Focal non granulomatous orchitis in a patient with Crohn’s disease

Crohn’s disease is a systemic disease and sometimes involves the testicle, usually leading to granulomatous lesions. We report herein a case of focal non-granulomatous orchitis in a 21-year-old patient with active Crohn’s disease treated by an anti-tumor necrosis factor monoclonal antibody. This circumscribed testicular lesion mimicked a tumor, leading to orchiectomy. Pre-operative blood tests (i.e. alpha-fetoprotein, lactate dehydrogenase and human chorionic gonadotrophin) were strictly normal Pathological examination of the testicle revealed a focal inflammatory infiltrate predominantly composed of lymphocytes accompanied by few plasma cells, lacking giant cells or granulomas. Importantly, intratubular germ cell neoplasia, atrophy or lithiasis were not observed. After discussing and excluding other plausible causes (burnt-out /regressed germ cell tumor, infection, vascular or traumatic lesions, iatrogenic effects), we concluded that this particular case of orchitis was most likely an extra-digestive manifestation of inflammatory bowel disease. To our knowledge, this is the first described case of focal non-granulomatous orchitis associated with Crohn’s disease. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/211774728416011

Neurosyphilis manifesting with unilateral visual loss and hyponatremia: a case report

<p>Abstract</p> <p>Background</p> <p>Syphilis is called the chameleon of the diseases due to its variety of its clinical presentations, potentially affecting every organ of the body. Incidence of this ancient disease is once again on the increase worldwide.</p> <p>Case presentation</p> <p>We here report an unusual case of neurosyphilis manifesting with unilateral visual loss and hyponatremia. The patient also had primary syphilitic lesions and was concomitantly diagnosed with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection. Treatment with ceftriaxone and prednisolone, completely resolved the hyponatremia and visual acuity was partially restored.</p> <p>Conclusion</p> <p>Awareness of syphilis as a differential diagnosis is important as previously unreported presentations of neurosyphilis can arise, especially in HIV infected patients.</p

Syphilis epidemiology in Norway, 1992-2008: resurgence among men who have sex with men

<p>Abstract</p> <p>Background</p> <p>In recent years, the number of syphilis cases has stabilised in many countries of Western Europe, however several countries have reported increases among men who have sex with men (MSM). The aim of this article was to describe the epidemiology of early syphilis in Norway in 1992-2008.</p> <p>Methods</p> <p>Cases of early syphilis and congenital syphilis reported to the Norwegian Surveillance System for Communicable Diseases (MSIS) 1992-2008 were described by route of transmission, gender, age, birthplace, stage of disease, HIV co-infection, source partner and place of infection.</p> <p>Results</p> <p>The incidence of reported syphilis ranged from 0.05 (1992) to 1.50 (2002) per 100 000 person-years. Of 562 cases reported to MSIS during the study period, 62% were men infected by another man. The proportion of those, infected homosexually increased from 0 (1992-1994) to 77% (2008). Most of them were Norwegians (83%). The proportion of HIV co-infection among homosexually infected increased over time and reached 39% in 2008. The majority reported being infected by a casual partner (73%) and in the municipality of Oslo (72%). Of 152 heterosexually infected men 64% were Norwegians; 51% were infected by casual contacts and 20% by commercial sex workers; 73% were infected abroad. Among 56 women, 57% were Norwegians, 57% were infected by a steady partner and 40% were infected abroad. Almost half (46%) were diagnosed in the early latent stage. Four cases had congenital syphilis, two of whom were adopted from abroad.</p> <p>Conclusions</p> <p>Syphilis is rare in Norway, but MSM represent almost two thirds of cases. The increase of HIV co-infected cases among MSM may enhance transmission of both infections. We recommend sexually active MSM to be tested for syphilis 2-4 times a year. Due to its variable clinical course, syphilis might be difficult to recognise at an early stage among women in a low-prevalence population. We estimate current practice of prenatal screening in Norway as sufficient.</p

Molecular Typing of Treponema pallidum: A Systematic Review and Meta-Analysis

Syphilis has been resurgent in many parts of the world in past decades. Understanding the epidemiology of syphilis is important for estimating disease burdens, monitoring epidemic trends, and evaluating intervention activities. Treponema pallidum (T. pallidum), the pathogen of syphilis, cannot be grown in vitro. Because T. pallidum cannot be cultured, molecular typing of T. pallidum is particularly useful and allows for investigation of infection diversity and epidemiology. We conducted a statistical analysis of available published data to investigate the current research progress of molecular typing of syphilis. Our analysis showed that primary lesion was a better specimen for obtaining T. pallidum DNA than blood. Blood specimens collected from scraping the ear lobes had high yield of T. pallidum DNA and high full typing efficiency. Ear lobe blood is a promising specimen for future T. pallidum molecular typing, but further research should verify this finding using a larger sample size. Within all studies, subtype 14d was most prevalent, and subtype distribution varied across geographic areas. Subtype data associated with macrolide resistance and neurosyphilis were limited. More research on molecular typing of T. pallidum can be useful for investigating syphilis epidemiology and designing syphilis control strategies

Footprint of Positive Selection in Treponema pallidum subsp. pallidum Genome Sequences Suggests Adaptive Microevolution of the Syphilis Pathogen

In the rabbit model of syphilis, infection phenotypes associated with the Nichols and Chicago strains of Treponema pallidum (T. pallidum), though similar, are not identical. Between these strains, significant differences are found in expression of, and antibody responses to some candidate virulence factors, suggesting the existence of functional genetic differences between isolates. The Chicago strain genome was therefore sequenced and compared to the Nichols genome, available since 1998. Initial comparative analysis suggested the presence of 44 single nucleotide polymorphisms (SNPs), 103 small (≤3 nucleotides) indels, and 1 large (1204 bp) insertion in the Chicago genome with respect to the Nichols genome. To confirm the above findings, Sanger sequencing was performed on most loci carrying differences using DNA from Chicago and the Nichols strain used in the original T. pallidum genome project. A majority of the previously identified differences were found to be due to errors in the published Nichols genome, while the accuracy of the Chicago genome was confirmed. However, 20 SNPs were confirmed between the two genomes, and 16 (80.0%) were found in coding regions, with all being of non-synonymous nature, strongly indicating action of positive selection. Sequencing of 16 genomic loci harboring SNPs in 12 additional T. pallidum strains, (SS14, Bal 3, Bal 7, Bal 9, Sea 81-3, Sea 81-8, Sea 86-1, Sea 87-1, Mexico A, UW231B, UW236B, and UW249C), was used to identify “Chicago-“ or “Nichols -specific” differences. All but one of the 16 SNPs were “Nichols-specific”, with Chicago having identical sequences at these positions to almost all of the additional strains examined. These mutations could reflect differential adaptation of the Nichols strain to the rabbit host or pathoadaptive mutations acquired during human infection. Our findings indicate that SNPs among T. pallidum strains emerge under positive selection and, therefore, are likely to be functional in nature

Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster

The abrupt onslaught of the syphilis pandemic that started in the late fifteenth century established this devastating infectious disease as one of the most feared in human history. Surprisingly, despite the availability of effective antibiotic treatment since the mid-twentieth century, this bacterial infection, which is caused by Treponema pallidum subsp. pallidum (TPA), has been re-emerging globally in the last few decades with an estimated 10.6 million cases in 2008. Although resistance to penicillin has not yet been identified, an increasing number of strains fail to respond to the secondline antibiotic azithromycin. Little is known about the genetic patterns in current infections or the evolutionary origins of the disease due to the low quantities of treponemal DNA in clinical samples and difficulties in cultivating the pathogen. Here, we used DNA capture and whole-genome sequencing to successfully interrogate genome-wide variation from syphilis patient specimens, combined with laboratory samples of TPA and two other subspecies. Phylogenetic comparisons based on the sequenced genomes indicate that the TPA strains examined share a common ancestor after the fifteenth century, within the early modern era. Moreover, most contemporary strains are azithromycin-resistant and are members of a globally dominant cluster, named here as SS14-Ω. The cluster diversified from a common ancestor in the mid-twentieth century subsequent to the discovery of antibiotics. Its recent phylogenetic divergence and global presence point to the emergence of a pandemic strain cluster

Genomic epidemiology of syphilis reveals independent emergence of macrolide resistance across multiple circulating lineages.

Syphilis is a sexually transmitted infection caused by Treponema pallidum subspecies pallidum and may lead to severe complications. Recent years have seen striking increases in syphilis in many countries. Previous analyses have suggested one lineage of syphilis, SS14, may have expanded recently, indicating emergence of a single pandemic azithromycin-resistant cluster. Here we use direct sequencing of T. pallidum combined with phylogenomic analyses to show that both SS14- and Nichols-lineages are simultaneously circulating in clinically relevant populations in multiple countries. We correlate the appearance of genotypic macrolide resistance with multiple independently evolved SS14 sub-lineages and show that genotypically resistant and sensitive sub-lineages are spreading contemporaneously. These findings inform our understanding of the current syphilis epidemic by demonstrating how macrolide resistance evolves in Treponema subspecies and provide a warning on broader issues of antimicrobial resistance

Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy

In the high malaria-transmission settings of sub-Saharan Africa, malaria in pregnancy is an important cause of maternal, perinatal and neonatal morbidity. Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) reduces the incidence of low birth-weight, pre-term delivery, intrauterine growth-retardation and maternal anaemia. However, the public health benefits of IPTp are declining due to SP resistance. The combination of azithromycin and chloroquine is a potential alternative to SP for IPTp. This review summarizes key in vitro and in vivo evidence of azithromycin and chloroquine activity against Plasmodium falciparum and Plasmodium vivax, as well as the anticipated secondary benefits that may result from their combined use in IPTp, including the cure and prevention of many sexually transmitted diseases. Drug costs and the necessity for external financing are discussed along with a range of issues related to drug resistance and surveillance. Several scientific and programmatic questions of interest to policymakers and programme managers are also presented that would need to be addressed before azithromycin-chloroquine could be adopted for use in IPTp

Long Lamai community ICT4D E‐commerce system modelling: an agent oriented role‐based approach

This paper presents the post‐mortem report upon completion of the Long Lamai e‐commerce development project. Some weaknesses with regards to the current software modelling approach are identified and an alternative role‐based approach is proposed. We argue that the existing software modelling technique is not suitable for modelling, making it difficult to establish a good contract between stakeholders causing delays in the project delivery. The role‐based approach is able to explicitly highlight the responsibilities among stakeholders, while also forming the contract agreement among them leading towards sustainable ICT4D

Characterizing the Syphilis-Causing Treponema pallidum ssp. pallidum Proteome Using Complementary Mass Spectrometry

YesBackground. The spirochete bacterium Treponema pallidum ssp. pallidum is the etiological agent of syphilis, a chronic multistage disease. Little is known about the global T. pallidum proteome, therefore mass spectrometry studies are needed to bring insights into pathogenicity and protein expression profiles during infection. Methodology/Principal Findings. To better understand the T. pallidum proteome profile during infection, we studied T. pallidum ssp. pallidum DAL-1 strain bacteria isolated from rabbits using complementary mass spectrometry techniques, including multidimensional peptide separation and protein identification via matrix-assisted laser desorption ionization-time of flight (MALDI-TOF/TOF) and electrospray ionization (ESI-LTQ-Orbitrap) tandem mass spectrometry. A total of 6033 peptides were detected, corresponding to 557 unique T. pallidum proteins at a high level of confidence, representing 54% of the predicted proteome. A previous gel-based T. pallidum MS proteome study detected 58 of these proteins. One hundred fourteen of the detected proteins were previously annotated as hypothetical or uncharacterized proteins; this is the first account of 106 of these proteins at the protein level. Detected proteins were characterized according to their predicted biological function and localization; half were allocated into a wide range of functional categories. Proteins annotated as potential membrane proteins and proteins with unclear functional annotations were subjected to an additional bioinformatics pipeline analysis to facilitate further characterization. A total of 116 potential membrane proteins were identified, of which 16 have evidence supporting outer membrane localization. We found 8/12 proteins related to the paralogous tpr gene family: TprB, TprC/D, TprE, TprG, TprH, TprI and TprJ. Protein abundance was semi-quantified using label-free spectral counting methods. A low correlation (r = 0.26) was found between previous microarray signal data and protein abundance. Conclusions. This is the most comprehensive description of the global T. pallidum proteome to date. These data provide valuable insights into in vivo T. pallidum protein expression, paving the way for improved understanding of the pathogenicity of this enigmatic organism.This work was supported by the grants from the Flanders Research Foundation, SOFI-B Grant to CRK, http://www.fwo.be/, a Public Health Service Grant from the National Institutes of Health to CEC, (grant # AI-051334), https://www.nih.gov/ and a grant from the Grant Agency of the Czech Republic to DS and MS (P302/12/0574, GP14-29596P), https:// gacr.cz/