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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    • "Other sequelae include adverse pregnancy outcomes (pre-term birth, spontaneous abortion, stillbirth, low infant birth weight, ectopic pregnancy, chorioamnionitis, postpartum endometriosis or sepsis, ophthalmia neonatorum), infertility, and disseminated gonococcal infection [9]. Infection with N. gonorrhoeae also increases HIV replication, transmission, and infection [15] [16] [17]. In terms of economic burden, gonococcal infections are estimated to account for annual medical costs exceeding $1.1 billion in the United States alone [18]. "
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    ABSTRACT: Gonorrhea, one of the most common sexually transmitted infections worldwide, can lead to serious sequelae, including infertility and increased HIV transmission. Recently, untreatable, multidrug-resistant Neisseria gonorrhoeae strains have been reported. In the absence of new antibiotics, and given the speed with which resistance has emerged to all previously used antibiotics, development of a vaccine would be the ideal solution to this public health emergency. Understanding the desired characteristics, target population, and expected impact of an anti-gonococcal vaccine is essential to facilitate vaccine design, assessment and implementation. The modeling presented herein aims to fill these conceptual gaps, and inform future gonococcal vaccine development. Using an individual-based, epidemiological simulation model, gonococcal prevalence was simulated in a heterosexual population of 100,000 individuals after the introduction of vaccines with varied efficacy (10-100%) and duration of protection (2.5-20 years). Model simulations predict that gonococcal prevalence could be reduced by at least 90% after 20 years, if all 13-year-olds were given a non-waning vaccine with 50% efficacy, or a vaccine with 100% efficacy that wanes after 7.5 years. A 40% reduction in prevalence is achievable with a non-waning vaccine of only 20% efficacy. We conclude that a vaccine of moderate efficacy and duration could have a substantive impact on gonococcal prevalence, and disease sequelae, if coverage is high and protection lasts over the highest risk period (i.e., most sexual partner change) among young people. Copyright © 2015. Published by Elsevier Ltd.
    Vaccine 07/2015; 33(36). DOI:10.1016/j.vaccine.2015.07.015 · 3.62 Impact Factor
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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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