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.

Proctitis: An Approach to the Symptomatic Patient.

Proctitis is an inflammatory condition of the distal rectum that can be associated with common sexually transmitted infections (STIs), such as gonorrhea, chlamydia, and syphilis. For persons presenting with ulcerative findings on examination, in addition to syphilis, Mpox, lymphogranuloma venereum, and herpes simplex virus should be in the differential. Providers should also be aware that there are evolving data to support a role for Mycoplasma genitalium in proctitis. Performing a comprehensive history, clinical evaluation including anoscopy, and rectal nucleic amplification STI testing may be useful in identifying the cause of proctitis and targeting treatment.

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.

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.

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.

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.

[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.

Chronic epididymitis due to Chlamydia trachomatis LGV-L2 in an HIV-negative heterosexual patient: a case report.

Chlamydia trachomatis is an obligate intracellular pathogen and the leading bacterial cause of sexually transmitted infections worldwide. Chlamydia trachomatis genovars L1-L3 are responsible for lymphogranuloma venereum (LGV), an invasive sexually transmitted disease endemic in tropical and subtropical regions of Africa, South America, the Caribbean, India and South East Asia. The typical signs and symptoms of C. trachomatis LGV urogenital infections in men include herpetiform ulcers, inguinal buboes, and/or lymphadenopathies. Since 2003, endemic cases of proctitis and proctocolitis caused by C. trachomatis LGV emerged in Europe, mainly in HIV-positive men who have sex with men (MSM). Scarce data have been reported about unusual clinical presentations of C. trachomatis LGV urogenital infections. Herein, we report a case of a 36-year-old heterosexual, HIV-negative male declaring he did not have sex with men or trans women, who presented to the Urology and Andrology outpatient clinic of a healthcare center from Cordoba, Argentina, with intermittent testicular pain over the preceding 6 months. Doppler ultrasound indicated right epididymitis and funiculitis. Out of 17 sexually transmitted infections (STIs) investigated, a positive result was obtained only for C. trachomatis. Also, semen analysis revealed oligoasthenozoospermia, reduced sperm viability as well as increased sperm DNA fragmentation and necrosis, together with augmented reactive oxygen species (ROS) levels and the presence of anti-sperm IgG autoantibodies. In this context, doxycycline 100 mg/12 h for 45 days was prescribed. A post-treatment control documented microbiological cure along with resolution of clinical signs and symptoms and improved semen quality. Strikingly, sequencing of the ompA gene revealed C. trachomatis LGV L2 as the causative uropathogen. Remarkably, the patient did not present the typical signs and symptoms of LGV. Instead, the infection associated with chronic testicular pain, semen inflammation and markedly reduced sperm quality. To our knowledge, this is the first reported evidence of chronic epididymitis due to C. trachomatis LGV L2 infection in an HIV-negative heterosexual man. These findings constitute important and valuable information for researchers and practitioners and highlight that C. trachomatis LGV-L2 should be considered as putative etiologic agent of chronic epididymitis, even in the absence of the typical LGV signs and symptoms.

[A man with cervical lymph node swelling]. / Een man met een zwelling in de hals.

A 48-year-old HIV-positive patient presented at the otorhinolaryngology department with a growing mass on the left side of his neck, fever and night sweats. Biopsy demonstrated a granulomatous, necrotizing inflammation. After extensive additional testing, PCR on lesion punctate material was positive for Chlamydia trachomatis, yielding a diagnosis of cervical lymphogranuloma venereum.

Mpox proctitis as a likely predisposing factor for chlamydial perihepatitis in a male patient.

Perihepatitis (Fitz-Hugh-Curtis syndrome) is a rare complication of sexually transmitted infections, mostly seen in women. Only 12 male cases have been reported to date, of which Chlamydia trachomatis was confirmed in 2. We report a case of chlamydial perihepatitis in a male patient, occurring 1 month after Mpox and associated with the unusual LGV ST23 strain. Our case suggests that rectal Mpox lesions may facilitate chlamydial dissemination.

Sexually transmitted infections and clinical features in monkeypox (mpox) patients in Madrid, Spain.

Since the beginning of the monkeypox (mpox) virus outbreak in May 2022, there has been an increase in the number of cases worldwide in the setting of sexual transmission. We have tested by real-time PCR 187 mpox patients, of which 157 patients were screened for sexually transmitted infections (STI) in 245 samples. Thirty-six pathogens were detected in 30 patients: herpes simplex virus (HSV-I/II, 12/36, 33.3%), Neisseria gonorrhoeae (NG, 9/36, 25%), Chlamydia trachomatis (CT, 5/36, 13.8%), Chlamydia trachomatis-lymphogranuloma venereum (CT-LGV, 3/36, 8.3%), Treponema pallidum (TP, 4/36, 11.1%) and Mycoplasma genitalium (MG, 3/36, 8.3%). Screening of STI is recommended in mpox patients for the differential diagnosis of the main infections of sexual tract especially in patients with rectal involvement.

Linfogranuloma venéreo / Venereal lymphogranuloma

El Linfogranuloma venéreo (LGV) es una infección de transmisión sexual (ITS) ulcerativa poco frecuente causada por la bacteria Chlamydia trachomatis (CT), serotipos L1, L2 y L3, originada por el contacto no protegido genital, anal y/u oral. Se asocia con co-infecciones de otras ITS, entre ellas las ocasionadas por el virus de la inmunodeficiencia humana (VIH) y la sífilis. Endémico en áreas tropicales y subtropicales de África, Sudeste Asiático, Latinoamérica y el Caribe, a partir del 2003 se han registrado nuevos brotes en Europa, América del Norte y Australia, en especial entre la población de hombres que tienen sexo con hombres (HsH) y en pacientes VIH positivos. Si bien lo más frecuente de observar en HsH es la proctitis con escasa repercusión ganglionar regional, se debe sospechar LGV ante toda úlcera ano-genital transitoria y linfadenopatías inguinales en esta población. Se presenta un caso de LGV en un paciente HsH no VIH cuya forma de inicio genital permitió el diagnóstico y el tratamiento adecuado.

Lymphogranuloma venereum (LGV) is a rare ulcerative sexually transmitted infection (STI) caused by the bacterium Chlamydia trachomatis (CT), serotypes L1, L2 and L3, caused by unprotected genital, anal and/or oral contact. It is associated with co-infections with other STIs, including those caused by the human immunodeficiency virus (HIV) and syphilis. Endemic in tropical and subtropical areas of Africa, Southeast Asia, Latin America and the Caribbean, since 2003 there have been new outbreaks in Europe, North America and Australia, especially among the population of men who have sex with men (MSM) and in HIV positive patients. Although the most common sign to observe in MSM is proctitis with little regional lymph node repercussion, LGV should be suspected in the presence of any transient anogenital ulcer and inguinal lymphadenopathy in this population. We present a case of LGV in a non-HIV MSM patient whose form of genital onset led to diagnosis and treatment.

[Lymphogranuloma venerous genital in men who have sex with men: a non-imported case report in Chile]. / Linfogranuloma venéreo genital en un hombre que tiene sexo con hombre: reporte de caso no importado en Chile.

Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by Chlamydia trachomatis bacteria. In the past years, it has emerged as a relevant infectious agent, mainly affecting men who have sex with men (MSM), frequently associated with other sexually transmitted infections as human immunodeficiency virus (HIV) and syphilis. Even though genital lesions correspond to the classical presentation of LGV, nowadays anorectal syndrome is more frequently reported. We present a MSM patient, HIV infected, being treated with antiretroviral drugs, with a history of recurrent genital herpes, also recently treated for a syphilis in a latent stage. He had no recent trips. He referred inguinal fistulized enlarged lymph nodes, associated with a painful genital ulcer, he denied anorectal or systemic symptoms. He had been treated with multiple antibiotic and antiviral drugs, with no clinical response. Molecular studies from the content of the fistulized lymph node identified C. trachomatis. The patient received doxycycline for 6 weeks, showing good clinical response.

Chronic Lymphogranuloma Venereum Proctocolitis Masquerading as Inflammatory Bowel Disease.

Rectal infection with the L1, L2, and L3 serovars of Chlamydia trachomatis can cause lymphogranuloma venereum (LGV) proctocolitis, particularly among men who have sex with men (MSM). Symptoms of this sexually transmitted infection include anal pain, rectal bleeding and discharge, tenesmus, constipation, and fever. Clinicians should consider LGV when there is a history of receptive anal intercourse and symptoms of proctocolitis. A positive nucleic acid amplification test (NAAT) on a rectal sample is diagnostic. This report describes a man with HIV and chronic proctocolitis in whom the diagnosis of LGV was delayed because the clinical picture mimicked inflammatory bowel disease.

Linfogranuloma venéreo genital en un hombre que tiene sexo con hombre: reporte de caso no importado en Chile / Lymphogranuloma venerous genital in men who have sex with men: a non-imported case report in Chile

Resumen El linfogranuloma venéreo (LGV) es una infección de transmisión sexual (ITS) causada por Chlamydia trachomatis. En los últimos años, ha emergido principalmente en hombres que tienen sexo con hombres (HSH). Es frecuente su asociación con otras ITS como el virus de inmunodeficiencia humana (VIH) y la sífilis. Si bien el compromiso genital es la forma de presentación clásica, el síndrome anorrectal constituye el principal cuadro clínico en la actualidad. Presentamos el caso de un HSH con infección por VIH en terapia anti-retroviral, herpes genital recurrente y sífilis latente tratada, sin viajes recientes al extranjero, con adenopatías inguinales fistulizadas a piel, asociada a una úlcera genital dolorosa, sin síntomas anorrectales ni sistémicos, refractario a múltiples tratamientos antibacterianos y antivirales. El estudio con RPC de secreción de la fístula fue positiva a C. trachomatis. Se trató con doxiciclina por seis semanas, con buena respuesta clínica, sin complicaciones.

Abstract Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by Chlamydia trachomatis bacteria. In the past years, it has emerged as a relevant infectious agent, mainly affecting men who have sex with men (MSM), frequently associated with other sexually transmitted infections as human immunodeficiency virus (HIV) and syphilis. Even though genital lesions correspond to the classical presentation of LGV, nowadays anorectal syndrome is more frequently reported. We present a MSM patient, HIV infected, being treated with antiretroviral drugs, with a history of recurrent genital herpes, also recently treated for a syphilis in a latent stage. He had no recent trips. He referred inguinal fistulized enlarged lymph nodes, associated with a painful genital ulcer, he denied anorectal or systemic symptoms. He had been treated with multiple antibiotic and antiviral drugs, with no clinical response. Molecular studies from the content of the fistulized lymph node identified C. trachomatis. The patient received doxycycline for 6 weeks, showing good clinical response.