Mucosal Escherichia coli bactericidal activity and immune mediators are associated with HIV-1 seroconversion in women participating in the HPTN 035 trial.

The mucosal environment may impact the risk for human immunodeficiency virus type 1 (HIV-1) acquisition. Immune mediators were measured in vaginal fluid collected from HPTN 035 participants who acquired HIV-1 and from those who remained HIV-1 negative (controls). Mediator concentrations were similar in samples obtained before as compared to after HIV-1 acquisition in the 8 seroconverters. Compared with controls, seroconverters were more likely to have detectable levels of HßD-2 (odds ratio [OR], 2.39; P = .005) and greater Escherichia coli bactericidal activity (OR, 1.22; P = .01) prior to seroconversion. E. coli bactericidal activity remained significant in a multivariable analysis (P = .02) and may be a biomarker for HIV-1 acquisition.

Association of bactericidal activity of genital tract secretions with Escherichia coli colonization in pregnancy.

OBJECTIVE: Genital tract secretions exhibit bactericidal activity against Escherichia coli. We hypothesized that this defense may be modulated during pregnancy. STUDY DESIGN: Secretions were collected by vaginal swab from 70 pregnant women (35-37 weeks' gestation) and 35 nonpregnant controls. We mixed E coli with swab eluants or control buffer and colonies enumerated to measure bactericidal activity. Cytokines, chemokines, and antimicrobial peptides were quantified by multiplex or enzyme-linked immunosorbent assay. RESULTS: Pregnant women had significantly greater bactericidal activity, higher concentrations of proinflammatory cytokines, and lower levels of beta defensins compared to controls. Seven (10%) pregnant and 8 (23%) nonpregnant women were vaginally colonized with E coli; colonization was inversely associated with bactericidal activity. CONCLUSION: The soluble mucosal immune environment is altered in pregnancy. We speculate that the observed changes may protect against colonization and ascending infection and could provide a biomarker to identify pregnant women at risk for infectious complications including preterm birth.

Evaluation of a unilateral neck mass in a 16-year-old female: Kikuchi-Fujimoto disease with superimposed bacterial lymphadenitis.

The evaluation of pediatric neck masses offers the opportunity for consideration of a diverse range of pathologies, from infectious to neoplastic. A 16-year-old female presented with 2 weeks of worsening swelling and pain of a left-sided neck mass. Findings were consistent with Epstein-Barr virus and cytomegalovirus coinfection, but considering profound lymphadenopathy of the supraclavicular, mammillary, and axillary chains, further investigations were undertaken. Hematopathologic examination demonstrated necrotizing lymphadenitis, consistent with Kikuchi-Fujimoto disease. A diagnosis of Kikuchi-Fujimoto disease alongside chronic bacterial lymphadenitis was made on the basis of her response to clindamycin, and the chronic course of her illness and subsequent persistence of the swelling managed on an outpatient basis. The case study describes the initial diagnostic considerations and management as well as a review of the disease pathology.

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

Greater inhibitory activity against Escherichia coli and levels of human ß defensin (HBD)-2 in genital tract secretions predicted HIV acquisition in women in the HPTN 035 trial. We investigated whether higher levels of E. coli inhibitory activity and antimicrobial peptides in cervicovaginal lavage (CVL) samples predicted HIV acquisition in women in the CAPRISA 002 Acute Infection Study. E. coli inhibitory activity and antimicrobial peptides were quantified in CVL from a subset of CAPRISA 002 participants who did not seroconvert (n=39) and from seroconverting women prior to infection (n=17) and during acute infection (n=11). Women who acquired HIV had significantly greater preinfection CVL E. coli inhibitory activity (p=0.01) and HBD-1 levels (p=0.02) compared to women who remained uninfected. Preinfection E. coli inhibitory activity remained significantly associated with seroconversion following adjustment for the presence of bacterial vaginosis (OR 1.45; 95% CI 1.07, 1.97). Partial least squares discriminant analysis confirmed that preinfection CVL E. coli inhibitory activity, together with higher CVL concentrations of HBD-1 and secretory leukocyte protease inhibitor, distinguished seroconverters from nonseroconverters with 67% calibration accuracy. CVL concentrations of human neutrophil peptides (HNP) 1-3 increased significantly with acute infection (p=0.001) and correlated with plasma viral set point (r=0.66, p=0.03). E. coli inhibitory activity in genital tract secretions could provide a biomarker of HIV risk. The correlation between HNP 1-3 and viral set point merits further investigation of the relationship between mucosal inflammation during early HIV infection and disease progression.