Treponema denticola Promotes OSCC Development via the TGF-ß Signaling Pathway.

Numerous studies have demonstrated an association between periodontitis and oral squamous cell carcinoma (OSCC), and periodontal pathogens such as Treponema denticola are implicated in the pathogenesis of OSCC. Previous studies have mainly focused on T. denticola surface proteins-for example, chymotrypsin-like proteinase, which was detected in the majority of orodigestive tumor tissues.T. denticola may influence the development of OSCC. Nevertheless, the potential direct regulatory mechanism of T. denticola in OSCC is still unclear. Therefore, this study aimed to explore the direct effect of T. denticola on OSCC cell proliferation and elucidate potential mechanisms of T. denticola in contributing to cell proliferation. A series of in vitro experiments (e.g., CCK-8, EdU, flow cytometry) were performed to explore the effect of T. denticola on cell proliferation, cell cycle, and apoptosis. Mice experiments were performed to explore the effect of T. denticola on tumor growth. Whole mRNA transcriptome sequencing and quantitative real-time polymerase chain reaction were performed to explore the intracellular signaling pathway. Our study found that T. denticola could invade Cal-27 cells and directly promote cell proliferation, regulate the cell cycle, and inhibit apoptosis. T. denticola could also promote the growth of OSCC tumors in mice, and it upregulated Ki67 expression. Regarding the mechanism, T. denticola could promote the development of OSCC by activating the TGF-ß pathway. In conclusion, T. denticola could promote OSCC cell proliferation directly, and the mechanism was associated with intracellular TGF-ß pathway activation.

A Comparative Study of the Epidemiology of Treponemal Infection in the Volta and Oti Regions of Ghana: A Five-Year Multisite Parallel Population-Based Analysis vis-à-vis the Sentinel Survey.

Treponemal infections can be blood-borne with great public health consequences. This study is aimed at comparatively describing the five-year (2013-2017) regional epidemiology of treponemal infection using pregnant women in the sentinel survey and apparently healthy blood donors as a proxy for the general population at four sentinel sites in the Volta and Oti Regions of Ghana. We analyzed retrospective data from 17,744 prospective blood donors aged 18 to 58 years and 7,817 pregnant women in a sentinel survey with ages from 15 to 49 years at Hohoe, Ho, Tongu, and Krachi West sentinel sites in the Volta and Oti Regions. Laboratory data extracted include variables such as age, gender, date of blood donation, and Treponema pallidum chromatographic immunoassay results from the blood banks of the four study sites. The five-year treponemal infection rate among the pregnant women in the sentinel survey and prospective blood donors was 0.79% and 2.38%, respectively. Site-specific infection rate for population-based/sentinel survey was 4.6%/1.1%, 2.0%/0.5%, 1.3%/1.1, and 1.2%/0.3% for Hohoe, Ho, Krachi West, and Tongu, respectively. Significant gender disparity in Treponemal infection rate exists with a male preponderance. The regional infection rate in the sentinel survey is lower compared to the general population. Therefore, the use of pregnant women as a proxy for population estimates could underestimate the burden in the study jurisdiction.

Analysis of Biochemical Features of Hepatitis B Virus Infected Patients in Southwest China.

BACKGROUND: Hepatitis B is one of the most common infectious diseases in China, and it is necessary to study biochemical indicators of HBV infected patients. METHODS: Biochemical and basic features of 1765 HBV infected patients and 840 general controls were collected and analyzed from Southwest China. RESULTS: A total of 23.5% of the patients were children or young persons (less than 40 years old). The co-infected rate was only 0.3% for those who were co-infected with Hepatitis C virus (HCV) or Treponema pallidum (TPa). Most of patients (1081 individuals) were under convalescent condition, and 4.2% and 34.6% HBV patients were at acute and chronic phase, respectively. The indicators of liver function were significantly different between HBV patients and normal controls. In order to further study the variation of biochemical features in HBV patients in different phase, they were divided into three groups (sample #1: patients in acute infected phase; sample #2: patients in chronic infected phase; and sample #3: patients in convalescent condition). Excluding total protein and globin, all other indicators of liver function were statically different among the three groups. Total protein and albumin gradually decreased from convalescent patients, chronic HBV-infected patients, to acute HBV-infected patients. CONCLUSIONS: Biochemical features could be used to evaluate the progress and therapeutic effects of HBV-infection. Our analysis firstly reported basic and biochemical information of HBV patients in Southwest China.

A case report of lameness in two dairy goat herds; a suspected combination of nutritional factors concurrent with treponeme infection.

BACKGROUND: Two dairy goat farms with high level of lameness in lactating animals were presented for further investigation. Farm 1 and Farm 2 presented with 37 and 67% morbidity, respectively. Both farms had an all year round indoor system, feeding ad libitum concentrate with forage available at all times. CASE PRESENTATION: The lameness was found to be based in the foot. Previous treatments consisting of biweekly footbathing with zinc sulphate, spraying lesions with oxytetracycline spray and packing lesions with copper crystals on a single occasion and single injections with long acting oxytetracycline had not been successful. Mild cases had signs of haemorrhaging in the white line or on the sole of the foot. Moderate cases showed under running of the wall horn or small areas of exposed sole corium. Severe cases would consist of horn or wall separation with the corium exposed and infected. In extreme cases only the wall horn of the claw remained, with a large area of necrotic tissue in the centre and no healthy corium visible. Only one animal was seen to have interdigital lesions. Polymerase chain reaction (PCR) and culture of swabs taken from exposed corium and the interdigital space were negative for Dichelobacter nodosus but PCR for treponemes were positive in both the adults and the youngstock tested. Due to the high level of concentrate in the diet of these goats, nutrition was thought to contribute to the problem. Transcutaneous rumen fluid samples were taken and pH was measured on both farms, with 35% of the samples below pH value 5.5. CONCLUSION: No definite diagnosis could be made. However, the results suggest both treponemes and nutrition play a role in the aetiology of the lameness. The initial sole or wall horn lesions were thought to be secondarily infected by treponemes. Further investigation is needed to definitively diagnose the cause and contributing factors for this lameness.

Hypertrophic cervical spinal cord pachymeningitis due to Treponema pallidum infection.

Neurosyphilis is recognized as a potential cause of hypertrophic pachymeningitis, but modern reports are few. A middle-aged man presented to hospital with a 1 month history of lower limb pain and weakness. Cerebrospinal fluid analysis showed pleocytosis with high protein levels and a positive venereal disease research laboratory result. Cervical spinal cord resonance imaging disclosed a dural contrast enhancement suggestive of pachymeningitis. Biopsy of the dura mater revealed a thick inflammatory process. Despite being treated accordingly, the patient rapidly deteriorated and died. The patient was diagnosed as having subacute hypertrophic cervical pachymeningitis which caused spinal cord compression. Serological evidence of neurosyphilis was present. Physicians should still be aware of this cause of hypertrophic pachymeningitis.

Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria.

It is established that chronic spirochetal infection can cause slowly progressive dementia, brain atrophy and amyloid deposition in late neurosyphilis. Recently it has been suggested that various types of spirochetes, in an analogous way to Treponema pallidum, could cause dementia and may be involved in the pathogenesis of Alzheimer's disease (AD). Here, we review all data available in the literature on the detection of spirochetes in AD and critically analyze the association and causal relationship between spirochetes and AD following established criteria of Koch and Hill. The results show a statistically significant association between spirochetes and AD (P = 1.5 × 10-17, OR = 20, 95% CI = 8-60, N = 247). When neutral techniques recognizing all types of spirochetes were used, or the highly prevalent periodontal pathogen Treponemas were analyzed, spirochetes were observed in the brain in more than 90% of AD cases. Borrelia burgdorferi was detected in the brain in 25.3% of AD cases analyzed and was 13 times more frequent in AD compared to controls. Periodontal pathogen Treponemas (T. pectinovorum, T. amylovorum, T. lecithinolyticum, T. maltophilum, T. medium, T. socranskii) and Borrelia burgdorferi were detected using species specific PCR and antibodies. Importantly, co-infection with several spirochetes occurs in AD. The pathological and biological hallmarks of AD were reproduced in vitro by exposure of mammalian cells to spirochetes. The analysis of reviewed data following Koch's and Hill's postulates shows a probable causal relationship between neurospirochetosis and AD. Persisting inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection form together with the various hypotheses suggested to play a role in the pathogenesis of AD a comprehensive entity. As suggested by Hill, once the probability of a causal relationship is established prompt action is needed. Support and attention should be given to this field of AD research. Spirochetal infection occurs years or decades before the manifestation of dementia. As adequate antibiotic and anti-inflammatory therapies are available, as in syphilis, one might prevent and eradicate dementia.

Pénfigo sifilítico: ¿pasado, presente o futuro? / The past, present, and future of pemphigus syphiliticus

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Regional, social, and evolutionary perspectives on treponemal infection in the Southeastern United States.

The origin and geographic distribution of syphilis, a form of treponemal infection, have long been regarded as among the most important medical riddles of prehistoric and historic disease evolution. In this study, we expand on previous discussions of the origin, evolution, and relationship of treponemal infections as they occur in the prehistoric southeastern United States. Individuals from 25 skeletal series (n = 2,410 individuals) were examined for cranial and dental lesions characteristic of treponemal infection. They lived between the Archaic period (8000-1000 BC) and protohistoric period (AD 1500-1600), and in physiographic zones from the coast to the mountains of Alabama, Florida, North Carolina, and Tennessee. Radial cranial scars were found for 47 individuals, but none of the four cases of dental lesions could be attributed to congenital syphilis. Differences in frequency of cranial lesions by region were minimal, with the least number of cases found for the mountains, but the frequency of positive cases tended to increase through time. It is suggested that increasing population density and changing behaviors, rather than novel strains of the treponemal pathogen, are responsible for the chronological increase in the frequency of positive cases.

[Rare cause of cholestatic hepatitis]. / Seltene Ursache einer cholestatischen Hepatitis.

When bile duct obstruction is ruled out newly developed icterus is mainly caused by infection with hepatotropic viruses, autoimmune hepatitis or drug induced hepatopathy. We report on a 30 year old previously healthy patient with cholestatic hepatitis which was caused by infection with Treponema pallidum. Cholestatic hepatitis resolved after administration of penicillin without recurrence.

Neurosyphilis.

Treponema pallidum, the bacterium that causes syphilis, invades the central nervous system early in the course of disease but causes persistent infection in only a subset of infected persons. Individuals with persistent infection or asymptomatic meningitis are at risk for developing symptomatic neurosyphilis if they are not treated with a drug regimen that achieves sufficient drug levels in cerebrospinal fluid to kill the organism. In this article, recent studies that address the risk, diagnosis, and management of neurosyphilis are discussed within the context of a brief review. Particular attention is given to current controversies. In the developed world, these issues are particularly relevant to persons who are infected with HIV.

Frequent and preferential infection of Treponema denticola, Streptococcus mitis, and Streptococcus anginosus in esophageal cancers.

Multiple cancers frequently occur in the upper digestive tract. One possible explanation is that specific bacterial infection stimulates the normal epithelium to initiate inflammation and/or promotes carcinogenesis. This study was undertaken to determine which bacterial species is predominantly associated with esophageal cancer. We examined the bacterial diversity in this type of cancer and in the saliva from healthy people by using a culture-independent molecular method. Here we report the preferential and frequent infection of the oral periodontopathic spirochete Treponema denticola (T. denticola), Streptococcus mitis (S. mitis), and Streptococus anginosus (S. anginosus) in esophageal cancer from different regions of the world, and we also describe the induction of inflammatory cytokines by infection of S. anginosus and S. mitis. Our present data suggest that these three bacteria could have significant roles in the carcinogenic process of many cases of esophageal cancer by causing inflammation and by promoting the carcinogenic process, and that eradication of these three bacteria may decrease the risk of recurrence.

Mixed infections with Porphyromonas gingivalis and Treponema denticola cause excessive inflammatory responses in a mouse pneumonia model compared with monoinfections.

Periodontopathic anaerobes such as Porphyromonas gingivalis are frequently found in aspiration pneumonia and lung abscesses. However, defense mechanisms and responses to these bacterial infections in the lung in vivo remain poorly understood. The coexistence of P. gingivalis with Treponema denticola has been found at higher levels and proportions in periodontally diseased sites. We hypothesized that mixed infections with P. gingivalis and T. denticola can cause severe respiratory disease. In the present study, inflammatory responses to mono- and mixed inoculations with P. gingivalis and T. denticola in the bronchoalveolar lavage (BAL) fluid were investigated. Acute pneumonia and lung abscesses in mice with the mixed infection resulted in a 40% mortality rate within 72 h, compared with only 10% mortality for the respective monoinfections. Pulmonary clearance of P. gingivalis was delayed in the mice with mixed infections with P. gingivalis and T. denticola. Tumor necrosis factor alpha (TNFalpha) interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) levels from BAL fluid of mice with mixed infections at 24 h after inoculation were significantly higher than those after P. gingivalis monoinfection (TNFalpha: P < 0.05, Il-1beta: P < 0.001, IL-6: P < 0.05). The chemokine KC level from BAL fluid of mice at 48 h (P < 0.05) and 72 h after mixed infection was also significantly increased when compared with that after P. gingivalis monoinfection (P < 0.001). The present study demonstrates that a mixed infection of P. gingivalis with T. denticola in mouse causes a marked bronchopneumonia and lung abscess in the mouse model.

PCR-based identification of Treponema maltophilum, T amylovorum, T medium, and T lecithinolyticum in primary root canal infections.

OBJECTIVE: Molecular genetic methods have significantly contributed to the knowledge about the microbiota associated with infected root canals. Albeit spirochetes have been commonly observed in primary root canal infections, only recently they have been identified. The purpose of the present study was to investigate the occurrence of four treponemes-Treponema maltophilum, Treponema lecithinolyticum, Treponema amylovorum, and Treponema medium-in cases of primary endodontic infections associated with different forms of periradicular diseases through a 16S rDNA-based nested PCR assay. DESIGN: Samples were taken from thirty-one infected root canals associated with either asymptomatic or symptomatic apical periodontitis. DNA extracted from the samples was initially amplified using universal 16S rDNA primers, followed by a second round of amplification using the first PCR products to detect a specific fragment of the 16S rDNA of each target Treponema species. RESULTS: All cases were positive for the universal bacterial primers, indicating that samples contained bacterial DNA. Of the four target species, T. maltophilum was the most prevalent, being detected in 39% of the cases (33% of the asymptomatic cases and 50% of the symptomatic cases). T. lecithinolyticum was the next more prevalent among the species tested, being found in 26% of the samples (33% of asymptomatic cases and 10% of the symptomatic cases). T. amylovorum was found in 7% of the cases (5% of the asymptomatic cases and 10% of the symptomatic cases), while T. medium was in 13% of the cases (14% of the asymptomatic cases and 10% of the symptomatic cases). None of the species tested was significantly associated with clinical symptoms. CONCLUSIONS: This was possibly the hitherto first study to report the occurrence of T. lecithinolyticum, T. amylovorum, and T. medium in infections of endodontic origin. Overall, findings suggested that these oral treponemes, particularly T. maltophilum and T. lecithinolyticum, can be involved in the pathogenesis of periradicular diseases.

From tooth to hoof: treponemes in tissue-destructive diseases.

With the advent of new molecular and immunological tools, there is better understanding of the roles that difficult to cultivate bacteria, and not-yet-cultivated bacteria such as spirochaetes, play in polymicrobial diseases. Only relatively recently have studies implicated Treponema spirochaetes in human periodontal disease, a destructive condition of the tissues supporting the teeth. A number of different Treponema species have been isolated and their surface protein components that mediate adhesion, cytotoxicity, and tissue damage have been characterized. More recently Treponema strains closely related to human oral isolates have been cultivated from active lesions of digital dermatitis, an ulcerative condition affecting the feet of cows and sheep. This condition, like periodontal disease, appears to have a polymicrobial aetiology in which enrichment for Treponema may play a crucial part. This article reviews the known mechanisms by which Treponema interact with eukaryotic host cells and tissue proteins, and how these interactions may contribute to pathogenic diversity.

Bilateral treponema periostitis.

Symmetrical exuberant periostitis is a rare disease caused by variety of infectious and non-infectious causes. Treponematosis is one of the rare causes of this condition. We report a patient who presented with left arm swelling, secondary to onion peel periostitis of the humerus, which was caused by Treponema species.

Bejel in Malatya, Turkey.

Bejel is a form of endemic syphilis which is transmitted by non-venereal route. According to our knowledge, no cases of bejel have been reported from Turkey for more than 30 years. In this report, three children and their father who suffer from bejel are presented. The history, physical findings, laboratory investigations, treatment and results of the cases are reviewed, and the related literature is discussed.

Serological markers for hepatitis B and treponemal infection among HIV carriers from Ethiopia.

A group of 52 HIV carriers among immigrants who arrived in Israel from Ethiopia in Operation Solomon, 1991, is described. A control group was randomly chosen from the same population. HBV serology and treponemal antibodies were obtained from both groups. The frequency of HBV markers was similar in both groups (70% among the HIV carriers and 78.8% in the controls). HBsAg was more frequently found among HIV carriers (20%) than in the control group (8.6%). Treponemal antibodies were common among HIV carriers (31%), and infrequent in the controls (3%). These data indicate that HIV infection in this community is linked to treponemal infection and that these carriers handle HBV less efficiently then HIV-negative subjects.

PIP: In Jerusalem and the Negev, physicians examined and took blood samples from recent Jewish immigrants older than 10 years who came to Israel from Ethiopia during Operation Solomon in 1991. The physicians and other colleagues compared data on the 52 people who were HIV positive with 139 who were HIV negative to examine HIV's relationships with treponemal infection and hepatitis B infection. The 2 groups were essentially the same age (37 years for cases and 35.5 years for controls). No significant difference in the prevalence of hepatitis B virus (HBV) markers existed between the 2 groups (70% for HIV-positive migrants and 78.8% for HIV-negative migrants). This confirmed other research that HBV is transmitted vertically in developing countries. Yet, HIV-positive migrants were more likely to have markers for hepatitis B surface antigen than HIV-negative migrants (20% vs. 8.6%; p = .018). The HIV-positive migrants had a higher prevalence of treponemal markers than did HIV-negative migrants (31% vs. 3%), indicating that treponemal disease increased their risk of HIV infection. The earlier group of Jewish immigrants from Ethiopia during 1984-1985 (Operation Moses) also had a high prevalence of treponemal antibodies but no one had HIV infection. These immigrants walked through a rural area to a refugee camp in Sudan from which they were taken to Israel by air. The newer immigrants rode buses to Addis Ababa and waited 1 year before they immigrated to Israel. The results of this study suggests that the new immigrants (an ethnic homogenous group just like their earlier counterparts) became infected with HIV during the short period in Addis Ababa. Israeli physicians have designed a study to follow the HIV-positive immigrants to determine whether the environment in Africa is responsible for the different clinical picture of AIDS.