Home-based versus clinic-based specimen collection in the management of Chlamydia trachomatis and Neisseria gonorrhoeae infections

BACKGROUND Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most frequent causes of bacterial sexually transmitted infections (STIs). Management strategies that reduce losses in the clinical pathway from infection to cure might improve STI control and reduce complications resulting from lack of, or inadequate, treatment. OBJECTIVES To assess the effectiveness and safety of home-based specimen collection as part of the management strategy for Chlamydia trachomatis and Neisseria gonorrhoeae infections compared with clinic-based specimen collection in sexually-active people. SEARCH METHODS We searched the Cochrane Sexually Transmitted Infections Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS on 27 May 2015, together with the World Health Organization International Clinical Trials Registry (ICTRP) and ClinicalTrials.gov. We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. SELECTION CRITERIA Randomized controlled trials (RCTs) of home-based compared with clinic-based specimen collection in the management of C. trachomatis and N. gonorrhoeae infections. DATA COLLECTION AND ANALYSIS Three review authors independently assessed trials for inclusion, extracted data and assessed risk of bias. We contacted study authors for additional information. We resolved any disagreements through consensus. We used standard methodological procedures recommended by Cochrane. The primary outcome was index case management, defined as the number of participants tested, diagnosed and treated, if test positive. MAIN RESULTS Ten trials involving 10,479 participants were included. There was inconclusive evidence of an effect on the proportion of participants with index case management (defined as individuals tested, diagnosed and treated for CT or NG, or both) in the group with home-based (45/778, 5.8%) compared with clinic-based (51/788, 6.5%) specimen collection (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.60 to 1.29; 3 trials, I² = 0%, 1566 participants, moderate quality). Harms of home-based specimen collection were not evaluated in any trial. All 10 trials compared the proportions of individuals tested. The results for the proportion of participants completing testing had high heterogeneity (I² = 100%) and were not pooled. We could not combine data from individual studies looking at the number of participants tested because the proportions varied widely across the studies, ranging from 30% to 96% in home group and 6% to 97% in clinic group (low-quality evidence). The number of participants with positive test was lower in the home-based specimen collection group (240/2074, 11.6%) compared with the clinic-based group (179/967, 18.5%) (RR 0.72, 95% CI 0.61 to 0.86; 9 trials, I² = 0%, 3041 participants, moderate quality). AUTHORS' CONCLUSIONS Home-based specimen collection could result in similar levels of index case management for CT or NG infection when compared with clinic-based specimen collection. Increases in the proportion of individuals tested as a result of home-based, compared with clinic-based, specimen collection are offset by a lower proportion of positive results. The harms of home-based specimen collection compared with clinic-based specimen collection have not been evaluated. Future RCTs to assess the effectiveness of home-based specimen collection should be designed to measure biological outcomes of STI case management, such as proportion of participants with negative tests for the relevant STI at follow-up.

Azithromycin efficacy in treatment of Chlamydia trachomatis

Adolescents 15 – 19 years of age have the highest prevalence of Chlamydia trachomatis out of any age group, reaching 28.3% among detained youth [1]. The 2010 Center for Disease Control guidelines recommend one dose of azithromycin for the treatment of uncomplicated chlamydia infections based on 97% cure rate with azithromycin. Recent studies found an 8% or higher failure rate of azithromycin treatment in adolescents [2-5]. We conducted a prospective study beginning May, 2012 in the Harris County Juvenile Justice Center (HCJJC) medical department. Study subjects were detainees with positive urine NAAT tests for chlamydia on intake. We provided treatment with Azithromycin, completed questionnaires assessing risk factors and performed a test of cure for chlamydia three weeks after successful treatment. Those with treatment failure (positive TOC) received doxycycline for seven days. The preliminary results summarized herein are based on data collected from May 2012 to January 2013. Of the 97 youth enrolled in the study to date, 4 (4.1%) experienced treatment failure after administration of Azithromycin. Of these four patients, all were male, African-American and asymptomatic at the time of initial diagnosis and treatment. Of note, 37 (38%) patients in the cohort complained of abdominal pain with administration of Azithromycin. Results to date suggest that the efficacy of Azithromycin in our study is higher than the recent reported studies indicating a possible upper bound of Azithromycin. These results are preliminary and recruitment will continue until a sample size of 127 youth is reached.^

A recombinant Chlamydia trachomatis major outer membrane protein binds to heparan sulfate receptors on epithelial cells.

Chlamydial attachment to columnar conjunctival or urogenital epithelial cells is an initial and critical step in the pathogenesis of chlamydial mucosal infections. The chlamydial major outer membrane protein (MOMP) has been implicated as a putative chlamydial cytoadhesin; however, direct evidence supporting this hypothesis has not been reported. The function of MOMP as a cytoadhesin was directly investigated by expressing the protein as a fusion with the Escherichia coli maltose binding protein (MBP-MOMP) and studying its interaction with human epithelial cells. The recombinant MBP-MOMP bound specifically to HeLa cells at 4 degrees C but was not internalized after shifting the temperature to 37 degrees C. The MBP-MOMP competitively inhibited the infectivity of viable chlamydiae for epithelial cells, indicating that the MOMP and intact chlamydiae bind the same host receptor. Heparan sulfate markedly reduced binding of the MBP-MOMP to cells, whereas chondroitin sulfate had no effect on binding. Enzymatic treatment of cells with heparitinase but not chondroitinase inhibited the binding of MBP-MOMP. These same treatments were also shown to reduce the infectivity of chlamydiae for epithelial cells. Mutant cell lines defective in heparan sulfate synthesis but not chondroitin sulfate synthesis showed a marked reduction in the binding of MBP-MOMP and were also less susceptible to infection by chlamydiae. Collectively, these findings provide strong evidence that the MOMP functions as a chlamydial cytoadhesin and that heparan sulfate proteoglycans are the host-cell receptors to which the MOMP binds.

Lipid metabolism in Chlamydia trachomatis-infected cells: directed trafficking of Golgi-derived sphingolipids to the chlamydial inclusion.

Chlamydia trachomatis undergoes its entire life cycle within an uncharacterized intracellular vesicle that does not fuse with lysosomes. We used a fluorescent Golgi-specific probe, (N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]) aminocaproylsphingosine (C6-NBD-Cer), in conjunction with conventional fluorescence or confocal microscopy to identify interactions between the Golgi apparatus and the chlamydial inclusion. We observed not only a close physical association between the Golgi apparatus and the chlamydial inclusion but the eventual presence of a metabolite of this fluorescent probe associated with the chlamydiae themselves. Sphingomyelin, endogenously synthesized from C6-NBD-Cer, was specifically transported to the inclusion and incorporated into the cell wall of the intracellular chlamydiae. Incorporation of the fluorescent sphingolipid by chlamydiae was inhibited by brefeldin A. Chlamydiae therefore occupy a vesicle distal to the Golgi apparatus that receives anterograde vesicular traffic from the Golgi normally bound for the plasma membrane. Collectively, the data suggest that the chlamydial inclusion may represent a unique compartment within the trans-Golgi network.

An investigation into swab and urine samples for the detection of chlamydia trachomatis genital infections

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Caractérisation des infections à Chlamydia trachomatis persistantes induites par l'action des antibiotiques

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Defining the Role of Host Cell Chromatin Traps in Chlamydia trachomatis Pathogenesis

Chlamydia trachomatis (CT) is the most common bacterial agent of sexually transmitted infection and can cause damaging inflammation of the female reproductive tract. As an obligate intracellular pathogen, CT must exit exhausted host cells in a manner that favors successful dissemination. Epithelial cells infected with CT expel decondensed nuclear chromatin at the conclusion of an infectious cycle, and these ensnare CT particles. Whether these chromatin traps benefit the host or the pathogen is not obvious. The overall goal of this work is to begin discerning between these possibilities by determining how chromatin traps impact CT survival following exit and how traps contribute to CT-induced inflammatory processes.

Caractérisation des infections à Chlamydia trachomatis persistantes induites par l'action des antibiotiques

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Association of human papillomavirus and Chlamydia trachomatis with intraepithelial alterations in cervix samples

The influence of different infectious agents and their association with human papillomavirus (HPV) in cervical carcinogenesis have not been completely elucidated. This study describes the association between cytological changes in cervical epithelium and the detection of the most relevant aetiological agents of sexually transmitted diseases. Samples collected from 169 patients were evaluated by conventional cytology followed by molecular analysis to detect HPV DNA, Chlamydia trachomatis , herpes simplex virus 1 and 2, Neisseria gonorrhoeae , Mycoplasma genitalium , Trichomonas vaginalis, and Treponema pallidum , besides genotyping for most common high-risk HPV. An association between cytological lesions and different behavioural habits such as smoking and sedentariness was observed. Intraepithelial lesions were also associated with HPV and C. trachomatis detection. An association was also found between both simple and multiple genotype infection and cytological changes. The investigation of HPV and C. trachomatis proved its importance and may be considered in the future for including in screening programs, since these factors are linked to the early diagnosis of patients with precursor lesions of cervical cancer.

Effects of sugars and lactic acid isomers on Chlamydia trachomatis infectivity, an in vitro study

The thesis investigates two different in vitro aspects of Chlamydia trachomatis (CT). The thesis analyzes the effect of different sugars on CT infectivity. which is investigated on HeLa cells after 2 hour-incubation of elementary bodies (EBs) with glucose, sucrose or mannitol. Sugars effect on EB membrane fluidity is investigated by fluorescence anisotropy measurement, whereas changes in lipopolysaccharide exposure are examined by cytofluorimetric analysis. By Western blot experiments, the phosphorylation state of Focal Adhesion Kinase in cells infected with EBs pre-incubated with sugars it’s explored. Sugar significantly increase infectivity, acting on the EB structure. Sugars induce an increase of EB membrane fluidity, leading to changes in LPS exposure. After incubation with sucrose and mannitol, EBs lead to higher FAK phosphorylation, enhancing activation of anti-apoptotic and proliferative signals in the host. Secondly, the thesis explores the protective effect of different Lactobacilli against CT infection: Lactobacillus crispatus and Lactobacillus reuteri. CT infectivity is evaluated after host cells were treated for 1 hour with diluted supernatant cell-free fraction or with the bacterial cells. Assessed that L.crispatus is more protective than L.reuteri, lactic acid production is evaluated by HPLC. Subsequently Lactate dehydrogenases activity is evaluated by resazurin assay and by LC-MS. Then, D-lactate dehydrogenase specific activity has been investigated by measuring NADH formation. Afterwards, addition of D or L-lactic acid to L.reuteri supernatant has been performed and their effect in promoting protection in the host cells assessed. Then a metabolic analysis has been carried out by real-time measurement of mitochondrial respiration after treatment. Finally, histone acetylation and lactylation, and gene and protein expression of relevant targets, have been investigated. It is shown that the D isomer is more efficient in conferring protection, causing a shift in the host cell metabolic profile and a pattern of histone modifications that changes the expression of important targets.

Is Chlamydia-infected tubal fimbria the origin of ovarian cancer?

Ovarian cancer is a highly lethal disease and its underlying biology is poorly understood. Prophylactic salpingo-oophorectomies in BRCA + women have recently implicated the fimbria as a site of origin for high-grade serous carcinoma and its intraepithelial precursors. This suggests that at least some ovarian cancers, probably the most aggressive ones, may not originate in the ovary itself, but rather may arise in the uterine tubes. Chronic inflammation is associated with carcinogenesis in several tissues, including liver, esophagogastric junction (cardia), and the uterine cervix. The mechanisms underlying the relationship between inflammation and cancer are complex and involve common pathways, in addition to DNA damage. A critical source of uterine tube inflammation is infection with Chlamydia trachomatis. We hypothesize that C. trachomatis infection may be involved in chronic tubal, inflammation and subsequent fimbrial carcinogenesis. Fimbrial intraepithelial precursors can evolve into high grade serous carcinomas that spread rapidly to the ovarian surface and peritoneum; such tumors may appear to be primary ovarian neoplasia, though in reality being a secondary malignancy. This hypothesis must be further investigated to understand the intracellular signaling pathways involved in Chlamydia infection and its heating, and their relationship to carcinogenesis in order to discover potential therapeutic molecular targets. If our hypothesis were confirmed, salpingectomy instead of ovariectomy may also become the recommended surgery for high risk women. (C) 2008 Elsevier Ltd. All rights reserved.

Prevalência da C.trachomatis entre homens que fazem sexo com homens (HSH) que frequentam um centro clínico comunitário alternativo em Barcelona

RESUMO - Enquadramento: A infeção por Chlamydia trachomatis (CT) é considerada um grave problema de Saúde Pública. É causa de infeções sintomáticas tanto no homem como na mulher, bem como, de infeções assintomáticas que podem ter consequências muito graves a longo prazo. A presença de CT sem tratamento aumenta o risco de transmissão do vírus da imunodeficiência humana. Existem vários estudos publicados de prevalência da CT por todo o mundo, no entanto, estudos de prevalência da CT em populações assintomáticas, envolvendo homens que fazem sexo com homens (HSH) são raros na Europa. Assim, o presente estudo, ao estimar a prevalência e ao descrever as caraterísticas epidemiológicas e de conduta dos HSH, pretende contribuir para o plano de ação contra as IST´s e VIH na Catalunha, através de estratégias concretas para deteção e prevenção da CT. Métodos: Trata-se de um estudo observacional, transversal de prevalência da CT em HSH utentes de um serviço comunitário em Barcelona, com recurso a técnicas de diagnóstico de biologia molecular e a um questionário. Durante Março e Junho de 2015, foram recrutados 200 voluntários de um serviço comunitário em Barcelona que foram testados para CT e NG em três locais anatómicos através de uma PCR em tempo real utilizando o ensaio Anyplex™ CT/NG Real-time Detection. Resultados: O presente estudo permitiu uma caraterização da situação atual quanto á prevalência e aos fatores de risco associados á infeção por CT em HSH. A prevalência nesta população específica foi de 12,6% e os fatores risco associados foram o facto de serem VIH e praticarem sexo anal insertivo/recetivo com parceiro estável. Conclusões: Os resultados obtidos reforçam a necessidade do desenvolvimento de estratégias adequadas de controlo e prevenção da CT nesta população de risco, tais como: rastreios frequentes e tratamento dos casos positivos para quebrar a cadeia de transmissão, promoção da saúde, educação e notificação dos parceiros sexuais. Também demonstram a importância destes rastreios nos três locais anatómicos: uretra, reto e faringe.