Bacteria associated with BV increase genital-tract HIV RNA levels. Quantitative bacterial counts for lactobacilli and M. hominis are better correlates of CVL HIV RNA than are Nugent score or Amsel criteria. Since plasma virus and CD4 cell levels did not differ between the BV and no-BV groups, these data suggest that the bacterial flora associated with BV influence genital-tract HIV shedding.
Bacterial vaginosis (BV) is a clinical syndrome presenting with a malodorous vaginal discharge and increased vaginal pH. Diagnosis has been based on clinical Amsel criteria and direct Gram stain of vaginal secretions. Human immunodeficiency virus (HIV)-infected participants in the WomenOf the group with Nugent scores of 7 to 10, 83% and 81% had log 10 G. vaginalis counts and log 10 M. hominis counts greater than 6.81 and 4.82, respectively, while only 30% and 31% of the group with Nugent scores of 0 to 3 were above these thresholds, respectively. There was significant overlap in the log 10 lactobacillus counts between the two groups. Utilizing all three log 10 bacterial counts (G. vaginalis, M. hominis, and lactobacilli) in our model improved the sensitivity and specificity to 83% and 78%, respectively, in comparison with Nugent score. In this cohort, Amsel criteria were poorly predictive of BV. PCR quantification of G. vaginalis and M. hominis from CVL is significantly more sensitive than Amsel criteria for diagnosing BV.In women of childbearing age, bacterial vaginosis (BV) is the most common cause of vaginitis. In BV, normal vaginal flora, consisting of hydrogen peroxide-producing lactobacilli, are replaced by Gardnerella vaginalis, Mycoplasma hominis, Mobiluncus species, and anaerobic gram-negative rods (14). BV has been associated with preterm delivery, chorioamnionitis, postabortion infection, and pelvic inflammatory disease. In 1983, Amsel et al. established clinical criteria for diagnosing BV. The presence of three of the following four criteria is considered to be consistent with the presence of BV: vaginal pH of Ͼ4.5, clue cells on saline wet mount, release of a fish amine odor on addition of 10% KOH to a drop of vaginal discharge, and a characteristic thin, homogenous vaginal discharge (1). In 1991, Nugent et al. described a Gram stain scoring system of vaginal smears to diagnose BV (10). The Nugent score is calculated by assessing for the presence of large gram-positive rods (Lactobacillus morphotypes; decrease in Lactobacillus scored as 0 to 4), small gram-variable rods (G. vaginalis morphotypes; scored as 0 to 4), and curved gram-variable rods (Mobiluncus spp. morphotypes; scored as 0 to 2) and can range from 0 to 10. A score of 7 to 10 is consistent with BV.Compared to the Amsel criteria, the Nugent score allows for assessment of alteration in vaginal flora as a continuum rather than a dichotomy. Vaginal cultures for G. vaginalis are sensitive but not specific, as 50 to 60% of healthy asymptomatic women will be culture positive (14). Because Amsel criteria are dependent on the acumen of the clinician, the Nugent score has been favored for diagnosing BV due to superior reproducibility and sensitivity (9). Nevertheless evaluation of smears is also subjective and therefore requires an experienced slide reader (10).Recently we reported on a PCR method to quantify M. hominis, G. vaginalis, and lactobacilli in cervicovaginal lavage (CVL) samples obtained from human immunodeficiency virus (HIV)-infected ...
BackgroundMore than one million new cases of sexually transmitted diseases (STDs) occur each day. The immune responses and inflammation induced by STDs and other frequent non-STD microbial colonizations (i.e. Candida and bacterial vaginosis) can have serious pathologic consequences in women including adverse pregnancy outcomes, infertility and increased susceptibility to infection by other pathogens. Understanding the types of immune mediators that are elicited in the lower genital tract by these infections/colonizations can give important insights into the innate and adaptive immune pathways that are activated and lead to strategies for preventing pathologic effects.Methodology/Principal Findings32 immune mediators were measured by multiplexed immunoassays to assess the immune environment of the lower genital tract mucosa in 84 women attending an urban STD clinic. IL-3, IL-1ß, VEGF, angiogenin, IL-8, ß2Defensin and ß3Defensin were detected in all subjects, Interferon-α was detected in none, while the remaining mediators were detected in 40% to 93% of subjects. Angiogenin, VEGF, FGF, IL-9, IL-7, lymphotoxin-α and IL-3 had not been previously reported in genital mucosal fluid from women. Strong correlations were observed between levels of TNF-α, IL-1ß and IL-6, between chemokines IP-10 and MIG and between myeloperoxidase, IL-8 and G-CSF. Samples from women with any STD/colonization had significantly higher levels of IL-8, IL-3, IL-7, IL-1ß, lactoferrin and myeloperoxidase. IL-1ß and lactoferrin were significantly increased in gonorrhea, Chlamydia, cervicitis, bacterial vaginosis and trichomoniasis.Conclusions/SignificanceThese studies show that mucosal fluid in general appears to be an environment that is rich in immune mediators. Importantly, IL-1ß and lactoferrin are biomarkers for STDs/colonizations providing insights into immune responses and pathogenesis at this mucosal site.
Infections and inflammation in the genital tract can influence HIV expression or HIV susceptibility. The goal of this study was to determine if significant relationships exist between cytokines and HIV in genital tract secretions from 57 HIV-seropositive Rwandan women. Genital tract secretions were obtained by cervicovaginal lavage (CVL). Ten different cytokines in CVL were measured by multiplex Cytometric Bead Arrays. HIV RNA in CVL and plasma were measured by quantitative PCR. In univariate analysis, genital tract HIV RNA was significantly associated with plasma HIV RNA and several of the cytokines, while in multivariate analysis, genital tract HIV RNA was only significantly associated with plasma HIV RNA and IL-6. This association of IL-6 with HIV RNA levels suggests that IL-6 is an indicator for conditions that induce HIV expression and that IL-6 may contribute to induction of HIV expression in the genital tract.
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