Challenges in Chlamydial Serology: Insights from a Belgian and a Dutch Population Cohort.

Serology routinely serves as a diagnostic tool to confirm Chlamydia infections in humans. Particularly in delayed settings, such as post-outbreak scenarios where the acute phase of infection has subsided, serology is invaluable. Multiple studies, nonetheless, indicate deficiencies in specificity and sensitivity of current chlamydial antibody detection assays. Incorporation of multiple antigens per target is known to improve the accuracy of chlamydial serological assays. We, therefore, used the recomLine test (Mikrogen diagnostics) on serological samples of two cohorts, as it is the only commercially available test allowing detection of antibodies against three human pathogenic Chlamydia species (C. trachomatis, C. pneumoniae and C. psittaci) using multiple antigens per target. The first cohort (n = 156; samples collected between 2008 and 2022 during a C. trachomatis screening initiative) comprised women from the Netherlands (NL) with past exposure to C. trachomatis, while the second cohort (n = 44; samples collected in 2018 in a health examination survey) consisted of Belgian citizens (BE) with occupational or recreational exposure to chickens, representing a risk population for C. psittaci. The test indicated a statistically equivalent C. pneumoniae seroprevalence in both cohorts (39.10% in NL and 34.09% in BE; p = 0.337). As expected C. trachomatis seroprevalence was significantly higher (p < 0.001) in the Dutch cohort (48.72%), as compared to the Belgian cohort (4.55%). Lastly, C. psittaci seroprevalence did not significantly differ between the two groups (2.27% in BE and 1.92% in NL; p = 0.633), even though a higher prevalence was expected for the Belgian cohort. This prompts us to question whether the Belgian cohort truly constituted a C. psittaci risk population or whether the recomLine test is susceptible to cross-reaction of species-specific antibodies, thereby increasing C. psittaci prevalence in the Dutch cohort. We advocate for the development of affordable, highly sensitive antibody detection assays that can effectively distinguish between chlamydial species, addressing the increasing demand for enhanced serological testing methodologies.

Belgian Cross-Sectional Epidemiological Study on Zoonotic Avian Chlamydia spp. in Chickens.

Chlamydia psittaci, Chlamydia gallinacea, and Chlamydia abortus are the most common Chlamydia spp. in chickens and have a confirmed or suggested zoonotic potential. No recent data are available on their prevalence and impact in the Belgian chicken industry or in the recreational chicken branch. Therefore, a cross-sectional epidemiological study was executed where samples were collected from both factory-farmed and backyard chickens. More specifically, pharyngeal chicken swabs were obtained from 20 chicken farms, 5 chicken abattoirs, and 38 different backyard locations and were analyzed using species-specific Polymerase Chain Reactions (PCRs) for the presence of the three avian Chlamydia spp. To investigate their zoonotic potential, samples were simultaneously collected from 54 backyard chicken caretakes and 37 professional chicken caretakers or abattoir employees and analyzed using species-specific PCRs as well. This study confirmed the presence of DNA of all three Chlamydia species in both the chicken industry and backyard settings. Chlamydia psittaci was the most prevalent in the industry chickens (11.0%), whereas Chlamydia gallinacea was the dominant species in the backyard chickens (14.5%). Chlamydia abortus infections were more common in the commercial chickens (9.0%) compared to the backyard chickens (2.6%). The DNA of all three species was also detected in humans (3.9% Chlamydia psittaci, 2.9% Chlamydia gallinacea, and 1.0% Chlamydia abortus).

The association between non-viral sexually transmitted infections and pregnancy outcome in Latin America and the Caribbean: A systematic review.

Introduction: Non-viral sexually transmitted infections are known to be associated with adverse pregnancy outcomes. For these pathogens, standard antenatal screening is not broadly performed in Latin America and the Caribbean. The aim of this study was to comprehensively review the association of non-viral sexually transmitted infections and neonatal outcomes among pregnant women in the region. Methods: Four databases (PubMed, Embase, SciELO and LILACS) were examined to identify eligible studies published up to September 2022. English or Spanish cross-sectional, case-control and cohort studies assessing the association of non-viral sexually transmitted infections and adverse pregnancy outcomes were evaluated. Articles were firstly screened by means of title and abstract. Potential articles were fully read and assessed for inclusion according to the eligibility criteria. Snowballing search was performed by screening of bibliographies of the chosen potentially relevant papers. Risk of bias within studies was assessed using the Joanna Briggs Institute reviewer's manual. Results: A selection of 10 out of 9772 search records from five Latin America and the Caribbean countries were included. Six studies associated Treponema pallidum infection with preterm birth (1/6), history of previous spontaneous abortion (2/6), fetal and infant death (1/6), low birth weight (1/6) and funisitis of the umbilical cord (1/6). Three studies associated Chlamydia trachomatis infection with preterm birth (2/3), ectopic pregnancy (1/3) and respiratory symptoms on the newborn (1/3). One study associated Mycoplasma genitalium infection with preterm birth. Conclusion: This review provides evidence on the association of non-viral sexually transmitted infections with adverse pregnancy outcomes. Further investigation is needed to establish more associations between non-viral sexually transmitted infections and pregnancy outcome, especially for Mycoplasma genitalium, Trichomonas vaginalis and Neisseria gonorrhoeae. Overall, this review calls for more research for public health interventions to promote screening of non-viral sexually transmitted infections during pregnancy, among high-risk population groups of pregnant women living in the region.

Use of gene sequences as type for naming prokaryotes: Recommendations of the international committee on the taxonomy of chlamydiae.

The International Committee on Systematics of Prokaryotes (ICSP) discussed and rejected in 2020 a proposal to modify the International Code of Nomenclature of Prokaryotes to allow the use of gene sequences as type for naming prokaryotes. An alternative nomenclatural code, the Code of Nomenclature of Prokaryotes Described from Sequence Data (SeqCode), which considers genome sequences as type material for naming species, was published in 2022. Members of the ICSP subcommittee for the taxonomy of the phylum Chlamydiae (Chlamydiota) consider that the use of gene sequences as type would benefit the taxonomy of microorganisms that are difficult to culture such as the chlamydiae and other strictly intracellular bacteria. We recommend the registration of new names of uncultured prokaryotes in the SeqCode registry.

The association between adverse pregnancy outcomes and non-viral genital pathogens among women living in sub-Saharan Africa: a systematic review.

Adverse pregnancy outcomes are the main causes of maternal and neonatal morbidity and mortality, including long-term physical and psychological sequelae. These events are common in low- and middle-income countries, particularly in Sub Saharan Africa, despite national efforts. Maternal infections can cause complications at any stage of pregnancy and contribute to adverse outcomes. Among infections, those of the genital tract are a major public health concern worldwide, due to limited availability of prevention, diagnosis and treatment approaches. This applies even to treatable infections and holds true especially in Sub-Saharan Africa. As late as 2017, the region accounted for 40% of all reported treatable non-viral genital pathogens worldwide, many of which have been independently associated with various adverse pregnancy outcomes, and that include Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Treponema pallidum. Two databases (PubMed and Embase) were examined to identify eligible studies published up to October 2022. This study reviewed findings on the association between infections by treatable non-viral genital pathogens during pregnancy and adverse pregnancy outcomes among women living in Sub-Saharan Africa. Articles' title and abstract were screened at first using keywords as "sexually transmitted infections", "non-viral", "adverse pregnancy outcome", "Africa", "sub-Saharan Africa", "pregnant women", "pregnancy", and "pregnancy outcome". Subsequently, according to the eligibility criteria, potential articles were read in full. Results showed that higher risk of preterm birth is associated with Treponema pallidum, Chlamydia trachomatis and Candida albicans infections. Additionally, rates of stillbirth, neonatal death, low birth weight and intrauterine growth restriction are also associated with Treponema pallidum infection. A better insight on the burden of non-viral genital pathogens and their effect on pregnancy is needed to inform antenatal care guidelines and screening programs, to guide the development of innovative diagnostic tools and other strategies to minimize transmission, and to prevent short- and long-term complications for mothers and children.

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+, Ct-DNA+/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.

Frequency of Chlamydia trachomatis and Neisseria gonorrhoeae in Patients with Imminent Preterm Delivery on the Island of Curaçao.

Sexually transmitted infections are one of the important risk factors for preterm delivery, which is among the important contributors to perinatal morbidity and mortality. The aim of this study was to assess the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections in women with imminent preterm delivery in Curaçao, an island of the Dutch Caribbean. All women from Curaçao with either preterm premature rupture of the membranes or preterm labor, common indications of imminent preterm delivery, and presenting at the Curaçao Medical Center between 15 November 2019 and 31 December 2020, were included in this single cohort study. Data were retrospectively collected from medical records. The presence of Chlamydia trachomatis and Neisseria gonorrhoeae was assessed by Cepheid GeneXpert ® (Xpert) CT/NG assay (Sunnyvale, CA, USA). In the included cohort, the prevalence of Chlamydia trachomatis infection was 15.5% and of Neisseria gonorrhoeae infection was 2.1%. All patients infected with Neisseria gonorrhoeae were co-infected with Chlamydia trachomatis. The prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections in patients with imminent preterm delivery in Curaçao is high. It is recommended to test all patients with imminent preterm delivery for these sexually transmitted infections and possibly consider testing all women in early pregnancy on the island.

The Vaginal Microbiota Composition and Genital Infections during and after Pregnancy among Women in Pemba Island, Tanzania.

We investigated the vaginal microbiota (VMB) composition, prevalence of genital pathogens and their association among pregnant and post-delivery women in Pemba Island, Tanzania. Vaginal swabs were collected from 90 women, at two time points during pregnancy (<20 weeks of gestational age [GA] and ≥20 weeks GA) and once after delivery, when possible. IS-pro assay was used for VMB characterization. Chlamydia trachomatis (CT), Neisseria gonorrhea (NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) and human papillomavirus (HPV) were detected by qPCRs. VMB were mostly Lactobacillus dominant during pregnancy and non-Lactobacillus dominant post-delivery. A significant decrease in VMB richness was observed during pregnancy among paired and unpaired samples. Shannon diversity was significantly lower during pregnancy than post-delivery among unpaired samples. Klebsiella species and Streptococcus anginosus were the most commonly identified pathobionts at all timepoints. A high abundance of pathobionts was mostly seen in women with non-Lactobacillus dominant VMB. At ≥20 weeks GA timepoint during pregnancy, 63.0% of the women carrying one or more genital pathogen (either HPV, CT, TV, or MG) had L. iners dominant VMB. NG was not detected pre-delivery. This study contributes evidence on VMB composition, its changes during pregnancy and post-delivery, and their association with pathobionts and genital pathogens.

Association of genetic variations in ACE2, TIRAP and factor X with outcomes in COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest with varying disease severity and mortality. Genetic predisposition influences the clinical course of infectious diseases. We investigated whether genetic polymorphisms in candidate genes ACE2, TIRAP, and factor X are associated with clinical outcomes in COVID-19. METHODS: We conducted a single-centre retrospective cohort study. All patients who visited the emergency department with SARS-CoV-2 infection proven by polymerase chain reaction were included. Single nucleotide polymorphisms in ACE2 (rs2285666), TIRAP (rs8177374) and factor X (rs3211783) were assessed. The outcomes were mortality, respiratory failure and venous thromboembolism. Respiratory failure was defined as the necessity of >5 litres/minute oxygen, high flow nasal oxygen suppletion or mechanical ventilation. RESULTS: Between March and April 2020, 116 patients (35% female, median age 65 [inter quartile range 55-75] years) were included and treated according to the then applicable guidelines. Sixteen patients (14%) died, 44 patients (38%) had respiratory failure of whom 23 required endotracheal intubation for mechanical ventilation, and 20 patients (17%) developed venous thromboembolism. The percentage of TIRAP polymorphism carriers in the survivor group was 28% as compared to 0% in the non-survivor group (p = 0.01, Bonferroni corrected p = 0.02). Genotype distribution of ACE2 and factor X did not differ between survivors and non-survivors. CONCLUSION: This study shows that carriage of TIRAP polymorphism rs8177374 could be associated with a significantly lower mortality in COVID-19. This TIRAP polymorphism may be an important predictor in the outcome of COVID-19.

Composition of the vaginal microbiota during pregnancy in women living in sub-Saharan Africa: a PRISMA-compliant review.

BACKGROUND: The vaginal microbiota (VMB) are the set of microorganisms residing in the human vagina. During pregnancy, their composition is Lactobacillus-dominant in most Caucasian women. Previous studies suggest that the VMB of women with African ancestry is more likely to be non-Lactobacillus dominant (dysbiotic) compared to other populations, and possibly relate to the high incidence of pregnancy complications, such as preterm birth. This work reviewed the literature on VMB composition in pregnant women from sub-Saharan Africa. METHODS: A search was conducted in PubMed and Embase databases following PRISMA guidelines. Observational and intervention studies analysing VMB communities from sub-Saharan African pregnant women using molecular techniques were included. RESULTS: Ten studies performed in seven sub-Saharan African countries were identified. They independently showed that Lactobacillus-dominant VMB (particularly L. iners or L. crispatus) or VMB containing Lactobacilli are the most prevalent, followed by a more diverse anaerobe-dominant VMB, in the studied populations. The majority of pregnant women with a sexually-transmitted infection had a Lactobacillus-dominant VMB, but with a significantly higher presence of anaerobic species. CONCLUSION: In agreement with studies performed in other populations, Lactobacillus species are the most prevalent VMB species during pregnancy in sub-Saharan African women. The frequency of diverse anaerobe-dominant VMB is high in these populations. In Africa, studies on VMB in pregnancy are scant, heterogeneous in methodology, and knowledge remains limited. More insights on VMB composition and their possible sequalae among these populations is needed.

The Natural Course of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium in Pregnant and Post-Delivery Women in Pemba Island, Tanzania.

This study aimed to determine the persistence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG) infections during pregnancy and after delivery in vaginal swabs of women from Pemba Island, Tanzania. In the context of an earlier biobanking effort, vaginal swabs were collected at two timepoints during pregnancy and once post-delivery. Detection of CT, NG, TV, and MG was performed by PCR using validated detection kits in samples from 441 pregnant women aged 16-48 years old. Among those, 202 samples were matched during pregnancy and 38 at the second timepoint of the pregnancy and post-delivery CT infection persistence during pregnancy was 100% (n = 11) after an average of eight weeks, that of TV infection 82% (n = 11) after ten weeks, and that of MG infection 75% (n = 4) after ten weeks. Post-delivery (after approximately 22 weeks) infection persistence was 100% for CT (n = 1) and 20% for TV (n = 5). NG was only detected at the last collection timepoint, its persistence rate could not be determined. These results show persistence and clearance of curable infections during and after pregnancy. Analysis of biobanked samples is a valuable approach in the investigation of the natural history of curable pathogens.

Ongoing evolution of Chlamydia trachomatis lymphogranuloma venereum: exploring the genomic diversity of circulating strains.

Lymphogranuloma venereum (LGV), the invasive infection of the sexually transmissible infection (STI) Chlamydia trachomatis, is caused by strains from the LGV biovar, most commonly represented by ompA-genotypes L2b and L2. We investigated the diversity in LGV samples across an international collection over seven years using typing and genome sequencing. LGV-positive samples (n=321) from eight countries collected between 2011 and 2017 (Spain n=97, Netherlands n=67, Switzerland n=64, Australia n=53, Sweden n=37, Hungary n=31, Czechia n=30, Slovenia n=10) were genotyped for pmpH and ompA variants. All were found to contain the 9 bp insertion in the pmpH gene, previously associated with ompA-genotype L2b. However, analysis of the ompA gene shows ompA-genotype L2b (n=83), ompA-genotype L2 (n=180) and several variants of these (n=52; 12 variant types), as well as other/mixed ompA-genotypes (n=6). To elucidate the genomic diversity, whole genome sequencing (WGS) was performed from selected samples using SureSelect target enrichment, resulting in 42 genomes, covering a diversity of ompA-genotypes and representing most of the countries sampled. A phylogeny of these data clearly shows that these ompA-genotypes derive from an ompA-genotype L2b ancestor, carrying up to eight SNPs per isolate. SNPs within ompA are overrepresented among genomic changes in these samples, each of which results in an amino acid change in the variable domains of OmpA (major outer membrane protein, MOMP). A reversion to ompA-genotype L2 with the L2b genomic backbone is commonly seen. The wide diversity of ompA-genotypes found in these recent LGV samples indicates that this gene is under immunological selection. Our results suggest that the ompA-genotype L2b genomic backbone is the dominant strain circulating and evolving particularly in men who have sex with men (MSM) populations.

Chlamydia trachomatis, Neisseria gonorrhoea, and Trichomonas vaginalis infections among pregnant women and male partners in Dutch midwifery practices: prevalence, risk factors, and perinatal outcomes.

BACKGROUND: Antenatal screening for HIV, syphilis and HBV has been successfully implemented in The Netherlands, but data on other STI among pregnant women or male partners are limited. Our objectives: (i) to assess the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) among pregnant women and male partners, (ii) to identify risk factors for these STI during pregnancy, and (iii) to identify adverse perinatal outcomes (APO) associated with STI. METHODS: Cross-sectional study. Pregnant women aged ≤ 30 years (n = 548) and male partners (n = 425) were included at 30 midwifery practices during 2012-2016. Participants provided a self-collected vaginal swab (women) or urine sample (men) and completed a questionnaire. Perinatal data were derived from pregnancy cards. APO was defined as premature rupture of membranes, preterm delivery, low birthweight, stillbirth, neonatal conjunctival and respiratory infections. Data were analysed by logistic regression. RESULTS: STI were present in 2.4% of pregnant women (CT 1.8%, NG 0.4%, TV 0.4%), and in 2.2% of male partners (CT 2.2%, NG 0.2%, TV 0%). Of young women (≤ 20 years), 12.5% had a CT infection. Prevalent STI during pregnancy was associated with female young age (≤ 20 years vs ≥ 21 years) (adjusted OR 6.52, CI 95%: 1.11-38.33), male non-Western vs Western background (aOR 9.34, CI 2.34-37.21), and female with ≥ 2 sex partners < 12 months vs 0-1 (aOR 9.88, CI 2.08-46.91). APO was not associated with STI, but was associated with female low education (aOR 3.36, CI 1.12-10.09), complications with previous newborn (aOR 10.49, CI 3.21-34.25 vs no complications) and short duration (0-4 years) of relationship (aOR 2.75, CI 1.41-5.39 vs ≥ 5 years). Small-for-gestational-age was not associated with STI, but was associated with female low education (aOR 7.81, 2.01-30.27), female non-Western background (aOR 4.41, 1.74-11.17), and both parents smoking during pregnancy (aOR 2.94, 1.01-8.84 vs both non-smoking). CONCLUSIONS: Prevalence of STI was low among pregnant women and male partners in midwifery practices, except for CT among young women. The study could not confirm previously observed associations between STI and APO, which is probably due to low prevalence of STI, small study sample, and presumed treatment for STI.

Antenatal screening for HIV, syphilis and HBV has been successfully implemented in The Netherlands, but data on other STI among pregnant women or male partners are limited. Our objectives were: (i) to assess the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) among pregnant women and male partners, (ii) to identify risk factors for these STI during pregnancy, and (iii) to identify adverse perinatal outcomes (APO) associated with STI.Pregnant women aged ≤ 30 years and male partners were included at 30 midwifery practices. Women provided a vaginal swab, partners a urine sample; both completed a questionnaire. Perinatal data were derived from midwives.STI were present in 2.4% of pregnant women (CT 1.8%, NG 0.4%, TV 0.4%), and in 2.2% of male partners (CT 2.2%, NG 0.2%, TV 0%). Of women ≤ 20 years, 12.5% had a CT infection. Prevalent STI during pregnancy was associated with female young age, male non-Western background, and female with ≥ 2 sex partners < 12 months. APO was not associated with STI, but was associated with female low education, complications with previous newborn, and short duration of the relationship. Small-for-gestational-age was not associated with STI, but was associated with female low education, female non-Western background, and both parents smoking during pregnancy.Prevalence of STI was low among pregnant women and male partners in midwifery practices, except for CT among young women. The study could not confirm previously observed associations between STI and APO. Probably due to low prevalence of STI, small study sample, and presumed treatment for STI.

Can Previous Associations of Single Nucleotide Polymorphisms in the TLR2, NOD1, CXCR5, and IL10 Genes in the Susceptibility to and Severity of Chlamydia trachomatis Infections Be Confirmed?

Clear inter-individual differences exist in the response to C. trachomatis (CT) infections and reproductive tract complications in women. Host genetic variation like single nucleotide polymorphisms (SNPs) have been associated with differences in response to CT infection, and SNPs might be used as a genetic component in a tubal-pathology predicting algorithm. Our aim was to confirm the role of four genes by investigating proven associated SNPs in the susceptibility and severity of a CT infection. A total of 1201 women from five cohorts were genotyped and analyzed for TLR2 + 2477 G > A, NOD1 + 32656 T -> GG, CXCR5 + 10950 T > C, and IL10 - 1082 A > G. Results confirmed that NOD1 + 32656 T ->GG was associated with an increased risk of a symptomatic CT infection (OR: 1.9, 95%CI: 1.1-3.4, p = 0.02), but we did not observe an association with late complications. IL10 - 1082 A > G appeared to increase the risk of late complications (i.e., ectopic pregnancy/tubal factor infertility) following a CT infection (OR = 2.8, 95%CI: 1.1-7.1, p = 0.02). Other associations were not found. Confirmatory studies are important, and large cohorts are warranted to further investigate SNPs' role in the susceptibility and severity of a CT infection.

The Association Between Vaginal Microbiota Dysbiosis, Bacterial Vaginosis, and Aerobic Vaginitis, and Adverse Pregnancy Outcomes of Women Living in Sub-Saharan Africa: A Systematic Review.

Background: Previous studies have described the association between dysbiosis of the vaginal microbiota (VMB) and related dysbiotic conditions, such as bacterial vaginosis (BV) and aerobic vaginitis (AV), and various adverse pregnancy outcomes. There is limited overview of this association from countries in sub-Saharan Africa (SSA), which bear a disproportionally high burden of both vaginal dysbiotic conditions and adverse pregnancy outcomes. This systematic review assesses the evidence on the association between VMB dysbiosis, BV, and AV, and late adverse pregnancy outcomes in women living in SSA. Methods: The Preferred Reporting Items for Systematic Review and Meta-Analysis Statement (PRISMA) guidelines were followed. Three databases [PubMed, Embase (Ovid), and Cochrane] were used to retrieve observational and intervention studies conducted in SSA that associated VMB dysbiosis, BV, or AV and preterm birth/labor/delivery, preterm rupture of membranes (PROM), low birthweight, small for gestational age, intrauterine growth restriction, intrauterine infection, intrauterine (fetal) death, stillbirth, perinatal death, or perinatal mortality. Results: Twelve studies out of 693 search records from five SSA countries were included. One study identified a positive association between VMB dysbiosis and low birthweight. Despite considerable differences in study design and outcome reporting, studies reported an association between BV and preterm birth (7/9), low birthweight (2/6), PROM (2/4), intrauterine infections (1/1), and small for gestational age (1/1). None of the retrieved studies found an association between BV and pregnancy loss (5/5) or intrauterine growth retardation (1/1). At least two studies support the association between BV and PROM, low birthweight, and preterm birth in Nigerian pregnant women. No reports were identified investigating the association between AV and late adverse pregnancy outcomes in SSA. Conclusion: Two of the included studies from SSA support the association between BV and PROM. The remaining studies show discrepancies in supporting an association between BV and preterm birth or low birthweight. None of the studies found an association between BV and pregnancy loss. As for the role of VMB dysbiosis, BV, and AV during pregnancy among SSA women, additional research is needed. These results provide useful evidence for prevention efforts to decrease vaginal dysbiosis and its contribution to adverse pregnancy outcomes in SSA.

The Prevalence of Chlamydia trachomatis and Three Other Non-Viral Sexually Transmitted Infections among Pregnant Women in Pemba Island Tanzania.

Efforts to map the burden of infections globally have shown a high prevalence of genital infections, including Chlamydia trachomatis, in sub-Saharan Africa. This retrospective study aimed to investigate the prevalence of selected non-viral genital infections among pregnant women in Pemba Island, Tanzania. Vaginal swabs were collected during pregnancy and stored in eNAT buffer. Detection of C. trachomatis, Neisseria gonorrheae, Trichomonas vaginalis, and Mycoplasma genitalium pathogens was performed by PCR using validated detection kits. Vaginal samples of 439 pregnant women between 16 and 48 years were tested. In fifty-five (12.5%) of them, at least one genital pathogen was detected. The most prevalent pathogen was T. vaginalis (7.1%), followed by C. trachomatis (4.6%) and M. genitalium (2.1%). None of the vaginal samples tested positive for N. gonorrheae. Consequently, among positive samples, 7.3% were for C. trachomatis and at least one other genital pathogen. This study provides insights on the burden of the four studied genital infections, and on the coinfections among pregnant women in Pemba Island, Tanzania. These results offer a starting point that can be useful to design further research in the field of maternal and child health in Pemba Island.

Pregnancies and Time to Pregnancy in Women With and Without a Previous Chlamydia trachomatis Infection.

BACKGROUND: A Chlamydia trachomatis infection (chlamydia) can result in tubal factor infertility in women. To assess if this association results in fewer pregnant women, we aimed to assess pregnancy incidences and time to pregnancy among women with a previous chlamydia infection compared with women without one and who were participating in the Netherlands Chlamydia Cohort Study (NECCST). METHODS: The NECCST is a cohort of women of reproductive age tested for chlamydia in a chlamydia screening trial between 2008 and 2011 and reinvited for NECCST in 2015 to 2016. Chlamydia status (positive/negative) was defined using chlamydia screening trial-nucleic acid amplification test results, chlamydia immunoglobulin G presence in serum, or self-reported chlamydia infections. Data on pregnancies were collected via questionnaires in 2015-2016 and 2017-2018. Overall pregnancies (i.e., planned and unplanned) and time to pregnancy (among women with a pregnancy intention) were compared between chlamydia-positive and chlamydia-negative women using Cox regressions. RESULTS: Of 5704 women enrolled, 1717 (30.1%; 95% confidence interval [CI], 28.9-31.3) women was chlamydia positive. Overall pregnancy proportions were similar in chlamydia-positive and chlamydia-negative women (49.0% [95% CI, 46.5-51.4] versus 50.5% [95% CI, 48.9-52.0]). Pregnancies per 1000 person-years were 53.2 (95% CI, 51.5-55.0) for chlamydia negatives and 83.0 (95% CI, 78.5-87.9) for chlamydia positives. Among women with a pregnancy intention, 12% of chlamydia-positive women had a time to pregnancy of >12 months compared with 8% of chlamydia negatives (P < 0.01). CONCLUSIONS: Overall pregnancy rates were not lower in chlamydia-positive women compared with chlamydia-negative women, but among women with a pregnancy intention, time to pregnancy was longer and pregnancy rates were lower in chlamydia-positive women. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR-5597.

Screening of Chlamydia trachomatis and Waddlia chondrophila Antibodies in Women with Tubal Factor Infertility.

Waddlia chondrophila is an emerging intracellular pathogen belonging to the order of Chlamydiales, and was previously associated with adverse pregnancy outcomes, as well as tubal factor infertility (TFI). In this study, we investigate the link between both W. chondrophila and Chlamydia trachomatis IgG seropositivity and TFI. Antibodies against both bacteria were measured in 890 serum samples of women visiting a fertility clinic. After a hysterosalpingography and/or laparoscopy, they were classified as either TFI-negative (TFI-) or TFI-positive (TFI+). The total seroprevalence was 13.4% for C. trachomatis and 38.8% for W. chondrophila. C. trachomatis antibodies were present significantly more often in the TFI+ group than in the TFI- group, while for W. chondrophila no difference could be observed. In conclusion, our study confirms the association between C. trachomatis seropositivity and TFI, but no association was found between W. chondrophila seropositivity and TFI. The high percentage of W. chondrophila seropositivity in all women attending a fertility clinic does, however, demonstrate the need for further research on this Chlamydia-like bacterium and its possible role in infertility.

The Interplay Between Reproductive Tract Microbiota and Immunological System in Human Reproduction.

In the last decade, the microbiota, i.e., combined populations of microorganisms living inside and on the surface of the human body, has increasingly attracted attention of researchers in the medical field. Indeed, since the completion of the Human Microbiome Project, insight and interest in the role of microbiota in health and disease, also through study of its combined genomes, the microbiome, has been steadily expanding. One less explored field of microbiome research has been the female reproductive tract. Research mainly from the past decade suggests that microbial communities residing in the reproductive tract represent a large proportion of the female microbial network and appear to be involved in reproductive failure and pregnancy complications. Microbiome research is facing technological and methodological challenges, as detection techniques and analysis methods are far from being standardized. A further hurdle is understanding the complex host-microbiota interaction and the confounding effect of a multitude of constitutional and environmental factors. A key regulator of this interaction is the maternal immune system that, during the peri-conceptional stage and even more so during pregnancy, undergoes considerable modulation. This review aims to summarize the current literature on reproductive tract microbiota describing the composition of microbiota in different anatomical locations (vagina, cervix, endometrium, and placenta). We also discuss putative mechanisms of interaction between such microbial communities and various aspects of the immune system, with a focus on the characteristic immunological changes during normal pregnancy. Furthermore, we discuss how abnormal microbiota composition, "dysbiosis," is linked to a spectrum of clinical disorders related to the female reproductive system and how the maternal immune system is involved. Finally, based on the data presented in this review, the future perspectives in diagnostic approaches, research directions and therapeutic opportunities are explored.