Daniel V. Landers

Bacterial Vaginosis Is a Strong Predictor of Neisseria gonorrhoeae and Chlamydia trachomatis Infection

To evaluate whether bacterial vaginosis predicts the acquisition of sexually transmitted diseases (STDs), we studied 255 nonpregnant female subjects aged 15-30 who reported recent sexual contact with a male partner in whom either gonococcal or chlamydial urethritis or nongonococcal urethritis was diagnosed. Compared to subjects with normal vaginal flora, subjects with bacterial vaginosis were more likely to test positive for Neisseria gonorrhoeae (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.7-9.7) and Chlamydia trachomatis (OR, 3.4; 95% CI, 1.5-7.8). Subjects colonized vaginally by hydrogen peroxide-producing lactobacilli were less likely to receive a diagnosis of chlamydial infection or gonorrhea than subjects without such lactobacilli. Bacterial vaginosis was a strong predictor of gonorrhea and chlamydial infection among subjects who reported recent exposure to a male partner with urethritis. These data support the importance of vaginal flora in the defense against STD acquisition.

Lower genital tract infection and endometritis: Insight into Subclinical pelvic inflammatory disease

OBJECTIVE To investigate the association between lower genital tract infections and subclinical PID. Fallopian tube damage is a common complication of acute symptomatic pelvic inflammatory disease (PID), yet most women with tubal factor infertility do not have a history of acute PID. Subclinical PID is believed to be an important cause of tubal factor infertility. METHODS We conducted a cross‐sectional study among women attending a sexually transmitted diseases or ambulatory gynecology clinic. A convenience sample of 556 women with bacterial vaginosis, gonorrhea, or chlamydia, or women at risk for gonorrhea or chlamydia were enrolled. Women diagnosed with acute PID were not eligible to participate. The main outcome was subclinical PID, as defined by the presence of histologic endometritis. RESULTS Subclinical PID was more common in women with lower genital tract infection than in uninfected women. Subclinical PID was present in 27% of women with Chlamydia trachomatis (odds ratio 3.4; 95% confidence interval [CI] 1.8, 6.3) and in 26% of women infected with Neisseria gonorrhoeae (odds ratio 2.4; 95% CI 1.1, 5.1). Among women with bacterial vaginosis, 15% had endometritis (odds ratio 2.7; 95% CI 1.02, 7.2). CONCLUSION Subclinical PID is common among women with lower genital tract infections. Additional prospective studies are necessary to determine the reproductive impact of these asymptomatic upper genital tract infections.

Peritoneal fluid concentrations of the cytokine RANTES correlate with the severity of endometriosis

OBJECTIVE Endometriosis is a common gynecologic disorder in which the concentration and activation of peritoneal macrophages are increased. The goal of this study was to quantify pelvic fluid concentrations of two cytokines involved in macrophage recruitment and activation. STUDY DESIGN A case-control study of women undergoing pelvic surgery was conducted by collecting peritoneal fluid from 12 women without evidence of endometriosis (controls), 12 with mild, and 12 with moderate to severe endometriosis. Concentrations of RANTES and interferon gamma, soluble cytokines known to recruit and activate macrophages, were quantified by enzyme-linked immunosorbent assays. RESULTS Pelvic fluid concentrations of RANTES are elevated in women with endometriosis and the levels correlate with the severity of disease. By contrast, concentrations of interferon gamma appear unaffected by the presence of or severity of endometriosis. CONCLUSION The findings indicate that RANTES, a cytokine with potent chemotactic activity for human monocytes, may play an important role in the recruitment of peritoneal macrophages in endometriosis.

Development of an in vitro organ culture model to study transmission of HIV-1 in the female genital tract

Development of an in vitro organ culture model to study transmission of HIV-1 in the female genital tract

Plasma cell endometritis in women with symptomatic bacterial vaginosis

Objective To evaluate the endometrial microbiology and histopathology in women with symptomatic bacterial vaginosis but no signs or symptoms of upper genital tract disease or other vaginal or cervical infections. Methods Endometrial biopsies were performed on 41 women complaining of vaginal discharge or pelvic pain at a sexually transmitted disease clinic. These women had neither culture nor serologic evidence of Neisseria gonorrhoeae or Chlamydia trachomatis infection. Twenty-two women with bacterial vaginosis diagnosed by Gram stain examination of vaginal fluid, but with neither signs nor symptoms of upper genital tract infection, were compared with 19 women who had no evidence of bacterial vaginosis on vaginal fluid Gram stain. Endometrial biopsies were evaluated for histopathologic evidence of plasma cell endometritis and were cultured for N gonorrhoeae, C trachomatis, aerobic and anaerobic bacteria, Mycoplasma species, and Ureaplasma urealyticum. Results Ten of 22 women with bacterial vaginosis had plasma cell endometritis, compared with one of 19 controls (odds ratio [OR] 15, 95% confidence interval [CI] 2–686; P < .01). Bacterial vaginosis-associated organisms were cultured from the endometria of nine of 11 women with and eight of 30 women without plasma cell endometritis (OR 12.4, 95% CI 2–132; P = .002). Conclusion Plasma cell endometritis was frequently present in women with bacterial vaginosis and without other vaginal or cervical infections. This suggests the possibility of an association between bacterial vaginosis and nonchlamydial, nongonococcal, upper genital tract infection.

Vertical transmission of hepatitis C virus

There is evidence that hepatitis C virus (HCV) may be vertically transmitted from infected mothers to their children. To test this hypothesis, we prospectively studied 10 pregnant women at high risk from parenterally or sexually transmitted diseases with the polymerase chain reaction. HCV RNA was found in 8 newborn babies delivered by women who were anti-HCV seropositive, and persisted for 2-19 months of follow-up. Anti-HCV detected in 7 infants cleared by 9 months and remained undetectable thereafter. Serum alanine aminotransferase was raised in 3 infants. The findings provide evidence of vertical transmission of HCV and suggest that perinatal infection may initiate a silent disease process or chronic carrier state.

Memory CD4+ T Cells Are the Earliest Detectable Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Cells in the Female Genital Mucosal Tissue during HIV-1 Transmission in an Organ Culture System

ABSTRACT The virologic and cellular factors that are involved in transmission of human immunodeficiency virus type 1 (HIV-1) across the female genital tissue are poorly understood. We have recently developed a human cervical tissue-derived organ culture model to study heterosexual transmission of HIV-1 that mimics the in vivo situation. Using this model we investigated the role of phenotypic characteristics of HIV-1 and identified the cell types that are first infected during transmission. Our data indicate that the cell-free R5 HIV-1 was more efficiently transmitted than cell-free X4 HIV-1. Cell-free and cell-associated HIV-1 had comparable transmission efficiency regardless of whether the virus was of R5 or X4 type. We have demonstrated that memory CD4+ T cells and not Langerhans cells were the first HIV-1 RNA-positive cells detected at the epithelial-submucosal junction 6 h after virus exposure. Multicolor laser confocal microscopy demonstrated a globular distribution of HIV-1 gag-pol mRNA in the cytoplasm, and the distribution of CD4 and the CD45RO isoform was irregular on the cellular membrane. At 96 h postinoculation, in addition to memory CD4+ T cells, HIV-1 RNA-positive Langerhans cells and macrophages were also detected. The identification of CD4+ T cells in the tissue at 6 h was confirmed by flow cytometric simultaneous immunophenotyping and ultrasensitive fluorescence in situ hybridization assay on immune cells isolated from disaggregated tissue. Furthermore, PMPA {9-[2-(phosphonomethoxy)propyl] adenine}, an antiretroviral compound, and UC781, a microbicide, inhibited HIV-1 transmission across the mucosa, indicating the utility of the organ culture to screen topical microbicides for their ability to block sexual transmission of HIV-1.

Clinical and cervical cytokine response to treatment with oral or vaginal metronidazole for bacterial vaginosis during pregnancy: a randomized trial.

OBJECTIVE To compare the efficacy of oral versus vaginal metronidazole treatment in pregnant women with bacterial vaginosis, and to compare cytokine profiles (interleukin-1β, -6, and -8) in the cervical secretions of these women before and after treatment. METHODS Pregnant women with bacterial vaginosis diagnosed both by Gram stain and clinical criteria were randomized to receive oral (n = 52) or vaginal (n = 50) metronidazole therapy. Cervical specimens for cytokine analysis and vaginal fluid for evaluation of bacterial vaginosis were obtained at baseline and 4 weeks after treatment. RESULTS There was no significant difference in therapeutic cure rates (defined as a Gram stain score of 0–3 and the absence of all four clinical signs of bacterial vaginosis) between the two groups (71% and 70% for the oral and vaginal groups, respectively, P = 1.0). Cervical levels of interleukin-1β, -6, and -8 were significantly lower after treatment among the 72 women cured of bacterial vaginosis (P < .001, P = .001, and P = .02, respectively) but not among women who failed to respond to therapy. For interleukin-1β and -6, a significant decrease in cytokine level was observed in both the oral and vaginal treatment groups. CONCLUSION One week of oral metronidazole and 5 days of intravaginal metronidazole are equally efficacious for treatment of bacterial vaginosis during pregnancy. The decrease in cervical interleukin-1β, -6, and -8 levels among women who established a normal flora after treatment but not among those with persistent bacterial vaginosis suggests a direct linkage between vaginal flora abnormalities and elevated cervical levels of interleukin-1β, -6, and -8.

Current trends in the diagnosis and treatment of tuboovarian abscess

Tuboovarian abscess is a well-recognized complication of acute salpingitis and has been reported in as many as one third of hospital admissions for acute salpingitis. The incidence of tuboovarian abscess is expected to increase as a result of the current epidemic of sexually transmitted diseases and their sequelae. Patients with tuboovarian abscess most commonly present with lower abdominal pain and an adnexal mass(es). Fever and leukocytosis may be absent. Ultrasound, computed tomographic scans, laparoscopy, or laparotomy may be necessary to confirm the diagnosis. Tuboovarian abscess may be unilateral or bilateral regardless of intrauterine contraceptive device usage. Tuboovarian abscess is polymicrobial with a preponderance of anaerobic organisms. An initial conservative antimicrobial approach to the management of the unruptured tuboovarian abscess is appropriate if the antimicrobial agents used can penetrate abscesses, remain active within the abscess environment, and are active against the major pathogens in tuboovarian abscess, including the resistant gram-negative anaerobes such as Bacteroides fragilis and Bacteroides bivius. However, if the patient does not begin to show a response within a reasonable amount of time, about 48 to 72 hours, surgical intervention should be undertaken. Suspicion of rupture should remain an indication for immediate operation. Once operation is undertaken, a conservative approach with unilateral adnexectomy for one-side tuboovarian abscess is appropriate if future fertility or hormone production is desired.

Parturients Infected with Human Immunodeficiency Virus and Regional Anesthesia Clinical and Immunologic Response

Background It is estimated that 1.5 million Americans are infected with the human immunodeficiency virus (HIV‐1), and the consequences of HIV infection are a leading cause of death in women aged 15–44 yr. Thus, HIV‐1 disease, or acquired immunodeficiency syndrome, occurs with increasing frequency in the parturient, and there is little information concerning the risks of regional anesthesia. Fear of spreading infection to the central nervous system or adverse neurologic sequelae have led some clinicians to advise against regional anesthesia. Thus, this study was undertaken to evaluate the possible problems or risks associated with regional anesthesia in parturients infected with HIV‐1 and to determine whether anesthesia affected the clinical course of the disease. Methods The clinical course and immunologic function of 30 parturients infected with HIV‐1 were evaluated prospectively. Extensive medical and laboratory evaluation before delivery and 4–6 months postpartum was undertaken. Medical problems related to HIV‐1 disease and use of antiviral drugs also were monitored. The anesthetic management was dictated by the clinical situation and the patients wishes with careful postpartum follow‐up to evaluate possible neurologic changes or infection. Results Regional anesthesia was administered in 18 parturients, and 12 received small doses of opioids or no analgesia. There were no changes in the immunologic parameters studied (CD4 sup + p24, beta sub 2 microglobulins), and HIV‐1 disease remained stable in the peripartum period. There were no infections, complications, or neurologic changes in the peripartum period. Sixty‐eight percent of the infants were HIV‐l‐negative and, in 21% of infants, the HIV‐1 status was indeterminate (probably negative). Conclusions This prospective study of parturients infected with HIV‐1 demonstrated that regional anesthesia can be performed without adverse sequelae. There were no neurologic or infectious complications related to the obstetric or anesthetic course. The immune function of the parturient was stable in the peripartum period. Although the number of patients studied was small, with careful medical evaluation, regional anesthesia is an acceptable choice in the parturient infected with HIV‐1.