1,175 research outputs found
Doxycycline Prophylaxis for Bacterial Sexually Transmitted Infections
Bacterial sexually transmitted infections (STIs) have been increasing over the past 2 decades in gay, bisexual, and other men who have sex with men. With the widespread use of early human immunodeficiency virus (HIV) treatment, which virtually eliminates transmission risk, and the availability of HIV pre-exposure prophylaxis, there have been attitudinal changes regarding HIV infection with resultant increases in sexual contact and declines in condom use. Doxycycline is used for primary prophylaxis in a number of infectious diseases. We conducted a state-of-the-art review to examine the current state of research, knowledge gaps, and challenges around the use of doxycycline prophylaxis to prevent syphilis and other STIs. International academic and government experts met in March 2019 to frame the initial inquiry, which was supplemented by focused literature searches. Two small short-term randomized controlled trials examining doxycycline prophylaxis found high efficacy. Five additional clinical studies are underway or in development. Studies differed in design, population, outcomes, and safety measures. Doxycycline prophylaxis for bacterial STIs shows promise. Better and more robust data are needed on efficacy; target population; community acceptability; behavioral risk compensation; doxycycline dose, regimen, and formulation; long-term safety; antimicrobial resistance; cost-effectiveness; and risk–benefit
Performance and operational characteristics of point-of-care tests for the diagnosis of urogenital gonococcal infections.
BACKGROUND: In 2012, there was an estimated 78 million new cases of gonorrhoea globally. Untreated infection may lead to reproductive and neonatal morbidity and facilitate HIV transmission. Diagnosis and treatment are a priority for control and prevention, yet use of point-of-care tests (POCTs) for Neisseria gonorrhoeae (NG) is limited. OBJECTIVES: To review the performance and operational characteristics of NG POCTs for diagnosis of urogenital gonorrhoea. METHODS: We compiled and synthesised findings from two separate systematic reviews which included evaluations published until August 2015. RESULTS: Six tests were included: five were immunochromatographic tests (ICTs) or optical immunoassay (OIAs) based on antigen detection; with 5-7 steps and results in 25-40 min, and one (GeneXpert CT/NG) was a 'near-patient test' based on nucleic acid amplification technique (NAAT); with three steps, electricity required, and results in 90 min. When compared with laboratory-based NAATs as the reference tests, sensitivities of ICT and OIA-based POCTs ranged from 12.5% to 70% when cervical/vaginal swabs were tested. Specificities ranged from 89% to 99.8%. The near-patient NAAT had sensitivities of >95% and specificities of >99.8% consistently across all specimen types (urine, cervical and vaginal swabs). CONCLUSIONS: Based on a limited number of evaluations, antigen detection POCTs for NG lacked sufficient sensitivity to be used for screening. A near-patient NAAT has acceptable performance, only involved a few steps, but needs electricity, a temperature-controlled environment and has a 90 min run time. To achieve wider scale up of NG POCTs, we need strong evidence of cost-effectiveness, which should inform guidelines and ultimately increase test development, demand and reduce costs
Thromboxane Modulates Endothelial Permeability
The study tests the role of thromboxane in modulating microvascular
permeability in vitro. Cultured monolayers of bovine
aortic endothelial cells were challenged with the thromboxane (Tx)
mimic U46619. This led to disassembly of actin microfilaments, cell
rounding, border retraction and interendotheHal gap formation.
Pretreatment with the Tx receptor antagonist SQ 29,548 prevented the
Tx mimic-induced cytoskeletal changes. The Tx mimic also altered
endothelial cell barrier function. Increased permeability was
indicated by the increased passage of labelled albumin across
monolayers cultured on microcarriers, relative to untreated
endothelial cells (p < 0.05). Furthermore, electron microscopy
of endothelial cells cultured on the basement membrane of human
placental amnion indicated increased permeability based on wide,
interendotheHal gap formation and transit of the tracer horseradish
peroxidase. Quantification of interendothelial gaps revealed an
eleven-fold increase with the Tx mimic relative to untreated
endothial cells (p < 0.05) and prevention by pretreatment with
the Tx receptor antagonist (p < 0.05). These data indicate that
Tx directly modulates the permeability of endothelial cell in
vitro
Trichomonas vaginalis Infection and Associated Risk Factors in a Socially-Marginalized Female Population in Coastal Peru
Objective. The epidemiology of Trichomonas vaginalis infection among sexually active socially-marginalized women in three urban, coastal Peruvian cities was examined in order to quantify the prevalence of trichomonas infection and identify associated risk factors. Methods. We conducted a cross-sectional, venue-based study of women from socially-marginalized populations in three coastal Peruvian cities. Results. Among the 319 women enrolled, the overall prevalence of trichomonal infection was 9.1% (95% CI, 5.9%–12.3%). The mean age was 26.3 years, and 35.5% reported having had unprotected intercourse with nonprimary partners and 19.8% reported two or more sex partners in the last three months. Trichomonal infection was associated with increased number of sex partners (PR 2.5, 95% CI 1.4–4.6) and unprotected sex with nonprimary partner in the last three months (PR 2.3, 95% CI 1.1–4.9). Conclusions. A moderately high prevalence of trichomonal infection was found among women in our study. Trichomonal infection was associated with unprotected sex and multiple sex partners. Efforts to control the continued spread of trichomonal infection are warranted
Fine tuning Exo2, a small molecule inhibitor of secretion and retrograde trafficking pathways in mammalian cells
The small molecule 4-hydroxy-3-methoxybenzaldehyde (5,6,7,8-tetrahydro[1]benzothieno[2,3-
d]pyrimidin-4-yl)hydrazone (Exo2) stimulates morphological changes at the mammalian Golgi and
trans-Golgi network that are virtually indistinguishable from those induced by brefeldin A. Both
brefeldin A and Exo2 protect cells from intoxication by Shiga(-like) toxins by acting on other
targets that operate at the early endosome, but do so at the cost of high toxicity to target cells. The
advantage of Exo2 is that it is much more amenable to chemical modification and here we report a
range of Exo2 analogues produced by modifying the tetrahydrobenzothienopyrimidine core, the
vanillin moiety and the hydrazone bond that links these two. These compounds were examined for
the morphological changes they stimulated at the Golgi stack, the trans Golgi network and the
transferrin receptor-positive early endosomes and this activity correlated with their inherent
toxicity towards the protein manufacturing ability of the cell and their protective effect against
toxin challenge. We have developed derivatives that can separate organelle morphology, target
specificity, innate toxicity and toxin protection. Our results provide unique compounds with low
toxicity and enhanced specificity to unpick the complexity of membrane trafficking networks
- …