Impact of contraceptive initiation on vaginal microbiota Achilles, Sharon L.; Austin, Michele N.; Meyn, Leslie A. ...
American journal of obstetrics and gynecology,
June 2018, 2018-06-00, 20180601, Letnik:
218, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Data evaluating the impact of contraceptives on the vaginal microbiome are limited and inconsistent.
We hypothesized that women initiating copper intrauterine device use would have increased ...bacterial vaginosis and bacterial vaginosis-associated microbes with use compared to women initiating and using hormonal contraceptive methods.
Vaginal swabs (N = 1047 from 266 participants seeking contraception) for Nugent score determination of bacterial vaginosis and quantitative polymerase chain reaction analyses for assessment of specific microbiota were collected from asymptomatic, healthy women aged 18-35 years in Harare, Zimbabwe, who were confirmed to be free of nonstudy hormones by mass spectrometry at each visit. Contraception was initiated with an injectable (depot medroxyprogesterone acetate n = 41, norethisterone enanthate n = 44, or medroxyprogesterone acetate and ethinyl estradiol n = 40), implant (levonorgestrel n = 45 or etonogestrel n = 48), or copper intrauterine device (n = 48) and repeat vaginal swabs were collected after 30, 90, and 180 days of continuous use. Self-reported condom use was similar across all arms at baseline. Quantitative polymerase chain reaction was used to detect Lactobacillus crispatus, L jensenii, L gasseri/johnsonii group, L vaginalis, L iners, Gardnerella vaginalis, Atopobium vaginae, and Megasphaera-like bacterium phylotype I from swabs. Modified Poisson regression and mixed effects linear models were used to compare marginal prevalence and mean difference in quantity (expressed as gene copies/swab) prior to and during contraceptive use.
Bacterial vaginosis prevalence increased in women initiating copper intrauterine devices from 27% at baseline, 35% at 30 days, 40% at 90 days, and 49% at 180 days (P = .005 compared to marginal prevalence at enrollment). Women initiating hormonal methods had no change in bacterial vaginosis prevalence over 180 days. The mean increase in Nugent score was 1.2 (95% confidence interval, 0.5–2.0; P = .001) in women using copper intrauterine devices. Although the frequency and density of beneficial lactobacilli did not change among intrauterine device users over 6 months, there was an increase in the log concentration of G vaginalis (4.7, 5.2, 5.8, 5.9; P = .046) and A vaginae (3.0, 3.8, 4.6, 5.1; P = .002) between baseline and 30, 90, and 180 days after initiation. Among other contraceptive groups, women using depot medroxyprogesterone acetate had decreased L iners (mean decrease log concentration = 0.8; 95% confidence interval, 0.3–1.5; P = .004) and there were no significant changes in beneficial Lactobacillus species over 180 days regardless of contraceptive method used.
Copper intrauterine device use may increase colonization by bacterial vaginosis–associated microbiota, resulting in increased prevalence of bacterial vaginosis. Use of most hormonal contraception does not alter vaginal microbiota.
Abstract
Pelvic inflammatory disease (PID) is a syndrome that causes substantial morbidity, including chronic pelvic pain, to women globally. While limited data are available from low- and ...middle-income countries, national databases from the United States and Europe suggest that PID incidence may be decreasing but the rate of decrease may differ by the etiologic cause. Recent studies of women with PID have reported that fewer than half of women receiving a diagnosis of PID have gonococcal or chlamydial infection, while Mycoplasma genitalium, respiratory pathogens, and the constellation of bacteria associated with bacterial vaginosis may account for a substantial fraction of PID cases. The clinical diagnosis of PID is nonspecific, creating an urgent need to develop noninvasive tests to diagnose PID. Advances in serologic testing for Chlamydia trachomatis and Neisseria gonorrhoeae could advance epidemiologic studies, while the development of vaccines against these sexually transmitted pathogens could affect incident PID and associated morbidity.
Although vaginal symptoms are common, diagnosis of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and Trichomonas vaginalis (TV) is not standardized. Diagnostic approaches and ...appropriateness of treatment were evaluated for women with symptoms of vaginitis who were seeking care at community practice sites.
Three hundred three symptomatic women, across 8 University of Pittsburgh Medical Center-affiliated clinics, were evaluated per standard office-based practice. Four of 5 vaginal swabs (1 cryopreserved) were collected for a US Food and Drug Administration-authorized nucleic acid amplification test (NAAT) for vaginitis/vaginosis diagnosis; Nugent scoring (BV); yeast culture (VVC); and a second NAAT (for TV). Two hundred ninety women had evaluable samples. Medical record extraction facilitated verification of treatments prescribed within 7 days of the index visit and return visit frequency within 90 days.
Women had a mean age of 29.4 ± 6.5 years, 90% were not pregnant, 79% were of white race, and 38% reported vaginitis treatment within the past month. Point-of-care tests, including vaginal pH (15%), potassium hydroxide/whiff (21%), and wet mount microscopy (17%), were rarely performed. Of the 170 women having a laboratory-diagnosed cause of vaginitis, 81 (47%) received 1 or more inappropriate prescriptions. Of the 120 women without BV, TV, or VVC, 41 (34%) were prescribed antibiotics and/or antifungals. Among women without infectious vaginitis, return visits for vaginitis symptoms were more common among women treated empirically compared to those not receiving treatment (9/41 vs 5/79, P = .02).
Within a community practice setting, 42% of women having vaginitis symptoms received inappropriate treatment. Women without infections who received empiric treatment were more likely have recurrent visits within 90 days.
NCT03151928.
The same populations of women at risk for sexual acquisition of HIV are also at risk for pregnancy; many of these women use contraception. Combating the spread of HIV is a major global goal 1 ideally ...achievable with development of highly effective dual protection methods that prevent both sexual acquisition of HIV and unwanted pregnancy. Currently, emerging evidence 2 suggests that some commonly used contraceptives may increase risk of sexual HIV acquisition and transmission. There are several biologically plausible mechanisms by which hormonal contraceptives could increase HIV risk including disrupting epithelial barriers (thinning of the epithelium or altering epithelial integrity), causing changes in inflammatory responses that could in turn enhance HIV replication locally 3, or altering the vaginal microbiota which itself effects local immunity and genital inflammation. The objective of this manuscript is to review the evidence linking contraceptives to genital tract changes and to identify research gaps to be addressed with future studies.
Abstract
Pelvic inflammatory disease (PID) is a clinical syndrome that has been associated with a wide range of potential causal pathogens. Three broad groups of organisms have been isolated from the ...genital tract of people with PID: sexually transmitted organisms such as Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis; bacterial vaginosis (BV)-associated species and genera such as Atopobium vaginae, Sneathia, and Megasphaera; and genera and species usually associated with the gastrointestinal or respiratory tracts such as Bacteroides, Escherichia coli, Streptococcus, or Haemophilus influenza. Although PID is often considered to be synonymous with gonorrhea or chlamydia, these pathogens are found in only one quarter to one third of people with PID, suggesting that broader screening and diagnostic and treatment strategies need to be considered to reduce the burden of PID and its associated sequelae.
To prevent the global health burdens of human immunodeficiency virus HIV and unintended/mistimed pregnancies, we developed an intravaginal ring IVR that delivers tenofovir TFV at ~10mg/day alone or ...with levonorgestrel LNG at ~20μg/day for 90 days. We present safety, pharmacokinetics, pharmacodynamics, acceptability and drug release data in healthy women. CONRAD A13-128 was a randomized, placebo controlled phase I study. We screened 86 women; 51 were randomized to TFV, TFV/LNG or placebo IVR 2:2:1 and 50 completed all visits, using the IVR for approximately 15 days. We assessed safety by adverse events, colposcopy, vaginal microbiota, epithelial integrity, mucosal histology and immune cell numbers and phenotype, cervicovaginal CV cytokines and antimicrobial proteins and changes in systemic laboratory measurements, and LNG and TFV pharmacokinetics in multiple compartments. TFV pharmacodynamic activity was measured by evaluating CV fluid CVF and tissue for antiviral activity using in vitro models. LNG pharmacodynamic assessments were timed based on peak urinary luteinizing hormone levels. All IVRs were safe with no significant colposcopic, mucosal, immune and microbiota changes and were acceptable. Among TFV containing IVR users, median and mean CV aspirate TFV concentrations remained above 100,000 ng/mL 4 hours post IVR insertion and mean TFV-diphosphate DP concentrations in vaginal tissue remained above 1,000 fmol/mg even 3 days post IVR removal. CVF of women using TFV-containing IVRs completely inhibited 94-100% HIV infection in vitro. TFV/LNG IVR users had mean serum LNG concentrations exceeding 300 pg/mL within 1 hour, remaining high throughout IVR use. All LNG IVR users had a cervical mucus Insler score <10 and the majority 95% were anovulatory or had abnormal cervical mucus sperm penetration. Estimated in vivo TFV and LNG release rates were within expected ranges. All IVRs were safe with the active ones delivering sustained high concentrations of TFV locally. LNG caused changes in cervical mucus, sperm penetration, and ovulation compatible with contraceptive efficacy. The TFV and TFV/LNG rings are ready for expanded 90 day clinical testing. Trial registration ClinicalTrials.gov #NCT02235662.
Abstract
Background
Anaerobic organisms are important pathogens in acute pelvic inflammatory disease (PID). The currently recommended PID regimen of a single dose of ceftriaxone and doxycycline for ...14 days has limited anaerobic activity. The need for broader anaerobic coverage is unknown and concerns have been raised about metronidazole tolerability.
Methods
We conducted a randomized, double-blind, placebo-controlled trial comparing ceftriaxone 250 mg intramuscular single dose and doxycycline for 14 days, with or without 14 days of metronidazole in women with acute PID. The primary outcome was clinical improvement at 3 days following enrollment. Additional outcomes at 30 days following treatment were the presence of anaerobic organisms in the endometrium, clinical cure (absence of fever and reduction in tenderness), adherence, and tolerability.
Results
We enrolled 233 women (116 to metronidazole and 117 to placebo). Clinical improvement at 3 days was similar between the 2 groups. At 30 days following treatment, anaerobic organisms were less frequently recovered from the endometrium in women treated with metronidazole than placebo (8% vs 21%, P < .05) and cervical Mycoplasma genitalium was reduced (4% vs 14%, P < .05). Pelvic tenderness was also less common among women receiving metronidazole (9% vs 20%, P < .05). Adverse events and adherence were similar in each treatment group.
Conclusions
In women treated for acute PID, the addition of metronidazole to ceftriaxone and doxycycline was well tolerated and resulted in reduced endometrial anaerobes, decreased M. genitalium, and reduced pelvic tenderness compared to ceftriaxone and doxycycline. Metronidazole should be routinely added to ceftriaxone and doxycycline for the treatment of women with acute PID.
Clinical Trials Registration
NCT01160640.
Treatment of acute pelvic inflammatory disease with ceftriaxone, doxycycline, and metronidazole is associated with significantly less frequent recovery of anaerobic organisms from the upper genital tract, decreased Mycoplasma genitalium, and improved clinical response compared to ceftriaxone and doxycycline.
OBJECTIVE:The reported incidence of acute pelvic inflammatory disease (PID) has decreased but rates of tubal infertility have not, suggesting that a large proportion of PID leading to infertility may ...be undetected. Subclinical PID is common in women with uncomplicated chlamydial or gonococcal cervicitis or with bacterial vaginosis. We assessed whether women with subclinical PID are at an increased risk for infertility.
METHODS:A prospective observational cohort of 418 women with or at risk for gonorrhea or chlamydia or with bacterial vaginosis was recruited. Women with acute PID were excluded. An endometrial biopsy was performed to identify endometritis (subclinical PID). After provision of therapy for gonorrhea, chlamydia and bacterial vaginosis participants were followed-up for fertility outcomes.
RESULTS:There were 146 incident pregnancies during follow-up, 50 pregnancies in 120 (42%) women with subclinical PID and 96 in 187 (51%) women without subclinical PID. Women with subclinical PID diagnosed at enrollment had a 40% reduced incidence of pregnancy compared with women without subclinical PID (hazard ratio 0.6, 95% confidence interval 0.4–0.8). Women with Neisseria gonorrhoeae or Chlamydia trachomatis, in the absence of subclinical PID, were not at increased risk for infertility.
CONCLUSION:Subclinical PID decreases subsequent fertility despite provision of treatment for sexually transmitted diseases. These findings suggest that a proportion of female infertility is attributable to subclinical PID and indicate that current therapies for sexually transmitted diseases are inadequate for prevention of infertility.
LEVEL OF EVIDENCE:II
HIV topical microbicides are products with anti-HIV activity, generally incorporating a direct-acting antiretroviral agent, that when applied to the vagina or rectum have the potential to prevent the ...sexual acquisition of HIV in women and men. Topical microbicides may meet the prevention needs of individuals and groups for whom oral daily forms of pre-exposure prophylaxis (PrEP) have not been acceptable. Microbicides can provide personal control over HIV prevention and offer the possibility of discreet use, qualities that may be particularly important for receptive partners in sexual relationships such as women and transgender women and men, who together account for the clear majority of new HIV infections worldwide. Although the promise of such a product emerged nearly three decades ago, proof of concept has been demonstrated only within the last decade. A robust pipeline of microbicidal gels, films, inserts, and rings has been evaluated in multiple studies among at-risk women and men, and refinement of products for ease of use, reversibility, and high safety is the priority for the field.
Because of the opioid epidemic, hepatitis C virus (HCV) infection is increasing among pregnant women, resulting in an increased risk of perinatal transmission and HCV infection among children. Our ...primary objectives in this study were to determine the prevalence of HCV among pregnant women and the frequency of pediatric HCV screening.
A population-based, retrospective cohort of pregnant women who delivered between 2006 and 2014 was identified and classified as HCV infected or HCV uninfected by billing codes. Infant records linked to the HCV-infected pregnant women were identified and queried for HCV tests and the receipt of well-child services, which were defined as the presence of hemoglobin and/or lead testing at or after 9 months of age.
Between 2006 and 2014, 1043 (1.2%) HCV-infected pregnant women delivered, and the HCV prevalence increased by 60%. HCV-infected women were more likely to be <30 years of age (67% vs 53%;
< .001), white (93% vs 72%;
< .001), insured by Medicaid (77% vs 29%;
< .001), and have opiate use disorder (68% vs 1%;
< .001) than HCV-uninfected women. Infants born to HCV-infected women were more likely to be preterm (<37 weeks' gestation; 22% vs 10%;
< .001) and of low birth weight (<2500 g; 23% vs 8%;
< .001). Among 1025 HCV-exposed infants with available pediatric records, 323 (31%) received well-child services, and among these, only 96 (30%) were screened for HCV.
Despite the increased HCV prevalence among pregnant women and the risk of perinatal HCV transmission, HCV-exposed infants are not adequately screened, and many pediatric HCV infections remain undetected.
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