Trachoma: an update on prevention, diagnosis, and treatment.
ABSTRACT To review recent clinical and epidemiological studies regarding the prevention, diagnosis, and treatment of trachoma.
Newer studies propose novel diagnostic tests that appear sensitive for the detection of ocular chlamydial infection. For example, recent studies with ribosomal RNA-based nucleic acid amplification tests (NAATs) have demonstrated improved sensitivities compared to DNA-based NAATs; and the progression of scarring has now been characterized with confocal microscopy. Immunologic studies have further explored the etiology of clinical sequelae, suggesting that chronic inflammation can lead to progressive scarring even in the absence of Chlamydia. Mass oral azithromycin distributions remain a mainstay of treatment; studies have assessed the appropriate frequency and duration of treatment programs. Current studies have also explored ancillary effects of azithromycin distribution on mortality and bacterial infections.
Trachoma programs have had remarkable success at reducing chlamydial infection and clinical signs of trachoma. Recent work suggests improved methods to monitor infection and scarring, and better ways to distribute treatment. Whereas studies continue to demonstrate reduction in infection in hyperendemic areas, more work is necessary to achieve elimination of this blinding disease.
- SourceAvailable from: Niklas Sandler[Show abstract] [Hide abstract]
ABSTRACT: Given the established role of Chlamydia spp. as causative agents of both acute and chronic diseases, search for new antimicrobial agents against these intracellular bacteria is required to promote human health. Isoflavones are naturally occurring phytoestrogens, antioxidants and efflux pump inhibitors, but their therapeutic use is limited by poor water-solubility and intense first-pass metabolism. Here, we report on effects of isoflavones against C. pneumoniae and C. trachomatis and describe buccal permeability and initial formulation development for biochanin A. Biochanin A was the most potent Chlamydia growth inhibitor among the studied isoflavones, with an IC50 = 12 µM on C. pneumoniae inclusion counts and 6.5 µM on infectious progeny production, both determined by immunofluorescent staining of infected epithelial cell cultures. Encouraged by the permeation of biochanin A across porcine buccal mucosa without detectable metabolism, oromucosal film formulations were designed and prepared by a solvent casting method. The film formulations showed improved dissolution rate of biochanin A compared to powder or a physical mixture, presumably due to the solubilizing effect of hydrophilic additives and presence of biochanin A in amorphous state. In summary, biochanin A is a potent inhibitor of Chlamydia spp., and the in vitro dissolution results support the use of a buccal formulation to potentially improve its bioavailability in antichlamydial or other pharmaceutical applications.PLoS ONE 12/2014; 9(12):e115115. · 3.53 Impact Factor
Article: Host defense at the ocular surface.[Show abstract] [Hide abstract]
ABSTRACT: Microbial infections of the cornea frequently cause painful, blinding and debilitating disease that is often difficult to treat and may require corneal transplantation. In addition, sterile corneal infiltrates that are associated with contact lens wear cause pain, visual impairment and photophobia. In this article, we review the role of Toll-Like Receptors (TLR) in bacterial keratitis and sterile corneal infiltrates, and describe the role of MD-2 regulation in LPS responsiveness by corneal epithelial cells. We conclude that both live bacteria and bacterial products activate Toll-Like Receptors in the cornea, which leads to chemokine production and neutrophil recruitment to the corneal stroma. While neutrophils are essential for bacterial killing, they also cause tissue damage that results in loss of corneal clarity. These disparate outcomes, therefore, represent a spectrum of disease severity based on this pathway, and further indicate that targeting the TLR pathway is a feasible approach to treating inflammation caused by live bacteria and microbial products. Further, as the P. aeruginosa type III secretion system (T3SS) also plays a critical role in disease pathogenesis by inducing neutrophil apoptosis and facilitating bacterial growth in the cornea, T3SS exotoxins are additional targets for therapy for P. aeruginosa keratitis.International Reviews Of Immunology 02/2013; 32(1):4-18. · 5.28 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Since the inception of (the Global Elimination of Blinding Trachoma) GET 2020 in 1997 and the implementation of the SAFE strategy a year later, much progress has been made toward lowering the prevalence of trachoma worldwide with elimination of the disease in some countries. However, high recurrence of trichiasis after surgery, difficulty in controlling the reemergence of infection after mass distribution of azithromycin in some communities, the incomplete understanding of environment in relation to the disease, and the difficulty in establishing the prevalence of the disease in low endemic areas are some of the issues still facing completion of the GET 2020 goals. In this narrative review, literature was searched from 1998 to January 2013 in PubMed for original studies and reviews. Reasons for these ongoing problems are discussed, and several suggestions are made as avenues for exploration in relation to improving the SAFE strategy with emphasis on improving surgical quality and management of the mass treatment with antibiotics. In addition, more research needs to be done to better understand the approach to improve sanitation, hygiene, and environment. The main conclusion of this review is that scale-up is needed for all SAFE components, and more research should be generated from communities outside of Africa and Asia.The Scientific World Journal 01/2013; 2013:648106. · 1.22 Impact Factor