Yves Hansmann

Background: Tick-borne encephalitis (TBE) virus is transmitted to humans via tick bites and occasionally via the consumption of unpasteurized milk products. According to the literature, the most important driver of TBE emergence and increase in incidence in humans is changes in human behaviour/activities. Method and principal findings: To compensate for the lack of data, expert opinions were gathered to identify the risk factors for exposure to tick bites linked to twenty-eight human activities (professional or recreational) in forests and to target prevention messages at the populations most at risk. Opinions were elicited from a total of twenty-five European experts. Seven criteria were included in the analysis for each activity: frequency, seasonality, duration of exposure, distance covered, degree of contact with vegetation, speed and average level of protection against tick bites. The activities considered to be the most at risk of exposure to tick bites are, in descending order: three occupational activities (forest monitoring activities, forestry and wood industry activities and scientific and/or analytical activities), five recreational activities and one hunting activity (mushroom picking, spending the night in the forest, hunting, naturalist activities, orienteering, and berry or fruit picking). Conclusions and significance: Prevention messages regarding tick bites could be targeted at people who engage in activities considered in this analysis to be at highest risk of exposure to tick bites.

Background: Within the International Health Regulations framework, the French High Council for Public Health was mandated in 2022 by health authorities to establish a list of priority infectious diseases for public health, surveillance and research in mainland and overseas France. Aim: Our objective was to establish this list. Methods: A multi-criteria decision analysis was used, as recommended by the European Centre for Disease Prevention and Control. A list of 95 entities (infectious diseases or groups of these, including the World Health Organization (WHO)-labelled ‘Disease X’) was established by 17 infectious disease experts. Ten criteria were defined to score entities: incidence rate, case fatality rate, potential for emergence and spread, impact on the individual, on society, on socially vulnerable groups, on the healthcare system, and need for new preventive tools, new curative therapies, and surveillance. Each criterion was assigned a relative weight by 77 multidisciplinary experts. For each entity, 98 physicians from various specialties rated each criterion against the entity, using a four-class Likert-type scale; the ratings were converted into numeric values with a nonlinear scale and respectively weighted to calculate the entity score. Results: Fifteen entities were ranked as high-priorities, including Disease X and 14 known pathologies (e.g. haemorrhagic fevers, various respiratory viral infections, arboviral infections, multidrug-resistant bacterial infections, invasive meningococcal and pneumococcal diseases, prion diseases, rabies, and tuberculosis). Conclusion: The priority entities agreed with those of the WHO in 2023; almost all were currently covered by the French surveillance and alert system. Repeating this analysis periodically would keep the list updated.

Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection is benign in >90% of the cases but can cause mild (<5%), moderate (<4%), or severe (<1%) encephalitis. We show here that ∼10% of patients hospitalized for severe TBE in cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-α2, -β, and/or -ω at the onset of disease, contrasting with only ∼1% of patients with moderate and mild TBE. These auto-Abs were found in two of eight patients who died and none of 13 with silent infection. The odds ratios (OR) for severe TBE in individuals with these auto-Abs relative to those without them in the general population were 4.9 (95% CI: 1.5–15.9, P < 0.0001) for the neutralization of only 100 pg/ml IFN-α2 and/or -ω, and 20.8 (95% CI: 4.5–97.4, P < 0.0001) for the neutralization of 10 ng/ml IFN-α2 and -ω. Auto-Abs neutralizing type I IFNs accounted for ∼10% of severe TBE cases in these three European cohorts.

TBE in France Yves Hansmann and Aurélie Velay E-CDC risk status: endemic (data as of end 2022, updated May 2023) History and current situation The first human case of tick-borne encephalitis virus (TBEV) infection in France was reported in 1968 in Alsace, an eastern region next to the German border: a gamekeeper working in a […]

High-dose amoxicillin and cloxacillin combination therapy is recommended for the empiric treatment of selected patients with infective endocarditis despite a low level of evidence. The main objective of this study was to evaluate the renal tolerance of high-dose intravenous amoxicillin and cloxacillin combination. We studied 27 patients treated with amoxicillin and cloxacillin (≥100 mg/kg daily) for at least 48 h. The primary endpoint was the occurrence of acute kidney injury (AKI). The median patient age was 68 ± 8 years, and 16 (59%) were male. The indication for this combination therapy was suspected or confirmed endocarditis with no bacterial identification in 22 (81%) patients. The primary endpoint occurred in 16 (59%) patients after initiating this combination therapy within an average of 4.4 ± 3.6 days. Among them, seven (26%) patients developed severe AKI, including four (15%) patients who required hemodialysis. Other risk factors for AKI were identified in all patients, including injection of iodinated contrast media in 21 (78%), acute heart failure in 18 (67%), cardiac surgery in 11 (41%), and aminoglycoside use in 9 (33%) patients. This study reports an incidence of 59% of AKI after initiating amoxicillin and cloxacillin combination therapy in a population at high renal risk.

The drivers of critical coronavirus disease 2019 (COVID-19) remain unknown. Given major confounding factors such as age and comorbidities, true mediators of this condition have remained elusive. We used a multi-omics analysis combined with artificial intelligence in a young patient cohort where major comorbidities were excluded at the onset. The cohort included 47 “critical” (in the intensive care unit under mechanical ventilation) and 25 “non-critical” (in a non-critical care ward) patients with COVID-19 and 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cell proteomics, cytokine profiling, and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing, and structural causal modeling were used. Patients with critical COVID-19 were characterized by exacerbated inflammation, perturbed lymphoid and myeloid compartments, increased coagulation, and viral cell biology. Among differentially expressed genes, we observed up-regulation of the metalloproteaseADAM9. This gene signature was validated in a second independent cohort of 81 critical and 73 recovered patients with COVID-19 and was further confirmed at the transcriptional and protein level and by proteolytic activity. Ex vivo ADAM9 inhibition decreased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, cohort of individuals with COVID-19, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. We further identifiedADAM9as a driver of disease severity and a candidate therapeutic target.

Objective: Correct and timely identification of SARS-CoV-2-positive patients is critical in the emergency department (ED) prior to admission to medical wards. Antigen-detecting rapid diagnostic tests (Ag-RDTs) are a rapid alternative to Reverse-transcriptase polymerase chain reaction (RT-PCR) for the diagnosis of COVID-19 but have lower sensitivity. Methods: We evaluated the performance in real-life conditions of a strategy combining Ag-RDT and chest computed tomography (CT) to rule out COVID-19 infection in 1015 patients presenting in the ED between 16 November 2020 and 18 January 2021 in order to allow non-COVID-19 patients to be hospitalized in dedicated units directly. The combined strategy performed in the ED for patients with COVID-19 symptoms was assessed and compared with RT-PCR. Results: Compared with RT-PCR, the negative predictive value was 96.7% for Ag-RDT alone, 98.5% for Ag-RDT/CT combined, and increased to 100% for patients with low viral load. Conclusion: A strategy combining Ag-RDT and chest CT is effective in ruling out COVID-19 in ED patients with high precision.

According to European Society of Cardiology guidelines (ESC2015) for infective endocarditis (IE) management, modified Duke criteria (mDC) are implemented with a degree of clinical suspicion degree, leading to grades such as “possible” or “rejected” IE despite a persisting high level of clinical suspicion. Herein, we evaluate the ¹⁸F-FDG PET/CT diagnostic and therapeutic impact in IE suspicion, with emphasis on possible/rejected IE with a high clinical suspicion. Excluding cases of definite IE diagnosis, 53 patients who underwent ¹⁸F-FDG PET/CT for IE suspicion were selected and afterwards classified according to both mDC (possible IE/Duke 1, rejected IE/Duke 0) and clinical suspicion degree (high and low IE suspicion). The final status regarding IE diagnosis (gold standard) was based on the multidisciplinary decision of the Endocarditis Team, including the ‘imaging specialist’. PET/CT images of the cardiac area were qualitatively interpreted and the intensity of each focus of extra-physiologic ¹⁸F-FDG uptake was evaluated by a maximum standardized uptake value (SUVmax) measurement. Extra-cardiac ¹⁸F-FDG PET/CT pathological findings were considered to be a possible embolic event, a possible source of IE, or even a concomitant infection. Based on the Endocarditis Team consensus, final diagnosis of IE was retained in 19 (36%) patients and excluded in 34 (64%). With a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and global accuracy of 79%, 100%, 100%, 89%, and 92%, respectively, PET/CT performed significantly better than mDC (p = 0.003), clinical suspicion degree (p = 0.001), and a combination of both (p = 0.001) for IE diagnosis. In 41 patients with possible/rejected IE but high clinical suspicion, sensitivity, specificity, PPV, NPV, and global accuracies were 78%, 100%, 100%, 85%, and 90%, respectively. Moreover, PET/CT contributed to patient management in 24 out of 53 (45%) cases. ¹⁸F-FDG PET/CT represents a valuable diagnostic tool that could be proposed for challenging IE cases with significant differences between mDC and clinical suspicion degree. ¹⁸F-FDG PET/CT allows a binary diagnosis (definite or rejected IE) by removing uncertain diagnostic situations, thus improving patient therapeutic management.