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Objective: Do metabolites in vaginal samples vary between women with different vaginal disorders.Design: Cross-sectional study.Setting: Campinas, Brazil.Sample: Seventy-seven women (39.9%) with no vaginal disorder, 52 women (26.9%) with vulvovaginal candidiasis (VVC), 43 women (22.3%) with bacterial vaginosis (BV), and 21 women (10.9%) with cytolytic vaginosis (CTV).Method: Concentrations of D- and L-lactic acid, extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinase-8 (MMP-8), and the influence of Candida albicans on EMMPRIN production by cultured vaginal epithelial cells, were determined by enzyme-linked immunosorbent assay (ELISA). Associations were determined by the Mann-Whitney U-test and by Spearman's rank correlation test.Main Outcome Measures: Metabolite levels and their correlation with diagnoses.Results: Vaginal concentrations of D- and L-lactic acid were reduced from control levels in BV (P < 0.0001); L-lactic acid levels were elevated in CTV (P = 0.0116). EMMPRIN and MMP-8 concentrations were elevated in VVC (P < 0.0001). EMMPRIN and L-lactic acid concentrations (P ≤ 0.008), but not EMMPRIN and D-lactic acid, were correlated in all groups. EMMPRIN also increased in proportion with the ratio of L- to D-lactic acid in controls and in women with BV (P ≤ 0.009). Concentrations of EMMPRIN and MMP-8 were correlated in controls and women with VVC (P ≤ 0.0002). Candida albicans induced EMMPRIN release from vaginal epithelial cells.Conclusions: Vaginal secretions from women with BV are deficient in D- and L-lactic acid, women with VVC have elevated EMMPRIN and MMP-8 levels, and women with CTV have elevated L-lactic acid levels. These deviations may contribute to the clinical signs, symptoms, and sequelae that are characteristic of these disorders. [ABSTRACT FROM AUTHOR]

Purpose: To investigate associations between bacterial species in the vagina in mid-trimester pregnant women from Brazil., Methods: The vaginal microbiome in 613 subjects was identified by analysis of the V1-V3 region of bacterial 16S ribosomal RNA and the relative prevalence of individual bacteria were determined., Results: The bacterial species present in the greatest number of women were Lactobacillus crispatus (306 women), L. iners (298 women) and Gardnerella vaginalis (179 women). When present in the vagina, L. crispatus was the most abundant bacterium more than 85% of the time. In contrast, L. iners and G. vaginalis were most abundant in 63% and 41% of women who were positive for these microorganisms, respectively (p < 0.0001 vs. L. crispatus). The proportion of L. crispatus was negatively associated with the proportions of L. iners, L. jensenii, L. gasseri, G. vaginalis, Megasphaera, Atopobium vaginae and Prevotella (p < 0.0001). In contrast, the proportion of G. vaginalis was positively associated with levels of Megasphaera, A. vaginae and Prevotella (p < 0.0001) while L. iners proportion was unrelated to the proportion of L. jensenii, G. vaginalis, Megasphaera, A. vaginae or Prevotella., Conclusion: The composition of the vaginal microbiota in mid-trimester pregnant women is influenced by the relative concentrations of L. crispatus, L. iners and G. vaginalis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Pelvic Inflammatory Disease is a topic included in the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. Pelvic inflammatory disease is an upper female genital tract acute infection due to canalicular spread of endogenous cervicovaginal microorganisms and especially the sexually transmitted microorganisms. Standing out among the etiological agents involved are Chlamydia trachomatis and Neisseria gonorrhoeae. The main sequelae are chronic pelvic pain, infertility, and ectopic pregnancy. Clinical diagnosis is the most important practical approach. Antibiotic treatment must start immediately after the clinical suspicion. Guidelines for health service managers and health professionals on diagnostic tests, treatment, follow-up, counseling, notification, handling sexual partners and special populations are described. Given the increased availability of the molecular biology techniques in Brazil, C. trachomatis and N. gonorrhoeae screening are recommended as a disease prevention strategy. Pelvic inflammatory disease is one of the most significant sexually transmitted infections, and in most cases, it is a main consequence of cervicitis.

Objective: To determine the presence and identity of extracellular bacteriophage (phage) families, genera and species in the vagina of pregnant women., Design: Descriptive, observational cohort study., Setting: São Paulo, Brazil., Population: Pregnant women at 21-24 weeks' gestation., Methods: Vaginal samples from 107 women whose vaginal microbiome and pregnancy outcomes were previously determined were analysed for phages by metagenomic sequencing., Main Outcome Measures: Identification of phage families, genera and species., Results: Phages were detected in 96 (89.7%) of the samples. Six different phage families were identified: Siphoviridae in 69.2%, Myoviridae in 49.5%, Microviridae in 37.4%, Podoviridae in 20.6%, Herelleviridae in 10.3% and Inviridae in 1.9% of the women. Four different phage families were present in 14 women (13.1%), three families in 20 women (18.7%), two families in 31 women (29.1%) and one family in 31 women (29.1%). The most common phage species detected were Bacillus phages in 48 (43.6%), Escherichia phages in 45 (40.9%), Staphylococcus phages in 40 (36.4%), Gokushovirus in 33 (30.0%) and Lactobacillus phages in 29 (26.4%) women. In a preliminary exploratory analysis, there were no associations between a particular phage family, the number of phage families present in the vagina or any particular phage species and either gestational age at delivery or the bacterial community state type present in the vagina., Conclusions: Multiple phages are present in the vagina of most mid-trimester pregnant women., Tweetable Abstract: Bacteriophages are present in the vagina of most pregnant women., (© 2020 John Wiley & Sons Ltd.)

Objectives: Short cervical length is a predictor of preterm birth. We evaluated if there were racial differences in variables associated with cervical length in pregnant Brazilian women., Methods: Cervical length was determined by vaginal ultrasound in 414 women at 21 weeks gestation. All women were seen at the same clinic and analyzed by the same investigators. Women found to have a short cervix (≤25 mm) received vaginal progesterone throughout gestation. Composition of the vaginal microbiome was determined by analysis of the V1-V3 region of the gene coding for bacterial 16S ribosomal RNA. Demographic, clinical and outcome variables were determined by chart review. Subjects were 53.4% White, 37.2% mixed race and 9.4% Black., Results: Pregnancy, medical history and education level were similar in all groups. Mean cervical length was shorter in Black women (28.4 mm) than in White (32.4 mm) or mixed race (32.8 mm) women (p≤0.016) as was the percentage of women with a short cervix (23.1, 12.2, 7.8% in Black, White, mixed race respectively) (p≤0.026). Mean cervical length increased with maternal age in White (p=0.001) and mixed race (p=0.045) women but not Black women. There were no differences in bacterial dominance in the vaginal microbiota between groups. Most women with a short cervix delivered at term., Conclusions: We conclude that Black women in Brazil have a shorter cervical length than White or mixed race women independent of maternal age, pregnancy and demographic history or composition of the vaginal microbiome., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Purpose: Factors influencing fallopian tube occlusion in women with a lower genital tract infection remain incompletely elucidated. We evaluated whether a polymorphism in the mannose-binding lectin (MBL) gene at codon 54 influences the occurrence of fallopian tube blockage in relation to exposure to Chlamydia trachomatis., Methods: In a case-control study at The Hospital das Clínicas, University of São Paulo, Brazil, 75 women with hysterosalpingography-documented tubal occlusion and 75 women with patent fallopian tubes were analyzed for detection of single-nucleotide polymorphism in codon 54 of the MBL gene and for IgG anti-C. trachomatis antibodies in their sera. Both groups were matched for age, race, and sexual variables., Results: Prior exposure to C. trachomatis, as evidenced by the presence of IgG antibodies, was comparable in both groups. Detection of the polymorphic MBL allele was more prevalent in women with blocked tubes (p < 0.01), regardless of whether or not there was evidence of prior chlamydial exposure., Conclusion: The level of MBL-related innate immunity influences the consequences of infection by C. trachomatis or other microbes.

Background: The repair of the immature squamous epithelium following HPV infection may mimic HSIL in adolescent women., Aim: to study the utility of p16 INK4a and Ki-67 in diagnosis of cervical squamous lesions in adolescents and young adults., Materials and Methods: In a cross-sectional study, the evaluation of p16 INK4a and Ki-67 immunohistochemistry was performed on 72 cervical biopsies of adolescents and young adults women diagnosed as negative for malignancy and intraepithelial lesion (NML) (n = 18) or positive for low grade (LSIL) (n = 31) and high grade (HSIL) (n = 23) squamous intraepithelial lesions in two references services in Fortaleza-Brazil. Data was evaluated using Fisher's test and Kappa index., Results: p16 INK4a was positive in 81% of HSIL, 19% of LSIL and in no NML (P < 0.0001). Ki-67 was positive in 74%, 32% and 5.5% of HSIL, LSIL and NML, respectively. p16 INK4a and Ki-67 in the diagnosis of HSIL showed high sensitivity and negative predictive value. Kappa index was very good for p16 INK4a (k = 0.72)., Conclusions: In adolescents and young adults p16 INK4a alone or with Ki-67 represents important tool to reduce mistaken diagnosis of HSIL and to avoid overtreatment.

Objective: The influence of functional polymorphisms in the genes coding for mannose-binding lectin (MBL) and interleukin-1 receptor antagonist (IL-1ra) on recurrent vulvovaginal candidiasis (RVVC) were examined in an urban Brazilian population., Methods: DNA was isolated from buccal swabs of 100 women with RVVC and 100 control women and tested by gene amplification for a single nucleotide polymorphism in codon 54 of the MBL2 gene and for a length polymorphism in intron 2 of the IL1RN gene. Genotype and allele frequencies were compared between groups., Results: The frequency of the variant MBL2 B allele, associated with reduced circulating and vaginal MBL concentrations, was 27.0% in RVVC and 8.5% in control women (p < .0001). The MBL2 B,B genotype was present in 12% of RVVC patients and 1% of controls (p = .0025). The IL1RN 2 allele frequency, associated with the highest level of unopposed IL-1β activity, was 24.0% in RVVC and 23.4% in controls. The IL1RN genotype distribution was also similar in both groups., Conclusion: Carriage of the MBL2 codon 54 polymorphism, but not the IL1RN length polymorphism, predisposes to RVVC in Brazilian women.

Problem: We evaluated associations between a length polymorphism in intron 2 of the gene coding for IL-1ra (gene symbol IL1RN) and pregnancy outcome in a population with a high rate of preterm birth., Method of Study: Subjects were pregnant women in Maceio, Brazil and their newborns. DNA was tested for IL1RN genotypes and alleles by gene amplification using primer pairs that spanned the polymorphic region. Every subject completed a detailed questionnaire., Results: The frequency of allele 2 (IL1RN*2) carriage was elevated in mothers with a spontaneous preterm birth (SPTB) in the current pregnancy (P = 0.02) and also with a prior preterm delivery (P = .01). Both SPTB with intact membranes (P = 0.01) and SPTB preceded by pre-term premature rupture of membranes (P = .03) were associated with ILlRN*2 carriage. A previous fetal demise was more than twice as prevalent in mothers positive for two copies of IL1RN*2., Conclusion: Maternal carriage of ILlRN*2 increases susceptibility to inflammation-triggered spontaneous pre-term birth.

Objective: To evaluate associations between polymorphisms in the gene coding for mannose-binding lectin (MBL) and the diagnosis of acute or recurrent vulvovaginal candidiasis and bacterial vaginosis, Methods: Women at two outpatient clinics in Brazil filled out a questionnaire and were examined for the presence of vulvovaginal candidiasis or bacterial vaginosis. A buccal swab was blindly tested for codons 54 and 57 MBL2 gene polymorphisms by polymerase chain reaction and endonuclease digestion., Results: A total of 177 women were enrolled. Vulvovaginal candidiasis was identified in 78 (44.1%) women, 33 (18.6%) had bacterial vaginosis, and 66 (37.3%) were normal controls. Recurrent vulvovaginal candidiasis was present in 50 (64.1%) of the women with vulvovaginal candidiasis; 20 (60.6%) of the bacterial vaginosis patients had recurrent disease. Vulvovaginal candidiasis was associated with white race (P=.007), bacterial vaginosis was associated with nonwhite race (P=.05), and both were associated with a history of allergy (P< or =.02) and having sexual intercourse at least three times a week (P<.001). Carriage of the variant MBL2 codon 54 allele B was more frequent in women with recurrent vulvovaginal candidiasis (25.0%) than in the women with acute vulvovaginal candidiasis (17.9%) or controls (10.6%) (P=.004). Allele B was also more prevalent in women with recurrent bacterial vaginosis (22.5%) than in those with acute bacterial vaginosis (0%) (P=.009). The MBL2 codon 57 polymorphism was infrequent and not associated with vulvovaginal candidiasis or bacterial vaginosis., Conclusion: The incidence of vulvovaginal candidiasis and bacterial vaginosis differs by ethnicity in Brazilian women. The MBL2 codon 54 gene polymorphism is associated with both recurrent vulvovaginal candidiasis and recurrent bacterial vaginosis.