Background: Aedes aegypti mosquitoes infected with Wolbachia pipientis ( w Mel strain) have reduced potential to transmit dengue viruses. Methods: We conducted a cluster randomised trial of deployments of w Mel-infected Ae. aegypti for control of dengue in Yogyakarta City, Indonesia. Twenty-four geographic clusters were randomly allocated to receive w Mel deployments as an adjunct to local mosquito control measures; or to continue with local mosquito control measures only. A test-negative design was used to measure efficacy. Study participants were persons 3–45 years old attending primary care clinics with acute undifferentiated fever. Laboratory testing identified virologically-confirmed dengue cases and test-negative controls. The primary endpoint was efficacy of w Mel in reducing the incidence of symptomatic, virologically-confirmed dengue, caused by any dengue virus serotype. Results: Following successful introgression of w Mel in intervention clusters, 8144 participants were enrolled; 3721 from w Mel-treated clusters and 4423 from untreated clusters. In the ITT analysis virologically-confirmed dengue occurred in 67 of 2905 (2.3%) participants in the w Mel-treated and 318 of 3401 (9.4%) in the untreated arm (OR 0.23, 95% CI, 0.15 to 0.35; P=0.004): protective efficacy of 77.1% (95% CI, 65.3 to 84.9). Protective efficacy was similar for the four serotypes. Hospitalisation for virologically-confirmed dengue was less frequent for participants resident in the w Mel-treated (13/2905, 2.8%) compared to the untreated arm (102/3401, 6.3%): protective efficacy 86.2% (95% CI, 66.2 to 94.3) Conclusions: w Mel introgression into Ae. aegypti populations was efficacious in reducing the incidence of symptomatic dengue, and also led to fewer dengue hospitalisations. Trial registration number: ClinicalTrials.gov Identifier: NCT03055585 and INA-A7OB6TW

Background: The wMel strain of Wolbachia has been successfully introduced into Aedes aegypti mosquitoes and subsequently shown in laboratory studies to reduce transmission of a range of viruses including dengue, Zika, chikungunya, yellow fever, and Mayaro viruses that cause human disease. Here we report the entomological and epidemiological outcomes of staged deployment of Wolbachia across nearly all significant dengue transmission risk areas in Australia. Methods: The  wMel strain of  Wolbachia was backcrossed into the local  Aedes aegypti genotype (Cairns and Townsville backgrounds) and mosquitoes were released in the field by staff or via community assisted methods. Mosquito monitoring was undertaken and mosquitoes were screened for the presence of  Wolbachia. Dengue case notifications were used to track dengue incidence in each location before and after releases. Results: Empirical analyses of the Wolbachia mosquito releases, including data on the density, frequency and duration of Wolbachia mosquito releases, indicate that Wolbachia can be readily established in local mosquito populations, using a variety of deployment options and over short release durations (mean release period 11 weeks, range 2-22 weeks). Importantly, Wolbachia frequencies have remained stable in mosquito populations since releases for up to 8 years. Analysis of dengue case notifications data demonstrates near-elimination of local dengue transmission for the past five years in locations where Wolbachia has been established. The regression model estimate of Wolbachia intervention effect from interrupted time series analyses of case notifications data prior to and after releases, indicated a 96% reduction in dengue incidence in Wolbachia treated populations (95% confidence interval: 84 – 99%). Conclusion: Deployment of the wMel strain of Wolbachia into local Ae. aegypti populations across the Australian regional cities of Cairns and most smaller regional communities with a past history of dengue has resulted in the reduction of local dengue transmission across all deployment areas.

The Mel strain of has been successfully

Purpose: There is an urgent need for a more effective intervention to slow or prevent progression of agerelated macular degeneration (AMD) from its early stages to vision-threatening late complications. Subthreshold nanosecond laser (SNL) treatment has shown promise in preclinical studies and a pilot study in intermediate AMD (iAMD) as a potential treatment. We aimed to evaluate the safety of SNL treatment in iAMD and its efficacy for slowing progression to late AMD.Design: The Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study is a 36month, multicenter, randomized, sham-controlled trial.Participants: Two hundred ninety-two participants with bilateral large drusen and without OCT signs of atrophy. Methods: Participants were assigned randomly to receive Retinal Rejuvenation Therapy (2RT Ò ; Ellex Pty Ltd, Adelaide, Australia) SNL or sham treatment to the study eye at 6-monthly intervals.Main Outcome Measures: The primary efficacy outcome was the time to development of late AMD defined by multimodal imaging (MMI). Safety was assessed by adverse events.Results: Overall, progression to late AMD was not slowed significantly with SNL treatment compared with sham treatment (adjusted hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.33e1.14; P ¼ 0.122). However, a post hoc analysis showed evidence of effect modification based on the coexistence of reticular pseudodrusen (RPD; adjusted interaction P ¼ 0.002), where progression was slowed for the 222 participants (76.0%) without coexistent RPD at baseline (adjusted HR, 0.23; 95% CI, 0.09e0.59; P ¼ 0.002), whereas an increased progression rate (adjusted HR, 2.56; 95% CI, 0.80e8.18; P ¼ 0.112) was observed for the 70 participants (24.0%) with RPD with SNL treatment. Differences between the groups in serious adverse events were not significant.Conclusions: In participants with iAMD without MMI-detected signs of late AMD, no significant difference in the overall progression rate to late AMD between those receiving SNL and sham treatment were observed. However, SNL treatment may have a role in slowing progression for those without coexistent RPD and may be inappropriate in those with RPD, warranting caution when considering treatment in clinical phenotypes with RPD. Our findings provide compelling evidence for further trials of the 2RT Ò laser, but they should not be extrapolated to other short-pulse lasers.

The prevalence of diabetes in pregnancy is increasing. Pre-existing diabetes is present in 1 in 167 pregnancies in Australia, divided equally between type 1 and type 2 diabetes. Diabetic retinopathy is a leading cause of blindness in women during their childbearing years, and pregnancy increases the short-term risk of diabetic retinopathy progression. We examine the risk factors for progression of diabetic retinopathy during pregnancy including duration of diabetes, baseline level of retinopathy, level of glycaemic control and hypertension. We also examine current screening and management guidelines and their levels of evidence, current treatment options for diabetic retinopathy and avenues for further research.

No abstract

Diabetic neuropathy, nephropathy, and retinopathy cause significant morbidity in patients with type 1 diabetes, even though improvements in treatment modalities delay the appearance and reduce the severity of these complications. To prevent or further delay the onset, it is necessary to better understand common underlying pathogenesis and to discover preclinical biomarkers of these complications. Retinal vessel calibers have been associated with the presence of microvascular complications, but their long-term predictive value has only been sparsely investigated. We examined retinal vessel calibers as 16-year predictors of diabetic nephropathy, neuropathy, and proliferative retinopathy in a young population-based Danish cohort with type 1 diabetes. We used semiautomated computer software to analyze vessel diameters on baseline retinal photos. Calibers of all vessels coursing through a zone 0.5-1 disc diameter from the disc margin were measured and summarized as the central artery and vein equivalents. In multiple regression analyses, we found wider venular diameters and smaller arteriolar diameters were both predictive of the 16-year development of nephropathy, neuropathy, and proliferative retinopathy. Early retinal vessel caliber changes are seemingly early markers of microvascular processes, precede the development of microvascular complications, and are a potential noninvasive predictive test on future risk of diabetic retinopathy, neuropathy, and nephropathy.Diabetic microvascular complications, namely diabetic peripheral neuropathy (DPN), diabetic nephropathy (DN), and diabetic retinopathy (DR), are common in type 1 diabetes (1) despite advances in metabolic care. Identifying new predictors of microvascular disease could be helpful for early individual risk stratification, which may provide better opportunity for timely implementation of effective interventions. For this purpose, the retinal vasculature provides a unique opportunity to assess vascular health directly and noninvasively in vivo.Studies have investigated how retinal vessel calibers are associated with microvascular complications in both type 1 and type 2 diabetes (2-14). The evidence to date suggests that wider retinal venular diameters are associated with presence of both DN and severe levels of DR in several cross-sectional studies (3,(8)(9)(10) and with incident DN (4,5) and progression to severe

Aims/hypothesis The purpose of the study was to evaluate the association between retinal vascular calibre and microand macrovascular complications in a population-based cohort of Danish type 1 diabetic patients. Methods This was a cross-sectional study of 208 longsurviving type 1 diabetic patients from a population-based Danish cohort. Retinal photographs were obtained at a clinical examination attended by each participant in [2007][2008], and retinal vascular calibre was measured and summarised as the central retinal artery or vein equivalent (CRAE or CRVE) using a computer-based program and a standardised protocol. Associations between retinal vascular calibre and micro-and macrovascular complications were examined after adjusting for confounding clinical characteristics.Results Retinal photographs were gradable for 188 of 208 patients (90.3%). The median age and duration of diabetes for patients with gradable photos were 57.9 and 42 years, respectively. After multivariate adjustments, individuals with narrower retinal arterioles were more likely to have nephropathy (OR 2.17, 95% CI 1.29-3.68, per SD decrease in CRAE) and macrovascular disease (OR 3.17, 95% CI 1.59-6.34, per SD decrease in CRAE), but not neuropathy (OR 1.10, 95% CI 0.70-1.71, per SD decrease in CRAE). Retinal venular calibre was not associated with any microor macrovascular complications. Conclusions/interpretation In type 1 diabetic patients, retinal arteriolar narrowing is associated with nephropathy and macrovascular disease independently of other clinical characteristics. If supported by further prospective studies, measurement of retinal vessel diameter may allow a non-invasive evaluation of the risk of diabetes-related complications.