Genetic characterisation of lymphogranuloma venereum in Spain: a multicentre study.

INTRODUCTION: Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by Chlamydia trachomatis genotypes L1-L3. A combination of techniques with high discriminatory capacity such as multilocus sequence typing (MLST) and the analysis of the ompA gene may be useful to determine the greater penetration of certain strains in transmission networks and their relationship with certain tropisms. AIM: The aim of this study was to investigate the molecular epidemiology of LGV isolates from different regions of Spain. METHODS: Genetic characterisation of LGV isolates detected in six hospitals from Spain between 2018 and 2019 was performed. MLST (five variable regions: hctB, CT058, CT144, CT172 and pbpB) and ompA sequence determination were used to study the LGV strains. RESULTS: Most of the 161 LGV isolates (93.8%) were detected in men who have sex with men (MSM). At least 43.5% of the patients presented with HIV coinfection and 53.4% were symptomatic, with proctitis being the most prevalent symptom (73.3%). Most isolates were detected in Barcelona (n=129).The distribution of ompA genovariants was as follows: 56.1% belonged to L2, 24.3% to L2b, 5.4% to L2bV1, 4.7% to L2bV4, 4.1% to L1, 2.7% to L2b/D-Da, 2.0% to L2bV2 and 0.7% to L2bV7. MLST was successfully performed in 81 samples and 9 different sequence types (STs) were detected. The ompA and MLST combination obtained 17 different genetic profiles, with L2-ST53 and L2-ST58 being the most prevalent (29.5% and 14.1%, respectively). L1 genotype strains belonged to ST23 (n=3) and ST2 (n=3). CONCLUSION: LGV infections were mainly found in MSM living with HIV and with proctitis. The joint analysis of ompA and MLST genetic characterisation techniques showed a high discriminatory capacity. Our findings suggest a cocirculation of L2 and L2b ompA genotypes, and with the inclusion of MLST characterisation, the most prevalent profiles were ompA genotype L2-MLST ST53 and L2-MLST ST58.

Clinically Defined Lymphogranuloma Venereum among US Veterans with Human Immunodeficiency Virus, 2016-2023.

We applied lymphogranuloma venereum (LGV) clinical case criteria to a cohort of 1381 Veterans positive for HIV and Chlamydia trachomatis (CT) from 2016 from 2023 and analyzed variables to ascertain risk factors for LGV and factors associated with the use of standard treatment regimens. In total, 284/1381 (20.6%) met the criteria for LGV. A total of 179/284 (63%) were probable cases, and 105/284 (37%) were possible cases (those meeting clinical criteria but with concurrent sexually transmitted infections (STI) associated with LGV-like symptoms). None had confirmatory CT L1-L3 testing. A total of 230 LGV cases (81%) presented with proctitis, 71 (25%) with ulcers, and 57 (20.1%) with lymphadenopathy. In total, 66 (23.2%) patients had >1 symptom of LGV. A total of 43 (15%) LGV cases were hospitalized. Primary risk factors for LGV were male birth sex (p = 0.004), men who have sex with men (p < 0.001), and the presence of STIs other than gonorrhea or syphilis (p = 0.011). In total, 124/284 (43.7%) LGV cases received standard recommended treatment regimens. Probable cases were more likely to receive standard treatment than possible cases (p = 0.003). We report that 20.6% of CT cases met clinical criteria for LGV among HIV-infected Veterans and that less than half of cases received recommended treatment regimens, indicating that LGV is likely underestimated and inadequately treated among this US population.

Anorectal lymphogranuloma venereum among men who have sex with men: a 3-year nationwide survey, France, 2020 to 2022.

BackgroundIn France, lymphogranuloma venereum (LGV) testing switched from universal to selective testing in 2016.AimTo investigate changes in LGV-affected populations, we performed a nationwide survey based on temporarily reinstated universal LGV testing from 2020 to 2022.MethodsEach year, during three consecutive months, laboratories voluntarily sent anorectal Chlamydia trachomatis-positive samples from men and women to the National Reference Centre for bacterial sexually transmitted infections. We collected patients' demographic, clinical and biological data. Genovars L of C. trachomatis were detected using real-time PCR. In LGV-positive samples, the ompA gene was sequenced.ResultsIn 2020, LGV positivity was 12.7% (146/1,147), 15.2% (138/907) in 2021 and 13.3% (151/1,137) in 2022 (p > 0.05). It occurred predominantly in men who have sex with men (MSM), with rare cases among transgender women. The proportion of HIV-negative individuals was higher than that of those living with HIV. Asymptomatic rectal LGV increased from 36.1% (44/122) in 2020 to 52.4% (66/126) in 2022 (p = 0.03). Among users of pre-exposure prophylaxis (PrEP), LGV positivity was 13.8% (49/354) in 2020, 15.6% (38/244) in 2021 and 10.9% (36/331) in 2022, and up to 50% reported no anorectal symptoms. Diversity of the LGV ompA genotypes in the Paris region increased during the survey period. An unexpectedly high number of ompA genotype L1 variant was reported in 2022.ConclusionIn rectal samples from MSM in France, LGV positivity was stable, but the proportion of asymptomatic cases increased in 2022. This underscores the need of universal LGV testing and the importance of continuous surveillance.

ompA Sequencing and Multilocus Sequence Typing of Lymphogranuloma Venereum Cases in Buenos Aires Reveal New Chlamydia trachomatis Genotypes.

Since the Lymphogranuloma venereum (LGV) outbreak was first described in Buenos Aires in 2017, the detected strains presented peculiar characteristics. Our goal was to increase the understanding of the strains involved in the LGV outbreak in Argentina. We characterized the ompA gene sequences, using Sanger sequencing, of 88 LGV strains from 239 symptomatic patients in Buenos Aires enrolled between 2017 and 2019, and selected 20 C. trachomatis strains for further characterization using Multilocus Sequence Typing (MLST). Following the ompA gene analysis of the 88 LGV strains, we detected 43% L2b, 31% L1-like, and 26% L2. Among the 38 L2b samples analyzed, there were 7 distinct sequences, 3 of them not previously reported (L2bv12, L2bv13, and L2bv14). Additionally, we detected a strain with a new mutation (AM884176.1:g.59122A>T) found in the position defining L2 or L2b, proposed as L2i. Using MLST, five different sequence types (STs) were detected, including the ST2 (corresponding to the L1-like strains) and a new one (ST60). ST58 was associated with the concomitant presence of another STI and HIV. A high genetic diversity in C. trachomatis LGV strains in Argentina was observed in a short period of time, with a relatively low number of samples from a limited geographical area.

Genotypic study of Chlamydia trachomatis for lymphogranuloma venereum diagnosis in rectal specimens from men who have sex with men: a cost-effectiveness analysis.

PURPOSE: The significant proportion of asymptomatic patients and the scarcity of genotypic analysis of lymphogranuloma venereum (LGV), mainly among men who have sex with men (MSM), triggers a high incidence of underdiagnosed patients, highlighting the importance of determining the most appropriate strategy for LGV diagnosis, at both clinical and economical levels. MATERIALS AND METHODS: We conducted L1-L3 serovar detection by molecular biology in stored Chlamydia trachomatis-positive samples from MSM patients with HIV, another STI or belonging to a Pre-exposure prophylaxis program, to make a cost effectiveness study of four diagnostic strategies with a clinical, molecular, or mixed approach. RESULTS: A total of 85 exudates were analyzed: 35urethral (31 symptomatic/4 positive) and 50 rectal (22 symptomatic/25 positive), 70/85 belonging to MSM with associated risk factors. The average cost per patient was €77.09 and €159.55 for clinical (Strategy I) and molecular (Strategy IV) strategies respectively. For molecular diagnosis by genotyping of all rectal exudate samples previously positive for CT (Strategy II), the cost was €123.84. For molecular diagnosis by genotyping of rectal and/or urethral exudate samples from all symptomatic patients (proctitis or urethritis) with a previous positive result for CT (Strategy III), the cost was €129.39. The effectiveness ratios were 0.80, 0.95, 0.91, and 1.00 for each strategy respectively. The smallest ICER was €311.67 for Strategy II compared to Strategy I. CONCLUSIONS: With 30% asymptomatic patients, the most cost-effective strategy was based on genotyping all rectal exudates. With less restrictive selection criteria, thus increasing the number of patients with negative results, the most sensitive strategies tend to be the most cost-effective, but with a high incremental cost-effectiveness ratio.

AEDV Expert Document on the Management of Ulcerative Venereal Infections. / Documento de expertos de la AEDV sobre el manejo de infecciones venéreas ulcerativas.

Currently, ulcerative sexually transmitted infections, including syphilis, herpes simplex virus (HSV), lymphogranuloma venereum (LGV), chancroid, donovanosis and, more recently, monkeypox (MPOX), represent a growing challenge for health care professionals. The incidence of syphilis and LGV has increased in recent years in Spain. Additionally, HSV, syphilis and chancroid can also increase the risk of HIV acquisition and transmission. The population groups most vulnerable to these infections are young people, men who have sex with men (MSM) and commercial sex workers. It is important to make a timely differential diagnosis since genital, anal, perianal, and oral ulcerative lesions may pose differential diagnosis with other infectious and non-infectious conditions such as candidiasis vulvovaginitis, traumatic lesions, carcinoma, aphthous ulcers, Behçet's disease, fixed drug eruption, or psoriasis. For this reason, the dermatologist plays a crucial role in the diagnosis and management of sexually transmitted infections. This chapter presents the main epidemiological, clinical and therapeutic features associated with these infections.

Asymptomatic lymphogranuloma venereum is commonly found among men who have sex with men in Austria.

BACKGROUND AND OBJECTIVES: Serovar L1-L3 of Chlamydia trachomatis (CT) causes lymphogranuloma venereum (LGV). A surge in LGV-cases has been observed among HIV-positive men who have sex with men (MSM). Discrimination between LGV and non-LGV is pivotal since it has major treatment implications. Here, we aimed to determine the prevalence and characteristics of LGV among CT-infections. PATIENTS AND METHODS: All CT-positive results from 04/2014-12/2021 at the four largest Austrian HIV and STI clinics were evaluated. Disease characteristics and patient demographics were analyzed. RESULTS: Overall, n  =  2,083 infections of CT were documented in n  =  1,479 individual patients: median age was 31.4 years, 81% were male, 59% MSM, 44% HIV-positive, 13% on HIV pre-exposure-prophylaxis. Available serovar analyses (61% [1,258/2,083]) showed L1-L3 in 15% (192/1,258). Considering only MSM with rectal CT-infection, LGV accounted for 23% (101/439). Cases of LGV vs. other CT-infections were primarily MSM (92% [177/192] vs. 62% [1,179/1,891], p < 0.001), more often HIV-positive (64% [116/180] vs. 46% [631/1,376]; p < 0.001) and had frequently concomitant syphilis infection (18% [32/180] vs. 7% [52/749]; p < 0.001). LGV commonly manifested as proctitis (38% [72/192]) whereas 45% (87/192) were asymptomatic. CONCLUSIONS: Lymphogranuloma venereum accounted for 23% of rectal CT-infections in MSM. Furthermore, 45% of all LGV-cases were asymptomatic. In the absence of CT-serovar analysis, a high LGV prevalence should be considered in risk-populations and guide empiric treatment selection.

Analytical and clinical validation of a multiplex PCR assay for detection of Neisseria gonorrhoeae and Chlamydia trachomatis including simultaneous LGV serotyping on an automated high-throughput PCR system.

For effective infection control measures for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), a reliable tool for screening and diagnosis is essential. Here, we aimed to establish and validate a multiplex PCR assay on an automated system using a dual-target approach for the detection of CT/NG and differentiation between lymphogranuloma venereum (LGV) and non-LGV from genital and extra-genital specimens. Published primer/probe sets (CT: pmpH, cryptic plasmid; NG: porA, opa) were modified for the cobas 5800/6800/8800. Standards quantified by digital PCR were used to determine linearity and lower limit of detection (LLoD; eSwab, urine). For clinical validation, prospective samples (n = 319) were compared with a CE-marked in vitro diagnostics (CE-IVD) assay. LLoDs ranged from 21.8 to 244 digital copies (dcp)/mL and 10.8 to 277 dcp/mL in swab and urine, respectively. A simple linear regression analysis yielded slopes ranging from -4.338 to -2.834 and Pearson correlation coefficients from 0.956 to 0.994. Inter- and intra-run variability was <0.5 and <1 cycle threshold (ct), respectively. No cross-reactivity was observed (n = 42). Clinical validation showed a sensitivity of 94.74% (95% confidence interval (CI): 87.23%-97.93%) and 95.51% (95% CI: 89.01%-98.24%), a specificity of 99.59% (95% CI: 97.71%-99.98%) and 99.57% (95% CI: 97.58%-99.98%), positive predictive values of 89.91% (estimated prevalence: 3.7%; 95% CI: 80.91%-95.6%) and 88.61% (estimated prevalence: 3.4%; 95% CI: 80.18%-94.34%), and negative predictive values of 99.81% (95% CI: 98.14%-100%) and 99.85% (95% CI: 98.14%-100%) for the detection of CT and NG, respectively. In conclusion, we established a dual-target, internally controlled PCR on an automated system for the detectiwon of CT/NG from genital and extra-genital specimens. Depending on local regulations, the assay can be used as a screening or a confirmatory/typing assay.IMPORTANCEChlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) represent a major global health burden, with the World Health Organization estimating that >128 million and >82 million people, respectively, were newly infected in 2020. For effective infection control measures, a reliable tool for sensitive diagnosis and screening of CT/NG is essential. We established a multiplex PCR assay for the detection of CT/NG and simultaneous discrimination between lymphogranuloma venereum (LGV) and non-LGV strains, which has been validated for genital and extra-genital specimens on a fully automated system. To increase assay sensitivity, a dual-target approach has been chosen for both pathogens. This strategy reduces false-positive results in oropharyngeal swabs due to the detection of commensal N. species that may harbor NG DNA fragments targeted in the PCR due to horizontal gene transmission following previous infection. In sum, the established assay provides a powerful tool for use as either a screening/diagnostic or a typing/confirmatory assay.

Membrane computing simulation of sexually transmitted bacterial infections in hotspots of individuals with various risk behaviors.

The epidemiology of sexually transmitted infections (STIs) is complex due to the coexistence of various pathogens, the variety of transmission modes derived from sexual orientations and behaviors at different ages and genders, and sexual contact hotspots resulting in network transmission. There is also a growing proportion of recreational drug users engaged in high-risk sexual activities, as well as pharmacological self-protection routines fostering non-condom practices. The frequency of asymptomatic patients makes it difficult to develop a comprehensive approach to STI epidemiology. Modeling approaches are required to deal with such complexity. Membrane computing is a natural computing methodology for the virtual reproduction of epidemics under the influence of deterministic and stochastic events with an unprecedented level of granularity. The application of the LOIMOS program to STI epidemiology illustrates the possibility of using it to shape appropriate interventions. Under the conditions of our basic landscape, including sexual hotspots of individuals with various risk behaviors, an increase in condom use reduces STIs in a larger proportion of heterosexuals than in same-gender sexual contacts and is much more efficient for reducing Neisseria gonorrhoeae than Chlamydia and lymphogranuloma venereum infections. Amelioration from diagnostic STI screening could be instrumental in reducing N. gonorrhoeae infections, particularly in men having sex with men (MSM), and Chlamydia trachomatis infections in the heterosexual population; however, screening was less effective in decreasing lymphogranuloma venereum infections in MSM. The influence of STI epidemiology of sexual contacts between different age groups (<35 and ≥35 years) and in bisexual populations was also submitted for simulation.IMPORTANCEThe epidemiology of sexually transmitted infections (STIs) is complex and significantly influences sexual and reproductive health worldwide. Gender, age, sexual orientation, sexual behavior (including recreational drug use and physical and pharmacological protection practices), the structure of sexual contact networks, and the limited application or efficiency of diagnostic screening procedures create variable landscapes in different countries. Modeling techniques are required to deal with such complexity. We propose the use of a simulation technology based on membrane computing, mimicking in silico STI epidemics under various local conditions with an unprecedented level of detail. This approach allows us to evaluate the relative weight of the various epidemic drivers in various populations at risk and the possible outcomes of interventions in particular epidemiological landscapes.

Single case of lymphogranuloma venereum on the tongue.

Traditionally, lymphogranuloma venereum (LGV) has been associated with disease of the genital area. However, atypical presentations and proctitis are increasingly observed. We report a case of LGV affecting the dorsum of the tongue, which presented as a very painful ulcer. The response to doxycycline (100 mg two times per day for 21 days) was satisfactory. This case may represent a paradigm shift in the differential diagnosis of lingual ulcers.

Rapid expansion of lymphogranuloma venereum infections with fast diversification and spread of Chlamydia trachomatis L genovariants.

IMPORTANCE: Numerous international organizations, including the World Health Organization, have been drawing attention to the global increase in sexually transmitted infections. Twenty years ago, lymphogranuloma venereum (LGV) was mainly considered a tropical disease; in recent decades, however, LGV has been increasingly present in high-income countries. This increase has been linked to men who have sex with men who participate in highly interconnected sexual networks, leading to a rapid spread of LGV. This study focuses on the spread of LGV, presenting the largest time series of LGV prevalence in Spain, which includes more than a thousand diagnosed cases in one large city. The number of LGV cases diagnosed was analyzed over time, and a selection of strains was subjected to molecular genotyping. The results indicate that the LGV epidemic is gradually evolving toward an increasingly complex diversification due to the selection of successful genovariants that have emerged by mutation and recombination events, suggesting that we are moving toward an unpredictable scenario.

Epidemiological Characteristics and Factors Associated with Repeat Sexually Transmitted Infections in Barcelona, Spain Over a Decade.

In the last few years, the frequency of sexually transmitted infections (STI) has increased, as has the number of people with multiple infections. The aim of our study was to describe the epidemiological characteristics of persons with repeated bacterial STI and to determine the risk factors for these episodes in persons living in Barcelona during the period 2007-2018. We studied all cases of bacterial STI included in the STI registry of Barcelona. Repeated STI were defined as a diagnosis of gonorrhea, syphilis, or lymphogranuloma venereum (LGV) after a first episode of one of these infections. Analysis was stratified by sex and place of birth. The factors associated with time to reinfection were determined by Kaplan-Meier estimates, while the factors associated with risk of infection were determined by a Cox proportional hazards model. Of 9927 persons with a diagnosis of bacterial STI, 1690 (17.0%) had at least two episodes of STI during the study period. On multivariate analysis, repeat STI were independently associated with male sex assigned at birth (HR: 3.45; 95%CI 2.22-5.36), age less than 34 years (HR: 1.22; 95%CI 1.10-1.35); gay, bisexual, and other men who have sex with men, and transgender o transsexual woman (GBSMS/Trans) (HR: 4.03; 95%CI 3.24-5.03), having gonorrhea as first diagnosis (HR:1.49, 95%CI 1.34-1.66) or LGV (HR:1.75; 95%CI 1.47-2.08) and coinfection with HIV (HR:1.98; 95%CI 1.78-2.21). Sexual health programs should be strengthened to prevent STI and reinfection in key populations.

Painful proctitis associated with anorectal mpox, syphilis, HSV, LGV, gonorrhoea and Mycoplasma genitalium in a person living with virologically suppressed HIV and vaccinated against mpox.

A gay man with well-controlled HIV and vaccinated against mpox presented with severe proctitis. Testing revealed anorectal mpox, herpes simplex virus, lymphogranuloma venereum, Neisseria gonorrhoeae and Mycoplasma genitalium Serology was indicative of infectious syphilis. This case highlights the need to consider a wide range of concurrent sexually transmitted infections in patients with proctitis, including those vaccinated against mpox.

Nódulos peneanos, una rara manifestación clínica de linfogranuloma venéreo / Penile nodules, a rare clinical manifestation of lympho granuloma venereum

Resumen El linfogranuloma venéreo es una infección de trans misión sexual (ITS) causada por las serovariedades L1, L2 y L3 de Chlamydia trachomatis. Una forma rara de presen tación del estadio primario es la linfangitis localizada en pene, con la formación de uno o más nódulos linfáticos tensos clásicamente llamados "bubonódulos" (bubón pe queño). Presentamos el caso de un paciente HIV positivo con conductas de riesgo para ITS con nódulos peneanos como manifestación de linfogranuloma venéreo.

Abstract Lymphogranuloma venereum is a sexually trans mitted disease caused by L1, L2 and L3 serovars of Chlamydia trachomatis. A rare clinical presentation of the primary stage is lymphangitis of the penis, with the appearance of one or more tense lymph nodes classically called "buboes". We report the case of an HIV-positive patient with sexually transmitted disease risk behaviors with penile nodules as a manifestation of lymphogranuloma venereum.

[Penile nodules, a rare clinical manifestation of lymphogranuloma venereum]. / Nódulos peneanos, una rara manifestación clínica de linfogranuloma venéreo.

Lymphogranuloma venereum is a sexually transmitted disease caused by L1, L2 and L3 serovars of Chlamydia trachomatis. A rare clinical presentation of the primary stage is lymphangitis of the penis, with the appearance of one or more tense lymph nodes classically called "buboes". We report the case of an HIV-positive patient with sexually transmitted disease risk behaviors with penile nodules as a manifestation of lymphogranuloma venereum.

El linfogranuloma venéreo es una infección de transmisión sexual (ITS) causada por las serovariedades L1, L2 y L3 de Chlamydia trachomatis. Una forma rara de presentación del estadio primario es la linfangitis localizada en pene, con la formación de uno o más nódulos linfáticos tensos clásicamente llamados "bubonódulos" (bubón pequeño). Presentamos el caso de un paciente HIV positivo con conductas de riesgo para ITS con nódulos peneanos como manifestación de linfogranuloma venéreo.

Chlamydia trachomatis-An Emerging Old Entity?

Chlamydia trachomatis is an evasive pathogen that can prompt severe clinical manifestations in humans such as vaginitis, epididymitis, lymphogranuloma venereum, trachoma, conjunctivitis and pneumonia. If left untreated, chronic infections with C. trachomatis can give rise to long-lasting and even permanent sequelae. To shed some light on its widespread nature, data from original research, systematic reviews and meta-analyses from three databases was collected and analyzed in the context of chlamydial infection, related symptoms and appropriate treatment modalities. This review describes the bacterium's pervasiveness on a global scale, especially in developing countries, and suggests ways to halt its transmission and spread. Infections with C. trachomatis often go unnoticed, as many individuals are asymptomatic and unaware of their diagnosis, contributing to a delay in diagnosis and treatment. The high prevalence of chlamydial infection highlights the need for a universal screening and detection method enabling immediate treatment at its onset. Prognosis is favorable with antibiotic therapy and education for high-risk groups and their sexual partners. In the future, a quick, easily accessible, and inexpensive test should be developed to diagnose and treat infected individuals early on. Along with a vaccine against C. trachomatis, it would halt the transmission and spread of the pathogen worldwide.

An Ulcer by Any Other Name: Non-herpes and Non-syphilis Ulcerative Sexually Transmitted Infections.

The myriad presentations of ulcerative sexually transmitted infections, other than genital herpes and syphilis, challenge even the most astute clinician given the considerable overlap in clinical presentation and lack of widely available diagnostic resources, such as nucleic acid testing, to confirm the diagnosis. Even so, case prevalence is relatively low, and incidence of chancroid and granuloma inguinale are declining. These diseases still cause substantial morbidity and increased chance for HIV acquisition, and with the recent advent of mpox as a cause, it remains imperative to identify and treat accurately.