Surge in Imported Cutaneous Leishmaniasis Cases from Mexico in 2023: A Case Series.

In Europe, American cutaneous leishmaniasis caused by Leishmania mexicana is a rare imported disease. A series of six cases in 2023 is a noteworthy escalation at our institutions compared to the past two decades. This surge is likely linked to an increase of cases and environmental changes in South-Eastern Mexico.

Prevalence of infectious diseases, immunity to vaccine-preventable diseases and chronic medical conditions among Ukrainian refugees in Germany - A cross sectional study from the German Network University Medicine (NUM).

BACKGROUND: Vulnerability to infectious diseases in refugees is dependent on country of origin, flight routes, and conditions. Information on specific medical needs of different groups of refugees is lacking. We assessed the prevalence of infectious diseases, immunity to vaccine-preventable diseases, and chronic medical conditions in children, adolescents, and adult refugees from Ukraine who arrived in Germany in 2022. METHODS: Using different media, we recruited Ukrainian refugees at 13 sites between 9-12/2022. An antigen test for acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, serologies for a range of vaccine-preventable diseases, as well as interferon gamma release assays (IGRAs) for tuberculosis (TB), and SARS-CoV-2 were performed. We assessed personal and family history of chronic medical conditions, infectious diseases, vaccination status, and conditions during migration. RESULTS: Overall, 1793 refugees (1401 adults and 392 children/adolescents) were included. Most participants were females (n = 1307; 72·3%) and from Eastern or Southern Ukraine. TB IGRA was positive in 13% (n = 184) of the adults and in 2% (n = 7) of the children. Serology-based immunological response was insufficient in approximately 21% (360/1793) of the participants for measles, 32% (572/1793) for diphtheria, and 74% (1289/1793) for hepatitis B. CONCLUSIONS: We show evidence of low serological response to vaccine-preventable infections and increased LTBI prevalence in Ukrainian refugees. These findings should be integrated into guidelines for screening and treatment of infectious diseases in migrants and refugees in Germany and Europe. Furthermore, low immunity for vaccine-preventable diseases in Ukrainians independent of their refugee status, calls for tailor-made communication efforts.

Panton-Valentine leukocidin-induced neutrophil extracellular traps lack antimicrobial activity and are readily induced in patients with recurrent PVL + -Staphylococcus aureus infections.

Staphylococcus aureus strains that produce the toxin Panton-Valentine leukocidin (PVL-SA) frequently cause recurrent skin and soft tissue infections. PVL binds to and kills human neutrophils, resulting in the formation of neutrophil extracellular traps (NETs), but the pathomechanism has not been extensively studied. Furthermore, it is unclear why some individuals colonized with PVL-SA experience recurring infections whereas others are asymptomatic. We thus aimed to (1) investigate how PVL exerts its pathogenicity on neutrophils and (2) identify factors that could help to explain the predisposition of patients with recurring infections. We provide genetic and pharmacological evidence that PVL-induced NET formation is independent of NADPH oxidase and reactive oxygen species production. Moreover, through NET proteome analysis we identified that the protein content of PVL-induced NETs is different from NETs induced by mitogen or the microbial toxin nigericin. The abundance of the proteins cathelicidin (CAMP), elastase (NE), and proteinase 3 (PRTN3) was lower on PVL-induced NETs, and as such they were unable to kill S. aureus. Furthermore, we found that neutrophils from affected patients express higher levels of CD45, one of the PVL receptors, and are more susceptible to be killed at a low PVL concentration than control neutrophils. Neutrophils from patients that experience recurring PVL-positive infections may thus be more sensitive to PVL-induced NET formation, which might impair their ability to combat the infection.

Percutaneous drainage and combined praziquantel-albendazole therapy: a novel approach for the treatment of simple echinococcal liver cysts.

Cystic echinococcosis (CE) is a worldwide helminthic zoonosis causing serious disease in humans. The WHO Informal Working Group on Echinococcosis recommends a stage-specific treatment approach of hepatic CE that facilitates the decision on what therapy option is most appropriate. Percutaneous aspiration, instillation of a scolicide, e.g., ethanol or hypertonic saline, and subsequent re-aspiration (PAIR) have been advocated for treating medium-size unilocular WHO-stage CE1 cysts. PAIR can pose a risk of toxic cholangitis because of spillage of ethanol in the case of a cysto-biliary fistula or of life-threatening hypernatriaemia when hypertonic saline is used. The purpose of our study is to develop an alternative, safe, minimally invasive method to treat CE1 cysts, avoiding the use of toxic topic scolicides.We opt for percutaneous drainage (PD) in four patients: the intrahepatic drainage catheter is placed under CT-fluoroscopy, intracystic fluid is aspirated, and the viability of intracystic echinococcal protoscolices is assessed microscopically. Oral praziquantel (PZQ) is added to albendazole (ABZ) instead of using topical scolicidals.Protoscolices degenerate within 5 to 10 days after PZQ co-medication at a cumulative dosage of 250 to 335 mg/kg, and the cysts collapse. The cysts degenerate, and no sign of spillage nor relapse is observed in the follow-up time of up to 24 months post-intervention.In conclusion, PD combined with oral PZQ under ABZ coverage is preferable to PAIR in patients with unilocular echinococcal cysts.

Comparing SARS-CoV-2 antigen-detection rapid diagnostic tests for COVID-19 self-testing/self-sampling with molecular and professional-use tests: a systematic review and meta-analysis.

Self-testing is an effective tool to bridge the testing gap for several infectious diseases; however, its performance in detecting SARS-CoV-2 using antigen-detection rapid diagnostic tests (Ag-RDTs) has not been systematically reviewed. This study aimed to inform WHO guidelines by evaluating the accuracy of COVID-19 self-testing and self-sampling coupled with professional Ag-RDT conduct and interpretation. Articles on this topic were searched until November 7th, 2022. Concordance between self-testing/self-sampling and fully professional-use Ag-RDTs was assessed using Cohen's kappa. Bivariate meta-analysis yielded pooled performance estimates. Quality and certainty of evidence were evaluated using QUADAS-2 and GRADE tools. Among 43 studies included, twelve reported on self-testing, and 31 assessed self-sampling only. Around 49.6% showed low risk of bias. Overall concordance with professional-use Ag-RDTs was high (kappa 0.91 [95% confidence interval (CI) 0.88-0.94]). Comparing self-testing/self-sampling to molecular testing, the pooled sensitivity and specificity were 70.5% (95% CI 64.3-76.0) and 99.4% (95% CI 99.1-99.6), respectively. Higher sensitivity (i.e., 93.6% [95% CI 90.4-96.8] for Ct < 25) was estimated in subgroups with higher viral loads using Ct values as a proxy. Despite high heterogeneity among studies, COVID-19 self-testing/self-sampling exhibits high concordance with professional-use Ag-RDTs. This suggests that self-testing/self-sampling can be offered as part of COVID-19 testing strategies.Trial registration: PROSPERO: CRD42021250706.

Corrigendum: Determinants of COVID-19 vaccine acceptance and access among people experiencing homelessness in Germany: a qualitative interview study.

[This corrects the article DOI: 10.3389/fpubh.2023.1148029.].

A COVID-19 isolation facility for people experiencing homelessness in Berlin, Germany: a retrospective patient record study.

Introduction: People experiencing homelessness (PEH) are disproportionately affected by the COVID-19 pandemic. For many PEH it is impossible to isolate due to the lack of permanent housing. Therefore, an isolation facility for SARS-CoV-2 positive PEH was opened in Berlin, Germany, in May 2020, offering medical care, opioid and alcohol substitution therapy and social services. This study aimed to assess the needs of the admitted patients and requirements of the facility. Materials and methods: This was a retrospective patient record study carried out in the isolation facility for PEH in Berlin, from December 2020 to June 2021. We extracted demographic and clinical data including observed psychological distress from records of all PEH tested positive for SARS-CoV-2 by RT-PCR. Data on duration and completion of isolation and the use of the facilities' services were analyzed. The association of patients' characteristics with the completion of isolation was assessed by Student's t-test or Fisher's exact test. Results: A total of 139 patients were included in the study (89% male, mean age 45 years, 41% with comorbidities, 41% non-German speakers). 81% of patients were symptomatic (median duration 5 days, range 1-26). The median length of stay at the facility was 14 days (range 2-41). Among the patients, 80% had non-COVID-19 related medical conditions, 46% required alcohol substitution and 17% opioid substitution therapy. Three patients were hospitalized due to low oxygen saturation. No deaths occurred. Psychological distress was observed in 20%, and social support services were used by 65% of PEH. The majority (82%) completed the required isolation period according to the health authority's order. We did not observe a statistically significant association between completion of the isolation period and sociodemographic characteristics. Conclusion: The specialized facility allowed PEH a high compliance with completion of the isolation period. Medical care, opioid and alcohol substitution, psychological care, language mediation and social support are essential components to address the specific needs of PEH. Besides contributing to infection prevention and control, isolation facilities may allow better access to medical care for SARS-CoV-2 infected PEH with possibly positive effects on the disease course.

Can haematological changes constitute a surrogate diagnostic parameter to detect schistosomiasis in migrants and travellers? - A retrospective analysis.

Background: Earlier studies found characteristic haematological changes in African patients with active schistosomiasis. If consistently present, full blood counts (FBC) may be helpful to diagnose schistosomiasis also in migrants and returning travellers. Methods: A retrospective patient record review was conducted on data from seven European travel clinics, comparing FBC of Schistosoma egg-positive travellers and migrants to reference values. Sub-analyses were performed for children, returned travellers, migrants and different Schistosoma species. Results: Data analysis included 382 subjects (median age 21.0 years [range 2-73]). In returned travellers, decreases in means of haemoglobin particularly in females (ß = -0.82 g/dL, p = 0.005), MCV (ß = -1.6 fL, p = 0.009), basophils, neutrophils, lymphocytes and monocytes (ß = -0.07, p < 0.001; -0.57, p = 0.012; -0.57, p < 0.001 and -0.13 103/µL, p < 0.001, respectively) were observed. As expected, eosinophils were increased (ß = +0.45 103/µL, p < 0.001). In migrants, a similar FBC profile was observed, yet thrombocytes and leukocytes were significantly lower in migrants (ß = -48 103/µL p < 0.001 and ß = -2.35 103/µL, p < 0.001, respectively). Conclusions: Active egg-producing Schistosoma infections are associated with haematological alterations in returned travellers and migrants. However, these differences are discrete and seem to vary among disease stage and Schistosoma species. Therefore, the FBC is unsuitable as a surrogate diagnostic parameter to detect schistosomiasis.

Increased Fusobacterium tumoural abundance affects immunogenicity in mucinous colorectal cancer and may be associated with improved clinical outcome.

There is currently an urgent need to identify factors predictive of immunogenicity in colorectal cancer (CRC). Mucinous CRC is a distinct histological subtype of CRC, associated with a poor response to chemotherapy. Recent evidence suggests the commensal facultative anaerobe Fusobacterium may be especially prevalent in mucinous CRC. The objectives of this study were to assess the association of Fusobacterium abundance with immune cell composition and prognosis in mucinous CRC. Our study included two independent colorectal cancer patient cohorts, The Cancer Genome Atlas (TCGA) cohort, and a cohort of rectal cancers from the Beaumont RCSI Cancer Centre (BRCC). Multiplexed immunofluorescence staining of a tumour microarray (TMA) from the BRCC cohort was undertaken using Cell DIVE technology. Our cohorts included 87 cases (13.3%) of mucinous and 565 cases (86.7%) of non-mucinous CRC. Mucinous CRC in the TCGA dataset was associated with an increased proportion of CD8 + lymphocytes (p = 0.018), regulatory T-cells (p = 0.001) and M2 macrophages (p = 0.001). In the BRCC cohort, mucinous RC was associated with enhanced CD8 + lymphocyte (p = 0.022), regulatory T-cell (p = 0.047), and B-cell (p = 0.025) counts. High Fusobacterium abundance was associated with an increased proportion of CD4 + lymphocytes (p = 0.031) and M1 macrophages (p = 0.006), whilst M2 macrophages (p = 0.043) were under-represented in this cohort. Patients with increased Fusobacterium relative abundance in our mucinous CRC TCGA cohort tended to have better clinical outcomes (DSS: likelihood ratio p = 0.04, logrank p = 0.052). Fusobacterium abundance may be associated with improved outcomes in mucinous CRC, possibly due to a modulatory effect on the host immune response. KEY MESSAGES: • Increased Fusobacterium relative abundance was not found to be associated with microsatellite instability in mucinous CRC. • Increased Fusobacterium relative abundance was associated with an M2/M1 macrophage switch, which is especially significant in mucinous CRC, where M2 macrophages are overexpressed. • Increased Fusobacterium relative abundance was associated with a significant improvement in disease specific survival in mucinous CRC. • Our findings were validated at a protein level within our own in house mucinous and non-mucinous rectal cancer cohorts.

COVID-19 impact on EuroTravNet infectious diseases sentinel surveillance in Europe.

BACKGROUND: The COVID-19 pandemic resulted in a sharp decline of post-travel patient encounters at the European sentinel surveillance network (EuroTravNet) of travellers' health. We report on the impact of COVID-19 on travel-related infectious diseases as recorded by EuroTravNet clinics. METHODS: Travelers who presented between January 1, 2019 and September 30, 2021 were included. Comparisons were made between the pre-pandemic period (14 months from January 1, 2019 to February 29, 2020); and the pandemic period (19 months from March 1, 2020 to September 30, 2021). RESULTS: Of the 15,124 visits to the network during the 33-month observation period, 10,941 (72%) were during the pre-pandemic period, and 4183 (28%) during the pandemic period. Average monthly visits declined from 782/month (pre-COVID-19 era) to 220/month (COVID-19 pandemic era). Among non-migrants, the top-10 countries of exposure changed after onset of the COVID-19 pandemic; destinations such as Italy and Austria, where COVID-19 exposure peaked in the first months, replaced typical travel destinations in Asia (Thailand, Indonesia, India). There was a small decline in migrant patients reported, with little change in the top countries of exposure (Bolivia, Mali). The three top diagnoses with the largest overall decreases in relative frequency were acute gastroenteritis (-5.3%), rabies post-exposure prophylaxis (-2.8%), and dengue (-2.6%). Apart from COVID-19 (which rose from 0.1% to 12.7%), the three top diagnoses with the largest overall relative frequency increase were schistosomiasis (+4.9%), strongyloidiasis (+2.7%), and latent tuberculosis (+2.4%). CONCLUSIONS: A marked COVID-19 pandemic-induced decline in global travel activities is reflected in reduced travel-related infectious diseases sentinel surveillance reporting.

Determinants of COVID-19 vaccine acceptance and access among people experiencing homelessness in Germany: A qualitative interview study.

Introduction: People experiencing homelessness face lower life expectancy, higher prevalence of somatic and mental diseases and a more difficult access to healthcare compared to people in secure living. During the COVID-19 pandemic transmission rates were higher among people experiencing homelessness and preventive public health measures were not properly adapted to the specific needs of people experiencing homelessness. Thus, goal of our study was understanding the determinants of acceptability and access of the COVID-19 vaccine. Materials and methods: We conducted a qualitative interview study with twenty guideline interviews with adult people currently experiencing homelessness in Berlin, Germany (August 2021 - April 2022). Participants were approached in a purposive sampling strategy. The interviews were analyzed with qualitative content analysis according to Mayring. Results: Acceptance and attitude toward the COVID-19 vaccine is influenced by confidence in the vaccine as well as in the political and healthcare system, the individual COVID-19 risk perception and sense of collective responsibility. Overall, the acceptance of the vaccine was high among our participants. Facilities offering low threshold COVID-19 vaccines for people experiencing homelessness were perceived as helpful. Language barriers and the need for identity documents were major barriers to access the COVID 19 vaccine. Discussion: People experiencing homelessness are a marginalized and vulnerable group often underrepresented in the public and scientific discourse. During the COVID-19 pandemic, preventive public health measures, including the COVID-19 vaccine, failed to consider specific needs of people experiencing homelessness. Multidimensional strategy to enhance inclusive healthcare are needed to improve access and to reduce discrimination and stigmatization.

SuSiPed: An initial step towards a universal, low-cost, 3D-printable platform for pediatric minimal-invasive surgery training.

BACKGROUND: Training platforms such as the Fundamentals of Laparoscopic Surgery have become an integral part of postgraduate adult general surgical education. So far, however, there is no such universal tool for pediatric minimal-invasive surgery (MIS). We therefore designed and validated a novel 3D printable pediatric MIS simulation program. METHODS: The SuSiPed (Surgical Simulation in Pediatrics) curriculum consists of 6 MIS training modules: camera guidance, shell transfer, figure cutting, cyst resection, single interrupted suturing, and slipknot suturing. All modules can be 3D printed, and thus manufactured in a low-cost, sustainable and reproducible fashion. Instructional videos for the participants for each module were created. For validation, a group of medical students and surgical residents were compared to a group of pediatric surgical specialists with experience in MIS. All participants performed the entire SuSiPed curriculum 3 times, measuring time to task completion and technical mistakes. The results of the last attempt were compared using Welch's T-test. RESULTS: There were 25 participants in the novice group and 5 in expert group. Times to task completion were lower in the expert group for all modules except camera guidance. Errors were significantly more frequent during slipknot suturing in the novice group, while there were no difference in the other modules. CONCLUSION: Our novel training platform showed good construct validity for 5 out of 6 modules, while scores of camera navigation was not associated with prior experience. The SuSiPed platform is useful for pediatric minimal-invasive surgery training and evaluation, even in low-resource countries where expensive simulators are not affordable. LEVEL OF EVIDENCE: Level III, Validation Study.

Multiplexed Immunofluorescence Imaging Reveals an Immune-Rich Tumor Microenvironment in Mucinous Rectal Cancer Characterized by Increased Lymphocyte Infiltration and Enhanced Programmed Cell Death Protein 1 Expression.

BACKGROUND: Mucinous rectal cancer is associated with a higher incidence of microsatellite instability and a poorer response to neoadjuvant chemoradiotherapy compared to other subtypes of rectal adenocarcinoma. Immune checkpoint inhibitors are an emerging family of anticancer therapeutics associated with highly variable outcomes in colorectal cancer. Although the immune landscape of mucinous rectal cancer has not been fully explored, the presence of mucin is thought to act as a barrier preventing immune-cell infiltration. OBJECTIVE: The aim of this study was to determine the immune properties of mucinous rectal cancer and investigate the degree of lymphocyte infiltration in this cohort. DESIGN: This is a retrospective cohort study that involved multiplexed immunofluorescence staining of tumor microarrays. SETTINGS: Samples originated from a single university teaching hospital. PATIENTS: Our cohort included 15 cases of mucinous and 43 cases of nonmucinous rectal cancer. MAIN OUTCOME MEASURES: Immune cells were classified and quantified. Immune-cell counts were compared between mucinous and nonmucinous cohorts. Immune marker expression within tumor epithelial tissue was evaluated to determine the degree of lymphocyte infiltration. RESULTS: Cytotoxic ( p = 0.022) and regulatory T cells ( p = 0.010) were found to be overrepresented in the mucinous cohort compared to the nonmucinous group. Programmed cell death protein 1 expression was also found to be significantly greater in the mucinous group ( p = 0.001). CD3 ( p = 0.001) and CD8 ( p = 0.054) expressions within the tumor epithelium were also higher in the mucinous group, suggesting adequate immune infiltration despite the presence of mucin. In our analysis, microsatellite instability status was not a predictor of immune marker expression. LIMITATIONS: The relatively small size of the cohort. CONCLUSIONS: Mucinous rectal cancer is associated with an immune-rich tumor microenvironment, which was not associated with microsatellite instability status. See Video Abstract at http://links.lww.com/DCR/C65 . IMGENES DE INMUNOFLUORESCENCIA MULTIPLEXADAS REVELAN UN MICROAMBIENTE TUMORAL RICO EN INMUNIDAD EN EL CNCER RECTAL MUCINOSO CARACTERIZADO POR UNA MAYOR INFILTRACIN DE LINFOCITOS Y UNA EXPRESIN MEJORADA DE PD: ANTECEDENTES:El cáncer rectal mucinoso se asocia con una mayor incidencia de inestabilidad de microsatélites y una peor respuesta a la quimiorradioterapia neoadyuvante en comparación con otros subtipos de adenocarcinoma rectal. Los inhibidores de puntos de control inmunitarios son una familia emergente de tratamientos contra el cáncer asociados con resultados muy variables en el cáncer colorrectal. Aunque el panorama inmunitario del cáncer rectal mucinoso no se ha explorado completamente, se cree que la presencia de mucina actúa como una barrera que previene la infiltración de células inmunitarias.OBJETIVO:El objetivo de este estudio fue determinar las propiedades inmunes del cáncer de recto mucinoso e investigar el grado de infiltración de linfocitos en esta cohorte.DISEÑO:Este es un estudio de cohorte retrospectivo que involucró la tinción de inmunofluorescencia multiplexada de micromatrices tumorales.AJUSTES:Las muestras se originaron en un solo hospital docente universitario.PACIENTES:Nuestra cohorte incluyó 15 casos de cáncer de recto mucinoso y 43 casos de cáncer de recto no mucinosoPRINCIPALES MEDIDAS DE RESULTADO:Las células inmunitarias se clasificaron y cuantificaron. Se compararon los recuentos de células inmunitarias entre cohortes mucinosas y no mucinosas. Se evaluó la expresión del marcador inmunitario dentro del tejido epitelial tumoral para determinar el grado de infiltración de linfocitos.RESULTADOS:Se encontró que las células T citotóxicas ( p = 0,022) y reguladoras ( p = 0,010) estaban sobrerrepresentadas en la cohorte mucinosa en comparación con el grupo no mucinoso. También se encontró que la expresión de PD-1 era significativamente mayor en el grupo mucinoso ( p = 0,001). La expresión de CD3 ( p = 0,001) y CD8 ( p = 0,054) dentro del epitelio tumoral también fue mayor en el grupo mucinoso, lo que sugiere una infiltración inmunitaria adecuada a pesar de la presencia de mucina. En nuestro análisis, no se encontró que el estado de inestabilidad de los microsatélites sea un predictor de la expresión del marcador inmunitario.LIMITACIONES:El tamaño relativamente pequeño de la cohorte.CONCLUSIONES:El cáncer rectal mucinoso se asocia con un microambiente tumoral rico en inmunidad, que no se asoció con el estado de inestabilidad de microsatélites. Consulte el Video del Resumen en http://links.lww.com/DCR/C65 . (Traducción- Dr. Yesenia Rojas-Khalil ).

Bcl-xL Is a Key Mediator of Apoptosis Following KRASG12C Inhibition in KRASG12C-mutant Colorectal Cancer.

Novel covalent inhibitors of KRASG12C have shown limited response rates in patients with KRASG12C-mutant (MT) colorectal cancer. Thus, novel KRASG12C inhibitor combination strategies that can achieve deep and durable responses are needed. Small-molecule KRASG12C inhibitors AZ'1569 and AZ'8037 were used. To identify novel candidate combination strategies for AZ'1569, we performed RNA sequencing, siRNA, and high-throughput drug screening. Top hits were validated in a panel of KRASG12CMT colorectal cancer cells and in vivo. AZ'1569-resistant colorectal cancer cells were generated and characterized. We found that response to AZ'1569 was heterogeneous across the KRASG12CMT models. AZ'1569 was ineffective at inducing apoptosis when used as a single agent or combined with chemotherapy or agents targeting the EGFR/KRAS/AKT axis. Using a systems biology approach, we identified the antiapoptotic BH3-family member BCL2L1/Bcl-xL as a top hit mediating resistance to AZ'1569. Further analyses identified acute increases in the proapoptotic protein BIM following AZ'1569 treatment. ABT-263 (navitoclax), a pharmacologic Bcl-2 family inhibitor that blocks the ability of Bcl-xL to bind and inhibit BIM, led to dramatic and universal apoptosis when combined with AZ'1569. Furthermore, this combination also resulted in dramatically attenuated tumor growth in KRASG12CMT xenografts. Finally, AZ'1569-resistant cells showed amplification of KRASG12C, EphA2/c-MET activation, increased proinflammatory chemokine profile and cross-resistance to several targeted agents. Importantly, KRAS amplification and AZ'1569 resistance were reversible upon drug withdrawal, arguing strongly for the use of drug holidays in the case of KRAS amplification. Taken together, combinatorial targeting of Bcl-xL and KRASG12C is highly effective, suggesting a novel therapeutic strategy for patients with KRASG12CMT colorectal cancer.

Anti-seizure effects of JNJ-54175446 in the intra-amygdala kainic acid model of drug-resistant temporal lobe epilepsy in mice.

There remains a need for new drug targets for treatment-resistant temporal lobe epilepsy. The ATP-gated P2X7 receptor coordinates neuroinflammatory responses to tissue injury. Previous studies in mice reported that the P2X7 receptor antagonist JNJ-47965567 suppressed spontaneous seizures in the intraamygdala kainic acid model of epilepsy and reduced attendant gliosis in the hippocampus. The drug-resistance profile of this model is not fully characterised, however, and newer P2X7 receptor antagonists with superior pharmacokinetic profiles have recently entered clinical trials. Using telemetry-based continuous EEG recordings in mice, we demonstrate that spontaneous recurrent seizures in the intraamygdala kainic acid model are refractory to the common anti-seizure medicine levetiracetam. In contrast, once-daily dosing of JNJ-54175446 (30 mg/kg, intraperitoneal) resulted in a significant reduction in spontaneous recurrent seizures which lasted several days after the end of drug administration. Using a combination of immunohistochemistry and ex vivo radiotracer assay, we find that JNJ-54175446-treated mice at the end of recordings display a reduction in astrogliosis and altered microglia process morphology within the ipsilateral CA3 subfield of the hippocampus, but no difference in P2X7 receptor surface expression. The present study extends the characterisation of the drug-resistance profile of the intraamygdala kainic acid model in mice and provides further evidence that targeting the P2X7 receptor may have therapeutic applications in the treatment of temporal lobe epilepsy.

Participatory development and implementation of inclusive digital health communication on COVID-19 with homeless people.

Introduction: People experiencing homelessness (PEH) are disproportionally affected by the COVID-19 pandemic. The realities of their daily lives have been given little consideration in the pandemic response. They are not represented in existing health information campaigns, and many are structurally excluded from digital information. The project aimed to develop inclusive COVID-19-information material to strengthen infection prevention and control of PEH. Material and methods: In a participatory process, PEH were involved in the planning, production, and evaluation of poster and video information material on COVID-19. Various stakeholders were consulted for external supervision. Service providers all over Germany were informed about the material that could be ordered free of charge. For the evaluation, semi-structured interviews with homeless service providers and PEH were conducted, and the online views of the videos were measured. Results: Sixteen PEH participated actively in the project. Two COVID-19-information videos were launched in 5 languages in February 2021. Posters promoting vaccination against COVID-19 were produced in 9 languages. As of May 2022, the videos have been viewed more than 2,000 times. A total of 163 service providers for PEH and public institutions received the posters, thereof 72 upon request. Twelve service providers and 8 PEH participated in the evaluation. They pointed out the lack of targeted information material for PEH. The consideration of the concerns and the diverse representation of PEH was perceived as particularly important. Most of the service providers were unable to show the videos due to technical and spatial limitations. Digital challenges for PEH, like the lack of and maintenance of a smart phone, became apparent. Conclusion: The cooperation of research, practice and the community were key factors for the realization of this project. Strong links to the community and the involvement of relevant stakeholders are indispensable when working with PEH. Exclusion from digital information is an increasingly important component of the structural marginalization of PEH. Digital inclusion for PEH and service providers can help to counteract social and health inequalities. The lessons learned through this project can contribute to strengthen participation of PEH and to consider their perspectives in future health communication strategies.

A Multicenter Clinical Diagnostic Accuracy Study of SureStatus, an Affordable, WHO Emergency Use-Listed, Rapid, Point-Of-Care Antigen-Detecting Diagnostic Test for SARS-CoV-2.

Access to reverse transcription-PCR (RT-PCR) testing, the gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection, is limited throughout the world, due to restricted resources, available infrastructure, and high costs. Antigen-detecting rapid diagnostic tests (Ag-RDTs) overcome some of these barriers, but independent clinical validations in settings of intended use are scarce. To inform the World Health Organization's (WHO) emergency use listing (EUL) procedure and ensure affordable, high-quality Ag-RDTs, we assessed the performance and ease of use of the SureStatus for SARS-CoV-2. For this prospective, multicenter diagnostic accuracy study, we recruited unvaccinated participants with presumed SARS-CoV-2 infection in India and Germany from December 2020 to March 2021, when the Alpha (B.1.1.7) variant was predominantly circulating. Paired swabs were performed for (i) routine clinical RT-PCR testing (sampling was either nasopharyngeal [NP] or combined NP and oropharyngeal [NP/OP]) and (ii) Ag-RDT (sampling was NP). Performance of the Ag-RDT was compared to RT-PCR overall and by predefined subgroups, e.g., cycle threshold (CT) value, symptoms, and days from symptom onset. To understand the usability, a system usability scale (SUS) questionnaire and ease-of-use (EoU) assessment were performed. A total of 1,119 participants were included in the analysis, of whom 205 (18.3%) were RT-PCR positive. SureStatus detected 169 out of 205 RT-PCR-positive participants, reporting a sensitivity of 82.4% (95% confidence interval [CI]: 76.6% to 87.1%) and a specificity of 98.5% (95% CI: 97.4% to 99.1%). In the first 7 days post-symptom onset, the sensitivity was 90.7% (95% CI: 83.5% to 94.9%), when CT values were low and viral loads were high. The test was characterized as easy to use (SUS, 85/100) and considered suitable for point-of-care settings, although quality concerns were raised due to visibly contaminated packaging of swabs included in the test kits. The SureStatus diagnostic test can be considered a reliable test during the first week of SARS-CoV-2 infection, with high sensitivity in combination with excellent usability. IMPORTANCE Our manufacturer-independent, prospective diagnostic accuracy study assessed clinical performance in participants presumed to have a SARS-CoV-2 infection at three study sites in two countries. We assessed the accuracy overall and in predefined subgroups (CT values and symptom duration). SureStatus performed with high sensitivity. Its sensitivity was particularly high in the first 3 days after symptom onset and when CT values were low (i.e., the viral load was high). The system usability and ease-of-use assessment complements the accuracy assessment of the test and highlights critical factors to facilitate the widespread use of SureStatus in point-of-care settings. The high sensitivity demonstrated by the evaluated Ag-RDT within the first days of symptoms, when most transmission occurs, supports the role of Ag-RDTs for public health-relevant screening. Evidence from this study was used to inform the World Health Organization Emergency Use Listing procedure.

Skin Infections Due to Panton-Valentine Leukocidin-Producing S. Aureus.

BACKGROUND: Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus (PVL-SA) strains are frequently associated with large, recurring abscesses in otherwise healthy young individuals. The typical clinical presentation and the recommended diagnostic evaluation and treatment are not widely known. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed, with special attention to international recommendations. RESULTS: PVL-SA can cause leukocytolysis and dermatonecrosis through specific cell-wall pore formation. Unlike other types of pyoderma, such conditions caused by PVL-SA have no particular site of predilection. In Germany, the PVL gene can be detected in 61.3% (252/411) of skin and soft tissue infections with S. aureus. Skin and soft tissue infections with PVL-SA recur three times as frequently as those due to PVL-negative S. aureus. They are diagnosed by S. aureus culture from wound swabs and combined nasal/pharyngeal swabs, along with PCR for gene detection. The acute treatment of the skin abscesses consists of drainage, followed by antimicrobial therapy if needed. Important secondary preventive measures include topical cleansing with mupirocin nasal ointment and whole-body washing with chlorhexidine or octenidine. The limited evidence (level IIb) concerning PVL-SA is mainly derived from nonrandomized cohort studies and experimental analyses. CONCLUSION: PVL-SA skin infections are easily distinguished from other skin diseases with targeted history-taking and diagnostic evaluation.