Effect of Village-wide Use of Long-Lasting Insecticidal Nets on Visceral Leishmaniasis Vectors in India and Nepal: A Cluster Randomized Trial

Visceral leishmaniasis (VL) is a vector-borne disease causing at least 60,000 deaths each year amongst an estimated half million cases, and until recently there have been no significant initiatives to reduce this burden. However, in 2005, the governments of India, Bangladesh and Nepal signed a memorandum of understanding at the World Health Assembly in Geneva for the elimination of the disease by 2015. In the absence of an effective vaccine, the program will rely on the active detection and prompt treatment of cases throughout the endemic region, combined with a recurrent indoor residual spraying (IRS) of all villages at risk. Vector control programs based on IRS are notorious for failing to maintain comprehensive spray coverage over time owing to logistical problems and lack of compliance by householders. Long-lasting insecticidal nets (LNs) have been postulated as an alternative or complement to IRS. Here we describe how comprehensive coverage of LN in trial communities reduced the indoor density of sand flies by 25% compared to communities without LNs. This provides an indication that LNs could be usefully deployed as a component of the VL control program in the Indian subcontinent

Measurement of Recent Exposure to Phlebotomus argentipes, the Vector of Indian Visceral Leishmaniasis, by Using Human Antibody Responses to Sand Fly Saliva

Antibody (IgG) responses to the saliva of Phlebotomus argentipes were investigated using serum samples from regions of India endemic and non-endemic for visceral leishmaniasis (VL). By pre-adsorbing the sera against the saliva of the competing human-biting but non-VL vector P. papatasi, we significantly improved the specificity of a P. argentipes saliva enzyme-linked immunosorbent assay. Using this method, we observed a statistically significant correlation between antibodies to P. argenitpes saliva and the average indoor density of female sand flies. Additionally, the method was able to detect recent changes in vector exposure when sera from VL patients were assayed before, during, and after hospitalization and protected from sand fly bites under untreated bed nets. Collectively, these results highlight the utility of antibodies to P. argentipes saliva as an important tool to evaluate VL vector control programs

Insecticide Susceptibility of Phlebotomus argentipes in Visceral Leishmaniasis Endemic Districts in India and Nepal

Visceral leishmaniasis (VL), also know as kala azar, is one of the major public health concerns India, Nepal and Bangladesh. In the Indian subcontinent, VL is caused by Leishmania donovani which is transmitted by Phlebotomus argentipes. To date, Indoor Residual Spraying (IRS) campaigns have been unable to control the disease. Vector resistance to the insecticides used has been postulated as one of the possible reasons explaining this failure. A number of studies in the region have shown a variable degree of resistance to DDT in areas where this insecticide has been widely used for IRS (mainly India). However there is no coordinated and standardized program to monitor resistance to insecticides in the region. In this study we tested P. argentipes susceptibility to DDT and deltamethrin in VL endemic villages in India and Nepal. The results confirmed the DDT resistance in India and in a border village of Nepal. P. argentipes from both countries were in general susceptible to deltamethrin, an insecticide used in some long lasting insecticidal nets

Knockdown of Cytosolic Glutaredoxin 1 Leads to Loss of Mitochondrial Membrane Potential: Implication in Neurodegenerative Diseases

Mitochondrial dysfunction including that caused by oxidative stress has been implicated in the pathogenesis of neurodegenerative diseases. Glutaredoxin 1 (Grx1), a cytosolic thiol disulfide oxido-reductase, reduces glutathionylated proteins to protein thiols and helps maintain redox status of proteins during oxidative stress. Grx1 downregulation aggravates mitochondrial dysfunction in animal models of neurodegenerative diseases, such as Parkinson's and motor neuron disease. We examined the mechanism underlying the regulation of mitochondrial function by Grx1. Downregulation of Grx1 by shRNA results in loss of mitochondrial membrane potential (MMP), which is prevented by the thiol antioxidant, α-lipoic acid, or by cyclosporine A, an inhibitor of mitochondrial permeability transition. The thiol groups of voltage dependent anion channel (VDAC), an outer membrane protein in mitochondria but not adenosine nucleotide translocase (ANT), an inner membrane protein, are oxidized when Grx1 is downregulated. We then examined the effect of β-N-oxalyl amino-L-alanine (L-BOAA), an excitatory amino acid implicated in neurolathyrism (a type of motor neuron disease), that causes mitochondrial dysfunction. Exposure of cells to L-BOAA resulted in loss of MMP, which was prevented by overexpression of Grx1. Grx1 expression is regulated by estrogen in the CNS and treatment of SH-SY5Y cells with estrogen upregulated Grx1 and protected from L-BOAA mediated MMP loss. Our studies demonstrate that Grx1, a cytosolic oxido-reductase, helps maintain mitochondrial integrity and prevents MMP loss caused by oxidative insult. Further, downregulation of Grx1 leads to mitochondrial dysfunction through oxidative modification of the outer membrane protein, VDAC, providing support for the critical role of Grx1 in maintenance of MMP

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Location of the 12 clusters, 6 in Muzaffarpur district, India and 6 in Sunsari district, Nepal selected for the entomological trial.

<p>Intervention and control clusters are identified with a circle and a triangle respectively.</p