Lymphogranuloma Venereum

BackgroundDefining endpoints for trachoma programs can be a challenge as clinical signs of infection may persist in the absence of detectable bacteria. Antibody-based tests may provide an alternative testing strategy for surveillance during terminal phases of the program. Antibody-based assays, in particular ELISAs, have been shown to be useful to document C. trachomatis genital infections, but have not been explored extensively for ocular C. trachomatis infections.Methodology/principal findingsAn antibody-based multiplex assay was used to test two C. trachomatis antigens, pgp3 and CT694, for detection of trachoma antibodies in bloodspots from Tanzanian children (n = 160) collected after multiple rounds of mass azithromycin treatment. Using samples from C. trachomatis-positive (by PCR) children from Tanzania (n = 11) and control sera from a non-endemic group of U.S. children (n = 122), IgG responses to both pgp3 and CT694 were determined to be 91% sensitive and 98% specific. Antibody responses of Tanzanian children were analyzed with regard to clinical trachoma, PCR positivity, and age. In general, children with more intense ocular pathology (TF/TI = 2 or most severe) had a higher median antibody response to pgp3 (p = 0.0041) and CT694 (p = 0.0282) than those with normal exams (TF/TI = 0). However, 44% of children with no ocular pathology tested positive for antibody, suggesting prior infection. The median titer of antibody responses for children less than three years of age was significantly lower than those of older children. (pConclusions/significanceThe antibody-based multiplex assay is a sensitive and specific additional tool for evaluating trachoma transmission. The assay can also be expanded to include antigens representing different diseases, allowing for a robust assay for monitoring across NTD programs.

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.

Chlamydia trachomatis is a global cause of blinding trachoma and sexually transmitted infections (STIs). We used comparative genomics of the family Chlamydiaceae to select conserved housekeeping genes for C. trachomatis multilocus sequencing, characterizing 19 reference and 68 clinical isolates from 6 continental/subcontinental regions. There were 44 sequence types (ST). Identical STs for STI isolates were recovered from different regions, whereas STs for trachoma isolates were restricted by continent. Twenty-nine of 52 alleles had nonuniform distributions of frequencies across regions (p<0.001). Phylogenetic analysis showed 3 disease clusters: invasive lymphogranuloma venereum strains, globally prevalent noninvasive STI strains (ompA genotypes D/Da, E, and F), and nonprevalent STI strains with a trachoma subcluster. Recombinant strains were observed among STI clusters. Single nucleotide polymorphisms (SNPs) were predictive of disease specificity. Multilocus and SNP typing can now be used to detect diverse and emerging C. trachomatis strains for epidemiologic and evolutionary studies of trachoma and STI populations worldwide.

BackgroundLymphogranuloma venereum (LGV) caused by Chlamydia trachomatis serovars L1-L3 is increasingly reported among men who have sex with men (MSM) in Western Europe, yet appears to remain underrecognised in Central and Eastern Europe. We describe clinical characteristics, diagnostic pathways, and outcomes of LGV cases in Poland to highlight recognition barriers and public health implications.MethodsWe conducted a retrospective case series of symptomatic MSM diagnosed with LGV at a dermatovenereology outpatient clinic in Gdańsk, Poland, between 1 December 2023 and 31 October 2025. Cases were confirmed by C. trachomatis nucleic acid amplification test followed by LGV-discriminatory PCR. We extracted demographic, clinical, laboratory, and treatment data from electronic records.ResultsSeven MSM (median age 28 years, range 25-68) were diagnosed with LGV; five (71%) were living with HIV. Common symptoms included rectal bleeding, rectal pain, and mucopurulent discharge (each 71%). Median time from symptom onset to diagnosis was 6 months (range 2 weeks-7 months); patients consulted a median of 3 physicians (range 1-5) before diagnosis. Five underwent colonoscopy with findings initially suggesting inflammatory bowel disease or malignancy. Concurrent sexually transmitted infections were frequent, including gonorrhoea (57%), syphilis (29%), and herpes simplex virus (29%). All received doxycycline 100 mg twice daily for 21 days. Three patients-all with diagnostic delays ≥ 6 months-reported persistent anorectal symptoms post-treatment despite microbiological cure.ConclusionsLGV may be underdiagnosed in Poland, and diagnostic delays exceeding six months may be associated with persistent symptoms despite microbiological cure. Enhanced clinician awareness, routine sexual history-taking in both primary and specialist care, and improved access to LGV-discriminatory testing are needed to reduce morbidity and prevent irreversible complications in this vulnerable population.