Trachomatis Antigen Research Articles

Intranasal delivery of Salmonella OMVs decorated with Chlamydia trachomatis antigens induces specific local and systemic immune responses

ABSTRACT Chlamydia trachomatis is an obligate intracellular pathogen responsible for the most prevalent bacterial sexually transmitted disease globally. The high prevalence of chlamydial infections underscores the urgent need for licensed and effective vaccines to prevent transmission in populations. Bacterial outer membrane vesicles (OMVs) have emerged as promising mucosal vaccine carriers due to their inherent adjuvant properties and the ability to display heterologous antigens. In this proof-of-concept study, we evaluated the immunogenicity of Salmonella OMVs decorated with C. trachomatis MOMP-derived CTH522 or HtrA antigens in mice. Following a prime-boost intranasal vaccination approach, two OMV-based C. trachomatis vaccines elicited significant humoral responses specific to the antigens in both systemic and vaginal compartments. Furthermore, we demonstrated strong antigen-specific IFN-γ and IL17a responses in splenocytes and cervical lymph node cells of vaccinated mice, indicating CD4+ Th1 and Th17 biased immune responses. Notably, the OMV-CTH522 vaccine also induced the production of spleen-derived CD8+ T cells expressing IFN-γ. In conclusion, these results highlight the potential of OMV-based C. trachomatis vaccines for successful use in future challenge studies and demonstrate the suitability of our modular OMV platform for intranasal vaccine applications.

Serological Responses to Trachoma Antigens prior to the Start of Mass Drug Administration: Results from Population-Based Baseline Surveys, North Darfur, Sudan.

After years of programmatic inaccessibility, in 2019-2020 the Sudan Federal Ministry of Health Trachoma Control Program conducted population-based trachoma surveys in three localities (districts) in North Darfur state, Sudan. These baseline surveys were to determine the prevalence of trachomatous inflammation-follicular (TF) among children aged 1-9 years and to further use serological markers to understand the historical trachoma burden within this mass drug administration (MDA)-naive area. Trained and certified graders collected trachoma clinical data, and trained nurses collected dried blood spot (DBS) samples. The DBSs were assayed on a multiplex bead array for antibody responses to the Chlamydia trachomatis antigens Pgp3 and CT694. Across the three localities, 3,613 individuals aged 1-9 years and 3,542 individuals aged ≥15 years were examined for clinical signs, and 8,322 DBSs were collected. The prevalence of TF among children aged 1-9 years was endemic (≥5%) in two localities (El Seraif, 15.6%, and Saraf Omrah, 11.0%) and below the TF elimination threshold (<5%) in the third (Kotom, 1.4%). The Pgp3 seroprevalence among children aged 1-9 years was 34.1% in El Seraif, 35.0% in Saraf Omrah, and 11.0% in Kotom. Locality prevalence results were similar for Pgp3 and CT694. Seroprevalence increased with age in all three localities. Serological data collected within these surveys demonstrate that all three localities have had a long history of exposure to Chlamydia trachomatis and that two of the three localities require MDA to reach elimination as a public health problem threshold.

The serodiagnositic value of Chlamydia trachomatis antigens in antibody detection using luciferase immunosorbent assay.

Among the different antigens used in the detection of anti-Chlamydia trachomatis antibodies, significant differences in sensitivity and specificity have been observed. Further evaluation of C. trachomatis antigens in antibody detection is urgently needed for the development and application of C. trachomatis serologic assays. Chlamydia trachomatis antigens Pgp3, TmeA, InaC, and HSP60 were selected and used in luciferase immunosorbent assay (LISA). The detection results obtained from well-defined C. trachomatis positive and negative samples were compared with the commercial C. trachomatis ELISA (Mikrogen) for performance evaluation. Pgp3, TmeA, InaC, and HSP60-based LISA showed sensitivity of 92.8, 88.8, 90.4, and 94.4%, and specificity of 99.2, 99.2, 99.2, and 92%, respectively. ROC analysis indicated that Pgp3-based LISA showed similar performance to Mikrogen ELISA (AUC 0.986 vs. 0.993, p = 0.207). Furthermore, four C. trachomatis antigens achieved strong diagnostic efficiency, i.e., positive likelihood ratios [+LR] ≥ 10 in C. trachomatis-infected women and negative likelihood ratios [-LR] ≤ 0.1 in C. trachomatis negative low exposure risk children, but only Pgp3 and TmeA showed strong diagnostic value in general adults. In addition, Pgp3, TmeA, and InaC, but not HSP60, achieved high performance, i.e., both positive predictive value (PPV) and negative predictive value (NPV) ≥ 90.9%, and showed no significant cross-reactivity with anti-Chlamydiapneumoniae. Three C. trachomatis species-specific antigens Pgp3, TmeA, and InaC show superior performance in the detection of anti-C. trachomatis antibody, indicating the potential to be used in developing C. trachomatis serologic tests.

Chlamydial Proctitis Mimicking Inflammatory Bowel Disease in a Young Active Duty Sailor With Undiagnosed Human Immunodeficiency Virus Infection: A Case Report.

Proctitis is an inflammation of the lining of the rectum that can be either acute or chronic in presentation. Symptoms include rectal bleeding, constipation, rectal discharge, rectal pain, and tenesmus. It is commonly associated with inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn's disease. However, it is important to consider the infectious causes of proctitis such as the sexually transmitted infections (STIs), especially Chlamydia trachomatis and Neisseria gonorrhoeae, as these can mimic the symptoms and pathology of IBD. We present the case of a young male sailor with subacute rectal bleeding who was hospitalized with initial concern for an index presentation of IBD. Endoscopic evaluation revealed proctitis although findings were atypical for inflammation related to IBD. Acquisition of additional history revealed that he had both receptive and insertive anal intercourse with both male and female partners. A full STI screening, including HIV was performed. Results were positive for both rectal C. trachomatis and HIV antigen and antibody serology, which were confirmed as HIV-1 on confirmatory testing. He was treated with doxycycline for his chlamydial proctitis with symptom resolution and was also initiated on antiretroviral therapy for his HIV infection. This case highlights the importance of obtaining a sexual history and considering STIs as a cause of proctitis, as this will ensure proper screenings and prompt subsequent treatment and potentially avoid unnecessary endoscopic and medical evaluation, which could potentially worsen the underlying process.

In silico design and analysis of a multiepitope vaccine against Chlamydia.

Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterial infection worldwide, potentially leading to severe pathologies including pelvic inflammatory disease, ectopic pregnancy, and tubal infertility if left untreated. Current strategies, including screening and antibiotics, have limited effectiveness due to high rates of asymptomatic cases and logistical challenges. A multiepitope prophylactic vaccine could afford long-term protection against infection. Immunoinformatic analyses were employed to design a multiepitope Chlamydia vaccine antigen. B- and T-cell epitopes from five highly conserved and immunogenic Ct antigens were predicted and selected for the vaccine design. The final construct, adjuvanted with cholera toxin A1 subunit (CTA1), was further screened for immunogenicity. CTA1-MECA (multiepitope Chlamydia trachomatis antigen) was identified as antigenic and nonallergenic. A tertiary structure was predicted, refined, and validated as a good quality model. Molecular docking exhibited strong interactions between the vaccine and toll-like receptor 4 (TLR4). Additionally, immune responses consistent with protection including IFN-γ, IgG+IgM antibodies, and T- and B-cell responses were predicted following vaccination in an immune simulation. Expression of the construct in an Escherichia coli expression vector proved efficient. To further validate the vaccine efficacy, we assessed its immunogenicity in mice. Immunization with CTA1-MECA elicited high levels of Chlamydia-specific antibodies in mucosal and systemic compartments.

Antibody responses to Chlamydia trachomatis vaccine candidate antigens in Chlamydia-infected women and correlation with antibody-mediated phagocytosis of elementary bodies.

Murine research has revealed a significant role for antibody responses in protection against Chlamydia reinfection. To explore potential humoral immune markers of protection elicited by Chlamydia trachomatis (CT) antigens in humans in the context of presumed clinical correlates of protection, we used both an IgG1-based ELISA and a conventional total IgG ELISA to evaluate antibody responses. We evaluated responses to five CT outer membrane proteins (PmpE, PmpF, PmpG, PmpH, and MOMP), along with other promising CT antigens (Pgp3 and HSP60), negative control antigens (RecO and AtpE), and CT elementary bodies (EBs) in sera from a well-characterized cohort of 60 women with different CT infection outcomes, including two outcomes that are likely clinical correlates of protective immunity: spontaneous resolution of infection and absence of reinfection after treatment. Furthermore, we used a flow cytometry-based assay to measure antibody-mediated phagocytosis by neutrophils in these sera. Results demonstrated that IgG1 ELISA displayed higher sensitivity than conventional total IgG ELISA in assessing antibody responses to CT EBs and antigens. Pgp3 IgG1 ELISA exhibited the highest sensitivity compared to IgG1 ELISA incorporating CT EBs or other antigens, confirming Pgp3 IgG1 ELISA as an ideal assay for CT antibody detection. Most (95%) sera from women with CT infection outcomes exhibited antibody-mediated phagocytosis of CT EBs, which was significantly correlated with IgG1 antibody responses to MOMP, Pgp3, HSP60, and PmpF. However, neither IgG1 responses to CT antigens and EBs nor antibody-mediated phagocytosis were associated with clinical correlates of protection. These findings suggest that neither CT IgG1 antibody detection nor antibody-mediated phagocytosis will be useful as immune correlates of protection against CT infection in humans.

Seroreversion to Chlamydia trachomatis Pgp3 Antigen Among Children in a Hyperendemic Region of Amhara, Ethiopia.

Monitoring trachoma transmission with antibody data requires characterization of decay in IgG to Chlamydia trachomatis antigens. In a 3-year longitudinal cohort in a high-transmission setting, we estimated a median IgG half-life of 3 years and a seroreversion rate of 2.5 per 100 person-years (95% confidence interval, 1.6-3.5). Clinical Trials Registration NCT02754583.

Changes in trachoma indicators in Kiribati with two rounds of azithromycin mass drug administration, measured in serial population-based surveys.

Baseline mapping in the two major population centers of Kiribati showed that trachoma was a public health problem in need of programmatic interventions. After conducting two annual rounds of antibiotic mass drug administration (MDA), Kiribati undertook trachoma impact surveys in 2019, using standardized two-stage cluster surveys in the evaluation units of Kiritimati Island and Tarawa. In Kiritimati, 516 households were visited and in Tarawa, 772 households were visited. Nearly all households had a drinking water source and access to an improved latrine. The prevalence of trachomatous trichiasis remained above the elimination threshold (0.2% in ≥15-year-olds) and was virtually unchanged from baseline. The prevalence of trachomatous inflammation-follicular (TF) in 1-9-year-olds decreased by approximately 40% from baseline in both evaluation units but remained above the 5% TF prevalence threshold for stopping MDA. TF prevalence at impact survey was 11.5% in Kiritimati and 17.9% in Tarawa. Infection prevalence in 1-9-year-olds by PCR was 0.96% in Kiritimati and 3.3% in Tarawa. Using a multiplex bead assay to measure antibodies to the C. trachomatis antigen Pgp3, seroprevalence in 1-9-year-olds was 30.2% in Kiritimati and 31.4% in Tarawa. The seroconversion rate, in seroconversion events/100 children/year, was 9.0 in Kiritimati and 9.2 in Tarawa. Seroprevalence and seroconversion rates were both assessed by four different assays, with strong agreement between tests. These results show that, despite decreases in indicators associated with infection at impact survey, trachoma remains a public health problem in Kiribati, and provide additional information about changes in serological indicators after MDA.

A systems serology approach to the investigation of infection-induced antibody responses and protection in trachoma.

Ocular infections with Chlamydia trachomatis serovars A-C cause the neglected tropical disease trachoma. As infection does not confer complete immunity, repeated infections are common, leading to long-term sequelae such as scarring and blindness. Here, we apply a systems serology approach to investigate whether systemic antibody features are associated with susceptibility to infection. Sera from children in five trachoma endemic villages in the Gambia were assayed for 23 antibody features: IgG responses towards two C. trachomatis antigens and three serovars [elementary bodies and major outer membrane protein (MOMP), serovars A-C], IgG responses towards five MOMP peptides (serovars A-C), neutralization, and antibody-dependent phagocytosis. Participants were considered resistant if they subsequently developed infection only when over 70% of other children in the same compound were infected. The antibody features assayed were not associated with resistance to infection (false discovery rate < 0.05). Anti-MOMP SvA IgG and neutralization titer were higher in susceptible individuals (p < 0.05 before multiple testing adjustment). Classification using partial least squares performed only slightly better than chance in distinguishing between susceptible and resistant participants based on systemic antibody profile (specificity 71%, sensitivity 36%). Systemic infection-induced IgG and functional antibody responses do not appear to be protective against subsequent infection. Ocular responses, IgA, avidity, or cell-mediated responses may play a greater role in protective immunity than systemic IgG.

Chlamydia trachomatis antigen induces TLR4-TAB1-mediated inflammation, but not cell death, in maternal decidua cells.

During gestation, the decidua is an essential layer of the maternal-fetal interface, providing immune support and maintaining inflammatory homeostasis. Although Chlamydia (C.) trachomatis is associated with adverse pregnancy outcomes the pathogenic effects on maternal decidua contributing to adverse events are not understood. This study examined how C. trachomatis antigen affects cell signaling, cell death, and inflammation in the decidua. Primary decidua cells (pDECs) from term, not-in-labor, fetal membrane-decidua were cultured using the following conditions: (1) control - standard cell culture conditions, (2) 100ng/ml or (3) 200ng/ml of C. trachomatis antigen to model decidual cell infection in vitro. Differential expression of Toll-like receptor (TLR) 4 (receptor for C. trachomatis antigen), signaling pathway markers phosphorylated TGF-Beta Activated Kinase 1 (PTAB1), TAB1, phosphorylated p38 mitogen-activated protein kinases (Pp38 MAPK), and p38 MAPK (western blot), decidual cell apoptosis and necrosis (flow cytometry), and inflammation (ELISA for cytokines) were determined in cells exposed to C. trachomatis antigen. T-test was used to assess statistical significance (p<0.05). C. trachomatis antigen significantly induced expression of TLR4 (p=0.03) and activation of TAB1 (p=0.02) compared to controls. However, it did not induce p38 MAPK activation. In addition, pDECs maintained their stromal cell morphology when exposed to C. trachomatis antigen showing no signs of apoptosis and/or necrosis but did induce pro-inflammatory cytokine interleukin (IL)-6 (100ng/ml: p=0.02 and 200ng/ml: p=0.03), in pDECs compared to controls. Prenatal C. trachomatis infection can produce antigens that induce TLR4-TAB1 signaling and IL-6 inflammation independent of Pp38 MAPK and apoptosis and necrosis. This suggests that C. trachomatis can imbalance decidual inflammatory homeostasis, potentially contributing to adverse events during pregnancy.

"Detection of Chlamydia trachomatis Antigen and Associated Risk Factors among HIV Positive Men in a Tertiary Health Institution, South-West Nigeria"

"Detection of Chlamydia trachomatis Antigen and Associated Risk Factors among HIV Positive Men in a Tertiary Health Institution, South-West Nigeria"

Post-Validation Survey in Two Districts of Morocco after the Elimination of Trachoma as a Public Health Problem.

ABSTRACT.Trachoma is the leading infectious cause of blindness. In 2016, Morocco was validated by WHO as having eliminated trachoma as a public health problem. We evaluated two previously endemic districts in Morocco for trachomatous inflammation—follicular (TF), trachomatous trichiasis (TT), and antibodies against Chlamydia trachomatis, the causative agent of trachoma. Community-based cross-sectional surveys in the districts of Boumalene Dades and Agdez included 4,445 participants for whom both questionnaire and serology data were available; 58% were aged 1–9 years. Participants had eyes examined for TF and blood collected for analysis of antibodies to the C. trachomatis antigen Pgp3 by both a multiplex bead assay (MBA) and lateral flow assay (LFA). Seroconversion rates (SCR) per 100 people per year were used to estimate changes in the force of infection using Bayesian serocatalytic models. In Agdez, TF prevalence in 1–9-year-olds was 0.3%, seroprevalence ranged from 9.4% to 11.4%, and SCR estimates ranged from 2.4 to 3.0. In Boumalene Dades, TF prevalence in 1–9-year-olds was 0.07%, and modeling data from the different assays indicated a decrease in transmission between 20 and 24 years ago. The TF data support an absence of active trachoma in the two districts examined. However, seroprevalence and SCR in younger people were higher in Agdez than Boumalene Dades, showing that there can be differences in serology metrics in areas with similar TF prevalence. Data will be included in multicountry analyses to better understand potential thresholds for serological surveillance in trachoma.

High prevalence of sexually transmitted infections among asymptomatic women opting for the intrauterine contraceptive device use in Mwanza, Tanzania: An urgent call for control interventions.

Objective:Placement of intrauterine contraceptive device (IUCD) in asymptomatic woman infected with sexually transmitted infection (STIs) can lead to pelvic inflammatory diseases (PID) and infertility if not well treated. The current study investigated the magnitude of sexually transmitted infections among women opting for IUCD use in the city of Mwanza, Tanzania.Methods:A cross-sectional study involving 150 asymptomatic women was conducted from August to December 2017. Detection of Chlamydia trachomatis antigen from endocervical swabs was done using immunochromatographic rapid tests while sera were used for detection of Treponema pallidum, human immunodeficiency virus (HIV) and herpes simplex virus Type 2 (HSV-2) antibodies.Results:The overall prevalence of STIs was 45/150 (30%, 95% CI: 22–37) while that of individual STIs were 27.3%, 5.3%, and 2.6% for C trachomatis, T pallidum, and HSV-2, respectively. History of dysuria (aOR 6.6; 95% CI 2.3–18.8; p < 0.001) and history of STIs (aOR 4.6; 95%CI 1.0–20.8; p = 0.049) independently predicted presence of STIs.Conclusions:Prevalence of STIs among women opted for IUCD use in the city of Mwanza, Tanzania is alarmingly high and is predicted by past history of dysuria and history of partner’s STIs, calling for the need of screening of the STIs among high-risk women in low- and middle-income countries (LMICs) opting for IUCD use.

The Performance of Immunoassays to Measure Antibodies to the Chlamydia trachomatis Antigen Pgp3 in Different Epidemiological Settings for Trachoma.

ABSTRACT.Programs to eliminate trachoma as a public health problem use prevalence of the clinical sign trachomatous inflammation—follicular (TF) in 1- to 9-year-olds in endemic districts to make decisions to begin or end mass drug administration with azithromycin. Trachomatous inflammation—follicular is used as a proxy for transmission of ocular Chlamydia trachomatis infection. Long-term monitoring of previously endemic districts for recrudescence of ocular C. trachomatis infection would benefit from a simple blood test that could be integrated with other public health programs. In this study, we evaluated multiple tests to measure antibodies against the C. trachomatis antigen Pgp3—a multiplex bead assay (MBA), an ELISA, and two versions of a lateral flow assay (LFA)—in four districts of the Amhara region of Ethiopia with varying levels of TF. Seroprevalence and seroconversion rate (SCR) results were proportional to TF prevalence by district for most tests, with the notable exception of the LFA using colloidal gold as the developing reagent. Changing the test developing reagent to black latex improved agreement between serological measures and TF prevalence and in inter-rater agreement. Seroconversion rate estimates using data derived from the LFA-gold assay were inconsistent with the shape of the age-seroprevalence curve, which did not increase in older ages. These data revealed potential complications with using SCR that will need further evaluation. Data from MBA, ELISA, and LFA with the black test line showed good agreement with each other and proportionality to TF estimates, providing further data that serology has potential utility for trachoma surveillance.

No Serological Evidence of Trachoma or Yaws Among Residents of Registered Camps and Makeshift Settlements in Cox's Bazar, Bangladesh.

.Successful achievement of global targets for elimination of trachoma as a public health problem and eradication of yaws will require control efforts to reach marginalized populations, including refugees. Testing for serologic evidence of transmission of trachoma and yaws in residents of registered camps and a Makeshift Settlement in Cox’s Bazar District, Bangladesh, was added to a serosurvey for vaccine-preventable diseases (VPDs) conducted April–May 2018. The survey was primarily designed to estimate remaining immunity gaps for VPDs, including diphtheria, measles, rubella, and polio. Blood specimens from 1- to 14-year-olds from selected households were collected and tested for antibody responses against antigens from Treponema pallidum and Chlamydia trachomatis using a multiplex bead assay to evaluate for serologic evidence of the neglected tropical diseases (NTDs) yaws and trachoma, respectively. The prevalence of antibodies against two C. trachomatis antigens in children ranged from 1.4% to 1.5% for Pgp3 and 2.8% to 7.0% for CT694. The prevalence of antibody responses against both of two treponemal antigens (recombinant protein17 and treponemal membrane protein A) tested was 0% to 0.15% in two camps. The data are suggestive of very low or no transmission of trachoma and yaws, currently or previously, in children resident in these communities. This study illustrates how integrated serologic testing can provide needed data to help NTD programs prioritize limited resources.

Comparison of platforms for testing antibodies to Chlamydia trachomatis antigens in the Democratic Republic of the Congo and Togo

Trachoma, caused by repeated ocular infection with Chlamydia trachomatis (Ct), is targeted for elimination as a public health problem. Serological testing for antibodies is promising for surveillance; determining useful thresholds will require collection of serological data from settings with different prevalence of the indicator trachomatous inflammation—follicular (TF). Dried blood spots were collected during trachoma mapping in two districts each of Togo and Democratic Republic of the Congo. Anti-Ct antibodies were detected by multiplex bead assay (MBA) and three different lateral flow assays (LFA) and seroprevalence and seroconversion rate (SCR) were determined. By most tests, the district with > 5% TF (the elimination threshold) had five–sixfold higher seroprevalence and tenfold higher SCR than districts with < 5% TF. The agreement between LFA and MBA was improved using a black latex developing reagent. These data show optimization of antibody tests against Ct to better differentiate districts above or below trachoma elimination thresholds.

Clinical Background and Detection of Chlamydia trachomatis Antigen among Infertile Women Attending University of Maiduguri Teaching Hospital, Nigeria

Background: Chlamydia trachomatis infection is an established cause of pelvic inflammatory disease (PID), ectopic pregnancy, chronic pelvic pain and infertility among women. It is the most common bacterial sexually transmitted disease in the world. The infection is largely asymptomatic.&#x0D; Aim: The study was carried out to determine the Clinical background as well as detect the Chlamydia trachomatis antigen among infertile women attending University of Maiduguri Teaching Hospital (UMTH).&#x0D; Methods: A survey on the Clinical background and antigens to Chlamydia trachomatis was carried out among infertile and post natal women attending fertility Clinic UMTH. A total of 65 endocervical swab samples were collected from the aforementioned group of subjects within the age of 18-47 years, out of which 45 were collected from infertile women while the remaining 20 were obtained from post-natal women to serve as control subjects. The samples were analysed by using Chlamydia Rapid Test device swab/urine (Abon Biopharm(Hangzhou), Co., Ltd) that work on the principle of immunochromatographic technique.&#x0D; Results: Highest number of infertility was observed on women within the age of 30-35 years (33.3%). The result shows that those that attained tertiary educational level have the highest number of infertility (60%). The study demonstrated highest number of infertility among female civil servants (53.3%) followed by full-time house wife (33.3%). More infertility was observed among women who are not engaged in the use of contraceptive measures (95.6%). The overall result from this study shows no prevalence (0.0%) of C. trachomatis genital infection among infertile women in UMTH.&#x0D; Conclusion: Further research using more sensitive and specific procedures for the detection of C. trachomatis from clinical specimens such as nucleic acid amplification tests and cell culture are recommended among infertile women in Borno State, Nigeria.

Genital Chlamydia trachomatis infection and infertility in Malaysia

Background: Genital Chlamydia trachomatis infection can cause pelvic inflammatory disease and infertility in female by damaging cervical columnar epithelial cells. Recent reports have shown increased cases of newly reported chlamydial infection worldwide. However, at present, there is no effective vaccine available for the prevention of genital chlamydial infection. Insights into the host response of the human cervical epithelial cells against C. trachomatis infection are crucial to design a better prevention and vaccination strategy. Methods and materials: Here, we examined the prevalence of the C. trachomatis infection and the association with women's health in Malaysia. To investigate the influence of the C. trachomatis infection on human epithelial cells, we applied isobaric tags for relative and absolute quantitation (iTRAQ) labeling technique and liquid chromatography-tandem mass spectrometry (LC-MS3) analysis for elucidation of host proteome changes in the C. trachomatis-infected HeLa-229 human cervical epithelial cells. In addition, cytokine response following stimulation with multiple C. trachomatis antigens (CPAF, HSP60 and MOMP) were also examined. Results: Here, we reported that the prevalence of genital chlamydial infection among the ostetrics and gynecology patients was alarmingly high at 51.1% (92/180). Our data also showed that genital C. trachomatis infection was associated with infertility issues, inflammation in the reproductive tract (mucopurulent cervicitis or endometriosis), irregular menstrual cycles and polycystic ovarian syndrome (PCOS). Our proteomic work discovered a significant array of host proteins which participated in the early C. trachomatis infection. We highlighted involvement of eukaryotic initiation factor 2 (eIF2), mammalian target of rapamycin (mTOR), ubiquitination, clathrin-mediated endocytosis, tRNA charging and glycolysis signaling pathways in the host cells to eradicate the bacteria invasion. The bacteria infection was also associates with other complications such as increased inflammation and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) were robustly secreted following antigenic exposure. Conclusion: Our study describes a high prevalence of C. trachomatis among Malaysian O&G patients and highlights distinct ability of C. trachomatis in manipulating host proteins and triggering pro-inflammatory response.

Population-Based Prevalence of Chlamydia trachomatis Infection and Antibodies in Four Districts with Varying Levels of Trachoma Endemicity in Amhara, Ethiopia.

.The Trachoma Control Program in Amhara region, Ethiopia, scaled up the surgery, antibiotics, facial cleanliness, and environmental improvement (SAFE) strategy in all districts starting in 2007. Despite these efforts, many districts still require additional years of SAFE. In 2017, four districts were selected for the assessment of antibody responses against Chlamydia trachomatis antigens and C. trachomatis infection to better understand transmission. Districts with differing endemicity were chosen, whereby one had a previous trachomatous inflammation-follicular (TF) prevalence of ≥ 30% (Andabet), one had a prevalence between 10% and 29.9% (Dera), one had a prevalence between 5% and 10% (Woreta town), and one had a previous TF prevalence of < 5% (Alefa) and had not received antibiotic intervention for 2 years. Survey teams assessed trachoma clinical signs and took conjunctival swabs and dried blood spots (DBS) to measure infection and antibody responses. Trachomatous inflammation-follicular prevalence among children aged 1–9 years was 37.0% (95% CI: 31.1–43.3) for Andabet, 14.7% (95% CI: 10.0–20.5) for Dera, and < 5% for Woreta town and Alefa. Chlamydia trachomatis infection was only detected in Andabet (11.3%). Within these districts, 2,195 children provided DBS. The prevalence of antibody responses to the antigen Pgp3 was 36.9% (95% CI: 29.0–45.6%) for Andabet, 11.3% (95% CI: 5.9–20.6%) for Dera, and < 5% for Woreta town and Alefa. Seroconversion rate for Pgp3 in Andabet was 0.094 (95% CI: 0.069–0.128) events per year. In Andabet district, where SAFE implementation has occurred for 11 years, the antibody data support the finding of persistently high levels of trachoma transmission.

Antibodies to Variable Domain 4 Linear Epitopes of the Chlamydia trachomatis Major Outer Membrane Protein Are Not Associated with Chlamydia Resolution or Reinfection in Women.

Chlamydia trachomatis is an obligate intracellular bacterium. C. trachomatis infection is the most prevalent bacterial sexually transmitted infection and can lead to pelvic inflammatory disease and infertility in women. There is no licensed vaccine for C. trachomatis prevention, in part due to gaps in our knowledge of C. trachomatis-specific immune responses elicited during human infections. Previous investigations of the antibody response to C. trachomatis have identified immunodominant antigens and antibodies that can neutralize infection in cell culture. However, epitope-specific responses to C. trachomatis are not well characterized, and the impact of these antibodies on infection outcome is unknown. We recently developed a technology called deep sequence-coupled biopanning that uses bacteriophage virus-like particles to display peptides from antigens and affinity select against human serum IgG. Here, we used this technology to map C. trachomatis-specific antibodies in groups of women with defined outcomes following C. trachomatis infection: (i) C. trachomatis negative upon presentation for treatment ("spontaneous resolvers"), (ii) C. trachomatis negative at a 3-month follow-up visit after treatment ("nonreinfected"), and (iii) C. trachomatis positive at a 3-month follow-up after treatment ("reinfected"). This analysis yielded immunodominant epitopes that had been previously described but also identified new epitopes targeted by human antibody responses to C. trachomatis We focused on human antibody responses to the C. trachomatis variable domain 4 serovar-conserved region of the major outer membrane protein (VD4-MOMP), a previously described immunodominant epitope. All three groups of women produced IgG to the VD4-MOMP, suggesting that detection of serum antibodies to VD4-MOMP in women with urogenital C. trachomatis infection is not associated with protection against reinfection.IMPORTANCEC. trachomatis infection is the most common bacterial sexually transmitted infection, and infection in women can lead to pelvic inflammatory disease and infertility. No licensed vaccine exists to prevent C. trachomatis infection, and investigations of the natural immune response may inform the design of targeted vaccines for C. trachomatis Our study fills a gap in knowledge regarding the epitope specificity of antibody responses that are elicited in response to C. trachomatis infection in women. We identified several new B cell epitopes for C. trachomatis antigens and confirmed B cell epitopes that have been identified by other methods. Our finding that women produce antibodies to the VD4-MOMP regardless of infection outcome provides insight into vaccine development, suggesting that vaccines targeting VD4-MOMP may need to elicit higher-titer antibody responses than natural infection imparts or that additional vaccine targets should be pursued in the future.