identification of putative donor sites for new V region sequences, and we propose a model for generation of new V regions by segmental gene conversion. These findings suggest that antigenic variation of TprK occurs in T. pallidum and may be important in immune evasion and persistence.

Amino Acid Sequence↗

[Prevention and diagnosis of congenital syphilis from an immunological viewpoint].

Frequency of syphilitic infection among 5772 pregnant women in the Düsseldorf area was 0.4%. Of 91 mothers with a positive Treponema pallidum haemagglutination (TPHA) test, 23 required treatment. Congenital syphilis was found only in those children whose mothers were not known to have syphilis at the time of birth. Diagnosis of Treponema infection in the newborn can be made with certainty only if there is a positive IgM-antibody test. In the absence of Treponema pallidum-specific serum IgM-antibodies in the newborn or if a positive IgM-test is not plausible, the suspected diagnosis can be confirmed or excluded only by serial post-partum tests of antibody kinetics. In TPHA the test reacting IgG-antibodies are eliminated in non-infected infants with a half-life of 20.5 days. Prolonged elimination half-life or persistence of positive TPHA titres confirms intra-uterine or perinatal syphilitic infection.

Antibodies, Bacterial↗

Protein synthesis by Treponema pallidum extracted from infected rabbit tissue.

Virulent Treponema pallidum organisms, extracted from infected rabbit testes, incorporated amino acids into protein. A temperature of 34 C and a pH of 7.6 were optimal for protein synthesis, which was linear during in vitro incubation for 24 h. Selective inhibition of protein synthesis by erythromycin as judged by the incorporation of radiolabeled amino acids and radioautography demonstrated that treponemes were actively synthesizing proteins. Since addition of various sera and ultrafiltrates to the basal incubation mixture did not stimulate the level of protein synthesis, it was uncertain whether treponemes synthesized protein at a maximal or endogenous rate. Based upon the size of the unlabeled amino acid pool contained in infected testicular extract, it appeared that virulent treponemes utilized the majority of amino acids for protein synthesis but at varying efficiency.

Amino Acids↗

Susceptibility of inbred mouse strains to infection with Serpula (Treponema) hyodysenteriae.

Several inbred strains of mice were inoculated with Serpula (Treponema) hyodysenteriae B204 to determine susceptibility to infection. Challenge doses of 10(7) or 10(8) spirochetes induced cecal lesions in C3H/HeJ mice and other C3H strains of mice. However, more than a 100-fold difference existed between the dose required to induce lesions in 50% of the infected C3H/HeJ mice (8.3 x 10(7)) and that required to induce them in 50% of the infected C3H/HeN mice (5 x 10(5)). C3H/HeJ mice lack a splenocyte mitogenic response to Escherichia coli lipopolysaccharide but exhibited a mitogenic response comparable to those of other C3H strains of mice when stimulated with S. hyodysenteriae endotoxin (butanol-water extract). Different inbred strains exhibited different susceptibilities to infection, with the strain C3H/HeN being the most susceptible on the basis of colonization and development of macroscopic cecal lesions. The ity gene had no apparent effect on susceptibility of mice challenged with S. hyodysenteriae. The involvement of the H-2 haplotype with susceptibility is unclear, but the mice bearing H-2k were more susceptible than mice with the H-2b, H-2d, or H-2q haplotype. These data support the hypothesis that the host's responsiveness to lipopolysaccharide influences the susceptibility to infection with S. hyodysenteriae. However, differences in susceptibility between inbred mice exist independent of the lps locus, suggesting that there are other inherent differences between mouse strains that affect susceptibility to infection by S. hyodysenteriae.

Animals↗

Purification of Treponema pallidum from Infected Rabbit Tissue: Resolution into Two Treponemal Populations.

Virulent Treponema pallidum organisms, extracted from infected rabbit testes, were subjected to velocity sedimentation in discontinuous gradients of Hypaque, a high density, low viscosity material. After centrifugation of extracts at 20 C for 45 min at 100,000 x g, treponemes separated into two distinct bands based upon their relative velocities, although some variation was observed in the densities of the two bands and the number of treponemes per band. Rabbit tissue components sedimented more rapidly. Dark field and electron microscopy of preparations after velocity sedimentation indicated that treponemes retained general structural characteristics and no tissue contamination occurred in the treponemal fractions. Purification of treponemes in Hypaque resulted in their loss of motility and infectivity based upon animal inoculation. Antigenicity with respect to reactivity with antibody was preserved as shown by the high fluorescence intensity of treponemes in the fluorescent treponemal antibody adsorption test.

Journal Article↗

Fetal middle cerebral artery peak systolic velocity in the investigation of non-immune hydrops.

OBJECTIVE: In some cases of non-immune hydrops there is congenital or acquired fetal anemia. The aim of this study was to investigate the potential value of fetal middle cerebral artery peak systolic velocity (MCA-PSV) in the assessment and management of non-immune hydrops due to anemia. METHODS: Fetal MCA-PSV and fetal hemoglobin concentration, in blood obtained by cordocentesis, were measured in 16 singleton pregnancies referred to our unit for further investigations because of a diagnosis of non-immune hydrops fetalis. In all cases a detailed ultrasound examination demonstrated moderate or severe ascites, with or without skin edema, and pericardial or pleural effusions. Furthermore, there were no obvious malformations to account for the hydrops. In each fetus the measured MCA-PSV and hemoglobin concentration were expressed as delta values (the difference in SD from the normal mean for gestation). Regression analysis was used to determine the significance of the association between delta MCA-PSV and delta fetal hemoglobin concentration. In addition, we searched our database to identify the sonographic features and hemoglobin concentration of fetuses with congenital infection. RESULTS: In the 16 cases of non-immune hydrops there were seven with parvovirus B19 infection, one each of alpha-thalassemia and primary cardiomyopathy and seven with no obvious explanation for the hydrops. There was a significant association between delta MCA-PSV and delta hemoglobin concentration (delta hemoglobin = (delta MCA-PSV + 0.1437)/-0.4154; R(2) = 0.7202; P < 0.0001). In 10 of the cases the fetal hemoglobin concentration was more than 4 SD below the normal mean for gestation and in all these cases the MCA-PSV was more than 2 SD above the normal mean for gestation. Our computer search identified an additional nine fetuses with parvovirus B19 infection and in all cases the predominant sonographic finding was ascites and the hemoglobin concentration was more than 4 SD below the normal mean. In contrast, only 3/14 fetuses with cytomegalovirus, toxoplasmosis, coxsackie B or Treponema infection had ascites and only 2/14 had a hemoglobin deficit of 4-6 SD. CONCLUSION: In the management of non-immune hydrops, measurement of fetal MCA-PSV can help identify the subgroup with fetal anemia.

Anemia↗

Identification of a low moleculr weight IgM antibody with treponema pallidum specificity in sera of patients with chronic syphilis.

A low-molecular (8S) treponema-specific IgM antibody was isolated by means of Sephadex 200 G gel filtration and/or sucrose gradient ultracentrifugation in 78 of 4,120 sera of patients who had been identified to have had syphilis. The IgM specificity can be shown by indirect immunofluorescence using a mu-chain specific antiserum. The low molecular IgM (LMW-IgM) antibodies are not identical with the 19S-IgM as demonstrated in studies with gel filtration and sucrose gradient methods. They are not identical neither with 7S IgG or IgA. Neither the presence of antinuclear nor rheumatic factor could be shown in the LMW-IgM fraction. In most of the patients with LMW-IgM antibody, there existed a treponema infection of late latency.

Antibodies, Antinuclear↗

Gastrointestinal function and structure in HIV-positive patients.

We examined 19 patients (17 men) with human immunodeficiency virus (HIV) infection and gastrointestinal symptoms to determine whether those symptoms were due to either a gastrointestinal tract infection or a defect in mucosal absorption because of an enteropathy. The erythrocyte folate and serum vitamin B12 levels were within normal limits in all of the patients. The serum ferritin level was elevated in 12. The xylose absorption test results were abnormal in 8 of the 13 patients able to complete the study. None of the duodenal aspirates yielded a pathogen. Light microscopy revealed nonspecific lymphocytic inflammation without infection in the stomach (in seven patients), the esophagus (in five), the duodenum (in two) and the rectum (in two). However, biopsy specimens were positive for Candida albicans in the esophagus (four patients), cytomegalovirus in the esophagus (one) and the rectum (two), Helicobacter pylori in the antrum (two), Treponema infection in the rectum (two) and Mycobacterium avium-intracellulare in the small intestine (one). Only three patients had a normal series of biopsy specimens. All of the patients had similar ultrastructural changes at the epithelial-stromal junction of the antral glands and in the intestinal crypts. We conclude that abnormal biochemical and endoscopic findings are common in HIV-positive patients with gastrointestinal symptoms. Defects in carbohydrate absorption and ultrastructural changes may be responsible for some aspects of HIV enteropathy.

Bacterial Infections↗

Selective in vitro response of thymus-derived lymphocytes from Treponema pallidum-infected rabbits.

The blastogenic response of nylon wool-separated peripheral-blood lymphocytes from Treponema pallidum-infected rabbits was tested in vitro with mitogens and T. pallidum antigens. The mitogenic response of the enriched T-cell population to concanavalin A and phytohemagglutinin was depressed during the first 3 to 4 weeks of infection, similar to the pattern observed with unfractionated cells. Shortly thereafter, levels of blastogenesis returned to values of uninfected cultures. Enhanced blast transformation was seen immediately when purified T-cells from infected rabbits were exposed in vitro to T. pallidum antigens. Although these relatively high levels of blastogenesis were maintained for the duration of the experiment, cultures of unfractionated lymphocytes from infected rabbits did not exhibit an increased blastogenic response to the same antigen preparation until 3 to 4 weeks after infection. Autologous serum from infected rabbits decreased the lymphocyte response to T. pallidum antigen. The stimulatory effects of anti-immunoglobulin G and lipopolysaccharide on nylon wool-fractionated or unfractionated lymphocytes from both infected and control rabbits were similar throughout the course of infection. During the first 6 weeks of experimental disease, there was a 25 to 31% increase in the number of lymphocytes circulating in the peripheral blood of T. pallidum-infected rabbits.

Animals↗

Diseases of the skull in pre-Columbian South American mummies.

OBJECTIVE: The majority of paleopathological investigations focus on the study of the skull. This is because the skull is the most frequently preserved part of the human body recovered from archaeological excavations. From studying the skull, a variety of information can be obtained regarding the individual, such as sex, age, nutritional status, and other disease processes, if present. METHODS: This study represents the examination of more than 700 human skulls recovered from archaeological excavations from the Andean region of southern Peru and northern Chile and dating back more than 8000 years. RESULTS: A variety of skull abnormalities were encountered. The nonmetric variables of Huschke's foramina and palatine tori were common. Cranial deformation was observed in more than 85% of the cases. There were two cases of sagittal synostosis. Iron deficiency anemia resulting in porotic hyperostosis of the skull was evident in certain cultures. Exostoses of the external auditory canal resulting from chronic otitis was evident only among coastal populations. One skull demonstrated a periostitis consistent with Treponema infection. Trephination was encountered only in the skulls from Peru. Fifty-four cases of skull fractures were observed, half of which showed evidence of healing. Finally, only two cases of neoplastic skull lesions were encountered. CONCLUSION: The study of the human skull alone provides a large amount of information regarding the health and diseases of ancient populations.

Adult↗

Pathogenicity and persistence of pleural effusion disease virus isolates in rabbits.

Nine isolates of pleural effusion disease agent or virus (PEDV) from treponema-infected rabbits in various countries were examined for pathogenicity and persistence in rabbits. The isolates showed a wide range of pathogenicity and were categorized into three groups according to the severity of the acute infection. Group 1 comprised isolates causing more than 50% mortality, group 2 isolates causing mortality below 50%, while group 3 comprised isolates causing almost subclinical infections. The range between group 1 and group 3 was similar to that observed with virulent and avirulent progeny of the original PEDV isolate. Infection by each of the nine isolates resulted in a chronic low level viraemia which persisted for up to 2 years or more. Viral progeny of pathogenic isolates obtained in serum after the 2nd month of infection failed to induce clinical disease on rabbit inoculation. The chronic, subclinical infection was associated with a moderate, continued increase in serum IgG, but circulating immune complexes could not be demonstrated. Two years after infection slight histopathological changes were present in lymph nodes, spleen, liver, heart and lung. Evidence of immune complex disease could not be demonstrated.

Animals↗

[Liver involvement in early secondary syphilis].

Two patients with secondary new syphilis are described, abusing alcohol, developing early syphilitic hepatitis. The manifestations of this condition are similar to those of viral hepatitis. This necessitates a thorough examination of the skin integument, visible mucosae, genitals and perianal area, and of the peripheral lymph nodes in the patients with suspected viral hepatitis, in order to timely detect a possible liver involvement in Treponema infection. When such patients consult a doctor, specific serologic tests should be carried out and case history be carefully recorded.

Adult↗

In vitro cell response of Treponema pallidum-infected rabbits. I. Lymphocyte transformation.

Lymphocyte response to phytohaemagglutinin (PHA), Treponema pallidum, cultivable Reiter strain and cardiolipin reagent were examined using peripheral lymphocytes of T. pallidum-infected rabbits and control animals injected intratesticularly with saline extract of normal rabbit testes mixed with T. pallidum-free saline extract of infected testes. The response to PHA was significantly suppressed only in the infected animals, reaching the lowest level at 30 days after infection. A substantial increase of lymphocyte stimulation in the presence of cardiolipin reagent at 20 days after infection correlated well with the appearance of the maximum titre of Wassermann antibodies. Significant (P less than 0.02) increase in spontaneous response of cells incubated for 5 days made the response to T. pallidum and the Reiter strain difficult to interpret. An explanation for the spontaneous response is offered.

Animals↗