Ureaplasma Urealyticum Research Articles

External quality assessment for molecular detection of Ureaplasma urealyticum in China

Background and aimsA pilot external quality assessment (EQA) scheme for molecular detection of Ureaplasma urealyticum (UU) was conducted by the National Center for Clinical Laboratories (NCCL) to evaluate the testing capabilities of clinical laboratories and the actual performance of DNA-based nucleic acid amplification tests (NAAT) and RNA-based NAATs when applied in clinical settings. Materials and methodsThe EQA panel contained twelve lyophilized samples, including positive samples containing inactivated cell culture supernatants of UU at different concentrations and sterile saline for negative samples. The positive samples were further divided into three groups of high, moderate and low concentrations. The panels were distributed to the participants and the datasets were analyzed according to the qualitative results. ResultsA total of 365 laboratories participated in the EQA scheme, and 360 results submitted by 338 laboratories were collected, of which 96.11 % (346/360) of the returned results and 95.86 % (324/338) of the laboratories were deemed competent. The positive percentage agreement (PPA) was ≥ 97.5 % for high and moderate concentration samples, but varied significantly for low concentration samples, decreasing from 86.94 % to 51.94 % as the sample concentration decreased. Additionally, for low concentration samples, RNA-based NAAT showed higher PPAs than DNA-based NAATs, but these results were specific to UU supernatants used in this study. ConclusionMost of UU detection assays employed by the participants were generally consistent with their estimated limit of detection (LOD), and the majority of participants can reliably detect UU samples with high and moderate concentrations, while the poor analytical performance for low concentration samples requires further improvement and optimization.

Impact of Genital Infections and Antibiotic Use on Incidence of Preterm Birth: A Retrospective Observational Study.

This study investigates the complex interplay among genital infections, antibiotic usage, and preterm birth. This study aims to identify common genital pathogens associated with preterm births, assess the impact of various antibiotic treatments on pregnancy outcomes, and understand antibiotic resistance patterns among these pathogens. This study included 71 pregnant women who experienced preterm birth and 94 women with genital infections who delivered at term. Various maternal characteristics, medical history, signs and symptoms, gestational weight, gestational age, type of birth, vaginal pH, Nugent scores, and vaginal flora were analyzed. Antibiotic resistance patterns of isolated microorganisms were also examined. The prevalence of sexually transmitted diseases (STDs) and genital herpes was significantly higher in the preterm group. Preterm births were associated with fever, pelvic pain, vaginal spotting, and fatigue. Vaginal pH levels and Nugent scores were significantly higher in the preterm group, indicating disturbed vaginal flora. The presence of Extended-Spectrum Beta-Lactamases (ESBLs) was a particularly strong risk factor, increasing by more than four times the odds of preterm birth (OR = 4.45, p = 0.001). Vancomycin-Resistant Enterococci (VRE) presence was another critical factor, with a four-fold increase in the odds of preterm birth (OR = 4.01, p = 0.034). The overall presence of Multidrug-Resistant (MDR) organisms significantly increased the odds of preterm birth (OR = 3.73, p = 0.001). Specific pathogens like Chlamydia trachomatis (OR = 3.12, p = 0.020) and Mycoplasma hominis (OR = 3.64, p = 0.006) were also identified as significant risk factors. Ureaplasma urealyticum also showed a significantly higher risk of preterm birth (OR = 2.76, p = 0.009). This study highlights the importance of screening for and treating genital infections during pregnancy, especially STDs and genital herpes, as they can significantly increase the risk of preterm birth. Additionally, the presence of specific microorganisms and antibiotic resistance patterns plays an essential role in preterm birth risk. Early detection and targeted antibiotic treatment may help mitigate this risk and improve pregnancy outcomes.

Analysis of Vaginal Microbiota Variations in the Third Trimester of Pregnancy and Their Correlation with Preterm Birth: A Case-Control Study.

This study conducted a detailed analysis of the vaginal microbiota in pregnant women to explore its correlation with preterm birth (PTB) outcomes. The primary objective was to identify microbial variations associated with increased PTB risk. Secondary objectives included investigating how changes in microbial composition relate to the local immune environment and PTB. Utilizing a retrospective case-control design, the study involved pregnant women with liveborn infants between 2019 and 2023. In total, 89 women who delivered preterm and 106 term deliveries were included. Data collection focused on third-trimester vaginal cultures. Statistically significant differences were observed between the preterm and full-term groups in several areas. The median white blood cell count (10.2 × 103/mm3 vs. 7.6 × 103/mm3, p = 0.009) and neutrophil count (7.2 × 103/mm3 vs. 5.1 × 103/mm3, p < 0.001) were higher in the preterm group. Vaginal pH was also elevated in preterm births (5.6 vs. 4.4, p < 0.001), with a higher prevalence of bacterial vaginosis (29.2% vs. 12.3%, p = 0.001) as indicated by the Nugent Score. The study noted a significant association of PTB with the presence of Candida spp. (OR = 1.84, p = 0.018), Gardnerella vaginalis (OR = 2.29, p = 0.003), Mycoplasma hominis (OR = 1.97, p = 0.007), and Ureaplasma urealyticum (OR = 2.43, p = 0.001). Conversely, a reduction in Lactobacillus spp. correlated with a decreased PTB risk (OR = 0.46, p = 0.001). The study provides compelling evidence that specific vaginal microbiota components, particularly certain pathogenic bacteria and an altered Lactobacillus profile, are significantly associated with PTB risk. These findings highlight the potential of targeting microbial factors in strategies aimed at reducing PTB rates. Further research is necessary to fully understand the complex interplay between microbial dynamics, host immunity, and PTB outcomes.

Membrane inflammasome activation by choriodecidual Ureaplasma parvum infection without intra-amniotic infection in a Non-Human Primate model†.

Intrauterine infection is a significant cause of neonatal morbidity and mortality. Ureaplasma parvum is a microorganism commonly isolated from cases of preterm birth and preterm premature rupture of membranes (pPROM). However, the mechanisms of early stage ascending reproductive tract infection remain poorly understood. To examine inflammation in fetal (chorioamnionic) membranes we utilized a non-human primate (NHP) model of choriodecidual U. parvum infection. Eight chronically catheterized pregnant rhesus macaques underwent maternal-fetal catheterization surgery at ~105-112 days gestation and choriodecidual inoculation with U. parvum (105 CFU/mL, n =4) or sterile media (controls; n = 4) starting at 115-119 days, repeated at 5-day intervals until C-section at 136-140 days (term=167 days). The average inoculation to delivery interval was 21 days, and Ureaplasma infection of the amniotic fluid (AF) was undetectable in all animals. Choriodecidual Ureaplasma infection resulted in increased fetal membrane expression of MMP-9 and PTGS2, but did not result in preterm labor or increased concentrations of AF pro-inflammatory cytokines. However, membrane expression of inflammasome sensors, NLRP3, NLRC4, AIM2, and NOD2, and adaptor ASC (PYCARD) gene expression were significantly increased. Gene expression of IL-1β, IL-18, IL-18R1 , CASPASE-1, and pro-CASPASE-1 protein increased with Ureaplasma infection. Downstream inflammatory genes MYD88 and NFκB (Nuclear factor kappa-light-chain-enhancer of activated B cells) were also significantly upregulated. These results demonstrate that choriodecidualUreaplasma infection, can cause activation of inflammasome complexes and pathways associated with pPROM and preterm labor prior to microbes being detectable in the AF.

Molecular Detection of Ureaplasma Urealyticum in Pregnant Woman Suffering from Urinary Tract Infection

Mycoplasma is a genus of bacteria that lack a cell wall, The present study was designed to identify the Ureaplasma urelyticium which causes the pregnant women suffering uti. The study included 200 samples of 150 pregnant women and 50 controls from the Bint Al-Huda teaching Hospital and Al-Haboubi teaching Hospital in the Thi-Qar provainc. The presence of the GPO gene in urine samples by using the PCR used as an indicator for mycoplasma colonization of urinary tract of pregnant, then the species was detected by DNA sequencing. in this study Regarding the GPO gene most of the cases were carry mycoplasmas and majority of the control groups expressing the positive results so that there was no significant statistical differences where (p value = 0.069). The present results recorded that the presence of about 94% homology between studied samples with Ureaplasma urelyticium sequences. Twenty-one, 12 and 6 genetic variations of 16SrRNA gene were identified in Mycoplasma hominis, Mycoplasma, ureaplasma urelyticium. Some variations were variably distributed in the majority of the studied samples. The study showed that the ureaplasma urelyticium.is an important cause of UTI in pregnant women in Iraqi population.

Orogenital and anal infection by Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and other sexually transmitted infections in men who have sex with men in Lisbon.

Men who have sex with men (MSM) are at risk for sexually transmitted infections (STIs), but more data on extragenital carriage are needed. We assessed the genital and extragenital prevalence of bacterial and other STIs in MSM in a Lisbon sexual health clinic. We screened oral, anal, and urine samples of MSM visiting the GAT-CheckpointLX clinic June 2017-December 2021 for Chlamydia trachomatis (including lymphogranuloma venereum, LGV), Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, Mycoplasma hominis, Ureaplasma urealyticum, and U. parvum. Ano-oro-genital lesions were tested for LGV, Treponema pallidum, and Herpes Simplex Virus. Blood was tested for HIV and T. pallidum antibodies. N. gonorrhoeae was found in 16.6% of the MSM followed by C. trachomatis (13.2%), M. genitalium (10.3%) and T. vaginalis (0.2%). The most frequent occurrence was anorectal (C. trachomatis, M. genitalium) and oral (N. gonorrhoeae). We found high carriage of U. urealyticum (36.1%) and M. hominis (22.1%). LGV was detected in 21.8% of chlamydia-positive anorectal swabs. Syphilis was detected in 22.6% of tested MSM, while 13.8% had HIV. Gonorrhoea and chlamydia were significantly more prevalent in MSM with concomitant HIV or syphilis. The substantial extragenital prevalence of bacterial STIs in MSM, and HIV and syphilis coinfections, suggest screening has value in identifying hidden carriage and in contributing for providing better care.

Association between Ureaplasma urealyticum colonization and bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis.

Bronchopulmonary dysplasia (BPD) is the most prevalent chronic lung disease in preterm infants. Studies have shown that Ureaplasma urealyticum (UU) infection is linked to its pathogenesis. However, it remains controversial whether UU colonization in preterm infants increases the risk of developing BPD. This study aimed to conduct a systematic review and meta-analysis to summarize the correlation between UU and BPD. We searched PubMed, Embase, the Cochrane Library, Web of Science, Wanfang Database, Chinese National Knowledge Infrastructure Database, Chinese Science and Technique Journal Database, and the China Biology Medicine disc from their inception to March 15, 2024. We included cohort and case-control studies investigating the association between UU infections and BPD in preterm infants, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Newcastle-Ottawa Scale was used for quality assessment. The outcome was defined as the continued need for oxygen or respiratory support at 28 days after birth (BPD28) or at 36 weeks postmenstrual age (BPD36). Considering the potential publication bias in observational studies, we used a random-effects meta-analysis model, assessed heterogeneity (I2), performed subgroup analyses, evaluated publication bias, and graded the quality of evidence. The meta-analysis included 36 cohort studies encompassing 5,991 participants. Among these, 20 reported on BPD28, 13 on BPD36, and 3 on both. The results indicated a significant association between UU colonization and BPD28 (odds ratio (OR): 2.26, 95% confidence interval (CI): 1.78-2.85, P < 0.00001, 23 studies, very low certainty of evidence) and BPD36 (OR: 2.13, 95% CI: 1.47-3.07, P < 0.0001, 16 studies, very low certainty of evidence). There is a correlation between UU colonization and the development of BPD in preterm infants. Future research should prioritize well-designed, large-scale, high-quality randomized controlled trials (RCTs) to comprehensively assess the risk of BPD in neonates following UU infection and to provide stronger evidence for clinical screening and prevention strategies to improve the prognosis of affected newborns. https://www.crd.york.ac.uk/, identifier (CRD42024524846).

Study on Drug Resistance to Treatment for Ureaplasma Urealyticum Infections in the Female Genital Tract.

Ureaplasma urealyticum (U. urealyticum) commonly occurs in female genitourinary infections, and its different biovars and serotypes have varying degrees of resistance to different antibiotics. This study aimed to ex-plore the characteristics of U. urealyticum infection and drug-resistant profiles in Chinese females. We included 1,045 females with genital tract infections who visited Tangshan Workers' Hospital and Tangshan Maternal and Child Health Center from September 2017 to December 2018. The bacteria were selectively cultured, and drug sensitivity experiments were conducted. Eight pairs of oligonucleotide primers were designed, and polymerase chain reaction (PCR) was performed to amplify specific DNA fragments to perform bacterial strain typing. Among the 1,045 participants included, 566 (54.11%) participants were positive for mycoplasma infection. There were 432 (41.34%) participants with U. urealyticum infection, accounting for 76.33% of the positive participants. The infection rate of U. urealyticum was the highest in females who were 21 - 30 years old, followed by those who were 31 - 40 years old. Ureaplasma urealyticum showed the highest sensitivity to tetracyclines and the greatest resistance to quinolones. The biovar 1 of U. urealyticum with the highest detection rate of serotype 4, accounted for 66.88%. The biovar 2 of U. urealyticum mainly showed mixed subtypes 2 and 3. Biovar 2 showed higher resistance to sparfloxacin, clarithromycin, josamycin, and doxycycline than biovar 1. Women might be more susceptible to U. urealyticum, especially if they are of childbearing age. Urea-plasma urealyticum is mainly caused by a single serotype 6 infection. The resistance of U. urealyticum to quinolone (e.g., norfloxacin) is a great concern. Sparfloxacin, clarithromycin, ciprofloxacin, and doxycycline might be more suitable for people with biovar 1 infection. Biotyping may facilitate clinical drug use and help avoid the emergence of drug-resistant strains.

Ureaplasma urealyticum as a Cause of Ventriculitis in an Extremely Low Birth Weight Infant

Abstract Ureaplasma urealyticum (Uu) has rarely been described as a cause of ventriculitis in preterm infants. We report a preterm infant in whom Uu was detected in the tracheal secretion. Concurrent intraventricular hemorrhage III° with posthemorrhagic hydrocephalus occurred, necessitating the bilateral insertion of ventriculostomy access devices for treatment. Persisting high cerebrospinal fluid (CSF) protein and pleocytosis in the otherwise clinically unremarkable neonate subsequently led to the targeted detection of Uu in the CSF. Normalization of CSF parameters occurred only after prolonged intravenous and oral macrolide therapy.

2023 Korean sexually transmitted infections guidelines for non-gonococcal bacterial infection (chlamydia, syphilis, etc.) by the Korean Association of Urogenital Tract Infection and Inflammation.

Non-gonococcal sexually transmitted infections (STIs) include chlamydia, syphilis, and chancroids. Chlamydia is the most common STI caused by Chlamydia trachomatis and is mainly transmitted through sexual intercourse or vertical transmission at birth. Although symptoms are mostly absent or mild, untreated chlamydial infections in females can lead to pelvic inflammatory disease, chronic pelvic pain, and infertility due to the narrowing of fallopian tubes. Syphilis is caused by Treponema pallidum and is divided into phase I, phase II, latent syphilis, and phase III. The incidence of syphilis, including congenital syphilis, has significantly increased in the United States in recent years. The chronic status of this disease can significantly increase morbidity and potentially affect almost all body organs, which, in rare cases, can lead to death. Additionally, untreated maternal syphilis can lead to fetal death and fatal congenital infections in newborns. Chancroid is an STI caused by Haemophilus ducreyi, and its prevalence is gradually decreasing in Korea and worldwide. The symptoms include shallow genital ulcers with suppurative granulomatous inflammation and tender inguinal lymphadenopathy. Chancroids can be differentiated from syphilitic chancres based on their appearance. In contrast to painless chancres, chancroids are painful. Ureaplasma urealyticum, Ureaplasma parvum, and Mycoplasma hominis are considered symbiotic bacteria. Infections caused by these bacteria are usually not considered STIs and do not require treatment unless they are suspected of being associated with infertility. This article presents the 2023 Korean STI guidelines for non-gonococcal bacterial infections.

Стан мікробіоти піхви і матки в жінок із безпліддям та внутрішньоматковою патологією

This article examines the features of microbiocenosis of the vagina and endometrium in women with infertility and intrauterine pathology. Purpose - to study the peculiarities of the spectrum of microorganisms of the vagina and endometrium in women with infertility and intrauterine pathology in order to increase the effectiveness and prevention of complications of hysteroscopic interventions in such women. Materials and methods. An examination and dynamic observation of women was carried out for 6 months. The results of clinical-morphological, ultrasound, immunohistochemical and bacteriological monitoring are included. All patients underwent diagnostic and therapeutic hysteroscopy followed by bacteriological, morphological and immunohistochemical examination. Results. The study of quantitative indicators and species composition of the microbial flora of the uterine endothelium in women with infertility and intrauterine pathology showed a much wider spectrum of pathogenic and opportunistic microorganisms. Among the detected microorganisms are Esherichia coli (4%), Staphylococcus aureus (6%), Streptococcus B (2%), Lactobacillus spp. (2%). In a much larger number of women, pathogens of sexually transmitted infections were noted - Chlamydia trachomatis (12%), Mycoplasma hominis (14%), Ureaplasma urealyticum (10%). Obviously, one of the causes of the inflammatory process in the endometrium of the uterus is the imbalance of the microbiocenosis. Bacteriological research data showed a significant proportion of deviations in the vaginal biocenosis in the presence of intrauterine pathology, which is manifested by a significant decrease in the frequency of excretion of the main acid-forming lactobacilli compared to healthy patients. Thus, lactobacilli (21 strains) were detected in only 23 (46%) patients of the study group at a concentration of 6.2±1.1 lg CFU/ml, while in the control group - in 17 (85%) women at an average concentration of 6.8±1.2 lg CFU/ml. Conclusions. The obtained research results make it possible to determine the scientific position regarding the important role of an infectious factor in the development of intrauterine pathology, and the normalization of the microbiota of the genital tract is not only an important component of the treatment of hyperplastic processes, but also contributes to the prevention of possible relapses, the treatment of morphofunctional disorders in the endometrium of women with infertility. The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent of the women was obtained for the research. No conflict of interests was declared by the author.

The Adverse Outcomes of Chorioamnionitis on the Pregnant Female and Their Fetus

Introduction: Chorioamnionitis is an intra-amniotic infection caused by an ascending polymicrobial bacterial infection. Triple I (intrauterine inflammation or infection or both) is also proposed to replace chorioamnionitis due to its imprecise definition and variable clinical manifestations. Intraamniotic infection is characterized by inflammation of the amniotic fluid, placenta, fetus, fetal membranes, or decidua. Maternal fever, uterine tenderness, maternal tachycardia, fetal tachycardia, and purulent fluid coming from the cervical os (the cervical opening can be external, near the vagina, or internal, near the uterus) are the key clinical findings that are crucial for the diagnosis of clinical chorioamnionitis. Clinically, intra-amnionitic infections have been linked to severe morbidity and death in pregnant women, fetuses, and newborns. Method: A systematic search of PubMed, Embase, LitCovid, MedRxiv, BioRxiv, Google Scholar, EBSCO MEDLINE, CINAHL and Scopus electronic database was done using key words like Chorioamnionitis, adverse complication in pregnancy to mother and her fetus associated with intrauterine infection, Intraamniotic inflammation and triple I. Studies have been included from January 2015 to December 2022. Result: Chorioamnionitis is most typically caused by ascending infection and is frequently linked with premature membrane rupture. Chorioamnionitis is typically caused by a polymicrobial infection, with Ureaplasma urealyticum, Mycoplasma hominis, and Gram-negative anaerobes being common pathogens. Antimicrobial drugs, antipyretics, rapid treatment, and supportive care are the mainstays of management. Conclusion: Overall, this review provides a better understanding of Chorioamnionitis and its potential impact on public health. By shedding light on this emerging disease, we hope to contribute to ongoing efforts to prevent and treat of this serious disorder. Keywords: Chorioamnionitis, Intrauterine Infection, Pregnancy, adverse complication, Triple I, Intraamniotic Inflammation

Antimicrobial Activity of N,N-Diethyldithiocarbamate against Ureaplasma parvum and Ureaplasma urealyticum.

Ureaplasma species (Ureaplasma spp.) are commonly found as commensals in the human urogenital tracts, although their overgrowth can lead to infection in the urogenital tract and at distal sites. Furthermore, ureaplasmas lack a cell wall and do not synthesize folic acid, which causes all β-lactam and glycopeptide antibiotics, and sulfonamides and diaminopyrimidines, to be of no value. The antibiotics used in therapy belong to the fluoroquinolone, tetracycline, chloramphenicol and macrolide classes. However, the growing incidence of antibiotic-resistant Ureaplasma spp. in the population becomes a problem. Thus, there is a need to search for new drugs effective against these bacteria. Since 1951, the FDA-approved, well-tolerated, inexpensive, orally administered drug disulfiram (DSF) has been used in the treatment of chronic alcoholism, but recently, its antimicrobial effects have been demonstrated. The main biological metabolite of DSF, i.e., N,N-diethyldithiocarbamate (DDC), is generally believed to be responsible for most of the observed pharmacological effects of DSF. In the presented studies, the effect of DDC at concentrations of 2 µg/mL, 20 µg/mL and 200 µg/mL on the growth and survival of Ureaplasma urealyticum and Ureaplasma parvum was tested for the first time. The results indicated that all the used DDC concentrations showed both bacteriostatic and bactericidal activity against both tested strains.

The effect of seminal pathogens on standard semen parameters, sperm kinematics and seminal inflammatory markers

This study evaluated the effects of urogenital pathogens on standard semen parameters, sperm kinematics and host inflammatory response in a cohort of asymptomatic subfertile men. There were six groups based on the results of bacterial culture, including Ureaplasma urealyticum (U. Urealyticum) (n = 27), mixed comprising two or more pathogenic species (n = 28), Gardnerella Vaginalis (G. Vaginalis) (n = 15), gram-positive cocci and bacilli (g+cocci/bacilli) (n = 15), gram-negative bacilli (g-bacilli) (n = 10) and Chlamydia trachomatis (C. trachomatis) (n = 2). One control group (n = 20) and one leukocytospermic group (n = 10) were also included. Sperm quality parameters, seminal leukocytes and interleukin (IL)-6 of all groups, apart from C. trachomatis, were compared to the control group. Standard semen parameters were significantly worse in all groups except for that with g-bacilli. Progressive motility, total motility and normal sperm morphology demonstrated the most significant differences, when U. Urealyticum, leukocytospermia and mixed pathogens were detected in semen. Among sperm kinematics, the concentration of progressive motile sperm cells (CPMS), the percentage of progressive motile sperm cells (PPMS) and straightness (STR) were manifested significant declines in the presence of seminal pathogens. CPMS was affected in all groups except for G. vaginalis. Moreover, the presence of g+cocci/bacilli and g-bacilli were associated with increased seminal IL-6. Seminal leukocytes were elevated significantly only when g-bacilli were cultured in semen. We conclude that seminal pathogens can negatively affect sperm quality. The most negative effect is related to U. Urealyticum. Moreover, g+cocci/bacilli and g-bacilli can initiate an inflammatory response.

Structure, dynamics, and stability of the smallest and most complex 71 protein knot

Proteins can spontaneously tie a variety of intricate topological knots through twisting and threading of the polypeptide chains. Recently developed artificial intelligence algorithms have predicted several new classes of topological knotted proteins, but the predictions remain to be authenticated experimentally. Here, we showed by X-ray crystallography and solution-state NMR spectroscopy that Q9PR55, an 89-residue protein from Ureaplasma urealyticum, possesses a novel 71 knotted topology that is accurately predicted by AlphaFold 2, except for the flexible N terminus. Q9PR55 is monomeric in solution, making it the smallest and most complex knotted protein known to date. In addition to its exceptional chemical stability against urea-induced unfolding, Q9PR55 is remarkably robust to resist the mechanical unfolding-coupled proteolysis by a bacterial proteasome, ClpXP. Our results suggest that the mechanical resistance against pulling-induced unfolding is determined by the complexity of the knotted topology rather than the size of the molecule.

Genital tract infections, the vaginal microbiome and gestational age at birth among pregnant women in South Africa: a cohort study protocol

IntroductionPreterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving...

Role of Bacterial and Viral Infections and Co-Infections in Miscarriages

Abstract Aim To investigate the potential role of the following bacterial/viral panel (Chlamydia trachomatis, Ureaplasma urealyticum/parvum, Mycomplasma hominis/genitalium, Gardnerella vaginalis, HSV1/2, EBV, CMV, VZV, HHV6, HHV7, HHV8) as causative factors for miscarriages in women by testing endometrial biopsies. Anaerobic and aerobic microorganisms causing dysbiosis and endometrial bacterial colonization by unbalanced growth were additionally tested. Materials and methods In total, 65 patients with a history of early and late miscarriages were analyzed. DNA extractions, real-time qPCR, agarose gel-electrophoresis were applied. Comparative analysis of the current with previously obtained data on the described panel in menstrual tissue samples was performed. Results In 64,6% of all tested endometrial biopsies bacterial and/or viral pathogens were detected. In 49,23% of all tested samples we found bacterial, while in 15,3% – viral pathogens. These results are similar to our previous data on menstrual tissue samples of infertile women – 61,1% infected, as 48,8% had bacterial and 22,2% had viral pathogens. Gardnerella vaginalis and Ureaplasma parvum were detected in 31,25% and 3,12% of all bacterial infected endometrial biopsies, significantly lower in comparison to the estimated rate of 69,31% and 61,36% on menstrual tissue. Anaerobic and aerobic dysbiosis were detected in 53,33% and 27% of the bacterial infected endometrial samples. In 13,33% a dysbiosis with a mixed etiology was found, while in 7% a dysbiotic condition with a totally absent findings of targeted bacteria and Lactobacillus was observed. EBV, CMV, HHV6 and HHV7 were detected in 30%, 30%, 20% and 20% of the positive for viral factors endometrial biopsies and in 40%, 7,5%, 10% and 42,5% in menstrual tissue samples. In the current study 62,5% bacterial co-infection and 12,5% bacterial/viral co-infection variants were found. Infections with the rest of the target pathogens were not detected in the endometrial biopsies. In contrast to the endometrial biopsy results, Mycomplasma hominis, Ureaplasma urealyticum and HSV2 were detected in our previous research on menstrual tissue samples. Conclusions Our research suggests a possible dysbiosis as a consequence of bacterial/viral endometrial colonization, associated with miscarriages. We prove that menstrual tissue, containing parts of the functional endometrial layer, is a reliable and accurate noninvasive sample for infectious screening of the upper genital tract.

Characteristics of common pathogens of urogenital tract among outpatients in Shanghai, China from 2016 to 2021.

Ureaplasma urealyticum, Chlamydia trachomatis, and Neisseria gonorrhoeae are the prevalent causes of several genital diseases worldwide; however, their characteristics in different genders have not been well documented in Shanghai. The aim of this study is to describe the prevalence of common pathogens among outpatients, considering variations by gender and age. From January 1, 2016, to December 31, 2021, the urogenital swabs of 16216 outpatients aged 3-95 years from two general hospitals in Shanghai were collected. All participants' swabs were investigated for U. urealyticum, C. trachomatis, and N. gonorrhoeae by isothermal RNA-based simultaneous amplification and testing. The basic information of all participants was also recorded, including age and gender. The chi-square test was used to compare the prevalence between different genders, age groups, and infection patterns. There were 5,744 patients (35.42%) with positive samples whose ages ranged from 7 to 80 years (33.23 ± 8.63 years), and 62.14% of them were women. The most common pathogen detected was U. urealyticum (85.08%). The highest prevalence rate of all three pathogens was found in patients aged ≤ 20 years (40.53%, 95% confidence intervals [CI]: 33.80%-47.63%). The prevalent rate of U. urealyticum was higher in men (33.36%, 95% CI: 32.19%-34.55%). The overall prevalence rates of U. urealyticum, C. trachomatis, and N. gonorrhoeae were 30.14% (95% CI: 29.44%-30.85%), 6.00% (95% CI: 5.64%-6.38%), and 2.10% (95% CI: 1.89%-2.33%). Ureaplasma urealyticum was the most prevalent pathogen in the population, and its prevalence decreased with age. Young men aged ≤ 20 years were more frequently infected. Regular screening for sexually transmitted pathogens in different genders and age groups are warranted, particularly in young men.

Seroepidemiology of Treponema pallidum, Mycoplasma hominis, and Ureaplasma urealyticum in fertility treatment-seeking patients in the Emirate of Abu Dhabi, United Arab Emirates

BackgroundSeveral genital pathogens affect fertility. The study estimated the seroprevalence of Treponema pallidum, Ureaplasma urealyticum, and Mycoplasma hominis and identify specific factors associated with exposure to at least one of these pathogens in patients seeking fertility treatment in the Emirate of Abu Dhabi, United Arab Emirates. MethodsA seroepidemiological survey was conducted in a major fertility clinic in the Emirate of Abu Dhabi. Serum samples were screened for eight immunoglobulins (IgG, IgM, and IgA) against T. pallidum, U. urealyticum, and M. hominis using enzyme-linked immunoassays. Factors associated with seropositivity to at least one of the pathogens were investigated. ResultsThe study surveyed 308 patients seeking fertility treatment (mean age: 36.1 ± 6.8 years). Most patients were female (88.0%), 24.9% had at least one chronic comorbidity, 19.3% had a previous genital infection, and 68.1% had been diagnosed with infertility for ≥ 6 months. Ig seroprevalence of T. pallidum (IgG: 3.0%, IgM: 3.2%), U. urealyticum (IgG: 2.6%, IgM: 2.0%), and M. hominis (IgG: 33.9%) was 6.4%, 4.6%, and 49.0%, respectively. Nearly one quarter (23.0%) and one decile (9.2%) of the patients exhibited evidence of ongoing infection (IgM seropositivity) or recent infection (IgA seropositivity) with M. hominis, respectively. Overall, 53.0% of the patients were seropositive for at least one of the screened immunoglobulins. Patients with an education level of secondary schooling or below (66.2%) or those who were unemployed (61.1%) had a higher seroprevalence of IgG antibodies compared with patients with college or higher-level education (48.4%) or those who were employed (48.1%) (p < 0.05). ConclusionExposure to T. pallidum or U. urealyticum was relatively low, whereas that to M. hominis was common in the surveyed patients. Enhanced awareness and screening programmes for genital pathogens are crucial to prevent and control the transmission of infections and reduce the growing burden of infertility.

Ureaplasma-Induced Hyperammonemia Syndrome - an Acute Complication Post Allogeneic Stem Cell Transplant

Hyperammonemia syndrome is characterized by elevated serum ammonia levels and neurological dysfunction due to cerebral encephalopathy, andcauses lethargy, confusion, hyperventilation, seizures, death. In solid organ transplantation, hyperammonemia syndrome has been reported as a potentially fatal complication secondary to Ureaplasma infection ( Ureaplasma urealyticum or parvum). We present a patient with acute lymphoblastic leukemia (ALL) who underwent allogeneic stem cell transplant (HSCT) and developed hyperammonemia syndrome during systemic infection with Ureaplasma urealyticum. A 32-year-old female with B-ALL received a haploidentical HSCT complicated by stage II acute GvHD of the gut and skin. During her hospital course, on Day +43, cellulitis of the right arm was diagnosed and treated empirically with amoxicillin-clavulanate on discharge. She presented back to the hospital on Day +53 with bilateral elbow pain and cellulitis. She had no focal neurological deficits initially but became increasing drowsy with dilated pupils. She had no episodes of sustained fever throughout her hospitalization. Empiric antimicrobial coverage with Meropenem and Vancomycin was given, and she was intubated and admitted to the ICU all on the same day. CT head was normal, and blood cultures and lumbar puncture were negative. She developed status epilepticus and her ammonia level increased to &amp;gt;1500 μmol/L on Day +57. Liver function, renal function and extended electrolytes remained within normal limits. MRI was consistent with hyperammonemic encephalopathy, prompting initiation of intermittent hemodialysis, lactulose, Rifaximin, and L-carnitine. EEG revealed no discernible rhythms, and intensive life support was discontinued on Day +61. PCR testing of preserved lung tissue confirmed Ureaplasma urealyticum as the likely cause. Ureaplasma infections can be a serious complication of HSCT. The hydrolysis of urea by U reaplasma leads to elevated serum ammonia levels when systemic infections occur in immunocompromised patients. HSCT patients often have hypogammaglobulinemia due to conditioning and immunosuppressive therapies with a reduced ability to neutralize Ureaplasma. The role of neutrophil in controlling Ureaplasma is limited, as antibody-mediated defence is the sole mechanism of protection. Other contributing factors that can exacerbate hyperammonemia include Valproic acid, severe liver disease, and TPN. Ureaplasma is challenging to diagnose due to limited growth on standard culture medium PCR testing is required for diagnosis and was the method of detection in our reported case. Numerous cases in non-HSCT immunocompromised populations have reported soft tissue infections involving Ureaplasma species, indicating a possible source for infection in the current case. Although there are no other reported cases of cellulitis and Ureaplasma infection in HSCT, a previous case with polyarthritic involvement may be mechanistically similar. A literature review was completed with results presented in Table 1 outlining details of reported cases with confirmed Ureaplasma infection post-HSCT. The cases were quite heterogenous although two of the cases were treated for Non-Hodgkin's Lymphoma where they were heavily pretreated with agents targeting B-Cells and immunoglobulin production. Empirical doxycycline should be considered first line due to the Ureaplasma resistance to other agents such as Azathioprine. Beta-lactam antibiotics and vancomycin have limited efficacy as Ureaplasma's does not have a cell wall. Adjunct therapies to reduce ammonia production and increase elimination should also be considered. Ureaplasma should be considered in immunocompromised patients in the context of fever of unknown origin and altered level of consciousness, especially if rising serum ammonia levels and soft tissue infections is present. The overall 50% mortality associated with the six cases presented demonstrates the significant risk associated with the infection.