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Background In 2005, Bangladesh, India and Nepal agreed to eliminate visceral leishmaniasis (VL) as a public health problem. The approach to this was through improved case detection and treatment, and controlling transmission by the sand fly vector Phlebotomus argentipes, with indoor residual spraying (IRS) of insecticide. Initially, India applied DDT with stirrup pumps for IRS, however, this did not reduce transmission. After 2015 onwards, the pyrethroid alpha-cypermethrin was applied with compression pumps, and entomological surveillance was initiated in 2016. Methods Eight sentinel sites were established in the Indian states of Bihar, Jharkhand and West Bengal. IRS coverage was monitored by household survey, quality of insecticide application was measured by HPLC, presence and abundance of the VL vector was monitored by CDC light traps, insecticide resistance was measured with WHO diagnostic assays and case incidence was determined from the VL case register KAMIS. Results Complete treatment of houses with IRS increased across all sites from 57% in 2016 to 70% of houses in 2019, rising to >80% if partial house IRS coverage is included (except West Bengal). The quality of insecticide application has improved compared to previous studies, average doses of insecticide on filters papers ranged from 1.52 times the target dose of 25mg/m2 alpha-cypermethrin in 2019 to 1.67 times in 2018. Resistance to DDT has continued to increase, but the vector was not resistant to carbamates, organophosphates or pyrethroids. The annual and seasonal abundance of P. argentipes declined between 2016 to 2019 with an overall infection rate of 0.03%. This was associated with a decline in VL incidence for the blocks represented by the sentinel sites from 1.16 per 10,000 population in 2016 to 0.51 per 10,000 in 2019. Conclusion Through effective case detection and management reducing the infection reservoirs for P. argentipes in the human population combined with IRS keeping P. argentipes abundance and infectivity low has reduced VL transmission. This combination of effective case management and vector control has now brought India within reach of the VL elimination targets., Author summary Visceral Leishmaniasis (VL), also known as kala-azar, is a major parasitic disease in South Asia (Indian subcontinent), with 85% of the disease incidence in India. Historically VL had been controlled and almost eliminated with Indoor Residual Spraying (IRS) using dichlorodiphenyltrichloroethane (DDT). However, reinitiating this approach in 2015 failed due to high insecticide resistance in the sand fly vector and poor IRS quality, meaning that VL elimination targets were not met. To improve this the National Vector Borne Disease Control Programme changed to an effective insecticide, alpha-cypermethrin and altered the mode of application to compression pumps. Sentinel sites were established to monitor the entomological indicators, these showed the positive impact of these changes from 2016 to 2019. During this period the overall incidence of disease has decreased, and India is now on track to reach it’s target incidence for VL of less than 1/1000 people at the sub-district (block) level.

ObjectiveRising antibiotic resistance could reduce the effectiveness of antibiotics in preventing postoperative infections. We investigated trends in the efficacy of antibiotic prophylaxis regimens for 3 commonly performed surgical procedures—appendectomy, cesarean section, and colorectal surgery—and 1 invasive diagnostic procedure, transrectal prostate biopsy (TRPB).DesignSystematic review and meta-analysis.MethodsWe searched PubMed and Cochrane databases (through October 31, 2017) for randomized control trials (RCTs) that measured the efficacy of antibiotic prophylaxis for 4 index procedures in preventing postoperative infections (surgical site infections [SSIs] following the 3 surgical procedures and a combination of urinary tract infections [UTIs] and sepsis following TRPB).ResultsOf 399 RCTs, 74 studies (9 appendectomy, 11 cesarean section, 39 colorectal surgery, and 15 TRPB) were included. Multilevel logistic regression models with random intercepts for each study showed no statistically significant increase in SSIs over time for appendectomy (adjusted odds ratio [aOR] per year, 1.03; 95% confidence interval [CI], 0.92–1.16; P=.57), cesarean section (aOR per year, 1.01; 95% CI, 0.96–1.05; P=.80), and TRPB (aOR per year, 0.95; 95% CI, 0.77–1.18; P=.67). However, there was a significant increase in SSIs proportion following colorectal surgery (aOR per year, 1.049; 95% CI, 1.03–1.07; PConclusionThe efficacy of antibiotic prophylaxis agents in preventing SSIs following colorectal surgery has declined. Small number of RCTs and low infections rates limited our ability to assess true effect for simple appendectomy, cesarean section, or TRPB.

Objectives: Borderline personality disorder (BPD) is associated with frequent self-harm and suicidal behaviours. This study compared physician-assessed self-harm risk and intervention choice according to a (i) standard risk assessment and (ii) BPD-specific risk assessment methods. Methods: Forty-five junior and senior mental health physicians were assigned to standard or BPD-specific risk training groups. The assessment utilized a BPD case vignette containing four scenarios describing high/low lethality self-harm and chronic/new patterns of self-harm behaviour. Participants chose from among four interventions, each corresponding to a risk category. Results: Standard and BPD-specific groups were alike in their assessment of self-harm risk. Divergence occurred on intervention choice for assessments of low lethality, chronic risk ( pConclusions: Although standard and BPD-specific methods are well aligned for assessing self harm-associated risk, BPD-specific training raised awareness of BPD-appropriate interventions, particularly in the context of chronic patterns of self-harm behaviour. Wider dissemination of BPD-specific risk training may enhance the confidence of mental health clinicians in identifying the nature of self-harm risk as well as the most clinically appropriate interventions for clients with BPD.

Background Indoor residual spraying (IRS) is a key tool for controlling and eliminating malaria by targeting vectors. To support the development of effective intervention strategies it is important to understand the impact of vector control tools on malaria incidence and on the spread of insecticide resistance. In 2006, the World Health Organization (WHO) stated that countries should report on coverage and impact of IRS, yet IRS coverage data are still sparse and unspecific. Here, the subnational coverage of IRS across sub-Saharan Africa for the four main insecticide classes from 1997 to 2017 were estimated. Methods Data on IRS deployment were collated from a variety of sources, including the President’s Malaria Initiative spray reports and National Malaria Control Programme reports, for all 46 malaria-endemic countries in sub-Saharan Africa from 1997 to 2017. The data were mapped to the applicable administrative divisions and the proportion of households sprayed for each of the four main insecticide classes; carbamates, organochlorines, organophosphates and pyrethroids was calculated. Results The number of countries implementing IRS increased considerably over time, although the focal nature of deployment means the number of people protected remains low. From 1997 to 2010, DDT and pyrethroids were commonly used, then partly replaced by carbamates from 2011 and by organophosphates from 2013. IRS deployment since the publication of resistance management guidelines has typically avoided overlap between pyrethroid IRS and ITN use. However, annual rotations of insecticide classes with differing modes of action are not routinely used. Conclusion This study highlights the gaps between policy and practice, emphasizing the continuing potential of IRS to drive resistance. The data presented here can improve studies on the impact of IRS on malaria incidence and help to guide future malaria control efforts.

The development of insecticide resistance in African malaria vectors threatens the continued efficacy of important vector control methods that rely on a limited set of insecticides. To understand the operational significance of resistance we require quantitative information about levels of resistance in field populations to the suite of vector control insecticides. Estimation of resistance is complicated by the sparsity of observations in field populations, variation in resistance over time and space at local and regional scales, and cross-resistance between different insecticide types. Using observations of the prevalence of resistance in mosquito species from the Anopheles gambiae complex sampled from 1,183 locations throughout Africa, we applied Bayesian geostatistical models to quantify patterns of covariation in resistance phenotypes across different insecticides. For resistance to the three pyrethroids tested, deltamethrin, permethrin, and λ-cyhalothrin, we found consistent forms of covariation across sub-Saharan Africa and covariation between resistance to these pyrethroids and resistance to DDT. We found no evidence of resistance interactions between carbamate and organophosphate insecticides or between these insecticides and those from other classes. For pyrethroids and DDT we found significant associations between predicted mean resistance and the observed frequency of kdr mutations in the Vgsc gene in field mosquito samples, with DDT showing the strongest association. These results improve our capacity to understand and predict resistance patterns throughout Africa and can guide the development of monitoring strategies.

BACKGROUND: Acinetobacter baumannii is a common cause of healthcare-associated infections. Carbapenem-resistant (CR) A baumannii is a significant threat globally. We used a large reference laboratory database to study the epidemiology of A baumannii in children in the United States. METHODS: Antimicrobial susceptibility data from The Surveillance Network were used to phenotypically identify antibiotic resistance in A baumannii isolates in children 1–17 years of age between January 1999 and July 2012. Logistic regression analysis was used to calculate trends in the prevalence of antibiotic resistance in A baumannii. Isolates from infants (

Background There is a need for effective computational methods for quantifying the three-dimensional (3-D) spatial distribution, cellular arbor morphologies, and the morphological diversity of brain astrocytes to support quantitative studies of astrocytes in health, injury, and disease. New method Confocal fluorescence microscopy of multiplex-labeled (GFAP, DAPI) brain tissue is used to perform imaging of astrocytes in their tissue context. The proposed computational method identifies the astrocyte cell nuclei, and reconstructs their arbors using a local priority based parallel (LPP) tracing algorithm. Quantitative arbor measurements are extracted using Scorcioni's L-measure, and profiled by unsupervised harmonic co-clustering to reveal the morphological diversity. Results The proposed method identifies astrocyte nuclei, generates 3-D reconstructions of their arbors, and extracts quantitative arbor measurements, enabling a morphological grouping of the cell population. Comparison with existing methods Our method enables comprehensive spatial and morphological profiling of astrocyte populations in brain tissue for the first time, and overcomes limitations of prior methods. Visual proofreading of the results indicate a >95% accuracy in identifying astrocyte nuclei. The arbor reconstructions exhibited 3.2% fewer erroneous jumps in tracing, and 17.7% fewer false segments compared to the widely used fast-marching method that resulted in 9% jumps and 20.8% false segments. Conclusions The proposed method can be used for large-scale quantitative studies of brain astrocyte distribution and morphology.

Motivation: The arbor morphologies of brain microglia are important indicators of cell activation. This article fills the need for accurate, robust, adaptive and scalable methods for reconstructing 3-D microglial arbors and quantitatively mapping microglia activation states over extended brain tissue regions. Results: Thick rat brain sections (100–300 µm) were multiplex immunolabeled for IBA1 and Hoechst, and imaged by step-and-image confocal microscopy with automated 3-D image mosaicing, producing seamless images of extended brain regions (e.g. 5903 × 9874 × 229 voxels). An over-complete dictionary-based model was learned for the image-specific local structure of microglial processes. The microglial arbors were reconstructed seamlessly using an automated and scalable algorithm that exploits microglia-specific constraints. This method detected 80.1 and 92.8% more centered arbor points, and 53.5 and 55.5% fewer spurious points than existing vesselness and LoG-based methods, respectively, and the traces were 13.1 and 15.5% more accurate based on the DIADEM metric. The arbor morphologies were quantified using Scorcioni’s L-measure. Coifman’s harmonic co-clustering revealed four morphologically distinct classes that concord with known microglia activation patterns. This enabled us to map spatial distributions of microglial activation and cell abundances. Availability and implementation: Experimental protocols, sample datasets, scalable open-source multi-threaded software implementation (C++, MATLAB) in the electronic supplement, and website (www.farsight-toolkit.org). http://www.farsight-toolkit.org/wiki/Population-scale_Three-dimensional_Reconstruction_and_Quanti-tative_Profiling_of_Microglia_Arbors Contact: broysam@central.uh.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Large tertiary care hospitals (TCHs) are thought to have higher antimicrobial resistance (AMR) rates when compared to small community hospitals (SCHs) as they provide care to patients with higher disease severity. However, we found no systematic differences in AMR rates between TCHs and SCHs in the United States.

Antibiotics have revolutionized the treatment of bacterial infections. However, it is widely held that there is underinvestment in antibiotics research and development relative to the socially optimal level for a number of reasons. In this article, we discuss whether existing health technology assessment procedures recognize the full economic and societal value of new antibiotics to patients and society when making reimbursement decisions. We present three recommendations for modelling the unique attributes of value that are specific to novel antibiotics. We find, based on a review of the literature, that some of the value elements proposed by our framework have previously been discussed qualitatively by health technology assessment bodies when evaluating antibiotics, but are not yet formally captured via modelling. We present a worked example to show how it may be possible to capture these dimensions of value in a more quantitative manner. We conclude by answering the question of the title as follows: the unique attributes of novel antibiotics should be considered in reimbursement decision making, in a way that captures the full range of benefits these important technologies bring to patients, health care systems, and society.

In recent years, there has been an increase in resistance of malaria vectors to insecticides, particularly to pyrethroids which are widely used in insecticide-treated nets. The Global Plan for Insecticide Resistance Management in malaria vectors (GPIRM), released in May 2012, is a collective strategy for the malaria community to tackle this challenge. This review outlines progress made to date and the challenges experienced in the implementation of GPIRM, and outlines focus areas requiring urgent attention. Whilst there has been some advancement, uptake of GPIRM at the national level has generally been poor for various reasons, including limited availability of vector control tools with new mechanisms of action as well as critical financial, human and infrastructural resource deficiencies. There is an urgent need for a global response plan to address these deficits and ensure the correct and efficient use of available tools in order to maintain the effectiveness of current vector control efforts whilst novel vector control tools are under development. Emphasis must be placed on enhancing national capacities (such as human and infrastructural resources) to enable efficient monitoring and management of insecticide resistance, and to support availability and accessibility of appropriate new vector control products. Lack of action by the global community to address the threat of insecticide resistance is unacceptable and deprives affected communities of their basic right of universal access to effective malaria prevention. Aligning efforts and assigning the needed resources will ensure the optimal implementation of GPIRM with the ultimate goal of maintaining effective malaria vector control.

Microglia are the resident immune cell population in the mammalian central nervous system (CNS). These highly plastic cells exhibit ramified arbors in their resting state, and progressively less-complex arbors when activated. Our goal is to compare the spatial distributions of resting and activated microglia in normal brain tissue against tissue that is perturbed by insertion of a neural recording device. For this, microglia were imaged using multiplex immunostaining and confocal microscopy. The cell arbors were traced automatically, and 127 quantitative measurements based on the L-measure [8] were computed for each cell. A hierarchical extension of Coifman's [1,2] unsupervised harmonic analysis method was used to profile these multivariate data and identify groups of similar cells and the underlying features. This iterative procedure induces an orthogonal basis by constructing a coupled geometry over the row and column spaces of the feature matrix. Smoothing of the dataset, and the row and column clusters is achieved simultaneously when the algorithm converges. Experiments on real image datasets demonstrate the ability of this method to generate qualitative and quantitative groups that are biologically meaningful despite the existence of noise and missing values.

Microglia are Central Nervous System (CNS) cells that are similar to macrophages. They undergo characteristic changes in cell arbor morphology in response to tissue perturbation. Ensembles of microglia exhibit a progression of arbor morphologies. Our goal is to discover these progressions and determine the underlying arbor features from 3-D multi-channel fluorescence confocal microscope images of rat brain tissue multiplex stained with Hoechst to reveal cell nuclei, and immunolabeled for IBA-1 to reveal microglia. The microglia are automatically traced, and a set of 131 arbor features are computed. An agglomerative clustering algorithm based on Pearson's correlation is used to derive coherent modules of features. A k-NNG structural similarity analysis of feature modules enables us to construct a global similarity matrix, from which a global multi-level k-NNG is constructed to derive an interactive progression chart through a modified Fruchterman-Reingold algorithm that clearly reveals a progression from highly ramified microglia to round cells proximal to the injury site of an implanted neural recording device.