Predictive Values of Serum Chlamydia trachomatis TroA and HtrA IgG Antibodies as Markers of Persistent Infection in the Detection of Pelvic Adhesions and Tubal Occlusion

Chlamydia trachomatis IgG antibody testing (CAT) has been used as a screening test for tubal factor infertility (TFI), but as the CAT is only a marker of a past exposure to C. trachomatis and not of late sequelae, the positive predictive value (PPV) of the test is low. The persistence of C. trachomatis in the upper genital tract has been suggested as one of the key mechanisms in the development of TFI. Serum antibodies against C. trachomatis TroA and HtrA, proteins expressed specifically during persistent infection, have been suggested as novel biomarkers for TFI diagnostics. We studied serum IgG antibody responses against C. trachomatis TroA, HtrA and MOMP in 79 subfertile women, of whom 28 had laparoscopically proven TFI. We confirmed that the accuracy of CAT in diagnosing TFI is low, whereas TroA IgG and HtrA IgG are more accurate tests in detecting tubal occlusion and pelvic adhesions. However, the sensitivity and negative predictive value (NPV) of TroA IgG and HtrA IgG are still too low to justify their use as a screening test in clinical practice. Individual immunogenetic profiles combined with TroA and HtrA antibody responses might identify women with the highest risk for developing late complications after C. trachomatis infection

Predictive Values of Serum Chlamydia trachomatis TroA and HtrA IgG Antibodies as Markers of Persistent Infection in the Detection of Pelvic Adhesions and Tubal Occlusion

Chlamydia trachomatis IgG antibody testing (CAT) has been used as a screening test for tubal factor infertility (TFI), but as the CAT is only a marker of a past exposure to C. trachomatis and not of late sequelae, the positive predictive value (PPV) of the test is low. The persistence of C. trachomatis in the upper genital tract has been suggested as one of the key mechanisms in the development of TFI. Serum antibodies against C. trachomatis TroA and HtrA, proteins expressed specifically during persistent infection, have been suggested as novel biomarkers for TFI diagnostics. We studied serum IgG antibody responses against C. trachomatis TroA, HtrA and MOMP in 79 subfertile women, of whom 28 had laparoscopically proven TFI. We confirmed that the accuracy of CAT in diagnosing TFI is low, whereas TroA IgG and HtrA IgG are more accurate tests in detecting tubal occlusion and pelvic adhesions. However, the sensitivity and negative predictive value (NPV) of TroA IgG and HtrA IgG are still too low to justify their use as a screening test in clinical practice. Individual immunogenetic profiles combined with TroA and HtrA antibody responses might identify women with the highest risk for developing late complications after C. trachomatis infection

Study protocol: The Dutch 20|30 Postmeningitis study: a cross-sectional follow-up of two historical childhood bacterial meningitis cohorts on long-term outcomes

BACKGROUND: Bacterial meningitis (BM) is a serious, life-threatening infectious disease of the central nervous system that often occurs in young children. The most common severe to moderate sequelae following BM are sensorineural hearing loss, neuromotor disabilities and mental retardation, while subtle sequelae include academic and behavioral disabilities. It is largely unknown whether these more subtle sequelae persist into adolescence and adulthood. Therefore, this study will investigate the very long-term effects of childhood BM in later life. Better understanding of long-term effects and early identification of adverse outcomes after BM are essential for more timely interventions. Additionally, certain single nucleotide polymorphisms (SNPs) are associated with disease severity and might predict adverse sequelae. These include SNPs in genes encoding for pathogen recognition and immune response upon infection. Accordingly, a secondary objective of this study is to investigate the role of genetic variation in BM and use any insights to predict short- and long-term outcomes. METHODS: In the Dutch 20|30 Postmeningitis study, adolescents and young adults (n = 947) from two historical cohorts with a prior episode of BM during childhood will be enrolled into a cross-sectional follow-up investigation using mainly questionnaires that examine executive and behavioral functioning, health-related quality of life, subjective hearing, mood and sleeping disorders, academic performance, and economic self-sufficiency. The results will be compared to normative data by one-sample t-tests. Multivariable regression analysis will be used to assess for any associations with causative pathogens and severity of BM. Participants that complete the questionnaires will be approached to provide a swab for buccal DNA and subsequent sequencing analyses. Logistic regression models will be used to predict sequelae. DISCUSSION: The unique follow-up duration of this cohort will enable us to gain insights into the possible very long-term adverse effects of childhood BM and how these might impact on quality of life. The investigation of host genetic factors will contribute to the development of prediction models which will serve as prognostic tools to identify children who are at high risk of adverse outcome after BM. TRIAL REGISTRATION: Dutch Trial Register NTR-6891. Retrospectively registered 28 December 2017

Do host genetic traits in the bacterial sensing system play a role in the development of Chlamydia trachomatis-associated tubal pathology in subfertile women?

BACKGROUND: In women, Chlamydia (C.) trachomatis upper genital tract infection can cause distal tubal damage and occlusion, increasing the risk of tubal factor subfertility and ectopic pregnancy. Variations, like single nucleotide polymorphisms (SNPs), in immunologically important host genes are assumed to play a role in the course and outcome of a C. trachomatis infection. We studied whether genetic traits (carrying multiple SNPs in different genes) in the bacterial sensing system are associated with an aberrant immune response and subsequently with tubal pathology following a C. trachomatis infection. The genes studied all encode for pattern recognition receptors (PRRs) involved in sensing bacterial components. METHODS: Of 227 subfertile women, serum was available for C. trachomatis IgG antibody testing and genotyping (common versus rare allele) of the PRR genes TLR9, TLR4, CD14 and CARD15/NOD2. In all women, a laparoscopy was performed to assess the grade of tubal pathology. Tubal pathology was defined as extensive peri-adnexal adhesions and/or distal occlusion of at least one tube. RESULTS: Following a C. trachomatis infection (i.e. C. trachomatis IgG positive), subfertile women carrying two or more SNPs in C. trachomatis PRR genes were at increased risk of tubal pathology compared to women carrying less than two SNPs (73% vs 33% risk). The differences were not statistically significant (P = 0.15), but a trend was observed. CONCLUSION: Carrying multiple SNPs in C. trachomatis PRR genes tends to result in an aberrant immune response and a higher risk of tubal pathology following a C. trachomatis infection. Larger studies are needed to confirm our preliminary findings

Performance of the multitarget Mikrogen Chlamydia trachomatis IgG ELISA in the prediction of tubal factor infertility (TFI) in subfertile women:Comparison with the Medac MOMP IgG ELISA plus

There is a need for more accurate Chlamydia trachomatis (CT) IgG antibody tests for tubal factor infertility (TFI) diagnostics. We evaluated the predictive value for TFI of Medac ELISA plus (MOMP) and multitarget Mikrogen ELISA (MOMP-CPAF-TARP). Based on Medac ELISA plus results, 183 subfertile women underwent either hysterosalpingography or laparoscopy to diagnose TFI. TFI was defined as extensive adhesions and/or distal occlusion of at least one tube. Women not fulfilling the definition of TFI served as controls. Serum was subsequently tested with Mikrogen ELISA and results were compared. 48 patients had TFI, 135 were controls. Mikrogen ELISA tested 125 patients positive/borderline of which 32% had TFI. Medac ELISA plus tested 77 patients positive/borderline of which 29.9% had TFI. Mikrogen tested 40 out of 48 TFI patients positive/borderline, Medac 23 out of 48. Kappa value was 0.34. PPV of Mikrogen ELISA and Medac ELISA plus were respectively 32% (95% CI 26%-39%) and 30% (95% CI 24%-37%), and NPV 86% (95% CI 81%-91%) and 76% (95% CI 70%-82%). Both tests were comparable in the prediction of TFI. However, Mikrogen ELISA had a higher NPV and might be more reliable in identifying patients without TFI. Kappa-value showed limited concordance between both tests

Evaluation of Presto(plus) assay and LightMix kit Trichomonas vaginalis assay for detection of Trichomonas vaginalis in dry vaginal swabs

This is an evaluation study of the Prestoplus Assay for T. vaginalis by comparing to the TIB MOLBIOL LightMix Kit Trichomonas vaginalis Assay using 615 dry collected vaginal and rectal swabs. Discordant samples were analyzed by the Qiagen® Microbial DNA qPCR for TV Assay. Both assays showed comparable performances (McNemar p > 0.05).http://www.elsevier.com/ locate/jmicmeth2017-08-31hb2016Microbiology and Plant Patholog

Genetic variation in the MBL2 gene is associated with Chlamydia trachomatis infection and host humoral response to Chlamydia trachomatis infection

This study aims to assess the potential association of MBL2 gene single nucleotide polymorphisms (SNPs) to Chlamydia trachomatis infection. We analysed a selected sample of 492 DNA and serum specimens from Dutch Caucasian women. Women were categorized into four groups of infection status based on the results of DNA and antibody tests for C. trachomatis: Ct-DNA+/IgG+, CtDNA+/IgG−, Ct-DNA−/IgG+, and Ct-DNA−/IgG−. We compared six MBL2 SNPs (−619G > C (H/L), −290G > C (Y/X), −66C > T (P/Q), +154C > T (A/D), +161A > G (A/B), and +170A > G (A/C)) and their respective haplotypes in relation to these different subgroups. The −619C (L) allele was less present within the Ct-DNA−/IgG+ group compared with the Ct-DNA−/IgG− group (OR = 0.49; 95% CI: 0.28–0.83), while the +170G (C) allele was observed more in the Ct-DNA+/IgG+ group as compared with the Ct-DNA−/IgG− group (OR = 2.4; 95% CI: 1.1–5.4). The HYA/HYA haplotype was more often present in the Ct-DNA−/IgG− group compared with the Ct-DNA+/IgG+ group (OR = 0.37; 95% CI: 0.16–0.87). The +170G (C) allele was associated with increased IgG production (p = 0.048) in C. trachomatis PCR-positive women. This study shows associations for MBL in immune reactions to C. trachomatis. We showed clear associations between MBL2 genotypes, haplotypes, and individuals’ stages of C. trachomatis DNA and IgG positivity.NGI Life Sciences Pre-Seed and a EuroTransBio grant.https://www.mdpi.com/journal/ijerphMedical Microbiolog

Predictive Values of Serum Chlamydia trachomatis TroA and HtrA IgG Antibodies as Markers of Persistent Infection in the Detection of Pelvic Adhesions and Tubal Occlusion

Chlamydia trachomatis IgG antibody testing (CAT) has been used as a screening test for tubal factor infertility (TFI), but as the CAT is only a marker of a past exposure to C. trachomatis and not of late sequelae, the positive predictive value (PPV) of the test is low. The persistence of C. trachomatis in the upper genital tract has been suggested as one of the key mechanisms in the development of TFI. Serum antibodies against C. trachomatis TroA and HtrA, proteins expressed specifically during persistent infection, have been suggested as novel biomarkers for TFI diagnostics. We studied serum IgG antibody responses against C. trachomatis TroA, HtrA and MOMP in 79 subfertile women, of whom 28 had laparoscopically proven TFI. We confirmed that the accuracy of CAT in diagnosing TFI is low, whereas TroA IgG and HtrA IgG are more accurate tests in detecting tubal occlusion and pelvic adhesions. However, the sensitivity and negative predictive value (NPV) of TroA IgG and HtrA IgG are still too low to justify their use as a screening test in clinical practice. Individual immunogenetic profiles combined with TroA and HtrA antibody responses might identify women with the highest risk for developing late complications after C. trachomatis infection.Peer reviewe

Single Nucleotide Polymorphisms in TLR9 Are Highly Associated with Susceptibility to Bacterial Meningitis in Children

Background. Bacterial meningitis (BM) is a severe infection mainly caused by Streptococcus pneumoniae and Neisseria meningitidis (NM). However, genetically determined susceptibility to develop severe infections by these microorganisms is variable between individuals. Toll-like receptor 9 (TLR9) recognizes bacterial DNA leading to intracellular inflammatory signaling. Single nucleotide polymorphisms (SNPs) within the TLR9 gene are associated with susceptibility to several diseases, no such association with meningitis has been described. Methods. We studied the role of TLR9 SNPs in host defense against BM. Two TLR9 SNPs and 4 TLR9 haplotypes were determined in 472 survivors of BM and compared to 392 healthy controls. Results. Carriage of the TLR912848-A mutant was significantly decreased in meningococcal meningitis (MM) patients compared with controls (p: .0098, odds ratio [OR]: .6, 95% confidence interval [CI]: .4-.9). TLR9 haplotype I was associated with an increased susceptibility to MM (p: .0237, OR 1.3, 95% CI: 1.0-1.5). In silico analysis shows a very strong immunoinhibitory potential for DNA of NM upon recognition by TLR9 (CpG index of -106.8). Conclusions. We report an association of TLR9 SNPs with susceptibility to BM, specifically MM indicating a protective effect for the TLR912848-A allele. We hypothesize that the TLR912848-A mutant results in an upregulation of TLR9 induced immune response compensating the strong inhibitory potential of NM CpG DNA. BACKGROUN