[Late consequences of untreated lyme borreliosis]. / Odlegle nastepstwa nie leczonej boreliozy z Lyme.

The study aimed to evaluate late clinical symptoms and serological changes in persons with erythema migrans (EM) diagnosed 4-11 years ago who were not treated with antibiotics. Among initially included into the study 28 untreated EM cases, twelve persons responded for invitation to the Department. The symptoms and signs which could be related to previous Borrelia burgdorferi infection were present in 9 (75%) untreated patients. They included ischialgia (42%), arthritis (33%) and positive serological tests results (33% of patients, including 2 with clinical signs). These results demonstrate that lack of antibiotic treatment in the early LB stage can result in the development of late disease manifestations.

The major surface protein complex of Treponema denticola depolarizes and induces ion channels in HeLa cell membranes.

The oral spirochete Treponema denticola is closely associated with periodontal diseases in humans. The 53-kDa major surface protein (Msp) located in the outer membrane of T. denticola serovar a (ATCC 35405) has both pore-forming activity and adhesin activity. We have used standard patch clamp recording methods to study the effects of a partially purified outer membrane complex containing Msp on HeLa cells. The Msp complex was free of the chymotrypsin-like proteinase also found in the outer membrane of T. denticola. Msp bound to several HeLa cell proteins, including a 65-kDa surface protein and a 96-kDa cytoplasmic protein. The Msp complex depolarized and increased the conductance of the HeLa cell membrane in a manner which was not strongly selective for Na+, K+, Ca2+, and Cl- ions. Cell-attached patches of HeLa cell membrane exposed to Msp complex exhibited short-lived channels with a slope conductance of 0.4 nS in physiologically normal saline. These studies show that Msp binds both a putative epithelial cell surface receptor and cytoplasmic proteins and that the Msp complex can form large conductance ion channels in the cytoplasmic membrane of epithelial cells. These properties may contribute to the cytopathic effects of T. denticola on host epithelial cells.

Granulomatous infections: etiology and classification.

Granulomatous disorders are frequently due to a wide variety of infections. Over the past decade advances in molecular diagnostic techniques have allowed identification of organisms involved in granulomatous disorders that previously were of unknown etiology. On the basis of currently available information, granulomatous infections can now be classified in three categories. Group 1 infections are due to a well-recognized organism. Group 2 comprises infections due to organisms that have been recently identified in granulomas by molecular methods but are not readily isolated by conventional microbiological techniques. Group 3 consists of disorders for which the causal organisms have not yet been identified but are strongly suspected; further advances in diagnostic techniques will lead to reclassification of some of these disorders as group 2. This review describes the etiology, histopathologic features, and classification of granulomatous disorders, with an emphasis on those of groups 2 and 3.

Degradation of host protease inhibitors and activation of plasminogen by proteolytic enzymes from Porphyromonas gingivalis and Treponema denticola.

Bacterial proteases may participate in the pathogenesis of periodontal diseases through their action on host proteins. In the present study, the ability of selected periodontopathogens, as well as two proteases isolated from Porphyromonas gingivalis and Treponema denticola, to degrade host protease inhibitors was evaluated. The activation of human plasminogen by the two bacterial proteases was also investigated. Proteolytic breakdown of host protease inhibitors (alpha-1-antitrypsin, antichymotrypsin, alpha 2-macroglobulin, antithrombin III, antiplasmin and cystatin C) was evaluated by SDS-PAGE. The 80 kDa trypsin-like protease of P. gingivalis completely digested the six protease inhibitors under investigation, whereas the 95 kDa chymotrypsin-like protease of T. denticola was slightly less active, more particularly on alpha 2-macroglobulin and cystatin C. When whole cells from a number of oral bacterial species were tested, the most significant degradation was obtained with P. gingivalis, T. denticola, Prevotella intermedia, Prevotella nigrescens and Capnocytophaga spp. Peptostreptococcus micros and Propionibacterium acnes had only some degradative activity on selected inhibitors, whereas three bacterial species, Actinobacillus actinomycetemcomitans, Bacteroides forsythus and Fusobacterium nucleatum, had no effect on the protease inhibitors. The 80 kDa protease of P. gingivalis demonstrated strong plasminogen activation, whereas no such activity was associated with the 95 kDa protease of T. denticola. This study indicates the high potential of some periodontal pathogens to destroy protease inhibitors and activate plasminogen. This may result in an uncontrolled degradation of periodontal tissues and a rapid progression of the disease.

An enhanced murine model for studies of Serpulina (Treponema) hyodysenteriae pathogenesis.

A defined diet was used to increase the susceptibility of mice to Serpulina hyodysenteriae. BALB/cByJ, C3H/HeN, and C3H/HeJ mice, when fed the defined diet 7 to 14 days prior to and throughout the challenge period, consistently showed higher incidences of disease than mice maintained on normal rodent chow. The use of this defined diet will increase the consistency of in vivo studies following infection with S. hyodysenteriae in the mouse model.

Morphologic analysis of enteric lesions in conventional and streptomycin-treated inbred C3H/HeN mice infected with Serpulina (Treponema) hyodysenteriae.

Oral administration of streptomycin is known to enhance the susceptibility of mice to enteric pathogens by altering the indigenous flora. We examined the effect of oral streptomycin treatment on the susceptibility of inbred C3H/HeN mice to infection with Serpulina (Treponema) hyodysenteriae. A total of 56 mice were randomly divided into four groups (A-D) of 14 each. From days 0 to 7, mice in groups A and B received streptomycin in their drinking water and mice in groups C and D served as controls. On day 7, mice in groups A and C were inoculated intragastrically with S. hyodysenteriae serotype 4, strain A1, and groups B and D served as uninoculated controls and received sterile trypticase soy broth. Clinical signs were monitored daily and body weights were recorded weekly. Mice were euthanized and necropsied for bacteriologic and histopathologic examinations on day 7 (2/group) and on days 14, 21, 28, and 35 (3/group) of the experiment. Soft fecal pellets were noticed in infected groups (A and C), but no significant differences in body weights were observed between groups (P greater than 0.05). Macroscopic changes were noted only in infected groups (A and C) beginning on day 21 of the experiment and consisted of catarrhal typhlitis, cecal emptiness, and atrophy. Histologically, the cecum and colon of mice in groups A and C had goblet cell hyperplasia, which preceded crypt epithelial cell hyperplasia, inflammatory cell infiltrates, and focal necrosis of mucosal epithelium. S. hyodysenteriae was reisolated from 10 of 12 mice in each infected group (A and C) from day 14 (7th day postinoculation) through day 35 (28th day postinoculation).(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiology and clinical similarities of human spirochetal diseases.

Lyme disease, first identified in 1975, is the most recently recognized of the seven human spirochetal diseases; the evolving clinical picture of Lyme disease indicates it shares many features with the other diseases. These similarities are striking in view of the diverse epidemiology of the seven diseases, which are caused by Treponema species (spread by human-to-human contact) or Leptospira or Borrelia species (zoonoses). These similarities include the following: (1) skin or mucous membrane as portal of entry; (2) spirochetemia early in the course of disease, with wide dissemination through tissue and body fluid; and (3) one or more subsequent stages of disease, often with intervening latent periods. Lyme disease shares with many spirochetal diseases a tropism for skin and neurologic and cardiovascular manifestations, whereas chronic arthritis is unique to Lyme disease. These similarities and dissimilarities offer opportunities to discover which properties unique to the pathogenic spirochetes are responsible for clinical manifestations and suggest that certain clinical features of patients with spirochetal diseases other than Lyme disease may someday be recognized in patients with Lyme disease.

Experimental infection of young broiler chicks with Treponema hyodysenteriae.

In young broiler chicks which were inoculated with 10(8) cells of Treponema hyodysenteriae within 24 hr after hatching, numerous treponemes were observed by scanning electron microscopy on the surface of the cecal mucosa 7 and 14 days after the inoculation. However, in the groups inoculated with 10(7) cells, treponemes were not observed on the cecal mucosa 14 days after the inoculation, and the isolation rate from the cecal contents was lower than that from cecal contents of chicks inoculated with 10(8) cells. While the cecal mucosa of noninfected chicks had a smooth surface, that of the chicks infected with treponemes was generally roughened and the epithelium was eroded. Numerous treponemes were also observed within the eroded epithelium.

Swine dysentery. Comparison of experimental diseases produced by infection with colonic mucosa or with Treponema hyodysenteriae, French strains, and of "natural" disease.

Oral inoculation of colonic mucosa scrapings and intestinal contents of animals affected with swine dysentery, or of pathogenic strains of Treponemia hyodysenteriae, as well as spontaneous contamination in infected pens caused in average swine dysentery to appear in 359 out of 409 SPF piglets. The morbidity is high irrespective of the method of contamination: after pen contamination, 75 out of 83 piglets were dysenteric; after only one ingestion of contaminated matter, 265 out of 280 animals were ill; and after inoculation of T. hyodysenteriae, 25 out of 35. Mortality in dysentery was always higher than 80%, respectively 48 out of 60 animals, 132 out of 154, and 13 out of 14. Very few animals were self-cured. The average incubation period varied according to the mode of contamination between 9 and 13 days. Animals having contracted an acute form of the disease died 16 to 23 days after contamination, and those with a chronic from 19 days, also after contamination. The increase in the number of Treponema, of Campylobacter and of Balantidium observed after the onset of the disease was approximately equivalent for all three modes of contamination. This disease was characterized by an alternance of dysentery stricto sensu and of mucoid diarrhea, the latter occurring more frequently in cases of self-cure and in chronic forms.

Studies on the pathogenesis of swine dysentery. II. Search for a cytotoxin in spirochetal broth cultures and colon content.

Broth cultures of Treponema hyodysenteriae and colonic content from pigs with swine dysentery were tested for cytotoxicity in cell cultures, erythrocyte suspensions and in ligated segments of pig colon. Live cells of T. hyodysenteriae attached to the surface of cells in all cultures tested but did not penetrate them nor cause morphologic change detectable by light microscopy. Only live T. hyodysenteriae caused erythrolysis. Broth cultures or colonic content sterilized by filtration or by disruption with ultrasound had no visible effect on the cell cultures, erythrocyte suspensions or the mucosa of ligated colonic segments.

Swine dysentery: pathogenicity of Treponema hyodysenteriae.

When pure cultures of Treponema hyodysenteriae were orally inoculated into pigs, severe disease characteristic of swine dysentery developed. Less severe lesions were produced by oral inoculation of infective minced colon. Noninoculated pigs were used as controls. Inoculations of surgically isolated porcine colonic loops with either pure cultures or infective minced colon produced lesions only in the injected loop; the adjacent noninjected colon remained normal. Pigs and other experimental animals, including rabbits, guinea pigs, and mice, inoculated with washed cultures by various parenteral routes remained normal.