Increase in Endocervical CD4 Lymphocytes among Women with Nonulcerative Sexually Transmitted Diseases

Division of Sexually Transmitted Disease Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, and Fulton County Health Department, Atlanta, Georgia 30333, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 01/1998; 177(1):167-74. DOI: 10.1086/513820
Source: PubMed


To assess associations of nonulcerative sexually transmitted diseases (STDs) with human immunodeficiency virus (HIV)-susceptible leukocytes on female genital mucosa, cervicovaginal specimens from 32 HIV-negative STD clinic patients with gonorrhea, chlamydial infection, or trichomoniasis were compared with specimens from 32 clinic patients without these infections. Twenty-eight patients had single infections (15 gonorrhea, 10 chlamydial infection, 3 trichomoniasis), and 4 had dual infections. A saline vaginal wash and saline suspensions of vaginal wall scrapings, ectocervical scrapings, and endocervical brushings were analyzed by flow cytometry. Specimens from the endocervix had the highest proportions of lymphocytes, monocytes, and Langerhans' cells. The median number of endocervical CD4 lymphocytes/10,000 cells was greater among patients with STDs than among those without (476 vs. 245; P < .001). These data suggest that the endocervix may have a particularly important role in heterosexual HIV transmission and that nonulcerative STDs may facilitate HIV transmission by increasing the presence of CD4 lymphocytes at this site.

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Available from: Akbar Ali Zaidi, Oct 13, 2015
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    • "Gonorrhoea has consistently been identified as a risk factor for incident HIV infection in both heterosexual and MSM populations [5-7]. This is thought to result from increased HIV viral shedding in genital secretions [8,9] and from an increased concentration of target cells for HIV in the locally inflamed mucosa found in individuals with gonorrhoea [10]. Ensuring effective gonorrhoea testing and treatment is therefore important to both reduce the global incidence of curable sexually transmitted infections and control the spread of HIV. "
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    ABSTRACT: A high level of resistance in Neisseria gonorrhoeae has developed against penicillins, sulphonamides, tetracyclines and quinolones, and recent surveillance data have shown a gradual reduction in sensitivity to current first-line agents with an upward drift in the minimum inhibitory concentration of ceftriaxone. Laboratory sensitivity testing suggests that gentamicin, an aminoglycoside, may be an effective treatment option for gonorrhoea infection when used as a single intramuscular dose. A search of electronic reference databases and grey literature was used to identify randomised trials and well-conducted prospective studies with concurrent controls evaluating single-dose gentamicin against placebo or a comparator regimen in the treatment of uncomplicated gonorrhoea infection in men and women aged 16 years and over. The primary outcome was microbiological cure of N. gonorrhoeae. Eight hundred and thirty-nine studies were identified, of which five (1,063 total participants) were included. All five studies administered single-dose gentamicin via intramuscular injection to men with uncomplicated gonococcal urethritis. Three studies were randomised trials, one was quasi-randomised and one was non-randomised but included a comparator arm. Comparator antibiotics included an alternative aminoglycoside or antibiotic used in the syndromic management of male urethritis. Methodology was poorly described in all five included studies. The high risk of bias within studies and clinical heterogeneity between studies meant that it was inappropriate to pool data for meta-analysis. Cure rates of 62% to 98% were reported with gentamicin treatment. The relative risk of cure was comparable between gentamicin and comparator antibiotics. The studies identified provide insufficient data to support or refute the efficacy and safety of single-dose intramuscular gentamicin in the treatment of uncomplicated gonorrhoea infection. Additional randomised trials to evaluate gentamicin for this indication are therefore required. Systematic review registration PROSPERO CRD42012002490
    Systematic Reviews 09/2014; 3(1):104. DOI:10.1186/2046-4053-3-104
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    • "In this human study, we observed elevated levels of chemokines such as RANTES and MIP- 1␣ in endocervical secretions from C. trachomatis-positive women compared with post-treatment samples. Induction of these chemokines may contribute to the recruitment of endocervical CD4+ T cells found in women with C. trachomatis infection (Mittal et al., 2004; Ficarra et al., 2008; Levine et al., 1998). In the rhesus macaque model, in response to SIV challenges, the endocervical epithelium produces MIP-3␣ to recruit pDCs that produce cytokines (IFN␣) and chemokines (MIP-1␣ and MIP-1␤), leading to the migration of CCR5-expressing cells such as CD4+ T cells, which are SIV/HIV target cells (Li et al., 2009). "
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    ABSTRACT: Chlamydia trachomatis infection is one of the most prevalent bacterial STIs in the USA and worldwide, and women with C. trachomatis infection are at increased risk of acquiring HIV. Because immune activation at the genital mucosa facilitates HIV/SIV infection, C. trachomatis-mediated cytokine induction may contribute to increased HIV transmission in asymptomatic women. To begin to elucidate the mechanisms, we longitudinally analyzed profiles of innate immune factors and HIV infectivity in genital secretions from anatomically specific sites in asymptomatic women during C. trachomatis infection and post-antibiotic treatment. We found higher levels of cytokines and chemokines in endocervical secretions than vaginal secretions. Compared with the convalescent state, G-CSF, IL-1α, and RANTES were elevated in endocervical secretions, IFN-γ and TNF-α were elevated in vaginal secretions, and IFNγ, IL-1β, and MIP1-α were elevated in cervicolavage fluid (CVL), before adjustment of multiple comparisons. Elevated endocervical levels of IP-10 and MCP-1 were associated with the use of hormonal contraception in infected women after successful treatment, suggesting the role of hormonal contraception in inflammation independent of STIs. Importantly, soluble factors found in endocervical secretions during infection enhanced HIV infectivity while no difference in HIV infectivity was found with vaginal secretions or CVL during infection or at convalescence. Taken together, the profiles of immune mediators and in vitro HIV infectivity indicate that the endocervical and vaginal mucosa are immunologically distinct. Our results underscore the importance of considering anatomical site and local sampling methodology when measuring mucosal responses, particularly in the presence of C. trachomatis infection.
    Journal of Reproductive Immunology 08/2013; 99(1-2). DOI:10.1016/j.jri.2013.07.003 · 2.82 Impact Factor
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    • "This relatively low frequency of transmission can be explained by a continuum of variables extending from the properties of the infectious inoculum to the properties of the exposed mucosal surfaces. The presence of pre-existing sexually transmitted infections (STI) is widely believed to increase susceptibility to HIV-1 infection for exposed women, presumably by causing damage to mucosal surfaces and signaling the recruitment of inflammatory cell infiltrates [24], [25], [26], [27]. Several previous studies have described interactions between herpes simplex virus (HSV-1 or HSV-2) and HIV-1 [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38]. "
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    ABSTRACT: Normal human premenopausal cervical tissue has been used to derive primary cell populations and to establish ex vivo organ culture systems to study infections with herpes simplex virus (HSV-1 or HSV-2) and human immunodeficiency virus type 1 (HIV-1). Infection with either HSV-1 or HSV-2 rapidly induced multinuclear giant cell formation and widespread damage in mucosal epithelial cells. Subsequent exposure of the damaged mucosal surfaces to HIV-1 revealed frequent co-localization of HSV and HIV-1 antigens. The short-term organ culture system provides direct experimental support for the epidemiological findings that pre-existing sexually transmitted infections, including primary and recurrent herpes virus infections at mucosal surfaces, represent major risk factors for acquisition of primary HIV-1 infection. Epithelial damage in combination with pre-existing inflammation, as described here for overtly normal human premenopausal cervix, creates a highly susceptible environment for the initiation and establishment of primary HIV-1 infection in the sub-mucosa of the cervical transformation zone.
    PLoS ONE 07/2011; 6(7):e22638. DOI:10.1371/journal.pone.0022638 · 3.23 Impact Factor
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