SARS-CoV-2 mRNA Vaccination in People with Multiple Sclerosis Treated with Fingolimod: Protective Humoral Immune Responses May Develop after the Preferred Third Shot.

Evidence suggests limited development of protective IgG responses to mRNA-based vaccines in sphingosine-1-phosphate receptor (S1PR)-modulator treated individuals with multiple sclerosis (MS). We studied the extent of the humoral immune response after the preferred third mRNA SARS-CoV-2 vaccine in S1PR-modulator treated people with MS (pwMS) and insufficient IgG responses after the standard immunization scheme. Eight pwMS that were treated with fingolimod received a third homologous SARS-CoV-2 mRNA vaccine dose, either the Moderna's mRNA-1273 or Pfizer-BioNTech's BNT162b2 vaccine. We quantified the serum levels of IgG antibodies against the receptor-binding domain of SARS-CoV-2 four weeks later. An antibody titer of 100 AU/mL or more was considered protective. After the third vaccination, we found clinically relevant IgG titers in four out of eight individuals (50%). We conclude that the humoral immune response may reach protective levels after the third preferred dose of the homologous SARS-CoV-2 mRNA vaccine. Vaccine shots in S1PR-modulator treated pwMS ahead of schedule may be a strategy to overcome insufficient humoral immune responses following the standard vaccination scheme

Management of neurosurgical implant-associated infections.

With the technical developments in neurosurgery, increasing numbers of neurosurgical implants are used in an increasingly aged population of patients with several comorbidities. Consequently, the number of neurosurgical implant-associated infections is continuously raising, resulting in significant morbidity and mortality, including disfiguring skull deformities and lack of brain protection. In this article we review infections associated with craniotomy, cranioplasty, neurostimulators, internal cerebrospinal fluid shunts, and external ventricular and lumbar cerebrospinal fluid drainages. In all implant-associated infections biofilms are involved, which are difficult to eradicate. A low number of microorganisms is sufficient to form a biofilm on the implant surface. In most infections, microorganisms of the skin flora are involved. Microorganisms reach the implant during surgery or immediately thereafter as a result of wound healing disturbances. In about two thirds of patients, implant-associated infections manifest early (within the first month after surgery), whereas the remaining infections present later as a result of low-grade infections or by direct extension from adjacent infections (per continuitatem) to the implants due to soft tissue damage. Except for ventriculo-atrial cerebrospinal fluid shunts, neurosurgical implants are rarely infected by the haematogenous route. In this article we review established and clinically validated concepts for the management of biofilm-associated infections in orthopaedic and trauma surgery, which can be extrapolated to other surgical disciplines that use implants. However, the evidence for the success of this extrapolation to neurosurgical patients is sparse and has not been evaluated in large patient populations. For favourable outcome, an optimised microbiological diagnosis including sonication of removed implants and prolonged incubation of cultures is required. Furthermore, a combined surgical and antimicrobial management strategy is needed. Surgery includes an appropriate debridement with or without implant exchange or removal, depending on the age of the biofilm and the soft tissue condition. Antimicrobial treatment includes a prolonged biofilm-active therapy, typically for 4–12 weeks. This concept is attractive, because in selected patients, implants can be retained or exchanged in a one-stage surgical procedure, which improves not only quality of life, but also decreases morbidity because every additional neurosurgical intervention can lead to secondary complications, including intracerebral bleeding or ischemia

Humoral Immune Response after the Third SARS-CoV-2 mRNA Vaccination in CD20 Depleted People with Multiple Sclerosis.

CD20 depletion is a risk factor for unfavorable outcomes of COVID-19 in people with MS (pwMS). Evidence suggests that protective IgG response to mRNA-based vaccines in B cell-depleted individuals is limited. We studied the seroconversion after the third mRNA SARS-CoV-2 vaccine in B cell-depleted pwMS with limited or no IgG response after the standard immunization. Sixteen pwMS treated with ocrelizumab or rituximab received a third homologous SARS-CoV-2 mRNA vaccine, either the Moderna mRNA-1273 or Pfizer-BioNTech's BNT162b2 vaccine. We quantified the response of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 four weeks later. An antibody titer of 100 AU/mL or more was considered clinically relevant. The median time between the last infusion of the anti-CD20 treatment and the third vaccination was 22.9 weeks (range 15.1-31.3). After the third vaccination, one out of 16 patients showed an IgG titer deemed clinically relevant. Only the seroconverted patient had measurable B-cell counts at the time of the third vaccination. The development of a humoral immune response remains rare in pwMS on anti-CD20 therapy, even after third dose of the homologous SARS-CoV-2 mRNA vaccine. It remains to be determined whether T-cell responses can compensate for the lack of seroconversion and provide sufficient protection against CoV-2 infections

H1N1 outbreak in a Swiss military boot camp--observations and suggestions

The A(H1N1)pdm09 influenza virus is a highly contagious pathogen which caused the 2009 influenza pandemic. The virus is known to affect mainly younger people and may be a problem in crowded living conditions. The aim of the study was to describe a major A(H1N1)pdm09 outbreak in a Swiss military boot camp and to develop suggestions for similar future situations

Risk of SARS-CoV-2 transmission by aerosols, the rational use of masks, and protection of healthcare workers from COVID-19.

OBJECTIVES To determine the risk of SARS-CoV-2 transmission by aerosols, to provide evidence on the rational use of masks, and to discuss additional measures important for the protection of healthcare workers from COVID-19. METHODS Literature review and expert opinion. SHORT CONCLUSION SARS-CoV-2, the pathogen causing COVID-19, is considered to be transmitted via droplets rather than aerosols, but droplets with strong directional airflow support may spread further than 2 m. High rates of COVID-19 infections in healthcare-workers (HCWs) have been reported from several countries. Respirators such as filtering face piece (FFP) 2 masks were designed to protect HCWs, while surgical masks were originally intended to protect patients (e.g., during surgery). Nevertheless, high quality standard surgical masks (type II/IIR according to European Norm EN 14683) appear to be as effective as FFP2 masks in preventing droplet-associated viral infections of HCWs as reported from influenza or SARS. So far, no head-to-head trials with these masks have been published for COVID-19. Neither mask type completely prevents transmission, which may be due to inappropriate handling and alternative transmission pathways. Therefore, compliance with a bundle of infection control measures including thorough hand hygiene is key. During high-risk procedures, both droplets and aerosols may be produced, reason why respirators are indicated for these interventions

Microbiological Screening Is Necessary to Distinguish Carriers of Plasmid-Mediated AmpC Beta-Lactamase-Producing Enterobacteriaceae and Extended-Spectrum Beta-Lactamase (ESBL)-Producing Enterobacteriaceae because of Clinical Similarity

Plasmid-mediated AmpC beta-lactamase-producing (pAmpC) Enterobacteriaceae are increasing worldwide, difficult to identify and often confounded with extended-spectrum beta-lactamase (ESBL) producers. The low prevalence precludes routine universal admission screening. Therefore, we evaluated potential risk factors for carriage of pAmpC-producing Enterobacteriaceae that would allow targeted screening to improve yield and reduce cost.; We performed a case control study at a tertiary care center from 1/2006 to 12/2010. Cases were adult patients in whom pAmpC-producing Enterobacteriaceae were isolated; controls were chosen among carriers of ESBL-producing Enterobacteriaceae. Both infected and colonized patients were included.; Over five years, we identified 40 pAmpC producers in 39 patients among 16,247 screened consecutive isolates of Enterobacteriaceae. The pAmpC prevalence was low (0.25%), but more than 30% of pAmpC carriers received incorrect empirical antibiotic treatment. When compared with 39 ESBL controls, pAmpC carriage was associated with clinically confirmed infections in 74% (versus 51%) (p=0.035), mainly of the urinary tract, previous antibiotic exposure in 63% (versus 36%) (p=0.035) and carriage of a nasogastric tube in 23% (versus 0%) (p=0.002). In the multivariate regression analysis only clinically confirmed infections remained significantly associated with pAmpC carriage (OR 1.44 (95%CI 1.15-2.57)). No other clinical and blood test-associated risk factor allowed discrimination of pAmpC-carrying patients from ESBL controls. The type of acquisition - nosocomial versus community-acquired - was also non-informative for resistance type, as 46% of pAmpC- and 44% of ESBL-producing Enterobacteriaceae were community-acquired.; This study could not identify a clinical profile that would allow targeted screening for pAmpC-producing Enterobacteriaceae when compared to ESBL carriers. Because empiric antimicrobial therapy was inappropriate in more than 30%, rapid identification of pAmpC carriers is needed. New microbiological methods are therefore required to simplify rapid and reliable detection of pAmpC carriers

Management of hepatitis C in decentralised versus centralised drug substitution programmes and minimally invasive point-of-care tests to close gaps in the HCV cascade

In Switzerland, intravenous drug use accounts for the majority of hepatitis C virus (HCV) infections. Early HCV treatment prevents further transmissions and reduces morbidity and mortality due to decompensated liver cirrhosis and hepatocellular carcinoma. Nevertheless, patients in drug substitution programmes are often insufficiently screened and treated.; The aim was to compare the current state of HCV management in centralised and decentralised drug substitution programmes of the canton Aargau. Objectives were human immunodeficiency virus (HIV) and HCV prevalence, compliance with guidelines and gaps in the HCV cascade, as well as feasibility/acceptance/validity of HIV/HCV rapid tests on finger-prick blood and noninvasive liver fibrosis assessment with Fibroscan®.; For the cross-sectional study, in June 2013, questionnaires and free rapid tests for HIV (Determine®) and HCV (OraQuick®) that used capillary blood (finger-stick) were sent to 161 physicians providing drug substitution treatment for 631 patients. Free liver fibrosis assessment with Fibroscan® by a member of the study team was offered to all patients. Additionally, patients were directly recruited by the study team in the heroin substitution programme and several addiction clinics visited every 4-6 months, as well as in the Infectious Diseases Outpatient Clinic (questionnaire, rapid tests and Fibroscan® in the same session).; Between July 2013 and July 2015, 205 (32.5%) of the 631 patients receiving opioid substitution in the canton Aargau were enrolled, 192 (93.7%) with HIV/HCV rapid tests and 167 (81.5%) with Fibroscan®. Acceptance of Fibroscan® was higher when offered in the same session (94.1 vs 69.2%). Overall, 77.8% had ever used intravenous drugs. HCV seroprevalence was 53.7% (109/203), HCV RNA prevalence 27.8%. Overall, 7.4% (15/202) were HIV infected, all of whom were HCV co-infected and under antiretroviral treatment. Of the 205 patients included, 104 (50.7%) were recruited in a decentralised setting (family practice / pharmacy) and 101 (49.3%) in a centralised setting (heroin programme, addiction clinic, Infectious Diseases Outpatient Clinic). Compliance with guidelines (regular HIV/HCV screening, workup of HCV-positive patients, availability of HAV/HBV serology) was consistently lower in the decentralised setting, characterised by a higher proportion of females, longer median time in the programme, lower percentage of daily attendance, ever-use of intravenous drugs and HIV and HCV infections. We identified several gaps in the HCV cascade: 23.9% (49/205) had never been HCV screened; 18.9% (18/95) of the HCV positive patients had no HCV RNA test. Of the 61 patients developing chronic HCV infection, 19.7% (12) were not HCV genotyped, 52.5% (32) had no liver fibrosis assessment (liver biopsy) and 54.1% (33) never received treatment; 25.0% (7/28) did not achieve a sustained virological response with interferon-based treatment. The 192 HCV rapid tests showed a sensitivity of 90.4% (94/104; 95% confidence interval 84.7-96.1%) and a specificity of 100% (88/88), and provided 14 new HCV diagnoses. Eight of ten patients with a false-negative HCV rapid test were HCV RNA negative (2 unknown). Among the 88.6% (39/44) currently HCV RNA-positive individuals with valid Fibroscan® results, 24 (61.5%) had a liver stiffness <7.5 kPa. Both HIV co-infection and alcohol overconsumption doubled the risk of severe fibrosis/cirrhosis in HCV positive patients.; In contrast to HIV, HCV transmission among intravenous drug users is still ongoing. The management of hepatitis C in drug substitution patients needs improvement, especially in family practices. Minimally invasive "point-of-care" diagnostics such as the HCV antibody rapid test using capillary blood and mobile Fibroscan® can close some of the gaps in the HCV cascade. HCV RNA determination in capillary blood is still an unmet need. A "one-stop strategy" might improve linkage to care. Restricting the new, highly efficient (90-100% sustained virological response for all genotypes) direct-acting antivirals to patients with at least stage F2 fibrosis withholds treatment from two thirds of the chronically infected and prevents us from reaching the WHO goal of 80% treatment uptake necessary to eliminate hepatitis C by 2030

Prevalence of plasmid-mediated AmpC beta-lactamase-producing Enterobacteriaceae from 2006 to 2010.

<p>* Number of positive compared to screened isolates (%)</p><p>Prevalence of plasmid-mediated AmpC beta-lactamase-producing Enterobacteriaceae from 2006 to 2010.</p

Distribution of species and molecular types of plasmid-mediated AmpC beta-lactamase- and ESBL-producing Enterobacteriaceae (each 39 patients).

<p>Abbreviations: pAmpC, plasmid-mediated AmpC beta-lactamase; ESBL, Extended-Spectrum Beta-Lactamase; n.a., not available</p><p>* In one patient both <i>E</i>. <i>coli</i> and <i>K</i>. <i>pneumoniae</i> were isolated; this patient counts only once for the <i>E</i>. <i>coli</i> group</p><p>Distribution of species and molecular types of plasmid-mediated AmpC beta-lactamase- and ESBL-producing Enterobacteriaceae (each 39 patients).</p