Metagenomics studies for the diagnosis and treatment of prostate cancer.

AIM: Mutation occurs in the prostate cell genes, leading to abnormal prostate proliferation and ultimately cancer. Prostate cancer (PC) is one of the most common cancers amongst men, and its prevalence worldwide increases relative to men's age. About 16% of the world's cancers are the result of microbes in the human body. Impaired population balance of symbiosis microbes in the human reproductive system is linked to PC development. DISCUSSION: With the advent of metagenomics science, the genome sequence of the microbiota of the human body has been unveiled. Therefore, it is now possible to identify a higher range of microbiome changes in PC tissue via the Next Generation Technique, which will have positive consequences in personalized medicine. In this review, we intend to question the role of metagenomics studies in the diagnosis and treatment of PC. CONCLUSION: The microbial imbalance in the men's genital tract might have an effect on prostate health. Based on next-generation sequencing-generated data, Proteobacteria, Firmicutes, Actinobacteria, and Bacteriodetes are the nine frequent phyla detected in a PC sample, which might be involved in inducing mutation in the prostate cells that cause cancer.

Protection and Risk: Male and Female Genital Microbiota and Sexually Transmitted Infections.

Unique compositional and functional features of the cervicovaginal microbiota have been associated with protection against and risk for sexually transmitted infections (STI). In men, our knowledge of the interaction between the penile microbiota and STI is less developed. The current state of our understanding of these microbiota and their role in select STIs is briefly reviewed, along with strategies that leverage existing findings to manipulate genital microbiota and optimize protection against STIs. Finally, we focus on major research gaps and present a framework for future studies.

Prevalence and sociodemographic correlates of anogenital Human Papillomavirus (HPV) carriage in a cross-sectional, multi-ethnic, community-based Asian male population.

BACKGROUND: Addressing the burden of HPV-associated diseases among men is increasingly becoming a public health issue. The main objective of this study was to determine HPV prevalence among a healthy community-based Malaysian men. METHOD: This was a cross-sectional study that recruited 503 healthy males from 3 community-based clinics in Selangor, Malaysia. Genital and anal samples were collected from each participant for 14 high risk and 2 low risk HPV DNA detection and genotyping. All participants responded to a set of detailed sociodemographic and sexual behaviour questionnaire. RESULTS: The median age at enrolment was 40 years old (IQR: 31-50). The anogenital HPV6/11 prevalence was 3.2% whereas high risk HPV prevalence was 27.1%. The genital HPV prevalence for HPV6/11 was 2.9% while high risk HPV was 18.8%. HPV6/11 prevalence in the anal canal was 1.6% and high risk HPV was 12.7%. HPV 18 was the most prevalent genotype detected in the anogenital area. There was a significant independent association between genital and anal HPV infections. CONCLUSION: Anogenital HPV infection is common among Malaysian men. These findings emphasize the ubiquity of HPV infection and thus the value of population-wide access to HPV prevention.

Bacterial infection of the male reproductive system causing infertility.

Bacterial infections play a disruptive and hidden role in male reproductive failure. Different kinds of bacteria are often able to interfere with reproductive function in both sexes and lead to infertility. In this study, to further evaluate the role of bacterial infections in male reproduction we provided an extensive overview of so far researches investigating the effects of bacterial infections on male fertility. We searched Medline, PubMed, Scopus and Google scholar databases to identify the potentially relevant studies on bacterial infections and their implications in male infertility. All the bacteria included in this article have negative effects on the male reproductive function; however, there is ample evidence to blame bacteria such as Escherichia coli, Chlamydia trachomatis, Ureaplasma, Mycoplasma and Staphylococcus aureus for reduced fertility and deterioration of sperm parameters. More studies are needed to clarify the molecular mechanisms by which different bacteria exert their detrimental effects on male reproductive system. Getting more insight into probable mechanisms, would significantly facilitate the production of new, advanced, and effective remedies in the future. In view of all evidence, we strongly suggest increasing awareness among people and considering screening programs for patients seeking fertility both to avoid transmission and to improve fertility outcomes among them.

Staphylococcal infections and infertility: mechanisms and management.

Infertility is a subject of worldwide concern as it affects approximately 15% of couples. Among the prime contributors of infertility, urogenital bacterial infections have lately gained much clinical importance. Staphylococcal species are commensal bacteria and major human pathogens mediating an array of reproductive tract infections. Emerging evidences are 'bit by bit' revealing the mechanisms by which Staphylococci strategically disrupt normal reproductive functions. Staphylococcal species can directly or through hematogenous routes can invade the reproductive tissues. In the testicular cells, epididymis as well as in various compartments of female reproductive tracts, the pathogen recognition receptors, toll-like receptors (TLRs), can recognize the pathogen-associated molecular patterns on the Staphylococci and thereby activate inflammatory signalling pathways. These elicit pro-inflammatory mediators trigger other immune cells to infiltrate and release further inflammatory agents and reactive oxygen species (ROS). Adaptive immune responses may intensify the inflammation-induced reproductive tissue damage, particularly via activation of T-helper (Th) cells, Th1 and Th17 by the innate components or by staphylococcal exotoxins. Staphylococcal surface factors binding with sperm membrane proteins can directly impair sperm functions. Although Staphylococci, being one of the most virulent bacterial species, are major contributors in infection-induced infertility in both males and females, the mechanisms of their operations remain under-discussed. The present review aims to provide a comprehensive perception of the possible mechanisms of staphylococcal infection-induced male and female infertility and aid potential interventions to address the lack of competent therapeutic measures for staphylococcal infection-induced infertility.

Effects of bacteria on male fertility: Spermatogenesis and sperm function.

Bacterial infection can negatively affect different parts of the male genital tract and subsequently cause impaired spermatogenesis and male fertility. However, most of the previous studies have focused on the infected organs of the male genital tract and there are not many studies that investigated the direct effect of bacteria on sperm and their mechanism of action. Interestingly, bacteria can induce different damages on sperm cells such as DNA fragmentation, cell membrane peroxidation, and acrosome impairment. Such negative effects can be mediated by bacteria-secreted toxins and metabolites or by direct attachment of bacteria on the sperm cells and subsequent activation of signaling pathways related to oxidative stress, apoptosis, and inflammation. These bacteria-induced changes can impair semen parameters and subsequently cause infertility. Given the significant destructive effect of some bacteria on sperm function and male fertility, in this study, we reviewed the impact of male urogenital bacteria on spermatogenesis and sperm functions as well as the underlying mechanisms by which the bacteria can damage sperm.

Prevalence of Coxiella burnetii in German sheep flocks and evaluation of a novel approach to detect an infection via preputial swabs at herd-level.

A prevalence study was conducted on German sheep flocks including goats if they cohabitated with sheep. In addition, a novel approach was applied to identify an infection at the herd-level before lambing season with preputial swabs, suspecting venereal transmission and ensuing colonisation of preputial mucosa with Coxiella (C.) burnetii. Blood samples and genital swabs were collected from breeding males and females after the mating season and were analysed by enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR) respectively. In total, 3367 animals were sampled across 71 flocks. The true herd-level prevalence adjusted for misclassification probabilities of the applied diagnostic tests using the Rogan-Gladen estimator for the prevalence estimate and a formula by Lang and Reiczigel (2014) for the confidence limits, ranged between 31.3% and 33% (95% confidence interval [95% CI] 17.3-45.5) detected by the ELISA and/or qPCR. Overall 26-36.6% (95% CI 13-56.8) were detected by ELISA, 13.9% (95% CI 4.5-23.2) by the qPCR and 7.9-11.2% (95% CI 0.08-22.3) by both tests simultaneously. The range of results is due to data obtained from literature with different specifications for test quality for ELISA. Among eight farms with females shedding C. burnetii, three farms (37.5%) could also be identified by preputial swabs from breeding sires. This indicates less reliability of preputial swabs if used as a single diagnostic tool to detect C. burnetii infection at the herd-level.

Composition and diversity of the preputial microbiota in healthy bulls.

Characterization of microbial communities inhabiting the reproductive tracts of cattle may lead to a better comprehension of bovine physiology and reproductive health. To date, reported studies have utilized culture-independent 16S ribosomal RNA (rRNA) for the classification of microbiota in the vaginal tract of cows but no studies have looked at the microbiota of the prepuce or penis of the bull. The aim of this study was to elucidate the microbiota present on the epithelial surface of the penis and prepuce of the post-pubertal bull using 16S rRNA gene sequencing. Ninety-two healthy bulls of a variety of ages and breeding history, presented for routine breeding soundness examinations, were utilized in this investigation. Bacteria belonging to Firmicutes, Fusobacteria, Bacteroidetes, Proteobacteria, and Actinobacteria were identified in the prepuce. From all the bulls, two major community types were found, those with low or high bacterial species richness (up to 400 operational taxonomic units in one sample). There was no animal characteristic (breed or age) or management practice (feed type, antibiotic use, co-housing, breeding history) that was correlated with the bull penile microbial community composition. However, Bradyrhizobium was a distinguishing genus only found in the low diversity samples. The bull penile microbial community includes members of genera that are common in soil, cow vagina, respiratory tract, and feces. The baseline preputial microbial community in healthy bulls is described in the current study. This knowledge can be used later when investigating the interactions between disease and the male urogenital tract microbial community.

Optimizing bacterial DNA extraction in urine.

Urine is an acceptable, non-invasive sample for investigating the human urogenital microbiota and for the diagnosis of sexually transmitted infections. However, low quantities of bacterial DNA and PCR inhibitors in urine may prevent efficient PCR amplification for molecular detection of bacteria. Furthermore, cold temperatures used to preserve DNA and bacteria in urine can promote precipitation of crystals that interfere with DNA extraction. Saline, Dulbecco's Phosphate Buffered Saline, or Tris-EDTA buffer were added to urine from adult men to determine if crystal precipitation could be reversed without heating samples beyond ambient temperature. Total bacterial DNA concentrations and PCR inhibition were measured using quantitative PCR assays to compare DNA yields with and without buffer addition. Dissolution of crystals with Tris-EDTA prior to urine centrifugation was most effective in increasing bacterial DNA recovery and reducing PCR inhibition. DNA recovery using Tris-EDTA was further tested by spiking urine with DNA from bacterial isolates and median concentrations of Lactobacillus jensenii and Escherichia coli 16S rRNA gene copies were found to be higher in urine processed with Tris-EDTA. Maximizing bacterial DNA yield from urine may facilitate more accurate assessment of bacterial populations and increase detection of specific bacteria in the genital tract.

Bacteria detected in the genital tract, semen or pre-ejaculatory fluid of Swedish stallions from 2007 to 2017.

BACKGROUND: Although artificial insemination (AI) was developed as a means of controlling disease transmission, pathogens can still be transmitted to females in semen used for AI. In addition, bacteria can cause deterioration in sperm quality during storage. Semen becomes contaminated by the male's normal bacterial flora as it passes out of the reproductive tract but potential pathogens may also contaminate the semen. Therefore, semen samples from stallions to be used for AI are tested before the breeding season to minimize transmission of pathogens to inseminated mares. In Sweden, semen samples are tested at the National Veterinary Institute, Uppsala (SVA). For the present study, a retrospective analysis was made of potentially pathogenic bacteria isolated from samples submitted to the SVA from 2007 to 2017. RESULTS: In our study, Taylorella equigenitalis was found infrequently (53 out of 25,512 samples), representing 11 out of 2308 stallions. If T. equigenitalis was detected, the stallions were treated with antibiotics and re-tested later in the same year. Klebsiella pneumoniae and beta haemolytic streptococci were the most commonly found potential pathogens, whereas Pseudomonas aeruginosa was also isolated occasionally. There were considerable differences in the number of species isolated each year. CONCLUSIONS: Potential pathogens were identified in relatively few of the samples submitted to SVA during this period, with T. equigenitalis not being identified since 2015. Of the other potential pathogens, K. pneumoniae and beta haemolytic streptococci were the most common. The information is relevant for determining guidelines on the testing and treatment of stallions before breeding.

A 'pathogenic needle' in a 'commensal haystack': Genetic virulence signatures of Corynebacterium glucuronolyticum that may drive its infectious propensity for the male urogenital system.

The predominance of the genus Corynebacterium in the healthy male urogenital system contributes to the resident microbiome of not only the distal urethra, but potentially the proximal urethra and urinary bladder as well. However, for certain species in this genus, pathogenic potential was described, and the salient representative is Corynebacterium glucuronolyticum (C. glucuronolyticum) implicated in cases of urethritis and prostatitis in men. Nonetheless, some still question whether C. glucuronolyticum can actually be considered pathogenic or rather just a commensal species fortuitously isolated in patients with urogenital symptoms and/or syndromes. Although pathogen/commensal dichotomy is not always clear-cut, we hypothesize that specific genetic markers may expose C. glucuronolyticum as a convincingly pathogenic Corynebacterium. More specifically, characteristic pathogenic gene constellation inherent to this species (most notably the presence of specific sortase/SpaA-type pili gene clusters, but also the augmentative role of type VII secretion system) may significantly facilitate host tissue adhesion, with subsequent suppression/evasion of the immune response and acquisition of vitally important nutrients. Consequently, these genetic markers differentiate C. glucuronolyticum from its commensal counterparts, and give this species a pathogenic facet, which can be even further influenced by the Allee effect. In this paper we also propose a specific methodological approach on how to analyze C. glucuronolyticum epithelial colonization capacity and explore inceptive host cell-pathogen interactions that manipulate host environment and immune responses. This entails moving from approaches based primarily on overall homology of primary sequences towards specific structure-function studies to precisely evaluate all stakeholders involved in pili assemblage, cell adhesion and the expression of other virulence traits. In the era of high precision medicine, the hypothesized roles of C. glucuronolyticum adhesion systems in both virulence and nutrient acquisition may also reveal promising targets for future drug developments.

Identification and evaluation of the microbiome in the female and male reproductive tracts.

BACKGROUND: The existence of an extensive microbiome in and on the human body has increasingly dominated the scientific literature during the last decade. A shift from culture-dependent to culture-independent identification of microbes has occurred since the emergence of next-generation sequencing (NGS) techniques, whole genome shotgun and metagenomic sequencing. These sequencing analyses have revealed the presence of a rich diversity of microbes in most exposed surfaces of the human body, such as throughout the reproductive tract. The results of microbiota analyses are influenced by the technical specifications of the applied methods of analyses. Therefore, it is difficult to correctly compare and interpret the results of different studies of the same anatomical niche. OBJECTIVES AND RATIONALE: The aim of this narrative review is to provide an overview of the currently used techniques and the reported microbiota compositions in the different anatomical parts of the female and male reproductive tracts since the introduction of NGS in 2005. This is crucial to understand and determine the interactions and roles of the different microbes necessary for successful reproduction. SEARCH METHODS: A search in Embase, Medline Ovid, Web of science, Cochrane and Google scholar was conducted. The search was limited to English language and studies published between January 2005 and April 2018. Included articles needed to be original microbiome research related to the reproductive tracts. OUTCOMES: The review provides an extensive up-to-date overview of current microbiome research in the field of human reproductive medicine. The possibility of drawing general conclusions is limited due to diversity in the execution of analytical steps in microbiome research, such as local protocols, sampling methods, primers used, sequencing techniques and bioinformatic pipelines, making it difficult to compare and interpret results of the available studies. Although some microbiota are associated with reproductive success and a good pregnancy outcome, it is still unknown whether a causal link exists. More research is needed to further explore the possible clinical implications and therapeutic interventions. WIDER IMPLICATIONS: For the field of reproductive medicine, determination of what is a favourable reproductive tract microbiome will provide insight into the mechanisms of both unsuccessful and successful human reproduction. To increase pregnancy chances with live birth and to reduce reproduction-related health costs, future research could focus on postponing treatment or conception in case of the presence of unfavourable microbiota and on the development of therapeutic interventions, such as microbial therapeutics and lifestyle adaptations.

IL-10 Producing B Cells Dampen Protective T Cell Response and Allow Chlamydia muridarum Infection of the Male Genital Tract.

A significant proportion of individuals develop chronic, persistent and recurrent genital tract infections with Chlamydia trachomatis, which has been attributed to the numerous strategies that the bacterium uses to subvert host immune responses. Animal chlamydia models have demonstrated that protective immune response is mediated by CD4+ Th1 cytokine responses. Herein, we demonstrate that early after infecting the male genital tract, C. muridarum triggers the production of IL-10 by splenic and lymph node cells. In addition, C. muridarum triggers IL-6 and TNFα secretion. Data obtained from in vitro and in vivo experiments revealed B cells as the major IL-10 contributors. Indeed, purified B cells produced high amounts of IL-10 and also exhibited enhanced expression of inhibitory molecules such as CD39, PD-L1 and PD1 after C. muridarum stimulation. In vitro experiments performed with sorted cell subsets revealed that Marginal Zone B cells were the main IL-10 producers. In vitro and in vivo studies using TLR-deficient mice indicated that TLR4 signaling pathway was essential for IL-10 production. In addition, in vivo treatments to neutralize IL-10 or deplete B cells indicated that IL-10 and B cells played a significant role in delaying bacterial clearance ability. Moreover, the latter was confirmed by adoptive cell transfer experiments in which the absence of IL-10-producing B cells conferred the host a greater capability to induce Th1 responses and clear the infection. Interestingly, NOD mice, which were the least efficient in clearing the infection, presented much more Marginal Zone B counts and also enhanced TLR4 expression on Marginal Zone B cells when compared to B6 and BALB/c mice. Besides, treatment with antibodies that selectively deplete Marginal Zone B cells rendered mice more capable of inducing enhanced IFNγ responses and clearing the infection. Our findings suggest that B cells play a detrimental role in C. muridarum infection and that activation by innate receptors like TLR4 and IL-10 production by these cells could be used by Chlamydia spp. as a strategy to modulate the immune response establishing chronic infections in susceptible hosts.

Pooling of genital swabs for detection by PCR of Taylorella equigenitalis, the cause of contagious equine metritis.

BACKGROUND: Sets of genital swabs are routinely taken from horses to screen for the presence of Taylorella equigenitalis, the cause of contagious equine metritis. Typically, two to four different sites are swabbed at a time and tested by culture or PCR. OBJECTIVES: This study explored the feasibility of pooling these swabs for a single PCR test per animal instead of testing each swab individually. STUDY DESIGN: In vitro. METHODS: PCR signal strengths (Ct values) from 149 historical PCR positive genital swabs, together with historical data on the number of swabs in a set expected to be positive, were used to assess the suitability of pooling for screening horses for T. equigenitalis infection in the population at large. Twenty-four sets of four equine genital swabs were tested. The sets were prepared in the laboratory using one or more swabs positive for T. equigenitalis from naturally infected cases. Positive and negative swabs were selected to reflect a typical range of PCR Ct values expected in field cases of T. equigenitalis infection. These pools were tested by an established PCR to assess the impact and suitability of a PCR test on pooled swabs compared to individual swab testing, by comparing the Ct values. RESULTS: Pooling one positive swab with three negative swabs produced a small drop in Ct value but all pools were still clearly positive. MAIN LIMITATIONS: Large numbers of field positive horses are not available, but the proof of concept approach with laboratory prepared pools shows the method is applicable to field cases. CONCLUSIONS: It was concluded that pooling of swabs would confer no appreciable drop in the ability to detect a positive animal compared to individual swab testing; pooling is therefore a suitable alternative to individual swab testing with reduced costs. The Summary is available in Spanish - see Supporting Information.

Chlamydia pecorum Infection in the Male Reproductive System of Koalas ( Phascolarctos cinereus).

Chlamydiosis is the most documented and serious disease of koalas, characterized by ocular, urinary, and reproductive lesions. Since little attention has been paid to the pathological effects of this infection in the male reproductive system, we aimed to determine the incidence and severity of reproductive pathology associated with chlamydial infection in male koalas submitted to koala hospitals in southeast Queensland. The entire reproductive tract from 62 sexually mature male koalas not suitable for rehabilitation was evaluated and 677 tissue samples were collected for histology, immunohistochemistry (IHC), and real-time polymerase chain reaction (qPCR). Lymphoplasmacytic inflammation was observed in 178 of 677 (26.3%) tissue samples from the upper and lower reproductive tract, mainly in the prostatic, penile, and membranous urethra. IHC was positive for the chlamydial antigen in 19 of 451 normal samples (4.2%) and 46 of 178 samples with inflammation (25.8%), located within the cytoplasm of epithelial cells of the epididymis, vas deferens, prostate, bulbourethral glands, and the prostatic membranous and penile urethra. Chlamydia pecorum was detected via qPCR in 319 of 451 normal samples (70.7%) and 159 of 178 samples with inflammation (89.3%), with the highest incidence in the penile urethra, prostate, membranous urethra, and bulbourethral glands. This study suggests that Chlamydia infection in the male reproductive tract is more widespread than originally thought. Furthermore, the male reproductive tract might be a reservoir for persistent chlamydial infections in koalas, with important implications for prophylactic strategies and epidemiology.

Application of direct polymerase chain reaction assays for Campylobacter fetus subsp. venerealis and Tritrichomonas foetus to screen preputial samples from breeding bulls in cow-calf herds in western Canada.

The primary objectives of this study were to estimate the prevalence of Campylobacter fetus subsp. venerealis (Cfv) and Tritrichomonas foetus in breeding bulls from a sentinel cohort of cow-calf herds in western Canada and to estimate the association between positive test status and non-pregnancy. The final objective was to evaluate the application of these tests when: i) screening bulls in the absence of a recognized problem with reproductive performance, and ii) testing for diagnosis of poor pregnancy rates. The crude apparent bull prevalence for Cfv was 1.1% [95% confidence interval (CI): 0.5% to 2.1%; 8/735] and herd prevalence was 2.6% (95% CI: 0.3% to 9.0%; 2/78). The crude apparent bull prevalence for T. foetus was < 0.001% (95% CI: 0.0% to 0.5%; 0/735) and herd prevalence was < 0.001% (95% CI: 0.0% to 4.6%; 0/78). Cows from herds where at least 1 bull was test positive for Cfv were 2.35 times more likely (95% CI: 1.01% to 5.48%; P = 0.047) to not be pregnant than those with no positive bulls. Polymerase chain reaction (PCR) testing of preputial material collected into phosphate-buffered saline (PBS) was recommended for screening for T. foetus when the pre-test probability of infection was > 1%. The same test for Cfv was not recommended for screening moderate- and low-risk herds due to the high risk of false positives. Tests for both T. foetus and Cfv can be used to investigate herds with reproductive problems when also ruling out other risk factors. Regardless of the type of test used, however, 3 negative tests are required to rule out infection in high-risk situations.

Les objectifs primaires de la présente étude étaient d'estimer la prévalence de Campylobacter fetus ssp. venerealis (Cfv) et Tritrichomonas foetus chez des taureaux reproducteurs d'une cohorte sentinelle issue de troupeaux vache-veau dans l'ouest canadien et d'estimer l'association entre un test positif et la non-gestation. L'objectif final était d'évaluer l'application de ces tests lors de : i) vérification des taureaux en absence d'un problème reconnu avec les performances de reproduction, et ii) épreuve diagnostique en présence de faibles taux de gestation. La prévalence apparente brute des taureaux pour Cfv était de 1,1 % [intervalle de confiance (IC) 95 % : 0,5 % à 2,1 %; 8/735] et la prévalence pour les troupeaux était de 2,6 % (IC 95 % : 0,3 % à 9,0 %; 2/78). La prévalence apparente brute des taureaux pour T. foetus était < 0,001 % (IC 95 % : 0,0 % à 0,5 %; 0/735) et la prévalence pour les troupeaux était < 0,001 % (IC 95 % 0,0 % à 4,6 %; 0/78). Les vaches provenant de troupeaux où au moins un taureau s'était avéré positif pour Cfv étaient 2,35 fois plus susceptibles (IC 95 % : 1,01 à 5,48; P = 0,047) de ne pas être gestante que celles provenant de troupeaux sans aucun taureau positif. L'analyse par réaction d'amplification en chaine par la polymérase de matériel prépucial prélevé dans de la saline tamponnée était recommandée pour vérifier la présence de T. foetus lorsque la probabilité d'infection pré-test était > 1 %. Le même type d'analyse pour Cfv n'était pas recommandé pour la vérification des troupeaux à risque modéré et faible étant donné le risque élevé de faux positifs. Les tests pour T. foetus et Cfv peuvent être utilisés pour investiguer les troupeaux avec des problèmes de reproduction en même temps que les autres facteurs de risque sont éliminés. Toutefois, indépendamment du type de test utilisé trois tests négatifs sont requis pour éliminer la possibilité de l'infection dans les situations à risque élevé.(Traduit par Docteur Serge Messier).

Lymphogranuloma Venereum-Serovar L2b Presenting With Painful Genital Ulceration: An Emerging Clinical Presentation?

These 5 cases of atypical inflammatory lymphogranula venereum (LGV) serovar L2b presenting initially with edema and persistent painful ulceration illustrate that clinical manifestations of LGV in the current outbreak in men who have sex with men reflect the influence of both the serovars virulence and the host immune system and are not confined to proctitis. L2b serovar could have a particular high virulence profile, and the need for awareness of LGV as a cause of genital ulceration is crucial.