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- Current trend on syphilis diagnosis: issues and challenges. [Journal Article]
- Adv Exp Med Biol 2014.:51-64.
Syphilis is a century old sexually transmitted infection transmitted worldwide. WHO reports 12 million new cases that were identified in 1999, with over 90 % of these infections reported from patients from low-income countries. This case number of syphilis is on the rise globally in the Men have sex with Men (MSM) population. Dark field microscopy (DFM) and direct fluorescence assay (DFA) have been used in clinical laboratories for decades to demonstrate Treponema pallidum in acutely infected human tissue and/or body fluids. Molecular technologies allow detecting T. pallidum and also determine drug resistance (by identifying DNA point mutation). It is evident from the published literature that PCR is useful as an adjunct test to DFA and DFM, and is useful in confirming syphilis in genital ulcer, tissue, and other body fluid samples, providing even more sensitive detection algorithm. Serological tests remain the mainstay tests since T. pallidum is nonculturable and also because blood collection is easy. The practice of serological testing is changing rapidly from traditional nontreponemal screening followed by confirmatory treponemal testing to screening by treponemal tests referred to as "Reverse Algorithm" followed by nontreponemal testing to determine active infections. Special and further complex algorithms are essential to deal with complex issues such as neurosyphilis or congenital syphilis. Due to the huge surge of syphilis in developing countries where access to medical care is not optimal, point of care or rapid tests may play an important role. This author took an attempt to summarize the current trend of syphilis diagnosis and challenges from a global perspective.
- Perinatal Treponema pallidum: evidence based guidelines to reduce mother to child transmission. [Journal Article]
- Ir Med J 2014 Jan; 107(1):14-6.
Universal antenatal screening for T. pallidum is standard in Irish maternity units. The prevalence of adult syphilis has increased in Ireland. We audited the neonatal management of infants exposed to T. pallidum in utero. A cross sectional retrospective analysis of all pregnancies with confirmed positive serology for T. pallidum from January 2005 to December 2010 was conducted at the National Maternity Hospital, Holles St. Data were analysed using SPSS 14.0. Ethical approval was obtained. There were 55,058 live births during the study period. Fifty-eight women had positive serology and 41 met inclusion criteria. Infant evaluation and follow up was decided by allocation to an evidence based algorithm. Twenty-one infants (51%) were accurately allocated and assessed, 5 (12%) had a partial assessment and the algorithm was incorrectly applied in 15 (36%) of cases. Failure to adhere to evidence based neonatal guidelines is common and undermines efficacy of the screening program.
- Awareness of and knowledge about mother-to-child infections in Japanese pregnant women. [Journal Article]
- Congenit Anom (Kyoto) 2014 Feb; 54(1):35-40.
To reduce the incidence of infants with congenital infections, women should be aware of and know prevention measures against maternal infection with mother-to-child infections during pregnancy. Our objective was to assess the awareness of and knowledge about mother-to-child infections in Japanese pregnant women. A survey of 343 Japanese pregnant women was completed. Awareness of 13 pathogens capable of mother-to-child transmission was surveyed. Knowledge about the transmission route, the most susceptible time of infection that may cause severe fetal disease during pregnancy, and methods to prevent maternal infection were investigated for four major pathogens (cytomegalovirus, rubella virus, Toxoplasma gondii, and parvovirus B19) and results were compared between these pathogens. The proportion of women aware of pathogens concerning TORCH syndrome was the following: rubella virus 76%, Treponema pallidum 69%, Toxoplasma gondii 58%, parvovirus B19 28%, herpes simplex virus 27%, and cytomegalovirus 18%. Only 8% knew how cytomegalovirus is transmitted, and only 12% knew how parvovirus B19 is transmitted; both were significantly lower than those who knew transmission routes for rubella virus or Toxoplasma gondii. The proportion of women who knew the most susceptible time for severe fetal infection by maternal acquisition of cytomegalovirus, Toxoplasma gondii, or parvovirus B19 was significantly lower than that for rubella virus. The vast majority of surveyed women were not aware of methods to prevent maternal infection with cytomegalovirus or parvovirus B19. In conclusion, current awareness of and knowledge about cytomegalovirus and parvovirus B19 infection are low in Japanese pregnant women.
- Major Membrane Protein TDE2508 Regulates Adhesive Potency in Treponema denticola. [Journal Article]
- PLoS One 2014; 9(2):e89051.
The cultivation and genetic manipulation of Treponema denticola, a Gram-negative oral spirochaeta associated with periodontal diseases, is still challenging. In this study, we formulated a simple medium based on a commercially available one, and established a transformation method with high efficiency. We then analyzed proteins in a membrane fraction in T. denticola and identified 16 major membrane-associated proteins, and characterized one of them, TDE2508, whose biological function was not yet known. Although this protein, which exhibited a complex conformation, was presumably localized in the outer membrane, we did not find conclusive evidence that it was exposed on the cell surface. Intriguingly, a TDE2508-deficient mutant exhibited significantly increased biofilm formation and adherent activity on human gingival epithelial cells. However, the protein deficiency did not alter autoaggregation, coaggregation with Porphyromonas gingivalis, hemagglutination, cell surface hydrophobicity, motility, or expression of Msp which was reported to be an adherent molecule in this bacteria. In conclusion, the major membrane protein TDE2508 regulates biofilm formation and the adhesive potency of T. denticola, although the underlying mechanism remains unclear.
- Invasion of oral and aortic tissues by Oral Spirochete Treponema denticola in ApoEnull mice causally links periodontal disease and Atherosclerosis. [JOURNAL ARTICLE]
- Infect Immun 2014 Feb 24.
Treponema denticola is a predominantly subgingival oral spirochete closely associated with periodontal disease and has been detected in atherosclerosis. This study was designed to evaluate causative links between T. denticola chronic oral-infection-induced periodontal disease and atherosclerosis in hyperlipidemic ApoE(null) mice. ApoE(null) mice (n=24) were orally infected (8 infections, 4 days/week consecutively) with T. denticola ATCC 35404 and were euthanized after 12 and 24 weeks. T. denticola genomic DNA was detected in oral plaque samples, indicating colonization of the oral cavity. Infection elicited significantly (P = 0.0172) higher IgG antibody levels and enhanced intrabony defects compared to sham-infection. T. denticola-infected mice had higher levels of horizontal alveolar bone resorption and associated significant increase in aortic plaque area (P ≤ 0.05). Increased atherosclerotic plaque correlated with reduced serum nitric oxide (NO) levels and increased serum-oxidized LDL levels when compared to sham-infected mice. T. denticola infection altered the expression of genes known to be involved in atherosclerotic development including, leukocyte/endothelial cell adhesion (Thbs4), connective tissue growth factor (Ctgf), selectin-E (Sele). Fluorescent in situ hybridization (FISH) revealed T. denticola clusters in both gingival and aortic tissue of infected mice. This is the first study examining the potential causative role of chronic T. denticola periodontal infection and vascular atherosclerosis in vivo in hyperlipidemic ApoE(null) mice. T. denticola is closely associated with periodontal disease and the rapid progression of atheroma in ApoE(null) mice. These studies confirm a causal link for active oral T. denticola infection with both atheroma and periodontal disease.
- Syphilis in the United States. [Journal Article]
- Clin Dermatol 2014 Mar-Apr; 32(2):213-8.
Syphilis gained notoriety in the 1500s, when it became widespread throughout Europe. While the origins of syphilis are not certain, recent data have shown that it may have originated in the Americas from a close relative that causes Yaws (Treponema pallidum pertenue).(1) For the past 500years, the disease has shown its various faces all over the world. The 19th century saw an entire medical subspecialty-syphilology (sometimes known as syphilography)-devoted to the study of the great disease, then known as "the great imitator." Syphilis has an entire textbook of presentations and can mimic many other infections and immune-mediated processes. At the beginning of the 20th century, the many faces of the disease led to Sir William Osler's well-known aphorism, "The physician who knows syphilis knows medicine."(2) When penicillin was discovered, and used to treat syphilis in 1943, some thought that syphilis would go by the wayside, but syphilis continued what it has been doing for so many years . . . inconspicuously infecting humans. The United States has seen the incidence of syphilis increase numerous times throughout the past 70years. Every decrease in the incidence of syphilis is followed shortly by an increase. A marked shift in the epidemiology occurred from 1990 to 2000. In the 1990s, syphilis primarily occurred in heterosexual minority groups. In the new millennium, a majority of cases of syphilis are now transmitted among men who have sex with men (MSM).(3) This contribution discusses the incidence of syphilis in the United States and the reasons these trends continue.
- Prevelance of periodontopathogenic bacteria in subgingival biofilm and atherosclerotic plaques of patients undergoing coronary revascularization surgery. [Journal Article]
- J Indian Soc Periodontol 2013 Nov; 17(6):719-24.
The objective of the present study was to detect the presence of specific periodontopathogenic bacteria in the coronary plaque of patients with coronary artery disease and to find out the significant association between the periodontal status and the presence of pathogenic bacteria in the coronary plaque.The study population consisted of 51 patients with chronic generalized periodontitis undergoing coronary artery bypass grafting. Periodontal parameters were recorded and deoxyribonucleic acid was extracted from the subgingival plaque and coronary atherosclerotic plaque samples of the same patients. Polymerase chain reaction was used to amplify the part of 16S ribosomal ribonucleic acid (rRNA) gene to detect the presence of Aggregatibacter actinomycetemcomitans (Aa), Tannerella forsythia (Tf), Porphyromonas gingivali (Pg), Porphyromonas gingivalis (fimA) gene and Treponema denticola (Td).Aa, Tf, Pg, Pg (fimA) gene and Td were detected in 0%, 31.4%, 45.1% 39.2% and 51% of atherosclerotic plaque samples, respectively. Tf was detected in 19.6%, Pg in 39.2%, Pg (fimA) gene in 33.3% and Td in 35.3% of both, subgingival plaque and atherosclerotic plaque samples. Periodontal parameters correlated with the presence of bacteria in coronary plaque. Aa could not be detected in coronary plaque samples.The study confirmed the detection of Red complex bacteria in coronary plaque samples and these bacteria correlated with the severity of periodontal destruction.
- Subgingival plaque sampling after combined mechanical and antibiotic nonsurgical periodontal therapy. [JOURNAL ARTICLE]
- Clin Oral Investig 2014 Feb 20.
This study aimed to make a comparison of two sampling strategies of subgingival plaque after combined mechanical-antibiotic periodontal therapy.Thirty patients (18 female) suffering from aggressive (n = 12) or generalised severe chronic (n = 18) periodontitis were included. Aggregatibacter actinomycetemcomitans had been detected subgingivally in all prior to anti-infective therapy (AT) and combined mechanical-antibiotic AT had been rendered. After AT clinical examinations were performed and subgingival plaque was sampled from the same four sites as prior to AT (ASPRE) as well as from the four deepest sites after AT (DEEP). Per patient two pooled samples (ASPRE/DEEP) were generated and analysed for A. actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola using a commercial 16S rRNA test.ASPRE failed to detect A. actinomycetemcomitans, DEEP detected A. actinomycetemcomitans only in two patients (7 %). Only for T. forsythia DEEP (53 %) provided higher detection frequencies than ASPRE (27 %; p = 0.005). Detection frequencies of P. gingivalis and T. denticola ranged from 47 to 53 %.After combined mechanical-antibiotic AT sampling the deepest sites revealed higher detection rates. Combined mechanical-antibiotic AT suppresses A. actinomycetemcomitans to a higher extent than P. gingivalis, T. forsythia and T. denticola.
- A case of tertiary neurosyphilis presenting with moth-eaten bone lesions. [Journal Article]
- Dermatol Ther 2013 Nov; 26(6):486-8.
Syphilis, the "great imitator," with regard to skin diseases, is a chronic systemic infectious disease with a clinical course that waxes and wanes. The incidence of tertiary syphilis had decreased drastically these decades. We report a case of tertiary neurosyphilis presenting with moth-eaten bone lesions of the lower extremities. To the best of our knowledge, we have not seen such reports.
- Analysis of 3 Algorithms for Syphilis Serodiagnosis and Implications for Clinical Management. [JOURNAL ARTICLE]
- Clin Infect Dis 2014 Mar 5.
Background. Algorithms for the diagnosis of syphilis continue to be a source of great controversy, and numerous test interpretations have perplexed many clinicians. Methods. We conducted a cross-sectional study of 24 124 subjects to analyze 3 syphilis testing algorithms: traditional algorithm, reverse algorithm, and the European Centre for Disease Prevention and Control (ECDC) algorithm. Every serum sample was simultaneously evaluated using the rapid plasma reagin, Treponema pallidum particle agglutination, and chemiluminescence immunoassay tests. With the results of clinical diagnoses of syphilis as a gold standard, we evaluated the diagnostic accuracy of the 3 syphilis testing algorithms. The κ coefficient was used to compare the concordance between the reverse algorithm and the ECDC algorithm. Results. Overall, 2749 patients in our cohort were diagnosed with syphilis. The traditional algorithm had the highest negative likelihood ratio (0.24), a missed diagnosis rate of 24.2%, and only 75.81% sensitivity. However, both the reverse and ECDC algorithms had higher diagnostic efficacy than the traditional algorithm. Their sensitivity, specificity, and accuracy were 99.38%-99.85%, 99.98%-100.00%, and 99.93%-99.96%, respectively. Moreover, the overall percentage of agreement and κ value between the reverse and the ECDC algorithms were 99.9% and 0.996, respectively. Conclusions. Our research supported use of the ECDC algorithm, in which syphilis screening begins with a treponemal immunoassay that is followed by a second, different treponemal assay as a confirmatory test in high-prevalence populations. In addition, our results indicated that nontreponemal assay is unnecessary for syphilis diagnosis but can be recommended for determining serological activity and the effect of syphilis treatment.