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Abstract Background Despite the availability of vaccination, TBE (tick-borne encephalitis) remains a global public health problem. Therefore, the aim of our study was to assess the long-term efficacy of vaccinations against tick-borne encephalitis using vaccines available on the European market. Methods The analysis was conducted on the results of a systematic review conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The search was performed in three databases, namely Medline (via PubMed), EMBASE (via Ovid), and the Cochrane Library database. The authors followed the PRISMA method and the selection of the articles was performed with two independent researchers. Results From a total of 199 citations, 9 studies were included in this review. According to the primary studies identified in the search, the efficacy of available anti-TBE vaccines ranges from 90.1% to 98.9%; however, in individuals above the age of 60, the protection wanes as early as one year after vaccination. Administration of a booster dose 3 years after completion of the basic vaccination schedule significantly extended the period of protection against TBE. Conclusions Anti-TBE vaccines available in Europe have a high level of efficacy. However, the level of protection against TBE is decreasing after vaccination. Therefore, in addition to the conventional schedule, booster vaccines should be administered every 5 years in individuals before the age of 60 and more frequently, e.g. every 3 years, in individuals aged 60 and beyond. …

IntroductionFebrile infants 90 days and younger are at risk of invasive bacterial infections (bacteraemia and meningitis) and urinary tract infections. Together this is previously termed serious bacterial infection with an incidence of approximately 10–20%. The National Institute for Health and Care Excellence guidance advocates a cautious approach with most infants requiring septic screening, parenteral broad-spectrum antibiotics and hospital admission. Internationally, variations exist in the approach to febrile infants, with European and North American guidance advocating a tailored approach based on clinical features and biomarker testing. None of the available international clinical decision aids (CDAs) has been validated in the UK and Irish cohorts. The aim of the Febrile Infant Diagnostic Assessment and Outcome (FIDO) Study is to prospectively validate a range of CDAs in a UK and Irish population including CDAs that use procalcitonin testing. Methods and analysisThe FIDO Study is a prospective multicentre mixed-methods cohort study conducted in UK and Irish hospitals. All infants aged 90 days and younger presenting with fever or history of fever (≥38°C) are eligible for inclusion. Infants will receive standard emergency clinical care without delay. Clinical data and blood samples will be collected, and consent will be obtained at the earliest appropriate opportunity using research without prior consent methodology. The performance and cost-effectiveness of CDAs will be assessed. An embedded qualitative study will explore clinician and caregiver views on different approaches to care and perceptions of risk. Ethics and disseminationThis study was reviewed and approved by the Office for Research Ethics Committees Northern Ireland-Health and Social Care Research Ethics Committee B, Public Benefit and Privacy Panel for Health and Social Care Scotland, and Children’s Health Ireland Research and Ethics Committee Ireland. The results of this study will be presented at academic conferences and in peer-reviewed publications. Trial registration numberNCT05259683. …

Abstract Background Dialister pneumosintes is an anaerobic, Gram negative bacillus, found in the human oral cavity and associated with periodontitis. It has also been isolated from gastric mucosa and stool samples. Recent case reports implicate D. pneumosintes in local infection such as dental root canals, sinusitis, Lemierres syndrome and brain abscesses, as well as distal infections of the liver and lung through haematogenous spread. Case presentation We present a novel case of aortic graft infection and aortoenteric fistula (AEF) in a 75 year old Caucasian male, associated with D. pneumosintes bacteraemia. Microbiological evaluation of septic emboli in the lower limbs revealed other gastrointestinal flora. This suggests either AEF leading to graft infection and subsequent distal emboli and bacteraemia, or a dental origin of infection which seeded to the graft, resulting in AEF and systemic infection. To our knowledge this is the first report of D. pneumosintes associated aortic graft infection. The patient underwent surgical explantation, oversew of the aorta and placement of extra-anatomical bypass graft in conjunction with antimicrobial therapy, making a good recovery with discharge home after a 35-day hospital admission. Conclusion We report a case of Dialister pneumosintes bacteraemia associated with aortic graft infection. To our knowledge, vascular graft-associated infection with D. pneumosintes has not been reported before. …

Abstract The objective of the study was to analyze the spatial distribution of vaccination coverage of bacterial meningitis vaccine: A, C, W and Y (menacwy) and identify the association between socioeconomic and social environment factors with menacwy vaccine coverage among adolescents in the state of Minas Gerais (MG), Brazil. This is an ecological, mixed study, conducted with secondary data from the 853 municipalities of the State of MG, Brazil, from 2020 to 2022, provided by the information system of the National Immunization Program. For spatial statistical analysis, spatial dependence and the presence of spatial clusters formed by municipalities with high and low vaccination coverage of Menacwy were evaluated. In the year 2021, MG presented the largest vaccination coverage (60.58%) since the introduction of the Menacwy vaccine by the PNI. Regarding the analysis of global regressions, it is observed that for the year 2020, as the MG Index of Social Responsibility-Health increased and MG Index of Social Responsibility—Public Security increased, increased the vaccination coverage of the municipalities of the Menacwy vaccine. Finally, compared to 2021, similar association was observed in relation to the proportion of the population served by the Family Health Strategy of the municipalities of the state of MG and per capita spending on education activities: as this indicator increased, with increased coverage of the Vaccine of the Menacwy vaccine of the state municipalities. They reinforce the importance of assessing the quality-of-care management and health surveillance system, professional training, and damage reduction to populations, especially adolescents. …

AbstractThe overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of monoantibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement). Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.

Abstract Background Dialister pneumosintes is an anaerobic, Gram negative bacillus, found in the human oral cavity and associated with periodontitis. It has also been isolated from gastric mucosa and stool samples. Recent case reports implicate D. pneumosintes in local infection such as dental root canals, sinusitis, Lemierres syndrome and brain abscesses, as well as distal infections of the liver and lung through haematogenous spread. Case presentation We present a novel case of aortic graft infection and aortoenteric fistula (AEF) in a 75 year old Caucasian male, associated with D. pneumosintes bacteraemia. Microbiological evaluation of septic emboli in the lower limbs revealed other gastrointestinal flora. This suggests either AEF leading to graft infection and subsequent distal emboli and bacteraemia, or a dental origin of infection which seeded to the graft, resulting in AEF and systemic infection. To our knowledge this is the first report of D. pneumosintes associated aortic graft infection. The patient underwent surgical explantation, oversew of the aorta and placement of extra-anatomical bypass graft in conjunction with antimicrobial therapy, making a good recovery with discharge home after a 35-day hospital admission. Conclusion We report a case of Dialister pneumosintes bacteraemia associated with aortic graft infection. To our knowledge, vascular graft-associated infection with D. pneumosintes has not been reported before. …

Abstract The objective of the study was to analyze the spatial distribution of vaccination coverage of bacterial meningitis vaccine: A, C, W and Y (menacwy) and identify the association between socioeconomic and social environment factors with menacwy vaccine coverage among adolescents in the state of Minas Gerais (MG), Brazil. This is an ecological, mixed study, conducted with secondary data from the 853 municipalities of the State of MG, Brazil, from 2020 to 2022, provided by the information system of the National Immunization Program. For spatial statistical analysis, spatial dependence and the presence of spatial clusters formed by municipalities with high and low vaccination coverage of Menacwy were evaluated. In the year 2021, MG presented the largest vaccination coverage (60.58%) since the introduction of the Menacwy vaccine by the PNI. Regarding the analysis of global regressions, it is observed that for the year 2020, as the MG Index of Social Responsibility-Health increased and MG Index of Social Responsibility—Public Security increased, increased the vaccination coverage of the municipalities of the Menacwy vaccine. Finally, compared to 2021, similar association was observed in relation to the proportion of the population served by the Family Health Strategy of the municipalities of the state of MG and per capita spending on education activities: as this indicator increased, with increased coverage of the Vaccine of the Menacwy vaccine of the state municipalities. They reinforce the importance of assessing the quality-of-care management and health surveillance system, professional training, and damage reduction to populations, especially adolescents. …

Bacterial meningitis is defined clinically by a triad that includes fever, neck stiffness and altered mental status and represents a medical emergency with a high mortality rate. Its worldwide incidence in high-income countries is estimated at 80/100,000 individuals per year. Delayed antimicrobial therapy increases mortality and neurological sequelae for survivors. Rapid diagnostic methods were developed to identify the most common pathogens responsible for community-acquired bacterial meningitis.

Purpose of review Congenital infections are a major cause of childhood multidomain neurodevelopmental disabilities. They contribute to a range of structural brain abnormalities that can cause severe neurodevelopmental impairment, cerebral palsy, epilepsy, and neurosensory impairments. New congenital infections and global viral pandemics have emerged, with some affecting the developing brain and causing neurodevelopmental concerns. This review aims to provide current understanding of fetal infections and their impact on neurodevelopment. Recent findings There are a growing list of congenital infections causing neurodevelopmental issues, including cytomegalovirus, Zika virus, syphilis, rubella, lymphocytic choriomeningitis virus, and toxoplasmosis. Fetal exposure to maternal SARS-CoV-2 may also pose risk to the developing brain and impact neurodevelopmental outcomes, although studies have conflicting results. As Zika virus was a recently identified congenital infection, there are several new reports on child neurodevelopment in the Caribbean and Central and South America. For many congenital infections, children with in-utero exposure, even if asymptomatic at birth, may have neurodevelopmental concerns manifest over time. Summary Congenital infections should be considered in the differential diagnosis of a child with neurodevelopmental impairments. Detailed pregnancy history, exposure risk, and testing should guide diagnosis and multidisciplinary evaluation. Children with congenital infections should have long-term follow-up to assess for neurodevelopmental delays and other neurosensory impairments. Children with confirmed delays or high-risk should be referred for rehabilitation therapies.

Objective: Cryptococcal meningitis (CM) is a leading cause of mortality in people living with HIV (PLHIV). Despite recommendation by the National programme, Cryptococcal Antigen (CrAg) screening in PLHIV with CD4 …

Tick‐borne encephalitis virus (TBEV) is a flavivirus commonly found in at least 27 European and Asian countries. It is an emerging public health problem, with steadily increasing case numbers over recent decades. Tick‐borne encephalitis virus affects between 10,000 and 15,000 patients annually. Infection occurs through the bite of an infected tick and, much less commonly, through infected milk consumption or aerosols. The TBEV genome comprises a positive‐sense single‐stranded RNA molecule of ∼11 kilobases. The open reading frame is > 10,000 bases long, flanked by untranslated regions (UTR), and encodes a polyprotein that is co‐ and post‐transcriptionally processed into three structural and seven non‐structural proteins. Tick‐borne encephalitis virus infection results in encephalitis, often with a characteristic biphasic disease course. After a short incubation time, the viraemic phase is characterised by non‐specific influenza‐like symptoms. After an asymptomatic period of 2–7 days, more than half of patients show progression to a neurological phase, usually characterised by central and, rarely, peripheral nervous system symptoms. Mortality is low—around 1% of confirmed cases, depending on the viral subtype. After acute tick‐borne encephalitis (TBE), a minority of patients experience long‐term neurological deficits. Additionally, 40%–50% of patients develop a post‐encephalitic syndrome, which significantly impairs daily activities and quality of life. Although TBEV has been described for several decades, no specific treatment exists. Much remains unknown regarding the objective assessment of long‐lasting sequelae. Additional research is needed to better understand, prevent, and treat TBE. In this review, we aim to provide a comprehensive overview of the epidemiology, virology, and clinical picture of TBE.

Monoamine oxidase (MAO) is a membrane‐bound mitochondrial enzyme that maintains the steady state of neurotransmitters and other biogenic amines in biological systems through catalytic oxidation and deamination. MAO dysfunction is closely related to human neurological and psychiatric diseases and cancers. However, little is known about the relationship between MAO and viral infections in humans. This review summarises current research on how viral infections participate in the occurrence and development of human diseases through MAO. The viruses discussed in this review include hepatitis C virus, dengue virus, severe acute respiratory syndrome coronavirus 2, human immunodeficiency virus, Japanese encephalitis virus, Epstein‐Barr virus, and human papillomavirus. This review also describes the effects of MAO inhibitors such as phenelzine, clorgyline, selegiline, M‐30, and isatin on viral infectious diseases. This information will not only help us to better understand the role of MAO in the pathogenesis of viruses but will also provide new insights into the treatment and diagnosis of these viral diseases.

Abstract Purpose There is an overlap in the cerebrospinal fluid (CSF) characteristics of patients presenting with different etiologies of CSF pleocytosis. Here, we characterized patients with CSF pleocytosis treated in a large hospital. Methods A retrospective cohort study of 1150 patients with an elevated CSF leukocyte count > 5 cells/µl treated at a university hospital in Germany from January 2015 to December 2017 was performed. Information on clinical presentation, laboratory parameters, diagnosis and outcome was collected. Clinical and laboratory features were tested for their potential to differentiate between bacterial meningitis (BM) and other causes of CSF pleocytosis. Results The most common etiologies of CSF pleocytosis were CNS infections (34%: 20% with detected pathogen, 14% without), autoimmune (21%) and neoplastic diseases (16%). CSF cell count was higher in CNS infections with detected pathogen (median 82 cells/µl) compared to autoimmune (11 cells/µl, p = 0.001), neoplastic diseases (19 cells/µl, p = 0.01) and other causes (11 cells/µl, p  100 cells/µl, CSF protein > 100 mg/dl, CRP > 5 mg/dl, elevated white blood cell count, abnormal mental status and nuchal rigidity are important indicators. The CHANCE score identified patients with BM with high sensitivity (92.1%) and specificity (90.9%) (derivation cohort: AUC: 0.955, validation cohort: AUC: 0.956). Conclusion Overall, the most common causes for CSF pleocytosis include infectious, neoplastic or autoimmune CNS diseases in ~ 70% of patients. The CHANCE score could be of help to identify patients with high likelihood of BM and support clinical decision making. …

Abstract Purpose There is an overlap in the cerebrospinal fluid (CSF) characteristics of patients presenting with different etiologies of CSF pleocytosis. Here, we characterized patients with CSF pleocytosis treated in a large hospital. Methods A retrospective cohort study of 1150 patients with an elevated CSF leukocyte count > 5 cells/µl treated at a university hospital in Germany from January 2015 to December 2017 was performed. Information on clinical presentation, laboratory parameters, diagnosis and outcome was collected. Clinical and laboratory features were tested for their potential to differentiate between bacterial meningitis (BM) and other causes of CSF pleocytosis. Results The most common etiologies of CSF pleocytosis were CNS infections (34%: 20% with detected pathogen, 14% without), autoimmune (21%) and neoplastic diseases (16%). CSF cell count was higher in CNS infections with detected pathogen (median 82 cells/µl) compared to autoimmune (11 cells/µl, p = 0.001), neoplastic diseases (19 cells/µl, p = 0.01) and other causes (11 cells/µl, p  100 cells/µl, CSF protein > 100 mg/dl, CRP > 5 mg/dl, elevated white blood cell count, abnormal mental status and nuchal rigidity are important indicators. The CHANCE score identified patients with BM with high sensitivity (92.1%) and specificity (90.9%) (derivation cohort: AUC: 0.955, validation cohort: AUC: 0.956). Conclusion Overall, the most common causes for CSF pleocytosis include infectious, neoplastic or autoimmune CNS diseases in ~ 70% of patients. The CHANCE score could be of help to identify patients with high likelihood of BM and support clinical decision making. …

Tropical Medicine &International Health, EarlyView.

These ESCMID guidelines are intended for clinicians involved in diagnosis and treatment of brain abscess in children and adults.

by Hui Wang, Yulu Fang, Yongtao Jia, Jiajie Tang, Changzheng Dong Enterovirus B (EVB) is a common species of enterovirus, mainly consisting of Echovirus (Echo) and Coxsackievirus B (CVB). The population is generally susceptible to EVB, especially among children. Since the 21st century, EVB has been widely prevalent worldwide, and can cause serious diseases, such as viral meningitis, myocarditis, and neonatal sepsis. By using cryo-electron microscopy, the three-dimensional (3D) structures of EVB and their uncoating receptors (FcRn and CAR) have been determined, laying the foundation for the study of viral pathogenesis and therapeutic antibodies. A limited number of epitopes bound to neutralizing antibodies have also been determined. It is unclear whether additional epitopes are present or whether epitope mutations play a key role in molecular evolutionary history and epidemics, as in influenza and SARS-CoV-2. In the current study, the conformational epitopes of six representative EVB serotypes (E6, E11, E30, CVB1, CVB3 and CVB5) were systematically predicted by bioinformatics-based epitope prediction algorithm. We found that their epitopes were distributed into three clusters, where the VP1 BC loop, C-terminus and VP2 EF loop were the main regions of EVB epitopes. Among them, the VP1 BC loop and VP2 EF loop may be the key epitope regions that determined the use of the uncoating receptors. Further molecular evolution analysis based on the VP1 and genome sequences showed that the VP1 C-terminus and VP2 EF loop, as well as a potential “breathing epitope” VP1 N-terminus, were common mutation hotspot regions, suggesting that the emergence of evolutionary clades was driven by epitope mutations. Finally, footprints showed mutations were located on or near epitopes, while mutations on the receptor binding sites were rare. This suggested that EVB promotes viral epidemics by breaking the immune barrier through epitope mutations, but the mutations avoided the receptor binding sites. The bioinformatics study of EVB epitopes may provide important information for the monitoring and early warning of EVB epidemics and developing therapeutic antibodies.