Chlamydia Trachomatis Serotype Research Articles

Immunoinformatics design of a multi-epitope vaccine for Chlamydia trachomatis major outer membrane proteins

Chlamydia trachomatis (CT) remains a significant infectious cause of blindness and sexually transmitted infections worldwide. The objective and novelty of this study lie in using different serovars of CT to design a broad-spectrum multi-epitope vaccine that might confer immunity against different CT infections. As the major outer membrane protein in CT has good immunodominance properties and high conservation and also determines the several serotypes of CT, it is selected as an antibody target in this study. T-cell and B-cell epitopes from serovars A, B, D, E, L1, and L2 were predicted and combined into a single construct by incorporating adjuvants and linkers to enhance immunogenicity and stability. Physicochemical characterization confirmed the constructed vaccine’s anti-allergic, immunogenicity, and thermostable characteristics, followed by structural modeling to refine its 3D configuration. The 3D model structure of the vaccine was validated through the Ramachandran plot and ProSA z-score. Molecular docking studies of the vaccine demonstrated stable binding with toll-like receptor 3, along with molecular dynamics simulations and binding free energy calculations supporting the complex’s stability. In silico cloning has indicated a high potential for expression in Escherichia coli. Lastly, immune simulations revealed robust activation of B cells, cytotoxic T cells, and antigen-presenting cells, alongside significant production of IgM, IgG antibodies, and balanced Th1/Th2 cytokine response, which is crucial for effective immunity. These results suggest the multi-epitope vaccine could effectively induce comprehensive immune responses against CT, highlighting the need for further in vivo validation to advance this promising candidate toward clinical use.

Brazilian Protocol for Sexually Transmitted Infections, 2020: infections that cause genital ulcers.

Infections that cause genital ulcers are one of the themes comprising the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. The Protocol and Guidelines have been developed based on scientific evidence and validated in discussions with specialists. This article addresses clinical genital ulcer syndrome caused by sexually transmitted infections and its most common etiological agents: Treponema pallidum (syphilis), herpes simplex virus-2 (genital herpes) and herpes simplex virus-1 (perioral herpes), Haemophilus ducreyi (chancroid), Chlamydia trachomatis serotypes L1, L2 and L3 (lymphogranuloma venereum), and Klebsiella granulomatis (donovanosis). Epidemiological and clinical aspects of these infections and guidelines for their diagnosis and treatment are presented, including strategies for surveillance, prevention, and control actions to support health managers and professionals in the qualification of care.

Brazilian Protocol for Sexually Transmitted Infections 2020: infections that cause genital ulcers

Infections that cause genital ulcers are one of the themes comprising the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. The Protocol and Guidelines have been developed based on scientific evidence and validated in discussions with specialists. This article addresses clinical genital ulcer syndrome caused by sexually transmitted infections, and its most common etiological agents: Treponema pallidum (syphilis), herpes simplex virus-2 (genital herpes) and herpes simplex virus-1 (perioral herpes), Haemophilus ducreyi (chancroid), Chlamydia trachomatis serotypes L1, L2 and L3 (venereal lymphogranuloma), and Klebsiella granulomatis (donovanosis). Epidemiological and clinical aspects of these infections are presented, as well as guidelines for their diagnosis and treatment, in addition to strategies for surveillance, prevention and control actions, with the purpose of supporting health managers and professionals in the qualification of care.

The ΦCPG1 chlamydiaphage can infect Chlamydia trachomatis and significantly reduce its infectivity

Recent years have seen a significant increase in rates of persistent, antibiotic-resistant infection of Chlamydia trachomatis (CT) infections, representing an increasingly serious public health threat. At present there are no effective vaccines or antibodies available to treat CT, prompting the need for novel treatment strategies. One potential solution to this issue is the use of ΦCPG1, a chlamydia-specific lytic phage which has over 90% nucleotide sequence identity with other chlamydiaphages. Previous work has shown the Vp1 capsid protein of ΦCPG1 to exhibit broad inhibitory activity against all CT serotypes, inhibiting CT-mediated host cell toxicity. Patients with CT infections exhibit circulating antibodies against this Vp1 protein, suggesting that this or similar phages may be present in vivo in the context of CT infections, even though no phages have been specifically detected to date. Given these previous findings, we hypothesized that the ΦCPG1 chlamydiaphage may be able to infect CT, thereby inhibiting its growth and proliferation. To test this, we generated a recombinant pGFP-ΦCPG1 phage which we used to explore its effects on CT and chlamydia conjunctivitis of guinea pigs (GPIC). We found that pGFP insertion did not alter the packaging or infectivity of ΦCPG1, and that this recombinant phage was readily able to infect CT and GPIC and inhibit CT and GPIC in a dose-dependent fashion. This inhibition was most pronounced during the mid and late stages of the CT infection, disrupting the reticular body (RB) to EB transition, leading to the formation of enlarged RBs. These results indicate that ΦCPG1 is able to infect CT, highlighting this phage as a novel potential therapeutic agent for treating chlamydia infections. In addition, by engineering pGFP to express ΦCPG1, we have produced an valuable experimental tool useful for future studies of drug resistance, pathogenicity, and vaccine research aimed at improving CT treatment.

Chlamydia trachomatis serotype A infections in the Amazon region of Brazil: prevalence, entry and dissemination.

Chlamydia infection is associated with debilitating human diseases including trachoma, pneumonia, coronary heart disease and urogenital diseases. Serotypes of C. trachomatis show a fair correlation with the group of diseases they cause, and their distribution follows a well-described geographic pattern. Serotype A, a trachoma-associated strain, is known for its limited dissemination in the Middle East and Northern Africa. However, knowledge on the spread of bacteria from the genus Chlamydia as well as the distribution of serotypes in Brazil is quite limited. Blood samples of 1,710 individuals from ten human population groups in the Amazon region of Brazil were examined for antibodies to Chlamydia using indirect immunofluorescence and microimmunofluorescence assays. The prevalence of antibodies to Chlamydia ranged from 23.9% (Wayana-Apalai) to 90.7% (Awa-Guaja) with a mean prevalence of 50.2%. Seroreactivity was detected to C. pneumoniae and to all serotypes of C. trachomatis tested; furthermore, we report clear evidence of the as-yet-undescribed occurrence of serotype A of C. trachomatis. Specific seroreactivity not only accounts for the large extent of dissemination of C. trachomatis in the Amazon region of Brazil but also shows an expanded area of occurrence of serotype A outside the epidemiological settings previously described. Furthermore, these data suggest possible routes of Chlamydia introduction into the Amazon region from the massive human migration that occurred during the 1,700s.

Ongoing epidemic of lymphogranuloma venereum in HIV-positive men who have sex with men: how symptoms should guide treatment.

IntroductionLymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by chlamydia trachomatis (CT) genotype L (L1, L2 and L3). Recent outbreaks of LGV in Europe and North America affected mainly men who have sex with men (MSM). Infections with CT serotypes D-K are mostly associated with mild symptoms or may be clinically silent. However, infections with L genotypes are more invasive and induce anogenital ulcer or inguinal lymphadenopathy.Materials and MethodsBetween 2003 and 2013, anal or genital CT infections were diagnosed in 471 symptomatic patients attending the Infectious Diseases Center Hamburg (ICH). CT DNA was detected by PCR. CT genotyping of positive samples was performed by sequence analyses of omp1 PCR products (samples between 2003 and 2010). Samples between 2012 and 2013 were analyzed by genotype L specific real-time PCR.ResultsIn total, 221 LGV patients were identified (3 in 2003; 11 in 2004; 26 in 2005; 33 in 2006; 24 in 2007; 16 in 2008; 18 in 2009; 15 in 2010; 17 in 2011; 26 in 2012 and 32 in 2013). One hundred ninety-eight of 221 (89.6%) patients with LGV were HIV-infected; 10 of 221 (4.5%) were HIV-negative, and the HIV-status unknown in 13 (5.9%). The majority of LGV positive patients (204/221; 92%) had anorectal symptoms (bloody proctitis, rectal pain, purulent or mucous discharge, tenesmus, constipation), compared to 17/221 (8%) who presented with genital symptoms as urethritis, genital ulcer or inguinal lymphadenopathy. Of 283 CT-positive patients with anorectal symptoms, genotype L was detected in 205 (72%), while non-L genotypes (D-K) were found in 78 (28%). In contrast, genotype L was found in only 6% of patients with genital symptoms (11/177), whereas 94% (166/177) were infected with non-L genotypes only.ConclusionsThe epidemic of LGV among predominantly HIV+ MSM is ongoing. LGV might be underdiagnosed, especially in patients with anorectal symptoms. Infections with CT serotypes D-K are more often associated with urogenital symptoms or asymptomatic infection, whereas LGV genotypes are found most frequently in patients with rectal/intestinal symptoms. Anorectal CT infections in MSM should be further characterized by genotyping for LGV, as for LGV three weeks of doxycycline treatment are recommended. CT genotypes D-K generally require shorter antibiotic treatment. If CT genotyping is not available, the duration of treatment should be prolonged to three weeks empirically for CT-positive patients with anorectal or intestinal symptoms.

Changes over time in the Chlamydia trachomatis serotype distribution in Finnish women

The distribution of Chlamydia trachomatis serotypes in the sexually active population may change over time. Serum from C. trachomatis seropositive women representing the 1980s, 1990s, and 2000s were available from a stratified random sample (11,067) of the Finnish Maternity Cohort for microimmunofluorescence-based classification. The C. trachomatis serotype distributions in the 1980s and 2000s were comparable, with serotypes G, E, and J being the most prevalent. In the 1990s the numbers of women seropositive for ≥ 2 serotypes peaked, and serotypes G/J were replaced by serotypes E/D. The temporary C. trachomatis serotype replacement parallels changes in the sexually active population in the 1990s in Finland.

Changes of heat shock protein 60 levels during subcultures of clinical isolates of Chlamydia trachomatis serotype E and their relationship with treatment outcomes of patients

Objective To detect the changes of heat shock protein 60 (HSP60) during the subcultures of standard and clinical strains of Chlamydia trachomatis (Ct),and to determine if the absence of chlamydial inclusions is associated with the persistent infection of Ct.Methods A total of 40 Ct strains isolated by cell culture from patients were included in this study and classified into 2 groups according to whether inclusions appeared after initial culture.Reverse transcription PCR was conducted to quantify the levels of HSP60 in specimens containing Ct after 1-4 subcuhures.Chi-squared test was performed to analyze the relationship between the levels of HSP60 and treatment outcomes of patients.Results The levels of HSP60 in clinical specimens containing Ct serovar E were significantly higher in subcultures prior to the appearance of inclusions than in subcultures with the appearance of inclusions (P ＜ 0.05).The ratio of HSP60:16S rRNA mRNA expression after the first,second,third,fourth passage was 0.38 ± 0.06,0.39 ± 0.03,0.38 ± 0.04 and 0.39 ±0.03 respectively in 18 specimens with inclusions appearing after the initial culture,1.18 ± 0.10,0.28 ± 0.06,0.30 ± 0.03 and 0.29 ± 0.05 respectively in 12 specimens with inclusions appearing after the second culture,1.20 ± 0.04,1.20 ± 0.04,0.28 ± 0.04 and 0.28 ± 0.05 in 10 specimens with inclusions appearing after the third culture.Whether inclusions appeared after the initial culture was associated with the treatment outcome of patients.Inclusions were undetected after the initial culture in 16 of 20 specimens from patients with poor response to treatment,but observed in 14 of 20 specimens from patients who tested negative for Ct after one course of treatment.Conclusions It is implicated that no inclusions form after the initial culture in 80％ of specimens from patients experiencing treatment failure.The Ct strains whose inclusions do not form after passages may be in a persistent state,and the expression of HSP60 is high in these strains.Specimens should be subjected to at least 3 blind passages to avoid missed diagnosis of Ct infection.

Distribution of Chlamydia trachomatis Serotypes in Clinical Urogenital Samples from North-Eastern Croatia

The purpose of this study was to determine prevalence of Chlamydia trachomatis (Ct) urogenital infection and its serotype distribution from clinical samples in north-eastern Croatia. During a 3-year period, 2,379 urogenital samples were analyzed by real-time polymerase chain reaction (A group), while 4,846 genital swabs were analyzed by direct fluorescent antibody test (B group). 132 Ct positive specimens were genotyped by omp1 gene sequencing. The prevalence rate of Ct was 3.2 % in A and 1 % in B group. The most prevalent chlamydial genotype was E (44 %), followed by F (33 %), K (11.5 %), G (8 %), J/UW (5.3 %), D-IC (4.4 %), D-B120 (1.8 %), and B/IU, J/IU, Ia/IU (0.9 % each) serotypes. Single-nucleotide polymorphisms (SNPs) of omp1 gene were detected in E, K, and G serotypes. Some of these SNPs (C/T at position 272 and G/A at position 813 in E strain; C/T at position 884 in D strain) might represent novel omp1 variants.

Cellular immune responses induced by DNA vaccine against Chlamydia trachomatis E serotype.

Objective To study cellular immune responses induced by DNA vaccine against Chlamydia trachomatis (Ct) serotype E. Methods BALB/c mice were divided into three groups to be intramuscularly immunized by blank plasmid (negative control group), DNA vaccine against Ct serotype E (vaccine group), and inactivated Ct elementary body (positive control group), respectively. Two weeks after the last immunization,delayed-type hypersensitivity (DTH) response was evaluated; MTT assay was performed to detect the proliferation of spleen lymphocytes, ELISA to measure the serum level of interferon-γin mice. Some immunized mice underwent a genital challenge with Ct elementary body followed by isolation of Ct from exfoliated epithelial cells in genital tract and pathological examination of cervical tissue from the challenged mice. Results Compared to negative control group, vaccine group and positive control group experienced a stronger DTH response.The lymphocyte stimulating index and serum level of IFN-γwere highest in the positive control group (3.81 ±0.30, 2891.7 ± 1048.8 μg/L), followed by vaccine group (2.35 ± 0.25, 593.3 ± 342.6 μg/L) and negative control group (1.48 ± 0.15, 309.2 ± 157.9 μg/L), and significant difference was observed between the three groups (P ＜ 0.05 or 0.01 ). After Ct challenge, Ct was isolated from exfoliated epithelial cells and cervical tissue was damaged in the negative control group, while in the other two groups, Ct was undetected and genital tract tissue was intact. Conclusions The DNA vaccine against Ct serotype E could induce Ct-specific cellular immune responses to some extent, and offer a protection against vaginal challenge with Ct. Key words: Chlamydia trachomatis; Vaccines, DNA; Immunity, cellular; Hypersensitivity, delayed

Re‐emergence of lymphogranuloma venereum

Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by the L1, L2 and L3 serotypes of Chlamydia trachomatis. The disease has been in the spotlight recently because of recent outbreaks in Europe as well as the USA. A unique feature of the recent outbreaks has been that most cases have been caused by the L2 strain. Another unique feature of these outbreaks is the fact that most cases have occurred in men having sex with men, and most patients have presented with proctitis. Interestingly, most recent cases have occurred in human immunodeficiency virus-seropositive patients. Usually, the disease is divided into three phases: the primary stage characterized by a self-healing papule, the secondary stage characterized by proctitis or lymphadenopathy and the tertiary stage characterized by lymphedema and anal strictures. Tests used for diagnosis include polymerase chain reactions and compliment fixation tests. The treatment of choice is doxycycline.

Lymphogranuloma venereum: a review of literature.

Lymphogranuloma venereum (LGV) is a systemic STD caused by Chlamydia trachomatis serotypes L1, L2 and L3. The disease is endemic in parts of Africa, Asia, South America and the Caribbean but rare in Western countries where the disease occurs mainly in sporadic form. Large outbreaks occurred recently in Europe and America mostly among men who have sex with men (MSM). The clinical course of the disease is stratified into primary, secondary and late stages but the presentation may be atypical particularly when coexisting with HIV and may result in diagnostic confusion. We present here a review of literature on LGV.African Journal of Clinical and Experimental Microbiology Vol. 9 (1) 2008: pp. 53-58

Population-based genetic epidemiologic analysis of Chlamydia trachomatis serotypes and lack of association between ompA polymorphisms and clinical phenotypes

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted diseases worldwide. Urogenital strains are classified into serotypes and genotypes based on the major outer membrane protein and its gene, ompA, respectively. Studies of the association of serotypes with clinical signs and symptoms have produced conflicting results while no studies have evaluated associations with ompA polymorphisms. We designed a population-based cross-sectional study of 344 men and women with urogenital chlamydial infections (excluding co-pathogen infections) presenting to clinics serving five U.S. cities from 1995 to 1997. Signs, symptoms and sequelae of chlamydial infection (mucopurulent cervicitis, vaginal or urethral discharge; dysuria; lower abdominal pain; abnormal vaginal bleeding; and pelvic inflammatory disease) were analyzed for associations with serotype and ompA polymorphisms. One hundred and fifty-three (44.5%) of 344 patients had symptoms consistent with urogenital chlamydial infection. Gender, reason for visit and city were significant independent predictors of symptom status. Men were 2.2 times more likely than women to report any symptoms ( P = 0.03) and 2.8 times more likely to report a urethral discharge than women were to report a vaginal discharge in adjusted analyses ( P = 0.007). Differences in serotype or ompA were not predictive except for an association between serotype F and pelvic inflammatory disease ( P = 0.046); however, the number of these cases was small. While there was no clinically prognostic value associated with serotype or ompA polymorphism for urogenital chlamydial infections except for serotype F, future studies might utilize multilocus genomic typing to identify chlamydial strains associated with clinical phenotypes.

Emergence of lymphogranuloma venereum in Canada

Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by Chlamydia trachomatis serotypes L1, L2 and L3. Unlike other serotypes (A to K), those that cause LGV are invasive and preferentially target lymph tissue. LGV can be transmitted through vaginal, anal or oral sexual

Le trachome : Une infection pédiatrique toujours d'actualité

Trachoma is a chronic granular conjunctivitis due to Chlamydia trachomatis serotypes A to C. The primary infection arises in thechildhood while vision threatening complications occur in the adulthood. Vision decrease is mostly related to the opacification of the cornea which is due to the chronic friction of eyelashes on its surface (trichiasis), itself being a consequence of the conjunctival scarring secondary to relapsing infections. The trachoma rages in developing countries, not only in Africa but also and especially in Southeast Asia and in the region of the western Pacific. Even if the number of cases of trachoma in the world is now 6-fold lower than twenty years ago, still 83 millions of patients are affected by active trachoma, leading to the estimation that 490 millions of people should be treated in a curative or a preventive way. The fight against trachoma is based on the S.A.F.E. strategy, an acronym for surgery of trichiasis, antibiotics for patients and contact subjects, facial hygiene and environmental improvement. Concerning antibiotics, oral azithromycin is now considered as the gold standard for mass distribution against trachoma, but costs remain a major problem in developing countries. However, application of the four large-scale measures of the S.A.F.E. strategy should allow ending in the purpose fixed by the WHO organization, namely the Global Elimination of Trachoma by the year 2020.

Lymphogranuloma venereum in the differential diagnosis of proctitis

Background and epidemiology : Lymphogranuloma venereum (LGV) is a systemic STD caused by infection by Chlamydia trachomatis serotypes L1, L2 and L3, which are endemic in parts of Africa, Asia, South America and the Caribbean but rare in Western countries. Unlike the more common C. trachomatis

The Janus Serum Bank: forward thinking allows retrospective analysis

Named after the two-faced Roman god, the Janus Serum Bank symbolizes the possibility of looking for the causes of disease both retrospectively and prospectively. This vital biomedical resource was highlighted in a recent JAMA publication that linked Chlamydia trachomatis serotype and cervical squamous cell carcinoma [Anttila, T. et al. (2001) JAMA 285, 47–51]. Under the control of the Norwegian Cancer Society, the bank consists of 600 000 serum samples obtained from 300 000 Norwegians during medical examinations and when donating blood. Most individuals have a time-course of sera in the bank (up to 12 samples). The Janus project currently cooperates with groups from Scandinavia, the UK, Germany, the US and Australia. Researchers can obtain between 500 to 3000 samples for projects; each sample from a patient comes with three healthy age- and sex-matched controls. The samples are coded for anonymity and the experiments are done ‘blind’ – which samples are from controls and which from patients are only revealed once the results are in. Full details about the project and how to apply for samples are given on the Norweigan Cancer Societies website (http://www.kreft.no/forhelsepersonell/janusserumbank/english/). SG.

Serotypes of Chlamydia trachomatis and risk for development of cervical squamous cell carcinoma.

Human papillomavirus (HPV) infection has been established as a cause of cervical cancer. Epidemiologic studies suggest that Chlamydia trachomatis infection also confers increased risk for cervical squamous cell carcinoma (SCC). Whether this risk is serotype-specific is unknown. To study the association between exposure to different C trachomatis serotypes and subsequent development of cervical SCC. Longitudinal, nested case-control study within a cohort of 530 000 women who provided samples to serum banks in Finland, Norway, and Sweden. The data files were linked to respective national cancer registries. One hundred twenty-eight women who had developed invasive cervical SCC at least 12 months following serum donation. Each case had 3 matched controls. Risk for the development of cervical SCC by IgG antibodies to 10 different C trachomatis serotypes, adjusted for antibodies to HPV types 16, 18, and 33 and for serum cotinine levels. Of specific C trachomatis serotypes, serotype G was most strongly associated with SCC (adjusted odds ratio [OR], 6.6; 95% confidence interval [CI], 1. 6-27.0). Other serotypes associated with SCC were I (OR, 3.8; 95% CI, 1.3-11.0) and D (OR, 2.7; 95% CI, 1.3-5.6). Presence of serum IgG antibodies to more than 1 serotype increased the adjusted ORs for SCC (P<.001 for trend). Chlamydia trachomatis serotype G is most strongly associated with subsequent development of cervical SCC. Increasing numbers of exposures to different C trachomatis serotypes also increases risk. Our results strengthen the evidence that there is a link between past C trachomatis infection and cervical SCC.

Co-cultivation of conjunctival epithelial cells and Chlamydia trachomatis: electron microscopic findings.

This study used primary culture of rabbit conjunctival epithelial cells to investigate the infection process of chlamydia. The epithelial cells isolated from conjunctiva of rabbit were initially cultured for three weeks. After attaining confluence they were infected with Chlamydia trachomatis (C. trachomatis) serotype D, and after co-cultivation for 24, 48, and 96 hours, electron microscopic study was performed. An inclusion body, a characteristic finding of chlamydial infection, was observed in the vicinity of the nucleus after 24 hours of co-cultivation. It contained a large number of elementary and reticulate bodies and their intermediate forms. Infectious particles known as elementary bodies were noted in the inclusion as 20 to 30 microns sized round bodies with an electron dense core. Reticulate bodies were also noted; they too were round but somewhat pleomorphic and larger than elementary bodies. Some reticulate bodies multiplied actively by means of binary fission. In this study, we observed the characteristic changes of C. trachomatis-infected cells; this in-vitro system might provide a suitable model for the study of some aspects of the pathogenesis of ocular chlamydia infection.

Chlamydia trachomatis growth stimulates interleukin 8 production by human monocytic U-937 cells.

Growth of Chlamydia trachomatis serotypes L2 and L3 in a human monocytic cell line, U-937, increased the rate of interleukin 8 (IL-8) release 100-fold. Heat-killed chlamydiae induced a 10-fold-lower level of production of IL-8. IL-8 may play an important role in the inflammatory reaction to chlamydial infection.