scholarly journals Innate Antibacterial Activity in Female Genital Tract Secretions Is Associated with Increased Risk of HIV Acquisition

2015 ◽  
Vol 31 (11) ◽  
pp. 1153-1159 ◽  
Author(s):  
Rebecca Pellett Madan ◽  
Lindi Masson ◽  
Jessica Tugetman ◽  
Lise Werner ◽  
Anneke Grobler ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Increased Risk ◽  
Hiv Acquisition ◽  
Risk Of Hiv Acquisition ◽  
Female Genital

scholarly journals Vaginal microbiome-hormonal contraceptive interactions associate with the mucosal proteome and HIV acquisition

2020 ◽  
Vol 16 (12) ◽  
pp. e1009097
Author(s):  
Laura Noël-Romas ◽  
Michelle Perner ◽  
Refilwe Molatlhegi ◽  
Christina Farr Zuend ◽  
Amanda Mabhula ◽  
...  
Keyword(s):  
Genital Tract ◽  
Female Genital Tract ◽  
Hormonal Contraceptive ◽  
Hormonal Contraceptives ◽  
Vaginal Microbiome ◽  
Hiv Susceptibility ◽  
Hiv Acquisition ◽  
Risk Of Hiv Acquisition ◽  
Microbiome Data ◽  
Female Genital

Alterations to the mucosal environment of the female genital tract, such as genital inflammation, have been associated with increased HIV acquisition in women. As the microbiome and hormonal contraceptives can affect vaginal mucosal immunity, we hypothesized these components may interact in the context of HIV susceptibility. Using previously published microbiome data from 685 women in the CAPRISA-004 trial, we compared relative risk of HIV acquisition in this cohort who were using injectable depot medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN), and combined oral contraceptives (COC). In women who were Lactobacillus-dominant, HIV acquisition was 3-fold higher in women using DMPA relative to women using NET-EN or COC (OR: 3.27; 95% CI: 1.24–11.24, P = 0.0305). This was not observed in non-Lactobacillus-dominant women (OR: 0.95, 95% CI: 0.44–2.15, P = 0.895) (interaction P = 0.0686). Higher serum MPA levels associated with increased molecular pathways of inflammation in the vaginal mucosal fluid of Lactobacillus-dominant women, but no differences were seen in non-Lactobacillus dominant women. This study provides data suggesting an interaction between the microbiome, hormonal contraceptives, and HIV susceptibility.

scholarly journals Vaginal, Cervical and Uterine pH in Women with Normal and Abnormal Vaginal Microbiota

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 90
Author(s):  
Malene Risager Lykke ◽  
Naja Becher ◽  
Thor Haahr ◽  
Ebbe Boedtkjer ◽  
Jørgen Skov Jensen ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Genital Tract ◽  
Quantitative Polymerase Chain Reaction ◽  
Female Genital Tract ◽  
Uterine Cavity ◽  
Vaginal Microbiota ◽  
Reproductive Age ◽  
Ph Gradient ◽  
Increased Risk ◽  
Female Genital

Introduction: Healthy women of reproductive age have a vaginal pH around 4.5, whereas little is known about pH in the upper genital tract. A shift in the vaginal microbiota may result in an elevated pH in the upper genital tract. This might contribute to decreased fertility and increased risk of preterm birth. Therefore, we aimed to measure pH in different compartments of the female genital tract in both nonpregnant and pregnant women, stratifying into a normal and abnormal vaginal microbiota. Material and methods: In this descriptive study, we included 6 nonpregnant, 12 early-pregnant, and 8 term-pregnant women. A pH gradient was recorded with a flexible pH probe. An abnormal vaginal microbiota was diagnosed by a quantitative polymerase chain reaction technique for Atopobium vaginae; Sneathia sanguinegens; Leptotrichia amnionii; bacterial vaginosis-associated bacterium 1, 2, 3, and TM7; and Prevotella spp. among others. Results: In all participants we found the pH gradient in the lower reproductive canal to be most acidic in the lower vagina and most alkaline in the upper uterine cavity. Women with an abnormal vaginal microbiota had an increased pH in the lower vagina compared to the other groups. Conclusions: There is a pronounced pH gradient within the female genital tract. This gradient is not disrupted in women with an abnormal vaginal microbiota.

scholarly journals Depot Medroxyprogesterone Acetate and the Vaginal Microbiome as Modifiers of Tenofovir Diphosphate and Lamivudine Triphosphate Concentrations in the Female Genital Tract of Ugandan Women: Implications for Tenofovir Disoproxil Fumarate/Lamivudine in Preexposure Prophylaxis

2019 ◽  
Vol 70 (8) ◽  
pp. 1717-1724 ◽  
Author(s):  
Melanie R Nicol ◽  
Prosperity Eneh ◽  
Rita Nakalega ◽  
Thomas Kaiser ◽  
Samuel Kabwigu ◽  
...  
Keyword(s):  
Medroxyprogesterone Acetate ◽  
Tenofovir Disoproxil Fumarate ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Depot Medroxyprogesterone Acetate ◽  
Preexposure Prophylaxis ◽  
Increased Risk ◽  
Vaginal Swabs ◽  
Tenofovir Diphosphate ◽  
Female Genital

Abstract Background Effective concentrations of antiretrovirals in the female genital tract (FGT) are critical for suppression of viral shedding or effective preexposure prophylaxis. The disposition of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in the FGT have been previously described. Despite widespread use, however, lamivudine triphosphate (3TC-TP) exposure in the FGT is unknown. Depot medroxyprogesterone acetate (DMPA) and vaginal dysbiosis have been implicated in increased risk of human immunodeficiency virus (HIV) acquisition, but whether they alter TFV-DP or 3TC-TP exposure, and therefore compromise prevention efficacy, is unknown. Methods Fifty premenopausal women living with HIV in Kampala, Uganda, and receiving daily tenofovir disoproxil fumarate/lamivudine were recruited. Ectocervical biopsies were obtained for quantification of TFV-DP and 3TC-TP using liquid chromatography–mass spectrometry. 16S ribosomal RNA gene sequencing was performed on DNA extracted from vaginal swabs. Wilcoxon rank-sum was used to test for differences between contraceptive groups. Results 3TC-TP concentrations were on average 17-fold greater than TFV-DP concentrations in cervical tissues. TFV-DP concentrations in cervical biopsies were 76% greater in DMPA users compared with women using nonhormonal contraception (n = 23 per group). Abundance of Lactobacillus in vaginal swabs was correlated with 3TC-TP concentrations in cervical tissues. Conclusions We found that TFV-DP concentrations were significantly greater in DMPA users compared with women using nonhormonal contraception, suggesting that prevention efficacy is unlikely to be compromised by DMPA use. Similar to reports of FTC-TP, 3TC-TP exposure was significantly greater than TFV-DP in cervical tissue and was correlated with abundance of Lactobacillus. These data support lamivudine as an option for preexposure prophylaxis. Clinical Trials Registration NCT03377608.

scholarly journals Breech at the Border: An Atypical Case of Invasive Haemophilus influenzae in a Patient on a Novel Immunotherapeutic

2018 ◽  
Vol 5 (7) ◽  
Author(s):  
Jessica Howard-Anderson ◽  
Sarah W Satola ◽  
Matthew H Collins
Keyword(s):  
Haemophilus Influenzae ◽  
Mucosal Immunity ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Interleukin 17 ◽  
Immunomodulatory Treatment ◽  
Atypical Case ◽  
Increased Risk ◽  
Systemic Infections ◽  
Female Genital

Abstract Haemophilus influenzae rarely causes pyogenic infections in the female genital tract, and even less commonly does this lead to systemic infections. Novel monoclonal antibody therapies targeting interleukin-17 may impair mucosal immunity, but increased risk for H. influenzae infections has not been documented. Here, we describe a case of H. influenzae bacteremia associated with pyosalpinx and hypothesize that immunomodulatory treatment for psoriasis predisposed our patient to this infection.

scholarly journals Tumorigenic Effects of Tamoxifen on the Female Genital Tract

2008 ◽  
Vol 1 ◽  
pp. CPath.S487 ◽  
Author(s):  
Kaei Nasu ◽  
Noriyuki Takai ◽  
Masakazu Nishida ◽  
Hisashi Narahara
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Side Effects ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Tamoxifen Treatment ◽  
Endocrine Treatment ◽  
Gynecological Examination ◽  
Increased Risk ◽  
Female Genital

Tamoxifen is widely used for endocrine treatment and breast cancer prevention. It acts as both an estrogen antagonist in breast tissue and an estrogen agonist in the female lower genital tract. Tamoxifen causes severe gynecologic side effects, such as endometrial cancer. This review focuses on the effects of prolonged tamoxifen treatment on the human female genital tract and considers its tumorigenicity in the gynecologic organs through clinical data analysis. Tamoxifen is associated with an increased incidence of benign endometrial lesions such as polyps and hyperplasia and a two- to four-fold increased risk of endometrial cancer in postmenopausal patients. Moreover, the incidence of functional ovarian cysts is significantly high in premenopausal tamoxifen users. To prevent tamoxifen from having severe side effects in gynecologic organs, frequent gynecological examination should be performed for both premenopausal and postmenopausal patients with breast cancer who are treated with this drug.

scholarly journals Mucosal Immunity in the Female Genital Tract, HIV/AIDS

2014 ◽  
Vol 2014 ◽  
pp. 1-20 ◽  
Author(s):  
Juliana Reis Machado ◽  
Marcos Vinícius da Silva ◽  
Camila Lourencini Cavellani ◽  
Marlene Antônia dos Reis ◽  
Maria Luiza Gonçalves dos Reis Monteiro ◽  
...  
Keyword(s):  
Mucosal Immunity ◽  
Genital Tract ◽  
Hiv Transmission ◽  
Female Genital Tract ◽  
Sexually Transmitted ◽  
Systemic Spread ◽  
Increased Risk ◽  
Relationship Of ◽  
Female Genital ◽  
Hiv Aids

Mucosal immunity consists of innate and adaptive immune responses which can be influenced by systemic immunity. Despite having been the subject of intensive studies, it is not fully elucidated what exactly occurs after HIV contact with the female genital tract mucosa. The sexual route is the main route of HIV transmission, with an increased risk of infection in women compared to men. Several characteristics of the female genital tract make it suitable for inoculation, establishment of infection, and systemic spread of the virus, which causes local changes that may favor the development of infections by other pathogens, often called sexually transmitted diseases (STDs). The relationship of these STDs with HIV infection has been widely studied. Here we review the characteristics of mucosal immunity of the female genital tract, its alterations due to HIV/AIDS, and the characteristics of coinfections between HIV/AIDS and the most prevalent STDs.

Human Papillomavirus (HPV)-Attributable Subsequent Neoplasms (SNs) After Hematopoietic Cell Transplantation (HCT) – a Potentially Preventable Outcome

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 605-605
Author(s):  
J Berano Teh ◽  
Can-Lan Sun ◽  
Sharon Wilczynski ◽  
Joel Epstein ◽  
R. Spielberger ◽  
...  
Keyword(s):  
Oral Cancer ◽  
General Population ◽  
Genital Tract ◽  
Chronic Gvhd ◽  
Female Genital Tract ◽  
Unrelated Donor ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Autologous Hct ◽  
Female Genital

Abstract Abstract 605 Background: Centers for Disease Control estimate that 26,000 cancers diagnosed each year in the general population are attributable to HPV; oropharyngeal and female genital cancers account for 75% of these. We hypothesized that HCT recipients are at an especially increased risk of HPV-attributable SNs, because of exposure to high-intensity therapy, coupled with immune dysregulation. However, the magnitude of this risk and sub-populations at highest risk are not known. Clinically this information is important because of the ability to institute primary prevention (HPV vaccine) for the young (<26y-olds); and the need to develop targeted surveillance and intervention strategies across all age groups. Methods: We determined the risk of post-HCT oral/pharyngeal and female genital neoplasms in 5701 (2424 female, 3277 male) consecutive patients transplanted for hematologic malignancies (leukemia [49%], lymphoma [35%], myeloma [12%]) between 1976 and 2007 at a single institution. Near-complete ascertainment of SNs was accomplished by combining institutional follow-up with linkage of the cohort with California Cancer Registry, and National Death Index Plus programs. Results: Median age at HCT was 41y (0–78); 48% had received autologous HCT; 37% related and 15% unrelated donor HCT. Chronic graft vs. host disease (GvHD) developed in 44% of related and 66% of unrelated donor HCT recipients. Oral/pharyngeal cancer: After 34,621 p-y of observation, 25 patients developed oral cancer; 76% after allogeneic HCT. Squamous cell carcinoma (SCC) of tongue, lip, and mouth/alveolar ridge accounted for 84% of the oral SNs; 16% were salivary gland tumors. Pathology reports did not capture HPV status. Oral/cutaneous (adjacent to lip) chronic GvHD was present in 62% of SCC, and 6% of non-SCC oral cancers. Median latency from HCT to oral cancer was 7.7y (0.9–32); median age at diagnosis was 45y (24–69). While autologous HCT recipients were not at statistically significant increased risk (standardized incidence ratio [SIR] = 1.9 (p=0.12), related donor recipients were at a 9-fold (4.5–14.8, p<0.001) and unrelated donor HCT recipients at a 23-fold (10.7–43.4, p<0.001) increased risk of developing oral cancer compared with the age- and sex-matched general population. Multivariate Cox-regression analysis (adjusted for age at HCT, gender, race/ethnicity, conditioning, and year of HCT) revealed that unrelated donor HCT recipients with chronic GvHD were at a 10.8-fold increased risk of developing oral cancer (p=<0.001), compared with autologous HCT recipients. Female genital tract neoplasms: Evaluation of the 2424 female HCT recipients with 14,587 p-y of follow-up revealed 51 patients with genital tract neoplasms (premalignant and malignant lesions of the cervix, vagina, vulva and clitoris); 71% of the cases among allogeneic HCT recipients had chronic GvHD. Forty-nine of the 51 neoplasms were of squamous cell origin. Importantly, 39 of 41 (95%) evaluable cases had findings consistent with HPV infection. Median latency from HCT to genital tract SNs was 3.3y (0.2–16.5); median age at diagnosis was 42y (20–66). In an analysis restricted to SEER-reportable neoplasms, the cohort was at 5.8-fold (3.2–9.5, p<0.001) increased risk of developing genital tract neoplasms when compared with an age-matched general population. Autologous, allogeneic related and unrelated HCT female recipients were at 4.1- (1.5–8.7, p=0.002), 7.2- (2.9–14.6, p<0.001) and 10.8-fold (1.8–33.8, p<0.001) increased risk respectively, of developing genital tract neoplasms compared with the general population. Multivariate Cox-regression analysis (adjusted for age at HCT, race/ethnicity, conditioning, and year of HCT) revealed that unrelated donor HCT recipients with chronic GvHD were at a 2.5-fold increased risk of developing female genital tract neoplasms (p=0.04) when compared with autologous HCT recipients. Conclusion: Chronic GvHD significantly increases risk of oral and female genital tract neoplasms; populations at risk should be followed closely, with appropriate and aggressive management of suspicious lesions. Over 90% of post-HCT female genital tract neoplasms are attributable to HPV. The contribution of specific HPV strains to the development of post-HCT oral and female genital tract neoplasms is currently underway, as are studies examining immunogenicity/safety of HPV vaccine for the <26y-old HCT survivors. Disclosures: No relevant conflicts of interest to declare.

Elevated elafin/trappin-2 in the female genital tract is associated with protection against HIV acquisition

AIDS ◽  
2009 ◽  
Vol 23 (13) ◽  
pp. 1669-1677 ◽  
Author(s):  
Shehzad M Iqbal ◽  
Terry B Ball ◽  
Pauline Levinson ◽  
Lillian Maranan ◽  
Walter Jaoko ◽  
...  
Keyword(s):  
Genital Tract ◽  
Female Genital Tract ◽  
Hiv Acquisition ◽  
Female Genital
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