Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission.

Cyclic nucleotide-dependent phosphodiesterases (PDEs) play essential roles in regulating the malaria parasite life cycle, suggesting that they may be promising antimalarial drug targets. PDE inhibitors are used safely to treat a range of noninfectious human disorders. Here, we report three subseries of fast-acting and potent PDEβ inhibitors that block asexual blood-stage parasite development and that are also active against human clinical isolates.

Phenotypic evidence of deltamethrin resistance and identification of selective sweeps in Anopheles mosquitoes on the Bijagós Archipelago, Guinea-Bissau.

Vector control in the Bijagós Archipelago of Guinea-Bissau currently relies on pyrethroid insecticide-treated nets. However, data on insecticide resistance in Guinea-Bissau is limited. This study identified deltamethrin resistance in the Anopheles gambiae sensu lato complex on Bubaque island using WHO tube tests in November 2022.

A Pan Plasmodium lateral flow recombinase polymerase amplification assay for monitoring malaria parasites in vectors and human populations.

Robust diagnostic tools and surveillance are crucial for malaria control and elimination efforts. Malaria caused by neglected Plasmodium parasites is often underestimated due to the lack of rapid diagnostic tools that can accurately detect these species. While nucleic-acid amplification technologies stand out as the most sensitive methods for detecting and confirming Plasmodium species, their implementation in resource-constrained settings poses significant challenges.

Knockdown resistance mutations in Phlebotomus argentipes sand flies in Bihar, India.

Background: Vector control based on indoor residual spraying (IRS) is one of the main components of the visceral leishmaniasis (VL) elimination programme in India. Dichlorodiphenyltrichloroethane (DDT) was used for IRS until 2015 and was later replaced by the synthetic pyrethroid alpha-cypermethrin. Both classes of insecticides share the same target site, the voltage-gated sodium channel (Vgsc).

Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1.

With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1).

Dried Blood Spots (DBS): A suitable alternative to using whole blood samples for diagnostic testing of visceral leishmaniasis in the post-elimination era.

Background: Serum or whole blood collection, processing, transport and storage still present significant challenges in low resource settings where mass surveillance is required to sustain disease elimination. Therefore, in this study, we explored the diagnostic efficacy of dried blood spots (DBS) as a minimally invasive and potentially cost-effective alternative sampling technique to whole blood sampling procedures for subsequent detection of Leishmania donovani antibodies or DNA.

Methodology And Principal Findings: Archived serum, DNA samples from whole blood of visceral leishmaniasis (VL) cases and healthy controls, and DBS from corresponding cases and controls, were used.

Comparison of collection methods for Phlebotomus argentipes sand flies to use in a molecular xenomonitoring system for the surveillance of visceral leishmaniasis.

Background: The kala-azar elimination programme has resulted in a significant reduction in visceral leishmaniasis (VL) cases across the Indian Subcontinent. To detect any resurgence of transmission, a sensitive cost-effective surveillance system is required. Molecular xenomonitoring (MX), detection of pathogen DNA/RNA in vectors, provides a proxy of human infection in the lymphatic filariasis elimination programme.

Validation of a method for the dry preservation and rehydration of Anopheles gambiae sensu lato for parity analysis to assess the impact of vector control measures in the field.

Background: As the control of malaria remains heavily dependent on vector management interventions, it is important to understand the impact of these on mosquito populations. Age-grading is a valuable tool for this; however, logistical challenges in remote, resource-poor areas make current methodologies difficult to incorporate into clinical trials and routine surveillance. Our aim was to validate a methodology that could be easily implemented in such settings.

eWaSR-An Embedded-Compute-Ready Maritime Obstacle Detection Network.

Maritime obstacle detection is critical for safe navigation of autonomous surface vehicles (ASVs). While the accuracy of image-based detection methods has advanced substantially, their computational and memory requirements prohibit deployment on embedded devices. In this paper, we analyze the current best-performing maritime obstacle detection network, WaSR.

Identification of two insecticide resistance markers in Ethiopian Anopheles stephensi mosquitoes using a multiplex amplicon sequencing assay.

Since its first detection in 2012 in Djibouti, Anopheles stephensi has invaded and established in the Horn of Africa, and more recently Nigeria. The expansion of this vector poses a significant threat to malaria control and elimination efforts. Integrated vector management is the primary strategy used to interrupt disease transmission; however, growing insecticide resistance is threatening to reverse gains in global malaria control.

Towards environmental detection, quantification, and molecular characterization of Anopheles stephensi and Aedes aegypti from experimental larval breeding sites.

The invasion and establishment of An. stephensi mosquitoes in the Horn of Africa represents a significant regional threat, which may jeopardise malaria control, particularly in urban areas which were formally free from disease transmission. Novel vector surveillance methods are urgently needed, both agnostic to mosquito larval morphology, and simple to implement at the sampling stage.

Multi-centre discriminating concentration determination of broflanilide and potential for cross-resistance to other public health insecticides in Anopheles vector populations.

Novel insecticides are urgently needed to control insecticide-resistant populations of Anopheles malaria vectors. Broflanilide acts as a non-competitive antagonist of the gamma-aminobutyric acid receptor and has shown prolonged effectiveness as an indoor residual spraying product (VECTRON T500) in experimental hut trials against pyrethroid-resistant vector populations. This multi-centre study expanded upon initial discriminating concentration testing of broflanilide, using six Anopheles insectary colonies (An.

Learning with Weak Annotations for Robust Maritime Obstacle Detection.

Robust maritime obstacle detection is critical for safe navigation of autonomous boats and timely collision avoidance. The current state-of-the-art is based on deep segmentation networks trained on large datasets. However, per-pixel ground truth labeling of such datasets is labor-intensive and expensive.

High-throughput barcoding method for the genetic surveillance of insecticide resistance and species identification in Anopheles gambiae complex malaria vectors.

Surveillance of malaria vector species and the monitoring of insecticide resistance are essential to inform malaria control strategies and support the reduction of infections and disease. Genetic barcoding of mosquitoes is a useful tool to assist the high-throughput surveillance of insecticide resistance, discriminate between sibling species and to detect the presence of Plasmodium infections. In this study, we combined multiplex PCR, custom designed dual indexing, and Illumina next generation sequencing for high throughput single nucleotide polymorphism (SNP)-profiling of four species from the Anopheles (An.

Towards environmental detection of Chagas disease vectors and pathogen.

Chagas disease vector control relies on prompt, accurate identification of houses infested with triatomine bugs for targeted insecticide spraying. However, most current detection methods are laborious, lack standardization, have substantial operational costs and limited sensitivity, especially when triatomine bug densities are low or highly focal. We evaluated the use of FTA cards or cotton-tipped swabs to develop a low-technology, non-invasive method of detecting environmental DNA (eDNA) from both triatomine bugs and Trypanosoma cruzi for use in household surveillance in eastern Colombia, an endemic region for Chagas disease.

Immunotherapy-Associated Hypothyroidism: Comparison of the Pre-Existing With Hypothyroidism.

Background: Immunotherapy has revolutionized the treatment of solid malignancies, but is associated with endocrine-related adverse events. This study aims to dissect the natural course of immunotherapy-induced hypothyroidism and provide guidance regarding diagnosis and management in patients with and without pre-existing hypothyroidism.

Methods: A retrospective analysis was conducted using patients who received immunotherapy between 2010-2019 within a multicenter hospital system.

A Discriminative Single-Shot Segmentation Network for Visual Object Tracking.

Template-based discriminative trackers are currently the dominant tracking paradigm due to their robustness, but are restricted to bounding box tracking and a limited range of transformation models, which reduces their localization accuracy. We propose a discriminative single-shot segmentation tracker - D3S , which narrows the gap between visual object tracking and video object segmentation. A single-shot network applies two target models with complementary geometric properties, one invariant to a broad range of transformations, including non-rigid deformations, the other assuming a rigid object to simultaneously achieve robust online target segmentation.

Technical Workflow Development for Integrating Drone Surveys and Entomological Sampling to Characterise Aquatic Larval Habitats of in Agricultural Landscapes in Côte d'Ivoire.

Land-use practices such as agriculture can impact mosquito vector breeding ecology, resulting in changes in disease transmission. The typical breeding habitats of Africa's second most important malaria vector are large, semipermanent water bodies, which make them potential candidates for targeted larval source management. This is a technical workflow for the integration of drone surveys and mosquito larval sampling, designed for a case study aiming to characterise breeding sites near two villages in an agricultural setting in Côte d'Ivoire.

Overabundance of and Bacteria Is Associated with Deltamethrin Insecticide Susceptibility in from Agboville, Côte d'Ivoire.

Insecticide resistance among mosquito species is now a pervasive phenomenon that threatens to jeopardize global malaria vector control efforts. Evidence of links between the mosquito microbiota and insecticide resistance is emerging, with significant enrichment of insecticide degrading bacteria and enzymes in resistant populations. Using 16S rRNA amplicon sequencing, we characterized and compared the microbiota of Anopheles coluzzii in relation to their deltamethrin resistance and exposure profiles.

WaSR-A Water Segmentation and Refinement Maritime Obstacle Detection Network.

Obstacle detection using semantic segmentation has become an established approach in autonomous vehicles. However, existing segmentation methods, primarily developed for ground vehicles, are inadequate in an aquatic environment as they produce many false positive (FP) detections in the presence of water reflections and wakes. We propose a novel deep encoder-decoder architecture, a water segmentation and refinement (WaSR) network, specifically designed for the marine environment to address these issues.

Predictors of Severe COVID-19 in Patients With Diabetes: A Multicenter Review.

Objective: Diabetes is an independent risk factor for severe SARS-CoV-2 infections. This study aims to elucidate the risk factors predictive of more severe outcomes in patients with diabetes by comparing the clinical characteristics of those requiring inpatient admissions with those who remain outpatient.

Methods: A retrospective review identified 832 patients-631 inpatients and 201 outpatients-with diabetes and a positive SARS-CoV-2 test result between March 1 and June 15, 2020.

Effects of anti-diabetic treatments in type 2 diabetes and fatty liver disease.

: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are significant non-communicable diseases that often affect individuals concurrently. In individuals with both T2DM and NAFLD, there is evidence that anti-diabetic therapies may demonstrate potential combined beneficial metabolic and reduced hepatic inflammatory effects.: A PubMed and Google Scholar search was performed to find relevant literature.

Evidence for natural hybridization and novel strain superinfections in the complex from Guinea.

, a widespread bacterium which can influence mosquito-borne pathogen transmission, has recently been detected within (.) species that are malaria vectors in Sub-Saharan Africa. Although studies have reported strains in the complex, apparent low density and prevalence rates require confirmation.

Stable high-density and maternally inherited Wolbachia infections in Anopheles moucheti and Anopheles demeilloni mosquitoes.

Wolbachia, a widespread bacterium that can reduce pathogen transmission in mosquitoes, has recently been reported to be present in Anopheles (An.) species. In wild populations of the An.