Trichomonas vaginalis: Clinical relevance, pathogenicity and diagnosis

Trichomonas vaginalis is the etiological agent of trichomoniasis, the most prevalent non-viral sexually transmitted disease worldwide. Trichomoniasis is a widespread, global health concern and occurring at an increasing rate. Infections of the female genital tract can cause a range of symptoms, including vaginitis and cervicitis, while infections in males are generally asymptomatic. The relatively mild symptoms, and lack of evidence for any serious sequelae, have historically led to this disease being under diagnosed, and under researched. However, growing evidence that T. vaginalis infection is associated with other disease states with high morbidity in both men and women has increased the efforts to diagnose and treat patients harboring this parasite. The pathology of trichomoniasis results from damage to the host epithelia, caused by a variety of processes during infection and recent work has highlighted the complex interactions between the parasite and host, commensal microbiome and accompanying symbionts. The commercial release of a number of nucleic acid amplification tests (NAATs) has added to the available diagnostic options. Immunoassay based Point of Care testing is currently available, and a recent initial evaluation of a NAAT Point of Care system has given promising results, which would enable testing and treatment in a single visit

Anticoagulation in thrombocytopenic patients with hematological malignancy:A multinational clinical vignette-based experiment

Background: Thrombocytopenia in cancer patients with an indication for anticoagulation poses a unique clinical challenge. There are guidelines for the setting of venous thromboembolism but not atrial fibrillation (AF). Evidence is lacking and current practice is unclear.Objective: To identify patient and physician characteristics associated with anticoagulation management in hematological malignancy and thrombocytopenia.Methods: A clinical vignette-based experiment was designed. Eleven hematologists were interviewed, identifying 5 relevant variable categories with 2-5 options each. Thirty hypothetical vignettes were generated. Each physician received 5 vignettes and selected a management strategy (hold anticoagulation; no change; transfuse platelets; modify type/dose). The survey was distributed to hematologists and thrombosis specialists in 3 countries. Poisson regression models with cluster robust variance estimates were used to calculate relative risks for using one management option over the other, for each variable in comparison to a reference variable.Results: 168 physicians answered 774 cases and reported continuing anticoagulation for venous thromboembolism or AF in 607 (78%) cases, usually with dose reduction or platelet transfusion support. Overall, management was affected by platelet count, anticoagulation indication, time since indication, type of hematological disease and treatment, and prior major bleeding, as well as physician demographics and practice setting. The CHA(2)DS(2)-VASc score and time since AF diagnosis affected anticoagulation management in AF.Conclusion: This study indicates what the widely accepted management strategies are. These strategies, and possibly others, should be assessed prospectively to ascertain effectiveness. The decision process is intricate and compatible with current venous thromboembolism guidelines.</p

Expanded therapeutic potential in activity space of next-generation 5-nitroimidazole antimicrobials with broad structural diversity

Metronidazole and other 5-nitroimidazoles (5-NI) are among the most effective antimicrobials available against many important anaerobic pathogens, but evolving resistance is threatening their long-term clinical utility. The common 5-NIs were developed decades ago, yet little 5-NI drug development has since taken place, leaving the true potential of this important drug class unexplored. Here we report on a unique approach to the modular synthesis of diversified 5-NIs for broad exploration of their antimicrobial potential. Many of the more than 650 synthesized compounds, carrying structurally diverse functional groups, have vastly improved activity against a range of microbes, including the pathogenic protozoa Giardia lamblia and Trichomonas vaginalis, and the bacterial pathogens Helicobacter pylori, Clostridium difficile, and Bacteroides fragilis. Furthermore, they can overcome different forms of drug resistance, and are active and nontoxic in animal infection models. These findings provide impetus to the development of structurally diverse, next-generation 5-NI drugs as agents in the antimicrobial armamentarium, thus ensuring their future viability as primary therapeutic agents against many clinically important infections