Tick-Borne Encephalitis

Tick-borne encephalitis (TBE) is an important central nervous system infection in Europe and Asia. It is caused by three subtypes of TBE virus (TBEV): European, Siberian and Far-Eastern, belonging to the genus Flavivirus. TBE is delineated by three criteria: the presence of clinical signs of meningitis, meningoencephalitis or meningoencephalomyelitis; cerebrospinal fluid pleocytosis (>5 × 106 cells/L); and demonstration of a recent infection with TBEV by the presence of specific serum IgM and IgG antibodies or IgG seroconversion. Imaging of the brain and spinal cord has a low sensitivity and specificity, but it is useful for the differential diagnosis. Clinical course and outcome of TBE depend on the subtype of TBEV (the disease caused by the European subtype has a milder acute course and a more favorable long-term outcome than the disease caused by the other two virus subtypes), age of patients (increasing age is associated with more severe acute course and poorer outcome) and probably on some host genetic factors. Due to relatively severe clinical course combined with the absence of etiologic treatment, considerable proportion of patients with incomplete recovery after acute illness, and increasing incidence, TBE represents a growing (public) health problem that could be substantially reduced with vaccination

Antibiotic Combinations with Daptomycin for Treatment of Staphylococcus aureus Infections

Daptomycin is a lipopeptide antibiotic with a unique mechanism of action on Gram-positive bacteria. It is approved for treatment of skin and soft-tissue infections with Gram-positive bacteria, bacteraemia and right-sided infective endocarditis caused by Staphylococcus aureus. Diminishing susceptibility of S. aureus to daptomycin during treatment of complicated infections and clinical failure have been described. Combinations of daptomycin with other antibiotics including gentamicin, rifampin, beta-lactams, trimethoprim/sulfamethoxazole (TMP-SMX), or clarithromycin present a new approach for therapy. In vitro and animal studies have shown that such combinations may, in some cases, be superior to daptomycin monotherapy. In this paper we focus on the antibiotic combinations for complicated S. aureus infections

Concomitant Tickborne Encephalitis and Human Granulocytic Ehrlichiosis

We report a patient with febrile illness and epidemiologic and clinical findings consistent with human granulocytic ehrlichiosis and tickborne encephalitis, in whom infection with Anaplasma phagocytophilum was demonstrated by polymerase chain reaction and seroconversion. Tickborne encephalitis virus infection was established by serum immunoglobulin (Ig) M and IgG antibodies

Impact of Pre-Existing Treatment with Statins on the Course and Outcome of Tick-Borne Encephalitis

OBJECTIVES: Although statins have anti-inflammatory and potentially also antimicrobial (including antiviral) activity, their therapeutic impact on infectious diseases is controversial. In this study, we evaluated whether pre-existing statin use influenced the course and outcome of tick-borne encephalitis. METHODS: To assess the influence of statin usage on the severity of acute illness and the outcome of tick-borne encephalitis, univariate and multivariable analyses were performed for 700 adult patients with tick-borne encephalitis of whom 77 (11%) were being treated with statins, and for 410 patients of whom 53 (13%) were receiving statins, respectively. RESULTS: Multivariable analyses found no statistically significant association between statin usage and having a milder acute illness. There was also no statistically significant benefit with respect to a favorable outcome defined by the absence of post-encephalitic syndrome (ORs for a favorable outcome at 6 months was 0.96, 95% CI: 0.46-2.04, P = 0.926; at 12 months 0.29, 95% CI: 0.06-1.33, P = 0.111; at 2-7 years after acute illness 0.44, 95% CI: 0.09-2.22, P = 0.321), by a reduction in the frequency of six nonspecific symptoms (fatigue, myalgia/arthralgia memory disturbances, headache, concentration disturbances, irritability) occurring during the 4 week period before the last examination, or by higher SF-36 scores in any of the eight separate domains of health as well as in the physical and mental global overall component. Furthermore, there were no significant differences between patients receiving statins and those who were not in the cerebrospinal fluid or serum levels for any of the 24 cytokines/chemokines measured. CONCLUSIONS: In this observational study, we could not prove that pre-existing use of statins affected either the severity of the acute illness or the long-term outcome of tick-borne encephalitis

Detection of human coronaviruses in simultaneously collected stool samples and nasopharyngeal swabs from hospitalized children with acute gastroenteritis

BACKGROUND: Human coronaviruses (HCoVs) are a well-known cause of respiratory infections but their role in gastrointestinal infections is unclear. The objective of our study was to assess the significance of HCoVs in the etiology of acute gastroenteritis (AGE) in children <6 years of age. METHODS: Stool samples and nasopharyngeal (NP) swabs collected from 260 children hospitalized for AGE (160 also had respiratory symptoms) and 157 otherwise healthy control children admitted for elective surgery were tested for the presence of four HCoVs using real time RT-PCR. Registered at ClinicalTrials.gov (reg. NCT00987519). RESULTS: HCoVs were more frequent in patients with AGE than in controls (23/260, 8.8% versus 4/151, 2.6%; odds ratio, OR 3.3; 95% confidence interval, CI 1.3–10.0; P = 0.01). Three of four HCoV-positive members in the control group, asymptomatic when sampled, recalled gastrointestinal or respiratory symptoms within the previous 14 days. In patients with AGE, HCoVs were present in NP samples more often than in stools (22/256, 8.6%, versus 6/260, 2.3%; P = 0.0004). In 5/6 children with HCoVs detected in stools, the viruses were also detected in NP swabs. Patients had a significantly higher probability of HCoV detection in stool (OR 4; 95% CI 1.4–15.3; P = 0.006) and also in stool and/or NP (OR 3.3, 95% CI 1.3–10.0; P = 0.01) than healthy controls. All four HCoVs species were detected in stool and NP samples. CONCLUSIONS: Although HCoVs were more frequently detected in patients with AGE than in the control group, high prevalence of HCoVs in NP swabs compounded by their low occurrence in stool samples and detection of other viruses in stool samples, indicate that HCoVs probably play only a minor role in causing gastrointestinal illness in children <6 years old

Recommendations to Improve Tick-Borne Encephalitis Surveillance and Vaccine Uptake in Europe

There has been an increase in reported TBE cases in Europe since 2015, reaching a peak in some countries in 2020, highlighting the need for better management of TBE risk in Europe. TBE surveillance is currently limited, in part, due to varying diagnostic guidelines, access to testing, and awareness of TBE. Consequently, TBE prevalence is underestimated and vaccination recommendations inadequate. TBE vaccine uptake is unsatisfactory in many TBE-endemic European countries. This review summarizes the findings of a scientific workshop of experts to improve TBE surveillance and vaccine uptake in Europe. Strategies to improve TBE surveillance and vaccine uptake should focus on: aligning diagnostic criteria and testing across Europe; expanding current vaccine recommendations and reducing their complexity; and increasing public education of the potential risks posed by TBEV infection.Peer reviewe

Recommendations to Improve Tick-Borne Encephalitis Surveillance and Vaccine Uptake in Europe

There has been an increase in reported TBE cases in Europe since 2015, reaching a peak in some countries in 2020, highlighting the need for better management of TBE risk in Europe. TBE surveillance is currently limited, in part, due to varying diagnostic guidelines, access to testing, and awareness of TBE. Consequently, TBE prevalence is underestimated and vaccination recommendations inadequate. TBE vaccine uptake is unsatisfactory in many TBE-endemic European countries. This review summarizes the findings of a scientific workshop of experts to improve TBE surveillance and vaccine uptake in Europe. Strategies to improve TBE surveillance and vaccine uptake should focus on: aligning diagnostic criteria and testing across Europe; expanding current vaccine recommendations and reducing their complexity; and increasing public education of the potential risks posed by TBEV infection.Peer reviewe

Development and validation of a prediction model for invasive bacterial infections in febrile children at European Emergency Departments : MOFICHE, a prospective observational study

Funding Information: Funding This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 668303. The research was supported by the National Institute for Health Research Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University. Publisher Copyright: © 2021 Archives of Disease in ChildhoodObjectives: To develop and cross-validate a multivariable clinical prediction model to identify invasive bacterial infections (IBI) and to identify patient groups who might benefit from new biomarkers. Design: Prospective observational study. Setting: 12 emergency departments (EDs) in 8 European countries. Patients: Febrile children aged 0-18 years. Main outcome measures: IBI, defined as bacteraemia, meningitis and bone/joint infection. We derived and cross-validated a model for IBI using variables from the Feverkidstool (clinical symptoms, C reactive protein), neurological signs, non-blanching rash and comorbidity. We assessed discrimination (area under the receiver operating curve) and diagnostic performance at different risk thresholds for IBI: sensitivity, specificity, negative and positive likelihood ratios (LRs). Results: Of 16 268 patients, 135 (0.8%) had an IBI. The discriminative ability of the model was 0.84 (95% CI 0.81 to 0.88) and 0.78 (95% CI 0.74 to 0.82) in pooled cross-validations. The model performed well for the rule-out threshold of 0.1% (sensitivity 0.97 (95% CI 0.93 to 0.99), negative LR 0.1 (95% CI 0.0 to 0.2) and for the rule-in threshold of 2.0% (specificity 0.94 (95% CI 0.94 to 0.95), positive LR 8.4 (95% CI 6.9 to 10.0)). The intermediate thresholds of 0.1%-2.0% performed poorly (ranges: sensitivity 0.59-0.93, negative LR 0.14-0.57, specificity 0.52-0.88, positive LR 1.9-4.8) and comprised 9784 patients (60%). Conclusions: The rule-out threshold of this model has potential to reduce antibiotic treatment while the rule-in threshold could be used to target treatment in febrile children at the ED. In more than half of patients at intermediate risk, sensitive biomarkers could improve identification of IBI and potentially reduce unnecessary antibiotic prescriptions.publishersversionPeer reviewe