Hormonal contraceptive use and Staphylococcus aureus nasal and throat carriage in a Norwegian youth population.
ABSTRACT: BACKGROUND:Use of hormonal contraceptives has been associated with Staphylococcus aureus nasal carriage in adult women. However, the role of hormonal contraceptives in S. aureus colonization among adolescents and associations with progestin only contraceptives are unknown. METHODS:We obtained nasal and throat swab samples from 439 girls aged 17-21 years in the population-based Tromsø study Fit Futures, 2012-2013, Norway, with information on lifestyle, health and biomarkers. We used multivariable logistic regression to study the association between use of hormonal contraceptives and Staphylococcus aureus carriage while adjusting for potential confounding factors. RESULTS:Staphylococcus aureus nasal carriage prevalence were 34%, 42%, and 61% among progestin-only users, non-users, and progestin-estrogen combination contraceptive users, respectively (P<0.001). Use of combination contraceptives doubled the odds of nasal carriage (non-users reference; OR = 2.31, 95%CI = 1.43-3.74). The OR of nasal carriage was 0.29 among progestin-only users compared to combination contraceptives users (95% CI = 0.12-0.67). DISCUSSION:In this study, use of combination hormonal contraceptives was associated with higher risk of Staphylococcus aureus nasal carriage in adolescent girls. Experimental design studies are needed to establish the role of exogenous sex steroids in Staphylococcus aureus colonization in women.
Project description:<h4>Objective</h4>Staphylococcus aureus is a major human pathogen, and nasal carriers have an increased risk for infection and disease. The exploration of host determinants for nasal carriage is relevant to decrease infection burden. Former studies demonstrate lower carriage prevalence in women and among users of progestin-only contraceptives. The aim of this study was to investigate the possible associations between circulating sex-steroid hormones and nasal carriage of Staphylococcus aureus in a general population.<h4>Methods</h4>In the population-based sixth Tromsø study (2007-2008) nurses collected nasal swab samples from 724 women aged 30-87 not using any exogenous hormones, and 700 of the women had a repeated nasal swab taken (median interval 28 days). We analysed a panel of serum sex-steroids by liquid chromatography tandem mass spectrometry, and collected information about lifestyle, health and anthropometric measures. Multivariable logistic regression was used to study the association between circulating sex-steroids and Staphylococcus aureus carriage (one swab) and persistent carriage (two swabs), while adjusting for potential confounding factors. Women in luteal phase were excluded in the analysis of androgens.<h4>Results</h4>Staphylococcus aureus persistent nasal carriage prevalence was 22%. One standard deviation increase in testosterone and bioavailable testosterone was associated with lower odds of persistent nasal carriage, (OR = 0.57; 95% CI = 0.35-0.92 and OR = 0.52, 95% CI = 0.30-0.92) respectively. Analysis stratified by menopause gave similar findings. Persistent carriers had lower average levels of androstenedione and DHEA, however, not statistically significant.<h4>Conclusion</h4>This large population-based study supports that women with lower levels of circulating testosterone may have increased probability of Staphylococcus aureus persistent carriage.
Project description:OBJECTIVE:To evaluate whether hormonal contraceptives, used before or in early pregnancy, confer increased risk of preterm birth or reduced fetal growth. DESIGN:Population-based cohort study conducted by the Norwegian Institute of Public Health (Mother and Child Cohort Study, 1998-2008) with linkage to the Norwegian Prescription Registry and to the Medical Birth Registry of Norway. SETTING:Norway. POPULATION:Of the 48,615 pregnancies meeting study inclusion criteria, 44,734 pregnancies were included in the complete case analysis. METHODS:We characterised hormonal contraception by type (combination oral, progestin-only oral, vaginal ring, transdermal, and injectable) and specific progestin component. We used generalised estimating equations to estimate the odds of adverse outcome according to formulation used. Several sensitivity analyses were conducted. MAIN OUTCOME MEASURES:Preterm birth, small for gestational age. RESULTS:We observed a positive association between use of a combination oral contraceptive and preterm birth for all exposure periods (e.g. adjusted odds ratio 1.21, 95% confidence interval 1.04-1.41 for last use 12 to >4 months before conception); combination contraceptives containing the progestin norethisterone were consistently related to risk. Other types of hormonal contraception were generally not associated with preterm birth; none were related to small for gestational age. Observed associations were robust to sensitivity analyses. CONCLUSION:Hormonally active agents may exert dose-, agent-, and timing-specific effects on growth and development. We found that the particular progestin component is important when assessing the potential for adverse effects among former users of hormonal contraceptives.
Project description:<h4>Background</h4>Obesity and diabetes mellitus (DM) have been linked to increased risk of infections, and Staphylococcus aureus nasal colonization is a major risk factor for developing infections with the microbe. We therefore sought to find whether body mass index (BMI) and waist circumference (WC) could be associated with S. aureus colonization independent of DM.<h4>Methodology</h4>S. aureus colonization was assessed by nasal swab cultures among 2,169 women and 1,709 men, aged 30-87 years, in the population-based Tromsø Staph and Skin Study in 2007-08. Height (cm), weight (kg), WC (cm), and glycated haemoglobin (HbA1c,%) were measured. Multivariable logistic regression analyses including information on DM, HbA1c, hormonal contraceptive use and other potential confounders were used.<h4>Results</h4>In the female population, each 2.5 kg/m(2) increase in BMI was associated with a 7% higher odds of S. aureus nasal colonization (P?=?0.01). When comparing obese and lean women aged 30-43 years, we observed that BMI ?32.5 versus <22.5 kg/m(2) and WC ?101 versus <80 cm was associated with a 2.60 and 2.12 times higher odds of S. aureus colonization, respectively (95% confidence intervals 1.35-4.98 and 1.17-3.85). Among men, high WC was also associated with S. aureus nasal colonization. The associations did not change significantly when the analysis was restricted to participants without signs of pre-diabetes (HbA1c <6.0%) among women and men, and to non-users of hormonal contraceptives among women.<h4>Conclusion</h4>Our results support that obesity is a possible determinant for S. aureus nasal colonization independent of DM, in particular for premenopausal women. The role of obesity at different ages and by sex should be addressed in future prospective studies of S. aureus colonization.
Project description:Staphylococcus aureus is a colonizing opportunistic pathogen and a leading cause of bloodstream infection with high morbidity and mortality. S. aureus carriage frequency is reportedly between 20 and 40?% among healthy adults, with S. aureus colonization considered to be a risk factor for S. aureus bacteraemia. It is unknown whether a genetic component of the bacterium is associated with S. aureus bacteraemia in comparison to nasal carriage strains. Previous association studies primarily focusing on the clinical outcome of an S. aureus infection have produced conflicting results, often limited by study design challenged by sample collections and the clonal diversity of S. aureus. To date, no study has investigated whether genomic features separate nasal carriage isolates from S. aureus bacteraemia isolates within a single clonal lineage. Here we have investigated whether genomic features, including single-nucleotide polymorphisms (SNPs), genes, or kmers, distinguish S. aureus nasal carriage isolates from bacteraemia isolates that all belong to the same clonal lineage [clonal complex 45 (CC45)] using whole-genome sequencing (WGS) and a genome-wide association (GWA) approach. From CC45, 100 isolates (50 bacteraemia and 50 nasal carriage, geographically and temporally matched) from Denmark were whole-genome sequenced and subjected to GWA analyses involving gene copy number variation, SNPs, gene content, kmers and gene combinations, while correcting for lineage effects. No statistically significant association involving SNPs, specific genes, gene variants, gene copy number variation, or a combination of genes was identified that could distinguish bacteraemia isolates from nasal carriage isolates. The presented results suggest that all S. aureus nasal CC45 isolates carry the potential to cause invasive disease, as no core or accessory genome content or variations were statistically associated with invasiveness.
Project description:Carriage of Staphylococcus aureus is a risk for infections. Targeted decolonization reduces postoperative infections but depends on accurate screening.To compare detection of S. aureus carriage in healthy individuals between anatomical sites and nurse- versus self-swabbing; also to determine whether a single nasal swab predicted carriage over four weeks.Healthy individuals were recruited via general practices. After consent, nurses performed multi-site swabbing (nose, throat, and axilla). Participants performed nasal swabbing twice-weekly for four weeks. Swabs were returned by mail and cultured for S. aureus. All S. aureus isolates underwent spa typing. Persistent carriage in individuals returning more than three self-swabs was defined as culture of S. aureus from all or all but one self-swabs.In all, 102 individuals underwent multi-site swabbing; S. aureus carriage was detected from at least one site from 40 individuals (39%). There was no difference between nose (29/102, 28%) and throat (28/102, 27%) isolation rates: the combination increased total detection rate by 10%. Ninety-nine patients returned any self-swab, and 96 returned more than three. Nasal carriage detection was not significantly different on nurse or self-swab [28/99 (74%) vs 26/99 (72%); ?2: P=0.75]. Twenty-two out of 25 participants with first self-swab positive were persistent carriers and 69/71 with first self-swab negative were not, giving high positive predictive value (88%), and very high negative predictive value (97%).Nasal swabs detected the majority of carriage; throat swabs increased detection by 10%. Self-taken nasal swabs were equivalent to nurse-taken swabs and predicted persistent nasal carriage over four weeks.
Project description:The natural history of contemporary Staphylococcus aureus nasal colonization was evaluated in community children during a 1-year period. Methicillin-susceptible S. aureus nasal carriage was more persistent than methicillin-resistant S. aureus nasal carriage, which was usually self-limited. Children with persistent staphylococcal colonization often carried identical strains. Identification of persistent methicillin-resistant S. aureus carriers might inform strategies for decolonization and reduction of staphylococcal transmission.
Project description:It remains unclear how the bacterial populations which colonise many healthy humans occasionally give rise to severe disease. Staphylococcus aureus represents one such population. Here we describe mutations in invasive S. aureus which arose during human colonisation and inactivated rsp, a transcription factor. RNA-Seq was used to generate mRNA profiles of genes controlled by rsp. Overall design: mRNA samples were sequenced in duplicates from Staphylococcus aureus strains isolated from two patients with concomitant nasal carriage and bloodstream infection as well as from USA300 wild type and USA300 NE1304 NARSA (Network on Antimicrobial Resistance in Staphylococcus aureus) strain.
Project description:Staphylococcus aureus is a human commensal bacterium found in the nasal cavity and other body sites. Identifying risk factors for S. aureus nasal carriage is of interest, as nasal carriage is a risk factor for subsequent invasive infection. We recently investigated the influence of host genetics on S. aureus carriage in Danish middle-aged and elderly twins, which indicated no significant heritability that could account for the observed S. aureus carriage. In the present study, we performed a questionnaire-based study of S. aureus colonization on the same cohort of 2,196 Danish middle-aged and elderly twins to identify specific risk factors for S. aureus nasal colonization, including analyzing the paired twins (n?=?478) that were discordant for S. aureus colonization. We found associations between risk factors and S. aureus nasal colonization among middle-aged and elderly twins, including age, male gender, psoriasis, and atopic diseases. Also, present living on a farm is clearly associated with S. aureus colonization, while smoking had a borderline statistically significant protective effect.
Project description:Epidemiological studies indicate that progestin-containing contraceptives may increase susceptibility to HIV and other infections; however, underlying mechanisms involving the upper female reproductive tract are undefined. To determine the effects of depot medroxyprogesterone acetate (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) on gene expression and physiology of the human endometrial and cervical transformation zone (TZ), microarray analyses were performed on whole tissue biopsies. In endometrium, activated pathways included leukocyte chemotaxis, attachment, and inflammation in DMPA (z>2.5) and LNG-IUS (z>3.5) users, and regulation of pattern recognition receptors and other immune mediators. In cervical TZ, progestin treatment altered expression of tissue remodeling and viability genes, but not those of immune functions. Together, these results indicate that progestins influence expression of immune-related genes in endometrium that would be expected to result in the local recruitment of HIV target cells, and thus may increase HIV susceptibility. It is important to consider the upper reproductive tract in the assessment of effects of contraceptives that may influence susceptibility to pathogens, such as HIV. Cross-sectional study conducted at an academic medical center. Cervical transformation zone and endometrial biopsies were obtained from 3 groups of volunteers: those using no hormonal contraceptives (controls, mid-secretory phase, n=20 cervix, 11 endometrium), DMPA users (150mg, n=15, 8), or LNG-IUS users (n=17, 13). DMPA and LNG-IUS groups had used these contraceptives for at least 6 months.
Project description:Nasal carriage of Staphylococcus aureus is a major risk factor in clinical and community settings due to the range of etiologies caused by the organism. We have identified unique immunological and ultrastructural properties associated with nasal carriage isolates denoting a role for bacterial factors in nasal carriage. However, despite extensive molecular level characterizations by several groups suggesting factors necessary for colonization on nasal epithelium, genetic determinants of nasal carriage are unknown. Herein, we have set a genomic foundation for unraveling the bacterial determinants of nasal carriage in S. aureus.MLST analysis revealed no lineage specific differences between carrier and non-carrier strains suggesting a role for mobile genetic elements. We completely sequenced a model carrier isolate (D30) and a model non-carrier strain (930918-3) to identify differential gene content. Comparison revealed the presence of 84 genes unique to the carrier strain and strongly suggests a role for Type VII secretion systems in nasal carriage. These genes, along with a putative pathogenicity island (SaPIBov) present uniquely in the carrier strains are likely important in affecting carriage. Further, PCR-based genotyping of other clinical isolates for a specific subset of these 84 genes raise the possibility of nasal carriage being caused by multiple gene sets.Our data suggest that carriage is likely a heterogeneic phenotypic trait and implies a role for nucleotide level polymorphism in carriage. Complete genome level analyses of multiple carriage strains of S. aureus will be important in clarifying molecular determinants of S. aureus nasal carriage.