Incidence of COVID-19 mRNA vaccine symptomatic breakthrough infections during Omicron circulation in adults with or without infection prior to vaccination.

OBJECTIVES: COVID-19 vaccine breakthrough infections were frequently reported during circulation of the Omicron variant. The ANRS|MIE CoviCompareP study investigated these infections in adults vaccinated and boosted with BNT162b2 [Pfizer-BioNTech] and with/without SARS-CoV-2 infection before vaccination. METHODS: In the first half of 2021, healthy adults (aged 18-45, 65-74 and 75 or older) received either one dose of BNT162b2 (n = 120) if they had a documented history of SARS-CoV-2 infection at least five months previously, or two doses (n = 147) if they had no history confirmed by negative serological tests. A first booster dose was administered at least 6 months after the primary vaccination, and a second booster dose, if any, was reported in the database. Neutralizing antibodies (NAbs) against the European (D614G) strain and the Omicron BA.1 variant were assessed up to 28 days after the first booster dose. A case-control analysis was performed for the 252 participants who were followed up in 2022, during the Omicron waves. RESULTS: From January to October 2022, 78/252 (31%) had a documented symptomatic breakthrough infection after full vaccination: 21/117 (18%) in those who had been infected before vaccination vs. 57/135 (42%) in those who had not. In a multivariate logistic regression model, factors associated with a lower risk of breakthrough infection were older age, a higher number of booster doses, and higher levels of Omicron BA.1 NAb titers in adults with infection before vaccination, but not in those without prior infection. CONCLUSION: Our results highlight the need to consider immune markers of protection in association with infection and vaccination history.

Comparing ethanol lock therapy versus vancomycin lock in a salvation strategy for totally implantable vascular access device infections due to coagulase-negative staphylococci (the ETHALOCK study): a prospective double-blind randomized clinical trial.

OBJECTIVES: Little is known about efficacy and safety of ethanol lock therapy (ELT) to treat totally implantable venous access device (TIVAD) infections. The objective of this trial was to evaluate the effectiveness and safety profile of a local treatment with ELT without removal for TIVAD infection due to coagulase-negative staphylococci. METHODS: We performed a prospective, multicenter, double-blind, randomized clinical trial comparing the efficacy of 40% ELT versus vancomycin lock therapy (VLT) in TIVAD infections due to coagulase-negative staphylococci, complicated or not by bloodstream infection. RESULTS: Thirty-one patients were assigned to the ELT group and 30 to the VLT arm. Concomitant bacteremia was present in 41 patients (67.2%). Treatment success was 58.1 % (18 of 31) for the ELT arm and 46.7% (14 of 30) for the VLT arm (p = 0.37). The overall treatment success was 52.5% (32). The risk of treatment failure due to uncontrolled infections, superinfections, and mechanical complications did not differ significantly between participants receiving ELT (13 out of 31 [42%]) and those receiving VLT (16 out of 30 [53%]) with a hazard ratio of 0.70 (p = 0.343; 95% CI [0.34-1.46], Cox model). Catheter malfunctions were significantly more frequent in the ELT arm (11 patients versus 2 in the VLT group, p = 0.01). CONCLUSIONS: We found an overall high rate of treatment failure that did not differ between the ELT arm and the VLT arm. TIVAD removal must be prioritized to prevent complications (uncontrolled infections, superinfections, and catheter malfunctions) except in exceptional situations.

Exploring convolutional neural networks with transfer learning for diagnosing Lyme disease from skin lesion images.

BACKGROUND AND OBJECTIVE: Lyme disease which is one of the most common infectious vector-borne diseases manifests itself in most cases with erythema migrans (EM) skin lesions. Recent studies show that convolutional neural networks (CNNs) perform well to identify skin lesions from images. Lightweight CNN based pre-scanner applications for resource-constrained mobile devices can help users with early diagnosis of Lyme disease and prevent the transition to a severe late form thanks to appropriate antibiotic therapy. Also, resource-intensive CNN based robust computer applications can assist non-expert practitioners with an accurate diagnosis. The main objective of this study is to extensively analyze the effectiveness of CNNs for diagnosing Lyme disease from images and to find out the best CNN architectures considering resource constraints. METHODS: First, we created an EM dataset with the help of expert dermatologists from Clermont-Ferrand University Hospital Center of France. Second, we benchmarked this dataset for twenty-three CNN architectures customized from VGG, ResNet, DenseNet, MobileNet, Xception, NASNet, and EfficientNet architectures in terms of predictive performance, computational complexity, and statistical significance. Third, to improve the performance of the CNNs, we used custom transfer learning from ImageNet pre-trained models as well as pre-trained the CNNs with the skin lesion dataset HAM10000. Fourth, for model explainability, we utilized Gradient-weighted Class Activation Mapping to visualize the regions of input that are significant to the CNNs for making predictions. Fifth, we provided guidelines for model selection based on predictive performance and computational complexity. RESULTS: Customized ResNet50 architecture gave the best classification accuracy of 84.42% ±1.36, AUC of 0.9189±0.0115, precision of 83.1%±2.49, sensitivity of 87.93%±1.47, and specificity of 80.65%±3.59. A lightweight model customized from EfficientNetB0 also performed well with an accuracy of 83.13%±1.2, AUC of 0.9094±0.0129, precision of 82.83%±1.75, sensitivity of 85.21% ±3.91, and specificity of 80.89%±2.95. All the trained models are publicly available at https://dappem.limos.fr/download.html, which can be used by others for transfer learning and building pre-scanners for Lyme disease. CONCLUSION: Our study confirmed the effectiveness of even some lightweight CNNs for building Lyme disease pre-scanner mobile applications to assist people with an initial self-assessment and referring them to expert dermatologist for further diagnosis.

Impact of Vitamin D Supplementation on Influenza Vaccine Response and Immune Functions in Deficient Elderly Persons: A Randomized Placebo-Controlled Trial.

Background: Immunosenescence contributes to reduced vaccine response in elderly persons, and is worsened by deficiencies in nutrients such as Vitamin (Vit-D). The immune system is a well-known target of Vit-D, which can both potentiate the innate immune response and inhibit the adaptive system, and so modulate vaccination response. Objective: This randomized placebo-controlled double-blind trial investigated whether Vit-D supplementation in deficient elderly persons could improve influenza seroprotection and immune response. Design: Deficient volunteers (Vit-D serum <30 ng/mL) were assigned (V1) to receive either 100,000 IU/15 days of cholecalciferol (D, n = 19), or a placebo (P, n = 19), over a 3 month period. Influenza vaccination was performed at the end of this period (V2), and the vaccine response was evaluated 28 days later (V3). At each visit, serum cathelicidin, immune response to vaccination, plasma cytokines, lymphocyte phenotyping, and phagocyte ROS production were assessed. Results: Levels of serum 25-(OH)D increased after supplementation (D group, V1 vs. V2: 20.7 ± 5.7 vs. 44.3 ± 8.6 ng/mL, p < 0.001). No difference was observed for serum cathelicidin levels, antibody titers, and ROS production in D vs. P groups at V3. Lower plasma levels of TNFα (p = 0.040) and IL-6 (p = 0.046), and higher ones for TFGß (p = 0.0028) were observed at V3. The Th1/Th2 ratio was lower in the D group at V2 (D: 0.12 ± 0.05 vs. P: 0.18 ± 0.05, p = 0.039). Conclusions: Vit-D supplementation promotes a higher TGFß plasma level in response to influenza vaccination without improving antibody production. This supplementation seems to direct the lymphocyte polarization toward a tolerogenic immune response. A deeper characterization of metabolic and molecular pathways of these observations will aid in the understanding of Vit-D's effects on cell-mediated immunity in aging. This clinical trial was registered at clinicaltrials.gov as NCT01893385.

Clinical, virological and immunological features of HIV-positive children internationally adopted in France from 2005-2015.

OBJECTIVE(S): To describe the clinical, virological and immune characteristics of internationally adopted children on arrival in France and after 6-months follow-up. DESIGN: Multicenter retrospective study. METHODS: 30 centers from 24 cities were asked to include, after informed consent, HIV+ children living in France and internationally adopted between 1st Jan 2005 and 1st Jan 2015. Sociodemographic, medical and biological variables collected during the first medical evaluation in France and 6 months later were analyzed. RESULTS: 41 HIV+ adoptees were included (female: 56%; median age: 3.91 years) in 14 centers. Adoptees tend to represent an increasing part of newly diagnosed HIV positive children over the years. The majority came from East-Asia. At arrival, one child was diagnosed with lymphobronchial tuberculosis and three with latent chronic hepatitis B, cleared HBV infection and chronic active hepatitis C, respectively. The mean CD4% was 32.8 ± 9% (range: 13-49%). The 34 children (83%) have been initiated on treatment from their countries of origin. Of these, 25 (74%) had an undetectable viral load (VL) on arrival. Resistance to ART was detected in five. At 6 months, 36 adoptees received ART, and the VL was undetectable in 29 children (71%), with one acquired resistance to NRTI & NNRTI. CONCLUSIONS: An increasing number of HIV-infected children have been internationally adopted in France since 2005. Most of the children have been initiated on treatment from their countries of origin, had good immunity, with few opportunistic infections, and infrequently detectable VL. Low level of mutation conferring resistance was detected.

Skin diseases in internationally adopted children.

Internationally adopted children often present diseases contracted in the country of origin. Skin diseases are common in new arrivals, and diagnosis may prove challenging for GPs or even dermatologists if they are inexperienced in the extensive geographic and ethnic diversity of international adoptees. To analyse the frequency and characteristics of skin diseases in international adoptees. In total, 142 adoptees were evaluated for a cross-sectional cohort study. The most frequent diseases observed at arrival were dermatological conditions. Of the adoptees, 70% presented at least one skin disease, of which 57.5% were infectious; Tinea capitis being the most frequent (n = 42). The recovery rate of Tinea capitis was 89% (n = 32/36). Ten cases of scabies were diagnosed. Other diseases included viral skin infection (n = 22), with 16 cases of Molluscum contagiosum and bacterial infection. Skin diseases are very common in internationally adopted children. There is a need for close collaboration between dermatologists and paediatricians to diagnose such infections, as well as clear guidelines to treat them.

[Vancomycin-resistant Enterococcus in an epidemic situation: screening at admission for patients at risk of carriage]. / Entérocoques résistant aux glycopeptides dans un contexte endémo-épidémique. Stratégie d'isolement àl'admission des patients à risque.

OBJECTIVES: To evaluate a strategy based on screening and isolation at admission to a department of infectious diseases during an epidemic of vancomycin-resistant Enterococcus (VRE) at the University Hospital of Clermont-Ferrand. METHODS: Systematic screening for VRE by anal swabs began on November 15, 2004. Patients were isolated on admission if (a) they had been hospitalized more than 24 h in an at-risk department of our hospital or (b) they had received a course of wide-spectrum antimicrobial therapy for longer than 48 h in the three months preceding admission. Patients hospitalized in our department were screened weekly if they were treated with wide-spectrum antibiotics, had a urinary catheter left in place for one week, or were neutropenic. RESULTS: Through May 15, 2005, 12 (3.5%) of 341 swabs were found to be positive for VRE: eight were detected on admission and four during hospitalization. In all, 81 patients were isolated on admission. A case-control study confirmed that the criteria for patient isolation were indeed risk factors for VRE. Isolation was well accepted when it was clearly explained. No new case has been detected since March 2005. CONCLUSION: An isolation strategy based on known risk factors for VRE with systematic screening on admission appears to be an effective way to control an outbreak of VRE, perhaps in part because it helps to keep the medical staff alert to this problem. Isolation is well tolerated as long as it is explained clearly.