Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case-control study in the U.K.

OBJECTIVE: Since 2003, over 2000 cases of lymphogranuloma venereum (LGV) have been diagnosed in the U.K. in men who have sex with men (MSM). Most cases present with proctitis, but there are limited data on how to differentiate clinically between LGV and other pathology. We analysed the clinical presentations of rectal LGV in MSM to identify clinical characteristics predictive of LGV proctitis and produced a clinical prediction model. DESIGN: A prospective multicentre case-control study was conducted at six U.K. hospitals from 2008 to 2010. Cases of rectal LGV were compared with controls with rectal symptoms but without LGV. METHODS: Data from 98 LGV cases and 81 controls were collected from patients and clinicians using computer-assisted self-interviews and clinical report forms. Univariate and multivariate logistic regression was used to compare symptoms and signs. Clinical prediction models for LGV were compared using receiver operating curves. RESULTS: Tenesmus, constipation, anal discharge and weight loss were significantly more common in cases than controls. In multivariate analysis, tenesmus and constipation alone were suggestive of LGV (OR 2.98, 95% CI 0.99 to 8.98 and 2.87, 95% CI 1.01 to 8.15, respectively) and that tenesmus alone or in combination with constipation was a significant predictor of LGV (OR 6.97, 95% CI 2.71 to 17.92). The best clinical prediction was having one or more of tenesmus, constipation and exudate on proctoscopy, with a sensitivity of 77% and specificity of 65%. CONCLUSIONS: This study indicates that tenesmus alone or in combination with constipation makes a diagnosis of LGV in MSM presenting with rectal symptoms more likely.

Anal lymphogranuloma venereum infection screening with IgA anti-Chlamydia trachomatis-specific major outer membrane protein serology.

BACKGROUND: Anal lymphogranuloma venereum (LGV) infections, caused by Chlamydia trachomatis biovar L (Ct+/LGV+), are endemic among men who have sex with men (MSM). Anal non-LGV biovar Ct infections (Ct+/LGV-) can be eradicated with 1 week doxycycline, whereas Ct+/LGV+ infections require 3-week doxycycline. To differentiate Ct+/LGV+ from Ct+/LGV- infections, biovar-specific Nucleic Acid Amplification Test (NAAT) are standard, but also expensive and laborious. A chlamydia-specific serological assay could serve as an alternative test. METHODS: MSM were screened for anal Ct+/LGV+ and Ct+/LGV- infections with a commercial nonspecific NAAT and an in house biovar L-specific NAAT. Serum samples were evaluated with chlamydia-specific anti-Major Outer Membrane Protein (MOMP) and antilipopolysaccharide assays of IgA and IgG classes. Asymptomatic patients were identified as: (1) no anal complaints or (2) no microscopic inflammation (i.e., <10 leucocytes per high power field in anal smears). The best differentiating assay was subsequently evaluated in 100 Ct+/LGV+ and 100 Ct+/LGV- MSM using different cut-off points. RESULTS: The anti-MOMP IgA assay was the most accurate to differentiate Ct+/LGV+ (n = 42) from Ct+/LGV- (n = 19) with 85.7% sensitivity (95% confidence interval [CI], 72.2-93.3) and 84.2% specificity (95% CI, 62.4-94.5), even among asymptomatic patients. In a population comprising 98 Ct+/LGV+ and 105 Ct+/LGV- patients, the anti-MOMP IgA assay scored most accurate when the cut-off point was set to 2.0 with 75.5% (95% CI, 65.8-83.6) sensitivity and 74.3% (95% CI, 64.8-82.3) specificity. CONCLUSIONS: The IgA anti-MOMP assay can identify a considerable proportion of the (asymptomatic) anal LGV infections correctly. Yet, biovar L-specific NAAT are still the preferred diagnostic tests in clinical settings.

Lack of utility of risk score and gynecological examination for screening for sexually transmitted infections in sexually active adolescents.

BACKGROUND: Sexually transmitted infections constitute the main health risk among adolescents. In developing countries the diagnosis and treatment of cervical infections is based on the syndromic approach. In this study we estimated the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae among female adolescents from a Health Sector of the city of Goiânia, Brazil, and validated cervicitis diagnosis using World Health Organization/Ministry of Health risk score and gynecological examination. METHODS: A cross-sectional community-based sample of 914 15- to 19-year-old female teenagers was randomly selected and referred to the local Family Health Program. Of these, 472 (51.6%) were sexually active and gynecological examinations were carried out for 427. Endocervical samples were collected to perform the polymerase chain reaction for C. trachomatis and N. gonorrhoeae. Performance of risk score, the presence of mucopurulent discharge, friability, ectopia and pain during cervical maneuver were compared with the presence of C. trachomatis or N. gonorrhoeae or both. RESULTS: The prevalence of C. trachomatis and N. gonorrhoeae was 14.5% and 2.1%, respectively. The risk score had a specificity of 31.9% (95% confidence interval, 21.2 to 44.2) and a positive predictive value of 20.8% (95% confidence interval, 13.5 to 29.7). Friability was the component of the gynecological examination that presented the best performance with a sensitivity of 43.5%, specificity of 81.0%, and 30.6% of positive predictive value. CONCLUSION: The prevalence of infection by C. trachomatis and N. gonorrhoeae was high among these sexually active adolescents. The syndromic approach is clearly inadequate for screening and treating these infections in this population. Therefore, the implantation of other strategies to control these infections among adolescents is urgently required.

Recruitment of BAD by the Chlamydia trachomatis vacuole correlates with host-cell survival.

Chlamydiae replicate intracellularly in a vacuole called an inclusion. Chlamydial-infected host cells are protected from mitochondrion-dependent apoptosis, partly due to degradation of BH3-only proteins. The host-cell adapter protein 14-3-3beta can interact with host-cell apoptotic signaling pathways in a phosphorylation-dependent manner. In Chlamydia trachomatis-infected cells, 14-3-3beta co-localizes to the inclusion via direct interaction with a C. trachomatis-encoded inclusion membrane protein. We therefore explored the possibility that the phosphatidylinositol-3 kinase (PI3K) pathway may contribute to resistance of infected cells to apoptosis. We found that inhibition of PI3K renders C. trachomatis-infected cells sensitive to staurosporine-induced apoptosis, which is accompanied by mitochondrial cytochrome c release. 14-3-3beta does not associate with the Chlamydia pneumoniae inclusion, and inhibition of PI3K does not affect protection against apoptosis of C. pneumoniae-infected cells. In C. trachomatis-infected cells, the PI3K pathway activates AKT/protein kinase B, which leads to maintenance of the pro-apoptotic protein BAD in a phosphorylated state. Phosphorylated BAD is sequestered via 14-3-3beta to the inclusion, but it is released when PI3K is inhibited. Depletion of AKT through short-interfering RNA reverses the resistance to apoptosis of C. trachomatis-infected cells. BAD phosphorylation is not maintained and it is not recruited to the inclusion of Chlamydia muridarum, which protects poorly against apoptosis. Thus, sequestration of BAD away from mitochondria provides C. trachomatis with a mechanism to protect the host cell from apoptosis via the interaction of a C. trachomatis-encoded inclusion protein with a host-cell phosphoserine-binding protein.

Photo Rounds: Painless penile ulcer and tender inguinal lymphadenopathy.

Our patient had previously been treated for syphilis. But when his symptoms persisted, further testing revealed that he was being treated for the wrong STD.

Lymphogranuloma venereum in the United kingdom.

BACKGROUND: Over the past 2 years, lymphogranuloma venereum (LGV), caused by L serovars of Chlamydia trachomatis, has emerged as a significant problem among men who have sex with men (MSM). We report on, to our knowledge, the largest case series of LGV to date, with detailed epidemiological and clinical characteristics of the epidemic in the United Kingdom. METHODS: A national diagnostic service and surveillance system was established in October 2004. Cases were confirmed by the presence of C. trachomatis and an LGV serovar (L1, L2, or L3) from genotyping. For confirmed cases, an enhanced surveillance questionnaire was sent to the clinician. RESULTS: Through February 2006, a total of 327 cases of LGV were confirmed. Cases were diagnosed across the United Kingdom, with the majority from London (71%) and Brighton (13%). Case reports were received for 282 MSM. The majority (96%) had proctitis, many with severe local and systemic symptoms. There was a high level of coinfection with human immunodeficiency virus (76%), hepatitis C (19%), and other sexually transmitted infections (39%). Nine cases of human immunodeficiency virus infection were diagnosed around the same time as LGV. Most cases were acquired within the United Kingdom, although patients with early cases were more likely to report contacts in The Netherlands. CONCLUSIONS: We found a significant burden of this once-rare sexually transmitted infection among MSM in the United Kingdom. LGV may be contributing to the epidemic of human immunodeficiency virus infection by facilitating transmission. Further control efforts are required, including awareness campaigns, continued detailed surveillance, and expanded chlamydia testing among MSM.

Genital elephantiasis and sexually transmitted infections - revisited.

Genital elephantiasis is an important medical problem in the tropics. It usually affects young and productive age group, and is associated with physical disability and extreme mental anguish. The majority of cases are due to filariasis; however, a small but significant proportion of patients develop genital elephantiasis due to bacterial sexually transmitted infections (STIs), mainly lymphogranuloma venereum (LGV) and donovanosis. STI-related genital elephantiasis should be differentiated from elephantiasis due to other causes, including filariasis, tuberculosis, haematological malignancies, iatrogenic, or dermatological diseases. Laboratory investigations like microscopy of tissue smear and nucleic acid amplification test for donovanosis, and serology and polymerase chain reaction for LGV may help in the diagnosis, but in endemic areas, in the absence of laboratory facilities, diagnosis largely depends on clinical characteristics. The causative agent of LGV, Chlamydia trachomatis serovar L1-L3, is a lymphotropic organism which leads to the development of thrombolymphangitis and perilymphangitis, and lymphadenitis. Long-standing oedema, fibrosis and lymphogranulomatous infiltration result in the final picture of elephantiasis. Elephantiasis in donovanosis is mainly due to constriction of the lymphatics which are trapped in the chronic granulomatous inflammatory response generated by the causative agent, Calymmatobacterium (Klebsiella) granulomatis. The LGV-associated genital elephantiasis should be treated with a prolonged course of doxycycline given orally, while donovanosis should be treated with azithromycin or trimethoprim-sulphamethoxazole combination given for a minimum of three weeks. Genital elephantiasis is not completely reversible with medical therapy alone and often needs to be reduced surgically.

New Chlamydia trachomatis L2 strains identified in a recent outbreak of lymphogranuloma venereum in Vienna, Austria.

BACKGROUND: Since 2003, an ongoing outbreak of lymphogranuloma venereum (LGV), caused by Chlamydia trachomatis biovar L2b, has been reported among men who have sex with men. METHODS: Twenty-four samples positive for C. trachomatis were analyzed for specific biovars and genovariants by genotyping of the variable segment (VS) 4, VS2 and VS1 regions of the outer membrane protein (omp) A. In addition we assessed the patients' sociodemographic background and clinical signs and symptoms. RESULTS: Twenty-four men who have sex with men presented with either anorectal or inguinal symptoms and tested positive for C. trachomatis DNA. Of these, the L2 genotype accounted for 15 patients, with a high coinfection rate with HIV (73.3%) and other sexually transmitted infections (53.4%). Analysis of the VS1, VS2, and VS4 regions of the ompA gene revealed the variant L2b in 8 patients. In 4 patients, 3 new L2 sequences were identified with nucleotide changes in the VS1, VS2, and VS4 region, respectively, defining new strains designated L2c, d, e. CONCLUSIONS: This outbreak of LGV represents the further spread of C. trachomatis L2 infection. Sequence analysis of ompA regions shows heterogeneity of L2 variants, suggesting more than 1 source of the LGV infections diagnosed in Vienna.

Lymphogranuloma venereum proctitis: An emerging sexually transmitted disease in HIV-positive men in the Netherlands.

A recent outbreak of lymphogranuloma venereum (LVG) proctitis caused by Chlamydia trachomatis serovar L2 has been detected in HIV-positive men in the Netherlands and Belgium. This sexually transmitted disease (STD), which is well known and frequently occurring in tropical countries, was quite unusual in Europe until 2003. STDs with ulcerative lesions, such as LGV, facilitate transmission of other microorganisms, including HIV and hepatitis C. This in combination with risky sexual behavior, such as unprotected anal sexual intercourse or use of sex toys, increases the risk of blood-blood contact and hence the risk of contracting multiple STDs. Two cases of patients who in a short time period contracted multiple STDs, including LGV proctitis, is presented.

A prospective clinical and bacteriologic study of inguinal buboes in Thai men.

One-hundred thirteen men (mean age, 23 years) who presented with inguinal buboes to a government-operated hospital for sexually transmitted diseases (STDs) in Bangkok were studied between February 1987 and February 1989. The median duration of preceding symptoms was 7 days (range, 1-62 days). The majority of patients (74; 65%) had received treatment previously; 31 (27%) were febrile, 13 (12%) had extrainguinal lymphadenopathy, and 31 (27%) had concurrent active genital ulcers. There was no history of genital ulceration in 66 (58%) of the patients. Pus was obtained from 51 of the 110 buboes aspirated for culture; 21 (41%) of these cultures yielded Haemophilus ducreyi, and 2 (3.9%) were positive for Chlamydia trachomatis on immunofluorescence microscopy. Saline (1 mL) was injected and reaspirated from the buboes of 35 of the other 59 patients; 3 buboes yielded H. ducreyi and 9 were positive for C. trachomatis. All cultures for other aerobic and anaerobic bacteria and viruses in intact buboes were negative. Syphilis serology was positive in only one case. Patients attending STD clinics in this region who have large, fluctuant, edematous inguinal buboes containing pus should receive presumptive treatment for chancroid. If there is no pus, then the bubo is more likely to be caused by lymphogranuloma venereum.

Linfogranuloma venéreo: 160 anos de progressos clínicos e laboratoriais / Lymphogranuloma venereum: 160 years of clinical and laboratorial progress

O linfogranuloma venéro (LGV) é uma doença infecto-contagiosa, de transmissäo sexual, causada pela Chlamydia tracomatis. É mais freqüente nas regiöes tropicais e subtropicais, áreas de menor desenvolvimento sócio-econômico e maior promiscuidade sexual.