Lining the small intestine with mycobacteriophages protects from Mycobacterium avium subsp. paratuberculosis and eliminates fecal shedding.

Johne's disease (JD), a chronic, infectious enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), affects wild and domestic ruminants. There is no cure or effective prevention, and current vaccines have substantial limitations, leaving this disease widespread in all substantial dairy industries causing economic, and animal welfare implications. Mycobacteriophages (MPs) have been gaining interest in recent years and are proposed as a promising solution to curtailing MAP infection. Using a well-validated infection model, we have demonstrated the preventative potential of MPs to protect dairy calves against MAP infection. Calves were supplemented daily with a phage cocktail from birth till weaning at 2 m of age and inoculated with MAP at 2 wk of age. Infection status was measured for 4.5 mo through blood, fecal, and postmortem tissue samples. Our findings highlight the remarkable efficacy of orally administered MPs. Notably, fecal shedding of MAP was entirely eliminated within 10 wk, in contrast to the infected control group where shedding continued for the entirety of the trial period. Postmortem tissue culture analysis further supported the effectiveness of MPs, with only 1 out of 6 animals in the phage-treated group testing positive for MAP colonized tissues compared to 6 out of 6 animals in the infected control group. Additionally, plaque assay results demonstrated the ability of phages to persist within the intestinal tract. Collectively, these results underscore the potential of orally administered MP cocktails as a highly effective intervention strategy to combat JD in dairy calves and by extension in the dairy industry.

Airborne disease transmission during indoor gatherings over multiple time scales: Modeling framework and policy implications.

Indoor superspreading events are significant drivers of transmission of respiratory diseases. In this work, we study the dynamics of airborne transmission in consecutive meetings of individuals in enclosed spaces. In contrast to the usual pairwise-interaction models of infection where effective contacts transmit the disease, we focus on group interactions where individuals with distinct health states meet simultaneously. Specifically, the disease is transmitted by infected individuals exhaling droplets (contributing to the viral load in the closed space) and susceptible ones inhaling the contaminated air. We propose a modeling framework that couples the fast dynamics of the viral load attained over meetings in enclosed spaces and the slow dynamics of disease progression at the population level. Our modeling framework incorporates the multiple time scales involved in different setups in which indoor events may happen, from single-time events to events hosting multiple meetings per day, over many days. We present theoretical and numerical results of trade-offs between the room characteristics (ventilation system efficiency and air mass) and the group's behavioral and composition characteristics (group size, mask compliance, testing, meeting time, and break times), that inform indoor policies to achieve disease control in closed environments through different pathways. Our results emphasize the impact of break times, mask-wearing, and testing on facilitating the conditions to achieve disease control. We study scenarios of different break times, mask compliance, and testing. We also derive policy guidelines to contain the infection rate under a certain threshold.

Vortioxetine for the treatment of post-COVID-19 condition: a randomized controlled trial.

Hitherto no therapeutic has received regulatory approval for the treatment of post-COVID-19 condition (PCC). Cognitive deficits, mood symptoms and significant reduction in health-related quality of life (HRQoL) are highly replicated and debilitating aspects of PCC. We sought to determine the impact of vortioxetine on the foregoing symptoms and HRQoL in persons living with PCC. An 8-week randomized, double-blind, placebo-controlled study of adults ≥ 18 years of age residing in Canada and who are experiencing symptoms of World Health Organization (WHO)-defined PCC, with a history of confirmed SARS-CoV-2 infection, was conducted. Recruitment began November 2021 and ended January 2023. Of the 200 participants enrolled (487 invited: 121 ineligible and 59 eligible but declined participation; 307 cleared pre-screening stage), a total of 149 participants were randomized (1:1) to receive either vortioxetine (5-20 mg, n = 75) or placebo (n = 74) daily for 8 weeks of double-blind treatment (i.e. end point). The primary outcome was the change from baseline-to-end point in the Digit Symbol Substitution Test. Secondary outcomes included the effect on depressive symptoms and HRQoL, as measured by changes from baseline-to-end point on the Quick Inventory of Depressive Symptomatology 16-item and WHO Wellbeing Scale 5-item, respectively. A total of 68 (90.7%) participants randomized to vortioxetine and 73 (98.6%) participants randomized to placebo completed all 8 weeks. Between-group analysis did not show a significant difference in the overall change in cognitive function [P = 0.361, 95% confidence interval (CI) (-0.179, 0.492)]. However, in the fully adjusted model, a significant treatment × time interaction was observed in favour of vortioxetine treatment with baseline c-reactive protein (CRP) as a moderator (P = 0.012). In addition, a significant improvement in Digit Symbol Substitution Test scores were observed in vortioxetine versus placebo treated participants in those whose baseline CRP was above the mean (P = 0.045). Moreover, significant improvement was obtained in measures of depressive symptoms [P < 0.001, 95% CI (-4.378, -2.323)] and HRQoL [P < 0.001, 95% CI (2.297, 4.647)] in vortioxetine-treated participants and between the treatment groups [depressive symptoms: P = 0.026, 95% CI (-2.847, -0.185); HRQoL: P = 0.004, 95% CI (0.774, 3.938)]. Although vortioxetine did not improve cognitive function in the unadjusted model, when adjusting for CRP, a significant pro-cognitive effect was observed; antidepressant effects and improvement in HRQoL in this debilitating disorder were also noted.

Infectious Disease Physicians' Knowledge and Practices Regarding Wastewater Surveillance, United States, 2024.

A survey of US infectious disease physicians indicated that few regularly reviewed wastewater surveillance (WWS) data but many reported examples of how WWS has affected or could affect their clinical practice. WWS data can be useful for physicians, but increased communication between public health professionals and physicians regarding WWS could improve its utility.

Adding-on nivolumab to chemotherapy-stabilized patients is associated with improved survival in advanced pancreatic ductal adenocarcinoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are rarely used to treat advanced pancreatic ductal adenocarcinoma (PDAC) due to marginal efficacy. PATIENTS AND METHODS: This study included 92 consecutive patients diagnosed with advanced or recurrent PDAC who received nivolumab-based treatment. Univariate and multivariate analyses were used to identify prognostic factors. A control group of 301 patients with PDAC who achieved disease control with palliative chemotherapy but without ICIs was selected for comparison using propensity score matching (PSM). RESULTS: The median overall survival (OS) since nivolumab treatment was 15.8 (95% confidence interval [CI], 12.5-19.0), 2.4 (95% CI 1.2-3.6), and 1.1 (95% CI 1.0-1.2) months in patients who received add-on nivolumab after achieving disease control with chemotherapy, in those who received concomitant nivolumab and chemotherapy without prerequisite confirmation of disease control, and in those who received nivolumab without concomitant chemotherapy, respectively (P < 0.001). After PSM, the median overall survival (OS) since initiation of the concomitant chemotherapy that achieved disease control was significantly longer (P = 0.026) in patients who received add-on nivolumab (19.8 months; 95% CI 14.5-25.1) than in those who received chemotherapy alone (13.8 months; 95% CI 10.8-16.9). The immune profiling of the tumors in resected patients revealed higher scores of CD8+ T cells to Tregs in patients with add-on nivolumab comparing to those who received chemotherapy alone. CONCLUSION: Adding-on nivolumab was associated with improved OS in patients with advanced PDAC who achieved disease control following chemotherapy.

Building pyramids against the evolutionary emergence of pathogens.

Mutations allowing pathogens to escape host immunity promote the spread of infectious diseases in heterogeneous host populations and can lead to major epidemics. Understanding the conditions that slow down this evolution is key for the development of durable control strategies against pathogens. Here, we use theory and experiments to compare the efficacy of three strategies for the deployment of resistance: (i) a mixing strategy where the host population contains two single-resistant genotypes, (ii) a pyramiding strategy where the host carries a double-resistant genotype, (iii) a combining strategy where the host population is a mix of a single-resistant genotype and a double-resistant genotype. First, we use evolutionary epidemiology theory to clarify the interplay between demographic stochasticity and evolutionary dynamics to show that the pyramiding strategy always yields lower probability of evolutionary emergence. Second, we test experimentally these predictions with the introduction of bacteriophages into bacterial populations where we manipulated the diversity and the depth of immunity using a Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated (CRISPR-Cas) system. These biological assays confirm that pyramiding multiple defences into the same host genotype and avoiding combination with single-defence genotypes is a robust way to reduce pathogen evolutionary emergence. The experimental validation of these theoretical recommendations has practical implications in various areas, including for the optimal deployment of resistance varieties in agriculture and for the design of durable vaccination strategies.

RAS signalling genes can be used as host-induced gene silencing targets to control fungal diseases caused by Sclerotinia sclerotiorum and Botrytis cinerea.

Sclerotinia sclerotiorum causes white mold (also called stem rot, Sclerotinia blight, etc.) in many economically important plants. It is a notorious soilborne fungal pathogen due to its wide host range and ability to survive in soil for long periods of time as sclerotia. Although host-induced gene silencing (HIGS) was recently demonstrated to be an effective method for controlling white mold, limited gene targets are available. Here, using a forward genetics approach, we identified a RAS-GTPase activating protein, SsGAP1, which plays essential roles in sclerotia formation, compound appressoria production and virulence. In parallel, as revealed by our knockout analysis, the SsGAP1 ortholog in Botrytis cinerea, BcGAP1, plays similar roles in fungal development and virulence. By knocking down SsRAS1 and SsRAS2, we also revealed that both SsRAS1 and SsRAS2 are required for vegetative growth, sclerotia development, compound appressoria production and virulence in S. sclerotiorum. Due to the major roles these RAS signalling components play in Sclerotiniaceae biology, they can be used as HIGS targets to control diseases caused by both S. sclerotiorum and B. cinerea. Indeed, when we introduced HIGS constructs targeting SsGAP1, SsRAS1 and SsRAS2 in Nicotiana benthamiana and Arabidopsis thaliana, we observed reduced virulence. Taken together, our forward genetics gene discovery pipeline in S. sclerotiorum is highly effective in identifying novel HIGS targets to control S. sclerotiorum and B. cinerea.

Puzzles, challenges, and information reservoir of SARS-CoV-2 quasispecies.

Upon the emergence of SARS-CoV-2 in the human population, it was conjectured that for this coronavirus the dynamic intra-host heterogeneity typical of RNA viruses would be toned down. Nothing of this sort is observed. Here we review the main observations on the complexity and diverse composition of SARS-CoV-2 mutant spectra sampled from infected patients, within the framework of quasispecies dynamics. The analyses suggest that the information provided by myriads of genomic sequences within infected individuals may have a predictive value of the genomic sequences that acquire epidemiological relevance. Possibilities to reconcile the presence of broad mutant spectra in the large RNA coronavirus genome with its encoding a 3' to 5' exonuclease proofreading-repair activity are considered. Indeterminations in the behavior of individual viral genomes provide a benefit for the survival of the ensemble. We propose that this concept falls in the domain of "stochastic thinking," a notion that applies also to cellular processes, as a means for biological systems to face unexpected needs.

Convalescent plasma transfusion for immunocompromised viremic patients with COVID-19: A retrospective multicenter study.

This study aims to assess the safety, virological, and clinical outcomes of convalescent plasma transfusion (CPT) in immunocompromised patients hospitalized for coronavirus disease 2019 (COVID-19). We conducted a retrospective multicenter cohort study that included all immunosuppressed patients with COVID-19 and RNAemia from May 2020 to March 2023 treated with CPT. We included 81 patients with hematological malignancies (HM), transplants, or autoimmune diseases (69% treated with anti-CD20). Sixty patients (74%) were vaccinated, and 14 had pre-CPT serology >264 BAU/mL. The median delay between symptom onset and CPT was 23 days [13-31]. At D7 post-CPT, plasma PCR was negative in 43/64 patients (67.2%), and serology became positive in 25/30 patients (82%). Post-CPT positive serology was associated with RNAemia negativity (p < 0.001). The overall mortality rate at D28 was 26%, being higher in patients with non-B-cell HM (62%) than with B-cell HM (25%) or with no HM (11%) (p = 0.02). Patients receiving anti-CD20 without chemotherapy had the lowest mortality rate (8%). Positive RNAemia at D7 was associated with mortality at D28 in univariate analysis (HR: 3.05 [1.14-8.19]). Eight patients had adverse events, two of which were severe but transient. Our findings suggest that CPT can abolish RNAemia and ameliorate the clinical course in immunocompromised patients with COVID-19.

Correlation of Baseline Tumor Burden with Clinical Outcome in Melanoma Patients Treated with Ipilimumab.

INTRODUCTION: Tumor burden is a frequently mentioned parameter; however, a commonly accepted definition is still lacking. METHODS: In this double-center prospective and retrospective study, 76 patients with unresectable stage III or stage IV melanoma treated with ipilimumab were included. We defined the baseline tumor burden (BTB) as the global sum of all metastases' longest diameters before treatment started and correlated the calculated BTB with disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and with the baseline levels of LDH, S100B, and sULPB2. RESULTS: BTB correlated significantly with DCR (p = 0.009), PFS (p = 0.002), OS (p = 0.032), and the occurrence of NRAS mutation (p = 0.006). BTB was also correlated to baseline serum levels of LDH (p = 0.011), S100B (p = 0.027), and SULBP (p < 0.0001). Multivariate analysis revealed that BPB and LDH were independently correlated with PFS and OS. With increasing BTB, disease control was less likely; no patient with a BTB >200 mm achieved disease control. For patients with brain metastasis, no correlation of BTB with DCR (p = 0.251), PFS (p = 0.059), or OS (p = 0.981) was observed. CONCLUSION: Calculated BTB is an independent prognostic factor for patients with metastatic melanoma treated with ipilimumab. Using calculated BTB as a definition of tumor burden may help increase comparability of outcome of therapies in future studies.

Unlocking influenza B: exploring molecular biology and reverse genetics for epidemic control and vaccine innovation.

Influenza is a highly contagious acute viral illness that affects the respiratory system, posing a significant global public health concern. Influenza B virus (IBV) causes annual seasonal epidemics. The exploration of molecular biology and reverse genetics of IBV is pivotal for understanding its replication, pathogenesis, and evolution. Reverse genetics empowers us to purposefully alter the viral genome, engineer precise genetic modifications, and unveil the secrets of virulence and resistance mechanisms. It helps us in quickly analyzing new virus strains by viral genome manipulation and the development of innovative influenza vaccines. Reverse genetics has been employed to create mutant or reassortant influenza viruses for evaluating their virulence, pathogenicity, host range, and transmissibility. Without this technique, these tasks would be difficult or impossible, making it crucial for preparing for epidemics and protecting public health. Here, we bring together the latest information on how we can manipulate the genes of the influenza B virus using reverse genetics methods, most importantly helper virus-independent techniques.

The applicability of the central line-associated bloodstream infection (CLABSI) criteria for the evaluation of bacteremia episodes in pediatric oncology patients.

BACKGROUND: The aim of this study was to investigate the applicability of the central line-associated bloodstream infection (CLABSI) criteria of the Centers for Disease Control and Prevention in pediatric oncology patients. METHODS: Bacteremia episodes from 2020 to 2022 from a prospective cohort of pediatric oncology patients with a central venous catheter were included. Episodes were classified by three medical experts following the CLABSI criteria as either a CLABSI or non-CLABSI (i.e., contamination, other infection source, or mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI)). Subsequently, they were asked if and why they (dis)agreed with this diagnosis following the criteria. The primary outcome was the percentage of episodes where the experts clinically disagreed with the diagnosis given following the CLABSI criteria. RESULTS: Overall, 84 bacteremia episodes in 71 patients were evaluated. Following the CLABSI criteria, 34 (40%) episodes were classified as CLABSIs and 50 (60%) as non-CLABSIs. In 11 (13%) cases the experts clinically disagreed with the diagnosis following the CLABSI criteria. The discrepancy between the CLABSI criteria and clinical diagnosis was significant; McNemar's test p < .01. Disagreement by the experts with the CLABSI criteria mostly occurred when the experts found an MBI-LCBI a more plausible cause of the bacteremia than a CLABSI due to the presence of a gram negative bacteremia (Pseudomonas aeruginosa n = 3) and/or mucositis. CONCLUSIONS: A discrepancy between the CLABSI criteria and the evaluation of the experts was observed. Adding Pseudomonas aeruginosa as an MBI pathogen and incorporating the presence of mucositis in the MBI-LCBI criteria, might increase the applicability.

Current Situation and Consideration of Prefectural Plans for Promotion of Measures Against Cerebrovascular and Cardiovascular Disease in Japan　- Perspectives on Cardiovascular Disease.

In Japan, cerebrovascular diseases and cardiovascular diseases (CVDs) are major causes of death and long-term care. Against this, the Cerebrovascular and Cardiovascular Disease Control Act was passed by a legislative body and promulgated in December 2018, and enacted on December 1, 2019. Based on the Japanese National Plan for Promotion of Measures Against Cerebrovascular and Cardiovascular Disease (Japanese National Plan), prefectural plans have been formulated and published from March 2021 to January 2023. Although the majority of individual measures were comprehensively articulated in accordance with the Japanese National Plan, some prefectures did not describe individual measures such as research, collection of medical information, consultation support for patients with CVD, palliative care, assistance for patients with sequelae, support for maintaining a balance between treatment and work, and measures from childhood and adolescence. Furthermore, a few specific indicators were set for these measures and those related to chronic care. This review identifies the current status of prefectural plans and discusses future challenges and directions.

Real-time evaluation of a multi-agency TB-screening event for persons experiencing homelessness in a town with a low incidence of TB in England.

Real-time evaluation (RTE) supports populations (e.g., persons experiencing homelessness (PEH) to engage in evaluation of health interventions who may otherwise be overlooked. The aim of this RTE was to explore the understanding of TB amongst PEH, identify barriers/facilitators to attending screening for PEH alongside suggestions for improving TB-screening events targeting PEH, who have high and complex health needs. This RTE composed of free-text structured one-to-one interviews performed immediately after screening at a single tuberculosis (TB) screening event. Handwritten forms were transcribed for thematic analysis, with codes ascribed to answers that were developed into core themes. All RTE participants (n=15) learned about the screening event on the day it was held. Key concerns amongst screening attendees included: stigma around drug use, not understanding the purpose of TB screening, lack of trusted individuals/services present, too many partner organizations involved, and language barriers. Facilitators to screening included a positive welcome to the event, a satisfactory explanation of screening tests, and sharing of results. A need for improved event promotion alongside communication of the purpose of TB screening amongst PEH was also identified. A lack of trust identified by some participants suggests the range of services present should be reconsidered for future screening events.

Evaluation of the mpox surveillance system in Cameroon from 2018 to 2022: a laboratory cross-sectional study.

BACKGROUND: Formal assessment of a surveillance system's features and its ability to achieve objectives is crucial for disease control and prevention. Since the implementation of the mpox surveillance system in Cameroon, no evaluation has been conducted. METHODS: In a cross-sectional study, we assessed the performance of the mpox surveillance system in accordance with the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) guidelines. We collected mpox surveillance data from 2018 to 2022 and conducted a survey with key stakeholders of the surveillance program. The survey results were summarized. The rates of complete reporting and mpox detection, as well as the time lag between the different stages of surveillance were analyzed using R version 4.1. RESULTS: The mpox detection rate was 21.6% (29/134) over the five years under review. Surveillance indicators revealed that a combination of sample types, including vesicles, crust, and blood, was associated with higher case confirmation. Overall, the mpox surveillance system was effective. Weaknesses in terms of simplicity were identified. Most components of the assessed system failed to meet the timeliness and data quality goals, except for the laboratory component, which was commendable. The lack of a computerized shared database and the system's non-sustainability were a course of concern. CONCLUSIONS: Despite all identified bottlenecks in the mpox surveillance system in Cameroon, it was found to meet it stipulated goals. Recommendations are made for training on surveillance system features, particularly at the facility/field level. Therefore, there is a crucial need to globally improve the mpox surveillance system in Cameroon for better disease control.

Antimicrobial resistance in the United States: Origins and future directions.

Antimicrobial resistance (AMR) remains a critical public health problem that pervades hospitals and health systems worldwide. The ongoing AMR crisis is not only concerning for patient care but also healthcare delivery and quality. This article outlines key components of the origins of AMR in the United States and how it presents across the American healthcare system. Numerous factors contributed to the crisis, including agricultural antibiotic use, wasteful prescribing practices in health care, conflicting behaviours among patients and clinicians, patient demand and satisfaction, and payment and reimbursement models that incentivize inappropriate antibiotic use. To combat AMR, clinicians, healthcare professionals, and legislators must continue to promote and implement innovative solutions, including antibiotic stewardship programmes (ASPs), hand hygiene protocols, ample supply of personal protective equipment (PPE), standardized treatment guidelines for antibiotic prescribing, clinician and patient educational programmes, and health policy initiatives. With the rising prevalence of multi-drug resistant bacterial infections, AMR must become a greater priority to policymakers and healthcare stakeholders.

How to protect long-term care facilities from pandemic-like events? - A systematic review on the effectiveness of non-pharmacological measures to prevent viral respiratory infections.

BACKGROUND: The SARS-CoV-2 pandemic underscored the need for pandemic preparedness, with respiratory-transmitted viruses considered as a substantial risk. In pandemics, long-term care facilities (LTCFs) are a high-risk setting with severe outbreaks and burden of disease. Non-pharmacological interventions (NPIs) constitute the primary defence mechanism when pharmacological interventions are not available. However, evidence on the effectiveness of NPIs implemented in LTCFs remains unclear. METHODS: We conducted a systematic review assessing the effectiveness of NPIs implemented in LTCFs to protect residents and staff from viral respiratory pathogens with pandemic potential. We searched Medline, Embase, CINAHL, and two COVID-19 registries in 09/2022. Screening and data extraction was conducted independently by two experienced researchers. We included randomized controlled trials and non-randomized observational studies of intervention effects. Quality appraisal was conducted using ROBINS-I and RoB2. Primary outcomes encompassed number of outbreaks, infections, hospitalizations, and deaths. We synthesized findings narratively, focusing on the direction of effect. Certainty of evidence (CoE) was assessed using GRADE. RESULTS: We analysed 13 observational studies and three (cluster) randomized controlled trials. All studies were conducted in high-income countries, all but three focused on SARS-CoV-2 with the rest focusing on influenza or upper-respiratory tract infections. The evidence indicates that a combination of different measures and hand hygiene interventions can be effective in protecting residents and staff from infection-related outcomes (moderate CoE). Self-confinement of staff with residents, compartmentalization of staff in the LTCF, and the routine testing of residents and/or staff in LTCFs, among others, may be effective (low CoE). Other measures, such as restricting shared spaces, serving meals in room, cohorting infected and non-infected residents may be effective (very low CoE). An evidence gap map highlights the lack of evidence on important interventions, encompassing visiting restrictions, pre-entry testing, and air filtration systems. CONCLUSIONS: Although CoE of interventions was low or very low for most outcomes, the implementation of NPIs identified as potentially effective in this review often constitutes the sole viable option, particularly prior to the availability of vaccinations. Our evidence-gap map underscores the imperative for further research on several interventions. These gaps need to be addressed to prepare LTCFs for future pandemics. TRIAL REGISTRATION: CRD42022344149.

Efficacy and safety of low-dose interleukin 2 in the treatment of moderate-to-severe bullous pemphigoid: A single center perspective-controlled trial.

BACKGROUND: Regulatory T cells (Tregs) are reduced in the peripheral blood and skin lesions of patients with bullous pemphigoid (BP). Low-dose interleukin 2 (IL-2) therapy can stimulate Tregs specifically, suggesting potential for the treatment of BP. OBJECTIVE: To evaluate the response to low-dose IL-2 therapy in the treatment of moderate-to-severe BP. METHODS: Forty-three patients with moderate-to-severe BP were included. The therapy included systemic corticosteroids with an initial dose of 0.5 mg/kg/d for moderate and 1.0 mg/kg/d for severe disease, respectively, combined with allowed immunosuppressants for the control group, whereas in addition to the same corticosteroid therapy, IL-2 (half million IU) was administered subcutaneously every other day for the treatment group for 8 weeks. The primary outcome was the number of days required to achieve disease control. Secondary outcomes included other clinical responses. RESULTS: The number of days required to achieve disease control with the treatment group was (7.60 ± 3.00), which was shorter than in the control group (10.43 ± 3.06) (P = .008). The total amount of systemic corticosteroids was less, and no serious infections were detected in the treatment group. LIMITATIONS: Single center, open-label study with short duration and small size. CONCLUSION: Our trial supports the potential of low-dose IL-2 therapy for patients with moderate-to-severe BP, which showed earlier treatment responses.

Perceptions and practices of Swedish wild boar hunters in relation to African swine fever before the first outbreak in Sweden.

BACKGROUND: The first outbreak of African Swine Fever (ASF) in Sweden was detected in 2023 in wild boar. This study was conducted before the first ASF outbreak with the objective of investigating Swedish hunters' perceptions and practices pertaining to ASF ahead of any potential future outbreak. A mixed-methods interview study with Swedish wild boar hunters, consisting of focus group discussions and a questionnaire, was undertaken between October 2020 and December 2021. Six focus groups were conducted online, and an online questionnaire with questions related to practices and habits concerning hunting, the use of bait and hunting trips was sent to all members of the Swedish Hunting and Wildlife Association. A total of 3244 responses were received. RESULTS: Three general themes were identified in a thematic analysis of the data from the focus groups: hunters are willing to engage in ASF prevention and control, simplicity and feasibility are crucial for the implementation of reporting, sampling and control measures, and more information and the greater involvement of the authorities are required in ASF prevention and control. Results from the questionnaire showed that the use of bait was common. Products of animal origin were rarely used for baiting; the most common product used was maize. Hunting trips abroad, especially outside of the Nordic countries, were uncommon. CONCLUSIONS: Hunting tourism and the use of bait do not seem to constitute a major risk for the introduction of ASF to wild boar populations in Sweden. The accessibility of relevant information for each concerned stakeholder and the ease of reporting and sampling are crucial to maintain the positive engagement of hunters.

Bioproducts of Pseudomonas chlororaphis Suppress DMI Fungicide-Induced CsCYP51A and CsCYP51B Gene Expression in Colletotrichum siamense and Generate Synergistic Effects with Metconazole and Propiconazole.

Mixtures of fungicides with different modes of action are commonly used as disease and resistance management tools, but little is known of mixtures of natural and synthetic products. In this study, mixtures of metabolites from the rhizobacterium Pseudomonas chlororaphis strain ASF009 formulated as Howler EVO with below-label rates (50 µg/ml) of conventional sterol demethylation inhibitor (DMI) fungicides were investigated for control of anthracnose of cherry (Prunus avium) caused by Colletotrichum siamense. Howler mixed with metconazole or propiconazole synergistically reduced disease severity through lesion growth. Real-time PCR showed that difenoconazole, flutriafol, metconazole, and propiconazole induced the expression of DMI target genes CsCYP51A and CsCYP51B in C. siamense. The addition of Howler completely suppressed the DMI fungicide-induced expression of both CYP51 genes. We hypothesize that the downregulation of DMI fungicide-induced expression of the DMI target genes may, at least in part, explain the synergism observed in detached fruit assays.