Point of care tests for sexually transmitted infections (STIs)

A number of clinical/disease areas have been prioritised by the Technology Strategy Board (TSB) and Department of Health (DH) for the DIIA Innovation Platform. To support commissioning of technology development for detection of sexually transmitted infections (STIs) in humans, a scoping review has been undertaken to help identify the specific requirements for new diagnostic test development and likely economic payback for point of care (POC) tests for STIs in the UK

Timing of progression from Chlamydia trachomatis infection to pelvic inflammatory disease: a mathematical modelling study

PMCID: PMC3505463The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2334/12/187. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Penicillin kills chlamydia following the fusion of bacteria with Lysosomes and prevents genital inflammatory lesions in C. muridarum-infected mice

The obligate intracellular bacterium Chlamydia exists as two distinct forms. Elementary bodies (EBs) are infectious and extra-cellular, whereas reticulate bodies (RBs) replicate within a specialized intracellular compartment termed an ‘inclusion’. Alternative persistent intra-cellular forms can be induced in culture by diverse stimuli such as IFNγ or adenosine/EHNA. They do not grow or divide but revive upon withdrawal of the stimulus and are implicated in several widespread human diseases through ill-defined in vivo mechanisms. β-lactam antibiotics have also been claimed to induce persistence in vitro. The present report shows that upon penicillin G (pG) treatment, inclusions grow as fast as those in infected control cells. After removal of pG, Chlamydia do not revert to RBs. These effects are independent of host cell type, serovar, biovar and species of Chlamydia. Time-course experiments demonstrated that only RBs were susceptible to pG. pG-treated bacteria lost their control over host cell apoptotic pathways and no longer expressed pre-16S rRNA, in contrast to persistent bacteria induced with adenosine/EHNA. Confocal and live-video microscopy showed that bacteria within the inclusion fused with lysosomal compartments in pG-treated cells. That leads to recruitment of cathepsin D as early as 3 h post pG treatment, an event preceding bacterial death by several hours. These data demonstrate that pG treatment of cultured cells infected with Chlamydia results in the degradation of the bacteria. In addition we show that pG is significantly more efficient than doxycycline at preventing genital inflammatory lesions in C. muridarum-C57Bl/6 infected mice. These in vivo results support the physiological relevance of our findings and their potential therapeutic applications

Role of lactobacilli and lactoferrin in the mucosal cervicovaginal defense

Human lactoferrin is an iron-binding glycoprotein present at high concentrations in breast milk and colostrum. It is produced by many exocrine glands and widely distributed in a variety of body fluids. This protein has antimicrobial, immunomodulatory, antioxidant, and anticancer properties. Two important hLf receptors have been identified: LDL receptor related protein (LRP1), a low specificity receptor, and intelectin-1 (ITLN1), a high specificity receptor. No data are present on the role of hLf on the biliary epithelium. Our aims have been to evaluate the expression of Lf and its receptors in human and murine cholangiocytes and its effect on proliferation. Immunohistochemistry and immunofluorescence (IF) were conducted on human healthy and primary biliary cholangitis (PBC) liver samples as well as on liver samples obtained from normal and bile duct ligated (BDL) mice to evaluate the expression of Lf, LRP1 and ITLN1. Cell proliferation in vitro studies were performed on human cholangiocyte cell lines via 3-(4,5-dimetiltiazol-2-il)-2,5-diphenyltetrazolium assay as well as IF to evaluate proliferating cell nuclear antigen (PCNA) expression. Our results show that mouse and human cholangiocytes express Lf, LRP1 and ITLN1, at higher extent in cholangiocytes from BDL and PBC samples. Furthermore, the in vitro addition of bovine Lf (bLf) has a proliferative effect on human cholangiocyte cell line. The results support a proliferative role of hLf on the biliary epithelium; this pro-proliferative effect of hLf and bLf on cholangiocytes could be particularly relevant in human cholangiopathies such as PBC, characterized by cholangiocyte death and ductopenia

Costs and health consequences of chlamydia management strategies among pregnant women in sub-Saharan Africa

Objectives: Chlamydia is the most common bacterial sexually transmitted infection worldwide and a major cause of morbidity – particularly among women and neonates. We compared costs and health consequences of using point-of-care (POC) tests with current syndromic management among antenatal care attendees in sub-Saharan Africa. We also compared erythromycin with azithromycin treatment and universal with age-based chlamydia management. Methods: A decision analytic model was developed to compare diagnostic and treatment strategies, using Botswana as a case. Model input was based upon 1) a study of pregnant women in Botswana, 2) literature reviews and 3) expert opinion. We expressed the study outcome in terms of costs (US$), cases cured, magnitude of overtreatment and successful partner treatment. Results: Azithromycin was less costly and more effective than was erythromycin. Compared to syndromic management, testing all attendees on their first visit with a 75$38 per additional case cured. This cost was lower in high-prevalence populations or if testing was restricted to teenagers. The specific POC tests provided the advantage of substantial reductions in overtreatment with antibiotics and improved partner management. Conclusions: Using POC tests to diagnose chlamydia during antenatal care in sub-Saharan Africa entails greater health benefits than syndromic management does – and at acceptable costs – especially when restricted to younger women. Changes in diagnostic strategy and treatment regimens may improve people’s health and even reduce health care budgets.Chlamydia trachomatis (MeSH); Cost-effectiveness analysis (non-MeSH); Cost Analysis (MeSH); Developing countries (MeSH); Africa (MeSH); Sub-Saharan Africa (MeSH) Maternal health (non-MeSH); Maternal Health Services (MeSH); Women’s Health (MeSH); Point-of-care tests (non-MeSH); Diagnostic tests (non-MeSH); Diagnosis (MeSH); Syndromic approach (non-MeSH); STI management (non-MeSH)

Chlamydial infection from outside to inside

Chlamydia are obligate intracellular bacteria, characterized by a unique biphasic developmental cycle. Specific interactions with the host cell are crucial for the bacteria's survival and amplification because of the reduced chlamydial genome. At the start of infection, pathogen-host interactions are set in place in order for Chlamydia to enter the host cell and reach the nutrient-rich peri-Golgi region. Once intracellular localization is established, interactions with organelles and pathways of the host cell enable the necessary hijacking of host-derived nutrients. Detailed information on the aforementioned processes will increase our understanding on the intracellular pathogenesis of chlamydiae and hence might lead to new strategies to battle chlamydial infection. This review summarizes how chlamydiae generate their intracellular niche in the host cell, acquire host-derived nutrients in order to enable their growth and finally exit the host cell in order to infect new cells. Moreover, the evolution in the development of molecular genetic tools, necessary for studying the chlamydial infection biology in more depth, is discussed in great detail

Aspects of human chlamydial infections

This thesis takes a closer look at three aspects of human chlamydial infections. With regard to diagnosis the influence of logistics on the sensitivity of the culture method is discussed, along with optimalization of the culture itself and an evaluation of new diagnostic methods. Next, epidemiological data are discussed with regard to the prevalence and role of Chlamydia, on the one hand in asymptomatic persons from low-risk groups and on the other hand in women with postinflammatory tubal infertility. Finally the therapeutic problems are considered with reference to measurements of the in-vitro sensitivity of various chlamydial strains to tetracycline and some recently developed chemotherapeutic agents. The significance of Chlamydia for some of the sexually transmitted nongonococcal oculogeni tal infections was not generally recognised until relatively recently. One of the reasons for this was undou~tedly the lack of a culture method to isolate the organism for study of its biological characteristics. Even after the introduction of a technique to culture Chlamydia on cell lines, large scale epidemiological research was impeded by lack of adequately equipped laboratories where the complicated method might be employed. The manner of collecting patient material for culture, transport from outpatient clinic to laboratory, and the culture method employed are critical parameters which determine the ultimate result. A disadvantage of the culture method is the relatively long time required (6 days). Rapid diagnosis and if necessary treatment, especially of asymptomatic persons, is of great epidemiological importance. Chlamydial antigen-detecting methods have recently been developed which can present results within a few hours. They are based on the immunofluorescence (IF) technique and on the enzyme immunoassay (EIA). Both techniques employ monoclonal antibodies against genus-specific epitopes of the Major Outer Membrane Protein (IF technique) or of the lipopolysaccharide (EIA). The chlamydiae in patient material need no longer be alive for analysis, and transport to the laboratory therefore no longer influences the sensitivity of detection

Improved effectiveness of partner notification for patients with sexually transmitted infections: systematic review

Objective: To examine the effectiveness of methods to improve partner notification by patient referral (index patient has responsibility for informing sex partners of their exposure to a sexually transmitted infection). Design: Systematic review of randomised trials of any intervention to supplement simple patient referral. Data sources: Seven electronic databases searched (January 1990 to December 2005) without language restriction, and reference lists of retrieved articles. Review methods: Selection of trials, data extraction, and quality assessment were done by two independent reviewers. The primary outcome was a reduction of incidence or prevalence of sexually transmitted infections in index patients. If this was not reported data were extracted according to a hierarchy of secondary outcomes: number of partners treated; number of partners tested or testing positive; and number of partners notified, located, or elicited. Random effects meta-analysis was carried out when appropriate. Results: 14 trials were included with 12 389 women and men diagnosed as having gonorrhoea, chlamydia, non-gonococcal urethritis, trichomoniasis, or a sexually transmitted infection syndrome. All studies had methodological weaknesses that could have biased their results. Three strategies were used. Six trials examined patient delivered partner therapy. Meta-analysis of five of these showed a reduced risk of persistent or recurrent infection in patients with chlamydia or gonorrhoea (summary risk ratio 0.73, 95% confidence interval 0.57 to 0.93). Supplementing patient referral with information for partners was as effective as patient delivered partner therapy. Neither strategy was effective in women with trichomoniasis. Two trials found that providing index patients with chlamydia with sampling kits for their partners increased the number of partners who got treated. Conclusions: Involving index patients in shared responsibility for the management of sexual partners improves outcomes. Health professionals should consider the following strategies for the management of individual patients: patient delivered partner therapy, home sampling for partners, and providing additional information for partners

Specific-pathogen-free pigs as an animal model for studying Chlamydia trachomatis genital infection

The purpose of the present study was to evaluate pigs as a large-animal model for female genital infection with two Chlamydia trachomatis human serovar E strains. Sixteen-week-old specific-pathogen-free female pigs (gilts) were intravaginally infected with the trachoma type E reference strain Bour or the urogenital serovar E strain 468. Several conclusions can be drawn from our findings on the pathogenicity of a primary C. trachomatis genital infection in gilts. First of all, we demonstrated that the serovar E strains Bour and 468 could ascend in the genital tract of gilts. The serovar E strains could replicate in the superficial columnar cervical epithelium and in the superficial epithelial layer of the uterus, which are known to be the specific target sites for a C. trachomatis genital infection in women. Second, inflammation and pathology occurred at the replication sites. Third, the organisms could trigger a humoral immune response, as demonstrated by the presence of immunoglobulin M (IgM), IgG, and IgA in both serum and genital secretion samples. Our findings imply that the pig model might be useful for studying the pathology, pathogenesis, and immune response to a C. trachomatis infection of the genital system