Mother to child transmission of HIV--another complication of bacterial vaginosis?

Altered vaginal flora, labeled as bacterial vaginosis (BV), whether diagnosed by clinical examination, Gram stain of vaginal secretions, or molecular typing of bacteria, has been associated with an increased rate of multiple adverse events including sexual HIV acquisition and potentially transmission, acquisition of genital herpes simplex virus, human papilloma virus, Neisseria gonorrhoeae, Chlamydia trachomatis, pelvic inflammatory disease, postabortal and postoperative infections, and among pregnant women, an increased risk of preterm birth, chorioamnionitis, and postpartum infections. The alterations in vaginal flora include decreased levels of hydrogen-peroxide producing lactobacilli, increased prevalence and levels of Gardnerella vaginalis, Mycoplasma hominis, and several logarithm increases in levels of anaerobic bacteria including Prevotella spp, Porphyromonas spp. , and Mobiluncus spp. Clinically, the diagnosis may be made by the presence of increased homogenous vaginal discharge, vaginal pH above 4.5, amine odor with the addition of potassium hydroxide to vaginal secretions, and the presence of more than 20% clue cells, or vaginal epithelial cells coated with coccobacillary bacteria, on microscopic examination of vaginal fluid. The gold standard for diagnosis in research has been the Nugent score, which evaluates Lactobacillus morphotypes (scored inversely 0–4), small Gram-negative rods (scored 0–4), and Mobiluncus (scored 0–2) to provide a score of 0–10, with 0–3 being normal, 4–6 being intermediate, and 7–10 representing BV. More recently, molecular studies have confirmed the association of G. vaginalis and anaerobic bacteria with BV, but have identified additional species associated with the clinical and Gram stain diagnosis of BV, including Atopobium, Leptotrichia, Megasphaera, Eggerthella-like species, and the newly described BV-associated bacteria 1, 2, and 3. Although BV has classically not been associated with signs of inflammation or increased white blood cells in the vaginal discharge, leading to the name vaginosis rather than vaginitis, there still are associated cytokine and immune cell changes in the genital tract that may facilitate acquisition of other infections or lead to complications such as preterm labor. BV is associated with higher vaginal concentrations of interleukin (IL)-1beta, tumor necrosis factor (TNF), interferon-gamma, IL-2, and IL-4, IL-6, and IL-10. TNF is probably triggered by the lipopolysaccharide in the walls of the Gram-negative bacteria found in abundance in BV. Increased TNF leads to increased IL-1beta and other inflammatory cytokines. Interferon gamma induces macrophage activation, which may increase susceptibility to HIV-1 infection in the genital tract. IL-2 induces T and B lymphocyte activation, again potentially increasing HIV susceptibility or levels in the genital tract. The anti-inflammatory cytokines, IL-4 and IL-10, are also increased in BV, potentially balancing the effects of the cytokines discussed above and limiting inflammation. Of note, levels of IL-8, a potent neutrophil chemoattractant, are not increased in BV, potentially explaining the lack of white blood cells in the vagina with BV. BV has been associated with both increased risk of acquisition of HIV and among infected women, with an increased risk of genital tract detection. In studies evaluating incident HIV, BV was associated with an 1.61-fold increased risk of HIV (95% confidence interval: 1.21 to 2.13). Changes in cytokines discussed above that increase genital tract target cells along with elevated pH, loss of hydrogen peroxide production, and decreased secretory leukocyte protease inhibitor and other protective protein levels may