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Problem: Tubal factor infertility (TFI) is a severe complication of genital Chlamydia trachomatis infections. In fertility workup, chlamydia antibody test (CAT) is used to predict TFI. The predictive value for TFI of most commonly used CAT is moderate., Method of Study: A total of 183 infertile Dutch Caucasian women were included in this study. All underwent tubal patency testing (hysterosalpingography [HSG] or laparoscopy). Cases had TFI, and controls had no TFI (ie normal findings during HSG or laparoscopy). TFI was categorized based on severity (TFI 1-TFI 4). This study investigated the predictive values of major outer membrane protein (MOMP), translocated actin-recruiting phosphoprotein (TARP), chlamydial protease-like activity factor (CPAF), heat shock protein-60 (HSP60) and outer membrane protein 2 (OMP2) for TFI. A predictive algorithm is developed to detect TFI with a high certainty based on combinations of antibody titres. Serum was tested with the Mikrogen recomLine immunoblot and quantified with the recomScan. A greedy algorithm that explores all possible antibody combinations was developed., Results: Significant differences in the distributions of antigen titres between cases and controls were observed for CPAF (P = 0.0021), HSP60 (P = 0.0061), MOMP (P = 0.0497) and OMP2 (P = 0.0016). Single antibodies could not discriminate between TFI and controls by themselves. The greedy algorithm performs better in specificity, positive predictive value (PPV), accuracy and clinical utility index than the original Mikrogen algorithm. CPAF combined with HSP60 identified 18.2% of TFI cases with 100% certainty. Most of the TFI 4 cases were identified with cut-offs of CPAF > 10.7 or OMP2 > 3.9., Conclusion: This proof-of-principle study shows that combinations of antibodies in serum are predictive for TFI. A commercially available test can be adapted to predict TFI with a 100% specificity., (© 2019 The Authors. American Journal of Reproductive Immunology Published by John Wiley & Sons Ltd.)

Objectives: Chlamydia trachomatis (CT) IgG serology is used in many fertility clinics in order to estimate the risk for tubal factor infertility (TFI) in the fertility work-up. The predictive value for TFI of the currently used mono-target CT serology test should be improved. This study compares the performance of the new multi-target Mikrogen recomWell CT IgG ELISA with the Mikrogen recomLine CT immunoblot and visualizes distribution of individual antibodies in serum with the immunoblot in order to potentially improve the current CT IgG serology test that is clinically used., Methods: Study population consisted of 183 Dutch Caucasian infertile women who underwent laparoscopy and/or hysterosalpingography. 48 women had TFI, 135 were controls. Serum was tested with Mikrogen CT IgG ELISA, which detects 3 CT IgG antibodies in one well, and Mikrogen CT immunoblot, which can individually detect 5 CT IgG antibodies. Tests were compared based on the results in general and in the case and control group also taking the individual antibodies into account. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), Kappa value and distribution of individual antibodies in positive samples were calculated., Results: In 183 patients 51% tested positive in the ELISA versus 35% in the immunoblot. 32% versus 65% tested negative. Difference between PPV was not statistically significant (33% and 39% respectively) and NPV in both tests was 81%. Difference in sensitivity and specificity was statistically significant, respectively 65% vs. 52% and 54% vs. 71%. Kappa was only 45%. 64.5% of samples that tested positive with ELISA were positive for at least 4 individual CT antibodies with the immunoblot., Conclusion: The concordance between CT ELISA and CT immunoblot is moderate. Due to separate criteria for positivity of both tests there is a significant difference in sensitivity and specificity. PPV and NPV, the most relevant characteristics for clinicians, of both tests did not differ significantly. The distribution of individual antibodies and the adjustment of the immunoblot algorithm will be further explored in the future in order to develop a potentially better prediction method for TFI with a higher clinical accuracy., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Capillary blood collected in serum tubes was subjected to centrifugation delay while stored at room temperature. Chlamydia trachomatis (CT) IgG concentrations in aliquoted serum of these blood samples remained stable for seven days after collection. CT IgG concentrations can reliably be measured in mailed blood samples in epidemiological studies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Chlamydia trachomatis ( Ct ) is the leading cause of bacterial sexually transmitted diseases worldwide. The Ct Multi Locus Sequence Typing (MLST) scheme is effective in differentiating strain types (ST), deciphering transmission patterns and treatment failure, and identifying recombinant strains. Here, we analyzed 323 reference and clinical samples, including 58 samples from Russia, an area that has not previously been represented in Ct typing schemes, to expand our knowledge of the global diversification of Ct STs. The 323 samples resolved into 84 unique STs, a 3.23 higher typing resolution compared to the gold standard single locus omp A genotyping. Our MLST scheme showed a high discriminatory index, D , of 0.98 (95% CI 0.97-0.99) confirming the validity of this method for typing. Phylogenetic analyses revealed distinct branches for the phenotypic diseases of lymphogranuloma venereum, urethritis and cervicitis, and a sub-branch for ocular trachoma. Consistent with these findings, single nucleotide polymorphisms were identified that significantly correlated with each phenotype. While the overall number of unique STs per region was comparable across geographies, the number of STs was greater for Russia with a significantly higher ST/sample ratio of 0.45 (95% CI: 0.35-0.53) compared to Europe or the Americas ( p < 0.009), which may reflect a higher level of sexual mixing with the introduction of STs from other regions and/or reassortment of alleles. Four STs were found to be significantly associated with a particular geographic region. ST23 [ p = 0.032 (95% CI: 1-23)], ST34 [ p = 0.019 (95% CI: 1.1-25)]; and ST19 [ p = 0.001 (95% CI: 1.7-34.7)] were significantly associated with Netherlands compared to Russia or the Americas, while ST 30 [ p = 0.031 (95% CI: 1.1-17.8)] was significantly associated with the Americas. ST19 was significantly associated with Netherlands and Russia compared with the Americans [ p = 0.001 (95% CI: 1.7-34.7) and p = 0.006 (95% CI: 1.5-34.6), respectively]. Additionally, recombinant strains were ubiquitous in the data set [106 (32.8%)], although Europe had a significantly higher number than Russia or the Americas ( p < 0.04), the majority of which were from Amsterdam [43 (87.8%) of 49)]. The higher number of recombinants in Europe indicates selective pressure and/or adaptive diversification that will require additional studies to elucidate.

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., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Intracellular pattern-recognition receptors NOD1 and NOD2 are capable of sensing common structural units of bacterial walls. Recognition triggers specific immune signalling pathways and leads to pro-inflammatory cytokine upregulation and adequate immune response. We investigated whether two functional polymorphisms in NOD1 and NOD2 exert an effect on susceptibility to (STD patients) and severity of (female patients visiting the fertility clinic) Chlamydia trachomatis infection in 807 Dutch Caucasian women. A significant association of the NOD1 +32656 GG insertion variant with protection against infection with C. trachomatis has been detected [p: 0.0057; OR: 0.52]. When comparing C. trachomatis-positive women without symptoms to C. trachomatis-positive women with symptoms, and to C. trachomatis-positive women with TFI, we observed an increasing trend in carriage of the GG allele [Ptrend: 0.0003]. NOD2 1007fs failed to reveal an association. We hypothesize that the underlying mechanism might be a functional effect of the GG insertion on IFN-beta-dependent regulation of immune response in the genital tract. The research is part of an ongoing effort of identifying key polymorphisms that determine the risk of TFI and effectively translating them into the clinical setting for the purpose of optimizing diagnostic management of women at risk for developing TFI., (© The Author 2015. Published by Oxford University Press on behalf of FEMS. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)