HLA-DR and HLA-DQ Polymorphism Correlation with Sexually Transmitted Infection Caused by Chlamydia trachomatis.

Background and Objectives: Chlamydia trachomatis (C. trachomatis) represents one of the most prevalent bacterial sexually transmitted diseases. This study aims to explore the relationship between HLA alleles/genotypes/haplotypes and C. trachomatis infection to better understand high-risk individuals and potential complications. Materials and Methods: This prospective study recruited participants from Transylvania, Romania. Patients with positive NAAT tests for C. trachomatis from cervical/urethral secretion or urine were compared with controls regarding HLA-DR and -DQ alleles. DNA extraction for HLA typing was performed using venous blood samples. Results: Our analysis revealed that the presence of the DRB1*13 allele significantly heightened the likelihood of C. trachomatis infection (p = 0.017). Additionally, we observed that individuals carrying the DRB1*01/DRB1*13 and DQB1*03/DQB1*06 genotype had increased odds of C. trachomatis infection. Upon adjustment, the association between the DRB1*01/DRB1*13 genotype and C. trachomatis remained statistically significant. Conclusions: Our findings underscore the importance of specific HLA alleles and genotypes in influencing susceptibility to C. trachomatis infection. These results highlight the intricate relationship between host genetics and disease susceptibility, offering valuable insights for targeted prevention efforts and personalized healthcare strategies.

Single-Cell Sequencing in Human Genital Infections.

Human genital infections are one of the most concerning issues worldwide and can be categorized into sexually transmitted, urinary tract and vaginal infections. These infections, if left untreated, can disseminate to the other parts of the body and cause more complicated illnesses such as pelvic inflammatory disease, urethritis, and anogenital cancers. The effective treatment against these infections is further complicated by the emergence of antimicrobial resistance in the genital infection causing pathogens. Furthermore, the development and applications of single-cell sequencing technologies have open new possibilities to study the drug resistant clones, cell to cell variations, the discovery of acquired drug resistance mutations, transcriptional diversity of a pathogen across different infection stages, to identify rare cell types and investigate different cellular states of genital infection causing pathogens, and to develop novel therapeutical strategies. In this chapter, I will provide a complete review of the applications of single-cell sequencing in human genital infections before discussing their limitations and challenges.

Increase in Sexually Transmitted Infections among Men Who Have Sex with Men, England, 2014.

Surveillance data from sexual health clinics indicate recent increases in sexually transmitted infections, particularly among men who have sex with men. The largest annual increase in syphilis diagnoses in a decade was reported in 2014. Less condom use may be the primary reason for these increases.

Association of interleukin-8 gene polymorphisms in HIV patients with opportunistic infections in Limpopo Province, South Africa.

Opportunistic infections (OIs) are common among human immunodeficiency virus (HIV) patients; however, genetic susceptibility to these infections has not been studied. Recent studies have shown that interleukin-8 (IL-8) A/T genotype carriers are more susceptible to a variety of diseases. In this study, we showed the effects of IL-8 gene polymorphisms on OIs and symptoms such as sexually transmitted diseases (STDs), tuberculosis (TB), diarrhea, shortness of breath, weight loss, and viral load, in HIV and acquired immunodeficiency syndrome patients. Genomic DNA was purified from mouthwash samples collected from patients attending HIV centers in the Vhembe district. The IL-8 (-251) A/T locus was genotyped using allele-specific polymerase chain reaction followed by agarose gel electrophoresis. The results showed a weak association between the IL-8 AA genotype and OIs such as STDs (P = 0.143), diarrhea (P = 0.906), and TB (P = 0.762). Significant associations were found between the IL-8 AT genotype and weight loss (P = 0.019), shortness of breath (P = 0.043), and skin problems (P = 0.003). Low viral load was also found to be significantly associated with IL-8 AA genotype (P = 0.009). The present study suggests that different IL-8 genotypes are associated with resistance to various OIs. However, further studies using larger samples sizes are needed to confirm this hypothesis.

RNA Biosignatures in Adolescent Patients in a Pediatric Emergency Department With Pelvic Inflammatory Disease.

BACKGROUND: Adolescents are at high risk for pelvic inflammatory disease (PID). Because accurate diagnosis of PID is difficult, and complications of untreated PID are significant, novel methods to improve diagnosis are essential. OBJECTIVES: To determine if patients with PID have unique RNA expression patterns compared to controls. METHODS: Peripheral blood was collected from adolescent females with PID in the emergency department, and from control patients in the operating room. RNA was isolated, and microarray analysis was performed. Initial analysis involved a training set of 18 patients (9 PID patients with either Neisseria gonorrhoeae or Chlamydia trachomatis infection and 9 control patients). Supervised and unsupervised cluster analyses were performed, followed by network analysis. The training set was used to classify a set of 15 additional PID patients and 2 controls. RESULTS: Supervised cluster analysis of the training set revealed 170 genes which were differentially expressed in PID patients versus controls. Network analysis indicated that several differentially expressed genes are involved in immune activation. Analysis of additional PID patients based on the training set findings revealed that patients with positive testing for Trichomonas vaginalis partitioned with the PID group, whereas patients with no organism identified partitioned with both groups. CONCLUSIONS: RNA sample collection from adolescents in the emergency department is feasible. Genes were identified which were differentially expressed in PID patients versus controls, many of which are involved in inflammation. Future studies should confirm the training set findings on a larger sample and may lead to improved accuracy of PID diagnosis.

Potential diagnostic value of miRNAs in sexually transmitted infections.

MiRNAs are small endogenous non-coding RNAs that have been demonstrated to be involved in post-transcriptional gene silencing, regulating a number of metabolic functions in the human body, including immune response, cellular physiology, organ development, angiogenesis, signaling, and other aspects. As popular molecules that have been studied in previous years, given their extensive regulatory functions, miRNAs hold considerable promise as non-invasive biomarkers. Sexually transmitted infections(STIs) are still widespread and have an adverse effect on individuals, communities, and society worldwide. miRNAs in the regulatory networks are generally involved in their molecular processes of formation and development. In this review, we discuss the value of miRNAs for the diagnosis of STIs.

Cancer selection.

Cancers are often thought to be selectively neutral. This is because most of the individuals that they kill are post-reproductive. Some cancers, however, kill the young and so select for anticancer adaptations that reduce the chance of death. These adaptations could reduce the somatic mutation rate or the selective value of a mutant clone of cells, or increase the number of stages required for neoplasia. New theory predicts that cancer selection--selection to prevent or postpone deaths due to cancer--should be especially important as animals evolve new morphologies or larger, longer-lived bodies, and might account for some of the differences in the causes of cancer between mice and men.

Functional interferon-epsilon gene polymorphisms and sexually transmitted infections of the endometrium.

PROBLEM: Interferon-epsilon (IFNε) is the only type I IFN constitutively expressed in the female reproductive tract and fluctuates across the menstrual cycle in humans. Mouse models show that IFNε protects against Chlamydia trachomatis, Herpes Simplex Virus, HIV, and Zika in mice, but human studies are limited. Bacterial sexually transmitted infections (STI) can ascend to the upper genital tract and cause pelvic inflammatory disease (PID) and subsequent infertility. However, the host immunological mechanisms that play a role in the ascension and infection of the endometrium in individuals with clinically suspected PID are not elucidated. METHOD OF STUDY: This pilot investigation determined if IFNε gene variants are associated with bacterial vaginosis (BV) and endometrial infection with C. trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium using biospecimens from 154 self-report Black individuals who participated in the PID Evaluation and Clinical Health (PEACH) study. RESULTS: The T allele for rs2039381 was associated with endometrial STI infection (OR 2.7, 95% CI: 1.0-7.1) and the C allele for rs1125488 was inversely associated with BV (OR: .2, 95% CI: .05-.8). CONCLUSIONS: Few studies have examined IFNε gene variants, our study raises the possibility that IFNε gene variants may be a potential host contributor to STI pathogenesis.

STI PCR: An efficient method for amplification and de novo synthesis of long DNA sequences.

Despite continuous improvements, it is difficult to efficiently amplify large sequences from complex templates using current PCR methods. Here, we developed a suppression thermo-interlaced (STI) PCR method for the efficient and specific amplification of long DNA sequences from genomes and synthetic DNA pools. This method uses site-specific primers containing a common 5' tag to generate a stem-loop structure, thereby repressing the amplification of smaller non-specific products through PCR suppression (PS). However, large target products are less affected by PS and show enhanced amplification when the competitive amplification of non-specific products is suppressed. Furthermore, this method uses nested thermo-interlaced cycling with varied temperatures to optimize strand extension of long sequences with an uneven GC distribution. The combination of these two factors in STI PCR produces a multiplier effect, markedly increasing specificity and amplification capacity. We also developed a webtool, calGC, for analyzing the GC distribution of target DNA sequences and selecting suitable thermo-cycling programs for STI PCR. Using this method, we stably amplified very long genomic fragments (up to 38 kb) from plants and human and greatly increased the length of de novo DNA synthesis, which has many applications such as cloning, expression, and targeted genomic sequencing. Our method greatly extends PCR capacity and has great potential for use in biological fields.

Detection of Neisseria gonorrhoeae and Chlamydia trachomatis infections in pregnant women by multiplex recombinase polymerase amplification.

Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the main pathogenic microorganisms causing sexually transmitted infections. In this study, a multiplex thermostable recombinase polymerase amplification-lateral flow detection (RPA-LFD) assay was established, and the reaction conditions such as the ratio of primer concentration, magnesium ion concentration, amplification time and template DNA concentration in the multiplex RPA reaction were optimized. The optimized multiplex RPA-LFD method was used to detect both CT and NG positive control plasmids, and it was found that the LFD could be used to obtain visible results when the plasmid copy number was only 200. The sensitivity of the multiplex RPA-LFD method used for clinical samples was 85.62 (95% CI at 53.66-97.29) for NG detection and 90.90 (95% CI at 57.12-99.52) for CT detection.

Sexual network and detection of anogenital human papillomavirus in a community cohort of men who have sex with men in Taiwan.

OBJECTIVES: We examined the association between anogenital human papillomavirus (HPV) infection and sexual networks in men who have sex with men (MSM). METHODS: A total of 253 MSM, 20 years of age and older, were recruited from the community in Southern Taiwan in 2015-2016. At baseline and at each follow-up visit, MSM were screened for HPV to identify 37 HPV genotypes. At the six-month follow-up, MSM were asked to fill out an egocentric network assessment and to report the last five persons with whom they had sex regarding the characteristics of sexual behavior with each network member. RESULTS: A total of 182 participants (71.9%) returned for the follow-up and one third had at least one HPV type detected. A higher level of bridging network position calculated by the level of constraints in the network was significantly less likely to have HPV detection at the anal site. A high level of concurrency was associated with penile HPV detection (AOR = 3.16, 95% CI = 1.01-9.86). CONCLUSIONS: Identifying network-related characteristics can advance our understanding of high-risk populations and for prioritizing HPV vaccine recommendations.

Polymorphic variants in DC-SIGN, DC-SIGNR and SDF-1 in high risk seronegative and HIV-1 patients in Northern Asian Indians.

A single nucleotide polymorphism (SNP) in SDF-1, the natural ligand for the HIV-1 coreceptor CXCR4, is implicated to have protective effects against HIV-1 infection. Dendritic cells are the first to encounter HIV-1 at mucosal sites and virus binding occurs via receptors known as DC-SIGN. Variations in the number of repeats in the neck region of DC-SIGN and DC-SIGNR are reported to possibly influence host susceptibility to HIV-1 infection. We examined the SNP of SDF1-3'A by PCR-restriction fragment length polymorphism (RFLP) and repeat region polymorphisms in DC-SIGN and DC SIGNR by PCR in healthy HIV seronegative individuals, high risk STD patients seronegative for HIV, and HIV-1 seropositive patients from northern India. The detected polymorphisms were confirmed by cloning and sequencing. The genotypic frequency of SDF1-3'A/SDF1-3'A in the 100 HIV-seronegative healthy individuals, 150 HIV seronegative STD patients, and 100 HIV-1 seropositive patients were 4%, 18% and 7%, respectively. A significantly higher frequency of SDF1-3'A/SDF1-3'A was observed in high risk STD patients as compared to HIV seropositive (p=0.014) and healthy HIV-1 seronegative tested individuals (p=0.001), suggesting a protective role of SDF1-3'A in HIV-1 infection. DC-SIGN polymorphism was rare and genotype 7/7 was predominant in all groups studied. DC-SIGNR was highly polymorphic and 11 genotypes were observed among the different study groups. The precise role of the polymorphic variants of DC-SIGNR needs to be elucidated in the population.

Human papillomavirus in HNSCC: recognition of a distinct disease type.

Strong epidemiologic and molecular data now support the conclusion that human papillomavirus (HPV) infection is responsible for a distinct form of head and neck squamous cell carcinoma (HNSCC), independent from the traditional risk factors of tobacco and alcohol use. Patients with HPV-positive HNSCC have a different clinical presentation and better clinical outcomes than those with HPV-negative HNSCC. A diagnosis of HPV-positive HNSCC is associated not only with therapeutic relevance, but also has important implications for future prevention and screening strategies.

First report of sexually transmitted multi-drug resistant Shigella sonnei infections in Switzerland, investigated by whole genome sequencing.

Shigella sonnei causes foodborne infections, but has recently also been described as a sexually transmitted infection (STI), with increased levels of antimicrobial resistance. We describe three cases of sexually acquired Shigella sonnei infection - the first report of this emerging infection in Switzerland. We used in-house whole genome sequencing (WGS) to investigate possible transmission routes and epidemiological correlations between the three cases. The genomic analysis demonstrated that two of three case isolates were very closely related, with only two single nucleotide polymorphism differences between them, despite being isolated from two unrelated patients at time-points six months apart, and the infections having been acquired at different geographic locations within Europe. All three isolates were found to fall within two of the clusters (1 and 7) defined within UK men who have sex with men (MSM) isolate populations, but with higher divergence, suggesting a more diverse pool circulating within Europe. Phenotypic testing confirmed the genotypic findings, with all three isolates azithromycin resistant, and two out of three resistant to quinolones. This report underlines the importance of the implementation of new sequencing technologies in the investigation of epidemiological aspects of this STI circulating in the population of MSM. In such cases, therapy should always be guided by antimicrobial susceptibility testing owing to increasing resistances. Greater awareness of this emerging sexually transmitted infection is needed.

Nonpaternity and Half-Siblingships as Objective Measures of Extramarital Sex: Mathematical Modeling and Simulations.

BACKGROUND: Understanding the epidemiology of HIV and other sexually transmitted infections (STIs) requires knowledge of sexual behavior, but self-reported behavior has limitations. We explored the reliability and validity of nonpaternity and half-siblings ratios as biomarkers of current and past extramarital sex. METHODS: An individual-based Monte Carlo simulation model was constructed to describe partnering and conception in human populations with a focus on Sub-Saharan Africa (SSA). The model was parameterized with representative biological, behavioral, and demographic data. RESULTS: Nonpaternity and half-siblings ratios were strongly correlated with extramarital sex, with Pearson correlation coefficients (PCC) of 0.79 (95% CI: 0.71-0.86) and 0.77 (0.68-0.84), respectively. Age-specific nonpaternity ratios correlated with past extramarital sex at time of conception for different scenarios: for example, PCC, after smoothing by moving averages, was 0.75 (0.52-0.89) in a scenario of steadily decreasing nonmarital sex and 0.39 (0.01-0.73) in a scenario of transient drops in nonmarital sex. Simulations assuming self-reported levels of extramarital sex from Kenya yielded nonpaternity levels lower than global nonpaternity data, suggesting sizable underreporting of extramarital sex. CONCLUSIONS: Nonpaternity and half-siblings ratios are useful objective measures of extramarital sex that avoid limitations in self-reported sexual behavior.

Family history as a risk factor for development of uterine leiomyomas. Results of a pilot study.

OBJECTIVE: To determine (1) the association between maternal history of leiomyomas and those in women under the age of 50, and (2) the ability of subjects to report a family history of leiomyomas. STUDY DESIGN: We performed a hospital-based, case-control study. The cases were women with pathologically confirmed leiomyomas, and the controls were women with no leiomyomas after pathologic examination of the uterus or by transvaginal ultrasonography. All women were sent a questionnaire regarding potential risk factors for the development of leiomyomas. RESULTS: Eighty-one of 169 (47.9%) cases and 103 of 214 (48.1%) of controls completed the questionnaire. By multiple logistic regression, significant risk factors for the presence of leiomyomas were maternal history (odds ratio = 2.85, confidence intervals 1.25-6.52) and reduced parity (odds ratio = 0.75, confidence intervals .57-.98). Increasing age was nearly significant as a risk factor (odds ratio = 1.07, confidence intervals 1.00-1.15). Of the subjects, 24% did not know the maternal history of leiomyomas, while 29% and > 50% were not aware of this history in a sister or grandmother, respectively. Extended family histories of leiomyomas could not be ascertained by this questionnaire-based study. CONCLUSION: Our results suggest that a maternal history of leiomyomas might be the largest risk factor for development of leiomyomas in a largely Caucasian population of women. Further studies are needed to better understand the possible genetic contribution to the development of uterine leiomyomas. Given the ascertainment bias inherent in second-hand maternal histories, future studies should assess maternal leiomyoma presence by ultrasonographic or pathologic evaluation.

The chromosomes of the transmissible venereal tumour of dogs in Ibadan, Nigeria.

Cytogenetic studies on 11 transmissible venereal tumours in seven dogs in Ibadan, Nigeria, are reported. The number and the morphology of the chromosomes, as shown by the metaphase cells, revealed that the tumour cells have similar cytogenetic features to those reported in other parts of the world. The suggestion of common sources of infection for the animals in the different geographical locations of the world was supported.